CN107582560A - The thrombus dissolving effect and its application of akebiasaponin D - Google Patents
The thrombus dissolving effect and its application of akebiasaponin D Download PDFInfo
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- CN107582560A CN107582560A CN201710950361.6A CN201710950361A CN107582560A CN 107582560 A CN107582560 A CN 107582560A CN 201710950361 A CN201710950361 A CN 201710950361A CN 107582560 A CN107582560 A CN 107582560A
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Abstract
The invention discloses the effect of the thrombus dissolving of akebiasaponin D and its application.The discovery of akebiasaponin D antithrombotic acitivity of the present invention has novelty.Tested by anti-mouse lung thrombus and anti-rat carotid artery thrombosis, ASD is in body thrombolysis activity for research.There is significant application prospect in thrombotic diseases are treated.
Description
Technical field
The invention belongs to technical field of traditional Chinese medicines, and in particular to akebiasaponin D is in antithrombotic and thrombolytic agent is prepared
Using.
Background technology
Thrombotic diseases are one group of circulation system diseases for seriously endangering human health, it is characterized in that blocking after thrombosis
Regional flow comes off into embolus clog downstream blood flow, so as to cause organ-tissue ischemic, necrosis.Thrombotic diseases have a lot
Kind, including myocardial infarction (AMI), brain bolt dead (CE), lung thrombus (PE), dvt (DVT) and peripheral vessels embolism
(VIE) their morbidity mode differs, and its Crack cause has the causes of disease such as vascular injury, blood change, blood stream stasis.It is seriously to endanger
The disease of victimization class health and lives, its incidence of disease, disability rate and the death rate are all very high.Counted according to the World Health Organization, thrombus
Disease is the first big killer of the mankind, and it is to die from thrombus disease to have 23% every year, hence it is evident that more than diseases such as malignant tumour, pulmonary tuberculosis,
The year two thousand thirty is expected, the number for dying from cardiovascular and cerebrovascular disease (mainly heart disease and stroke) will be increased to 23,300,000 people, it is contemplated that
Cardiovascular and cerebrovascular disease will continue to turn into the primary cause of the death.
The treatment method of thrombotic diseases includes anti-bolt, thrombolysis, interventional therapy and operative treatment, anti-bolt, thromboembolism treatment quilt
It is considered to treat thrombotic disease most efficient method.Therefore, the thrombolytic drug developed efficiently, special, safe is very significant.
Although current anti-bolt, thrombolytic drug have been achieved for significant achievement on treatment thrombotic disease, from preferably anti-
Bolt, thrombolytic drug also have a certain distance.Comparatively, there is anti-bolt, the Chinese medicine of thrombolytic effect to show certain advantage, in
The advantages such as the active definite, Small side effects of medical instrument, are increasingly valued by people.Chinese medicine uses multi-disciplinary cooperation multi-angle
Study of Traditional Chinese Medicine mechanism of action promoting blood circulation and removing blood stasis, action target spot has diversity, in terms of antithrombotic, can not only suppress platelet aggregation
Collection, influence clotting mechanism, reduce blood viscosity, moreover it is possible to play a part of thrombolysis, brought newly for clinical treatment thrombus relevant disease
Hope.Study and find that antithrombotic reagent is significant from Chinese medicine.
The content of the invention
It is an object of the invention to provide application of the akebiasaponin D in antithrombotic or/and thrombolytic agent is prepared.
A further object of the present invention is in the application in providing akebiasaponin D and treating thrombotic diseases medicine in preparation.
The purpose of the present invention can be achieved through the following technical solutions：
Application of the akebiasaponin D in antithrombotic or/and thrombolytic agent is prepared.
Akebiasaponin D is preparing the application in treating thrombotic diseases medicine.Research finds that akebiasaponin D (ASD) has
The anti-bolt of conspicuousness, thrombolysis activity effect.
Described thrombotic diseases include dead myocardial infarction, brain bolt, lung thrombus, dvt and peripheral vessels bolt
Plug.
Described medicine includes akebiasaponin D and pharmaceutically acceptable carrier or customary adjuvant.
The formulation of the medicine includes injection type and peroral dosage form.Described injection type be preferably water/spindle agent or
Powder-injection；Described peroral dosage form is tablet, capsule, granule, dripping pill, oral liquid or powder.
Beneficial effects of the present invention：
The discovery of akebiasaponin D antithrombotic acitivity of the present invention has novelty.Pass through anti-mouse lung thrombus and anti-rat neck
Arterial thrombosis is tested, and ASD is in body thrombolysis activity for research.There is significant application prospect in thrombotic diseases are treated.
Embodiment
Embodiment 1ASD parenteral solution anti-mouse lungs thrombus acts on experimental study
1. experiment purpose：Probe into the effect of ASD parenteral solution anti-mouse lungs thrombus.
2. experiment material
2.1 drug material：
(self-control, preparation method is referring to the patent of inventor poplar middle forest, Patent No. ZL201210454454.7, patent by ASD
A kind of enrichment of entitled akebiasaponin D and purification process, its purity 97%), Danshen injection polyphenol hydrochlorate (upper sea green paddy system
Medicine Co., Ltd, lot number：20150247), urokinase injection (Livzon Pharmaceutical Factory, Livzon Group, lot number：
170207), collagen (Sigma, lot number：C7661), adrenaline (Shanghai Hefeng Pharmaceutical Co., Ltd., lot number：
10160606), physiological saline, distilled water, alcohol swab, 1ml syringes etc..
2.2 animal：Cleaning grade kunming mice 156 (male and female half and half).
3. experimental method
3.1 the preparation of reagent and decoction
3.1.1 each dosage parenteral solutions of ASD are prepared：
ASD active compound 15.1mg, 30.0mg, 60.1mg, 120mg, 240mg are taken respectively, respectively with physiological saline solution constant volume
To 10ml, filtered through No. 4 sintered glass funnels, respectively be made concentration be 1.5mg/ml, 3mg/ml, 6mg/ml, 12mg/ml,
24mg/ml ASD parenteral solutions.
3.1.2 each dosage oral administration solutions of ASD are prepared：
ASD active compound 57.0mg, 171.0mg, 513.0mg are taken respectively, is settled to 25ml with physiological saline solution respectively, respectively
With the ASD gavage solution that obtained concentration is 2.28mg/ml, 6.84mg/ml, 20.52mg/ml.
3.1.3 Danshen injection polyphenol acid salt solution is prepared
Danshen injection polyphenol hydrochlorate freeze-dried powder 26mg is taken, 10ml is settled to normal saline solution dissolving, it is dense with being made
Spend the Danshen injection polyphenol acid salt solution for 2.6mg/ml.
3.1.4 the preparation of urokinase injection liquid
Urokinase injection 1 (100,000U) is taken, adds physiological saline 10mL, is dissolved, is configured to concentration as 10,000U/
ML urokinase solution.
3.1.5 the preparation of modeling agent solution：
The type i collagen for weighing 2.03mg is put in 50mL EP pipes, adds 1mL adrenalin hydrochloride parenteral solutions (1mgmL- 1), 20mL is settled to physiological saline, that is, is obtained containing 0.1mgmL- 1Type i collagen and 0.05mgmL- 1On hydrochloric acid kidney
The modeling agent solution of parathyrine.
3.2 medications, volume and dosage
ASD and each positive drug group take tail vein injection to be administered, and administered volume is 10mL/kg, and dosage divides
It is not：ASD injection each group dosage is respectively 15mg/kg, 30mg/kg, 60mg/kg, 120mg/kg, 240mg/kg.Urokinase group
Dosage is 100,000U/kg, and Danshen injection polyphenol hydrochlorate group dosage is 26mg/kg.Orally each dosage group administered volume is equal by ASD
For 20mL/kg, dosage is respectively 45.6mg/kg, 136.8mg/kg, 410.4mg/kg.
3.3 observational technique
156 mouse are taken, are randomly divided into 12 groups, every group 13, male and female half and half, respectively blank group, model group, western positive group
(urokinase), middle-jiao yang, function of the spleen and stomach group (Danshen injection polyphenol hydrochlorate), ASD inject each dosage group (5 dosage groups), the oral each dosage of ASD
Group (3 dosage groups).In addition to model group tail vein is injected intravenously physiological saline, other organize the equal corresponding medicine of tail vein injection,
After 1h is administered, each group tail vein injection modeling agent, death condition in 15min after observation mouse modeling, after calculating mouse modeling
15min survival rate.
Survival rate (%)=animal survival number/animal number × 100%
4. experimental result
Each administration group mouse survival rate experimental result (n=10) in 15min after the lung thrombus model modeling of table 1
Note:Compared with blank group,#P ＜ 0.05,##P ＜ 0.01；Compared with model group, compared with model group, * P ＜
0.05, * * P ＜ 0.01.ASD 1. -5. group be drug administration by injection 15mg/kg, 30mg/kg, 60mg/kg, 120mg/kg, 240mg/
Kg, ASD 6. -8. group be gastric infusion 45.6mg/kg, 136.8mg/kg, 410.4mg/kg.
Table 1 is shown, compared with blank group, model group mouse survival rate has pole significant difference (P<0.01), lung thrombus
Mouse model modeling success.For remaining each administration group compared with model group, mouse survival rate is respectively provided with significant difference and extremely notable
Sex differernce (P<0.05, P<0.01), as a result show, each dosage group of ASD injections is respectively provided with internal conspicuousness and pole conspicuousness (P<
0.05, P<0.01) anti thrombotic action；There is obvious dose-effect relationship for ASD anti thrombotic actions；ASD anti-mouse lungs thrombus acts on
It is substantially better than positive control drug urokinase and Danshen injection polyphenol hydrochlorate.Each dosage group of ASD gavages is respectively provided with internal conspicuousness
(P<0.05) anti thrombotic action；There is obvious dose-effect relationship for ASD gavage each group anti thrombotic actions.
Embodiment 2
1. experiment purpose：The influence that research ASD parenteral solution different dosing dosage is formed to rat arteriovenous shunt thrombosis.
2. experiment material
2.1 reagents and medicine：
ASD (self-control, purity 97%), Danshen injection polyphenol hydrochlorate (Shanghai Lvgu Pharmaceutical Co., Ltd, lot number：
20150247), aspirin (Shanghai Aladdin biochemical technology limited company, c1720014), chloraldurate (Chinese medicines group
Chemical reagent Co., Ltd, lot number：20170421), physiological saline, distilled water, polyethylene pipe, baking oven, No. 4 operation silk threads, note
Emitter etc..
2.2 animal：SD rats (male and female half and half, 250-300 grams of body weight).
3. experimental method
The preparation of 3.1 reagents and decoction
3.1.1 the preparation of physiological saline
0.9g sodium chloride is weighed, is placed in 100mL volumetric flasks, adds dissolved in purified water, be settled to 100mL, produce.
3.1.2 the preparation (10mg/kg) of aspirin solution
Precision weighs aspirin 0.0506g, adds 50mL physiological saline, is configured to concentration and is filled for 1mg/mL aspirin
Gastric juice, it is stand-by.
3.1.3 the preparation (18mg/kg) of Danshen injection polyphenol acid salt solution
Precision weighs Danshen injection polyphenol hydrochlorate freeze-dried powder 0.1801g, adds 50mL physiological saline solutions, is hung down through No. 4
Molten glass funnel filtering, it is 3.6mg/mL Danshen injection polyphenol acid salt solutions to be configured to concentration, stand-by.
3.1.4 each dosage parenteral solutions of ASD are prepared：
ASD active compound 18.0mg, 36.1mg, 72.0mg, 144mg, 288mg are taken respectively, respectively with physiological saline solution constant volume
To 10ml, filtered through No. 4 sintered glass funnels, respectively be made concentration be 1.8mg/ml, 3.6mg/ml, 7.2mg/ml,
14.4mg/ml, 28.8mg/ml ASD parenteral solutions.
3.1.5 each gavage solution dosage formulations of ASD：
ASD active compound 150.0mg, 450.0mg, 1350.0mg are taken respectively, are settled to 100ml with physiological saline solution respectively,
Respectively with the ASD gavage solution that obtained concentration is 1.5mg/ml, 4.5mg/ml, 13.5mg/ml.
3.2 administration
Aspirin group administering mode is gastric infusion, administered volume 10ml/kg, dosage 10mg/kg.
Remaining group administering mode is tail vein injection, administered volume 5ml/kg.
The dosage of Danshen injection polyphenol hydrochlorate is 18mg/kg.
The dosage that ASD injects each dosage group is 9mg/kg, 18mg/kg, 36mg/kg, 72mg/kg, 144mg/ respectively
kg。
Orally each dosage group administered volume is 20mL/kg to ASD, and dosage is respectively 30mg/kg, 90mg/kg, 270mg/
kg。
4 observational techniques
SD rats 110 are taken, are randomly divided into 11 groups, every group 10, male and female half and half.Respectively blank group (gives isometric(al)
Physiological saline), aspirin group (western positive group), Danshen injection polyphenol hydrochlorate group (middle-jiao yang, function of the spleen and stomach group), ASD parenteral solutions are provided with 5 agent
Amount group, ASD gavages liquid are provided with 3 dosage groups.After ASD gavage liquid each groups and aspirin group gavage 1h, remaining each group tail vein
After 10min is administered, rat is anaesthetized with 10% chloral hydrate anesthesia (300mg/kg, ip), lies on the back and is fixed on operating table, neck
Median incision, right common carotid artery and left vena jugularis externa are separated, takes a sleeve pipe being made up of three sections of polyethylene pipes, wherein two sections of pipes
Internal diameter is 1mm, is about 6cm, and interlude internal diameter is 2mm, is about 6.5cm.No. 4 of a root long about 5cm are put into the stage casing of 3 sections of pipes
Surgical thread.Normal saline solution is full of polyethylene pipe, its one end is inserted into right carotid, the other end inserts quiet outside left neck
Arteries and veins, opens artery clamp, and blood returns to left vena jugularis externa from right common carotid artery through polyethylene pipe.Blood is interrupted after open blood flow 15min
Stream, the rapid silk thread that takes out are weighed, and gross weight subtracts silk thread weight, as wet weight of thrombus.Then it is fully dry thrombus to be put into baking oven
Dry (60 DEG C, 24h), weighed immediately after being placed on drier cooling, it is thrombus dry weight that this weight, which subtracts silk thread weight,.
Thrombus inhibiting rate (%)=(control group thrombus weight-administration group thrombus weight)/control group thrombus weight ×
100%.
5 experimental results
Experimental result refers to table 2.
The influence that the ASD parenteral solution different dosing dosage of table 2 is formed to rat arteriovenous shunt thrombosis
Remarks：Compared with blank group,#P<0.05,##P<0.01.ASD 1. -5. group be drug administration by injection 9mg/kg, 18mg/
Kg, 36mg/kg, 72mg/kg, 144mg/kg, ASD 6. -8. group be gastric infusion 30mg/kg, 90mg/kg, 270mg/kg.
The ASD medical intravenous administration of this research observation various dose and gastric infusion are to arteriovenous shunt thrombosis rat model
Internal thrombotic influence, as a result shows, the administration of ASD medical intravenous and gastric infusion are to rat arteriovenous shunt thrombosis
The reduction that weight in wet base and dry weight have pole conspicuousness acts on, and compared with model group, difference has pole conspicuousness statistical significance (P<
0.01).Compared with western sun group and middle-jiao yang, function of the spleen and stomach group, the administration of ASD medical intravenous reduces the weight in wet base of thrombus and dry weight is superior to the Chinese medicine positive
Control group Danshen injection polyphenol hydrochlorate and Western medicine positive controls aspirin.
The thrombus that rat neck arteriovenous the method for bypass is formed is platelet thrombus, is due to platelet adhesion reaction to producing on silk thread
Caused by raw aggregation, the thrombus structure of formation is similar to the white thrombus in artery, with pathologic condition relatively.This research is tied
Fruit confirms the antithrombotic validity of ASD medicines from body level.
The preparation of the ASD liquid drugs injections of embodiment 3
According to a conventional method, by ASD be prepared into it is sterile, without thermal source, clear and bright no-sundries, isotonic, pH value with blood equal or phase
Closely, the liquid drugs injection of safety (not haemolysis, non-sensitization) and stable different size.
The preparation of the ASD lyophilized injections of embodiment 4
The sterilizing powdery ASD raw materials of injection are fitted into ampulla or other suitable containers, are prepared into ASD powder pin
Agent.Face the used time with appropriate solvent dissolving or mixed choosing use.
The preparation of the ASD spray drying injections of embodiment 5
By the sterilizing powdery ASD raw materials of injection, aseptically, the chilled freeze drying powder injection for being prepared into ASD.
The preparation of the ASD oral formulations of embodiment 6
By ASD powder raw materials, add appropriate auxiliary material (pharmaceutically acceptable carrier or/and oral formulations customary adjuvant or/and
Conventional edible adjuvant), prepare piece agent, capsule, granule, dripping pill, oral liquid, powder by corresponding solid pharmaceutical preparation preparation method
Deng.
Claims (7)
1. application of the akebiasaponin D in antithrombotic or/and thrombolytic agent is prepared.
2. akebiasaponin D is preparing the application in treating thrombotic diseases medicine.
3. application according to claim 1, it is characterised in that described thrombotic diseases include myocardial infarction, brain bolt it is dead,
Lung thrombus, dvt and peripheral vessels embolism.
4. application according to claim 1 or 2, it is characterised in that described medicine includes akebiasaponin D and pharmaceutically may be used
The carrier or customary adjuvant of receiving.
5. application according to claim 4, it is characterised in that the formulation of the medicine includes injection type and peroral dosage form.
6. application according to claim 5, it is characterised in that described injection type is water/spindle agent or powder-injection.
7. application according to claim 5, it is characterised in that described peroral dosage form is tablet, capsule, granule, drop
Ball, oral liquid or powder.
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| CN201710950361.6A CN107582560B (en) | 2017-10-13 | 2017-10-13 | Thrombolytic effect of akebia saponin D and application thereof |
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| CN107582560B CN107582560B (en) | 2020-02-28 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101675934A (en) * | 2008-09-19 | 2010-03-24 | 山东绿叶天然药物研究开发有限公司 | New use of saponins X of dipsacus asperoides |
| KR20140012456A (en) * | 2012-07-20 | 2014-02-03 | 바이오스펙트럼 주식회사 | Composition for improving skin conditions comprising akebia saponin d |
| CN103908460A (en) * | 2013-01-09 | 2014-07-09 | 上海中医药大学 | Medical application of notoginsenoside Fc |
-
2017
- 2017-10-13 CN CN201710950361.6A patent/CN107582560B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101675934A (en) * | 2008-09-19 | 2010-03-24 | 山东绿叶天然药物研究开发有限公司 | New use of saponins X of dipsacus asperoides |
| KR20140012456A (en) * | 2012-07-20 | 2014-02-03 | 바이오스펙트럼 주식회사 | Composition for improving skin conditions comprising akebia saponin d |
| CN103908460A (en) * | 2013-01-09 | 2014-07-09 | 上海中医药大学 | Medical application of notoginsenoside Fc |
Non-Patent Citations (1)
| Title |
|---|
| 唐瑶等: "三萜皂苷结构及应用的研究进展", 《安徽化工》 * |
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