CN103908459B - Notoginsenoside Ft1 medical usage - Google Patents
Notoginsenoside Ft1 medical usage Download PDFInfo
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- CN103908459B CN103908459B CN201310007273.4A CN201310007273A CN103908459B CN 103908459 B CN103908459 B CN 103908459B CN 201310007273 A CN201310007273 A CN 201310007273A CN 103908459 B CN103908459 B CN 103908459B
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Abstract
The present invention relates to medicine, more particularly to a kind of notoginsenoside Ft1 medical usage.The notoginsenoside Ft1 of the present invention can be used for preventing and treating various hemorrhagic diseases such as dysfunction of platelet, coagulation disorders etc..
Description
Technical field
The present invention relates to Medicines and Health Product field, more particularly to a kind of notoginsenoside Ft1 medical usage.
Background technology
When obstacle occurs for the hemostasis function of human body, the hematostaxis of skin, mucous membrane and internal organ or slight damage can be caused
It is haemophilia after wound, every disease with this hemorrhagic tendency can be referred to as hemorrhagic disease.According to what is caused bleeding
Different mechanisms, hemorrhagic disease can be divided into two categories below：
（1）Blood platelet disorders：The dysfunction such as platelet counts change and adhesion, aggregation, release reaction can cause
Blood.ITP, drug induccd thrombopenia and piastrenemia etc., it is that platelet counts are different
Hemorrhagic disease caused by often.Thrombasthenia, huge thrombocytopathy etc. are the hemorrhagic disease caused by dysfunction of platelet
Disease.
（2）Clotting factor is abnormal：Including congenital factor and abnormal two aspect of the acquired clotting factor day after tomorrow.Such as blood
The sick first of friend（Lack VIII factor）And hemophilia B（Lack Ⅸ factor）It is autosomal recessive hereditary hemorrhagic disease.Vitamin
Bleeding caused by K deficiency diseases, liver diseases is mostly that acquired clotting factor is extremely caused.
Notoginsenoside Ft1（Notoginsenoside Ft1）It is a kind of natural saponins compound, is primarily present in three
In seven.Research finds that notoginsenoside has the effect such as reducing blood lipid, antitumor, elimination oxygen radical, anti-oxidant.
The content of the invention
The purpose of the present invention aims to provide a kind of notoginsenoside Ft1 new medical usage.
Specifically, the application the invention provides a kind of notoginsenoside Ft1 in blood coagulation accelerator is prepared.
The second aspect of the present invention there is provided a kind of notoginsenoside Ft1 answering in platelet aggregation accelerator is prepared
With.
The third aspect of the present invention there is provided a kind of pharmaceutical composition or food with hemorrhagic disease preventive and therapeutic effect
Or amenities, it includes the notoginsenoside Ft1 of therapeutically effective amount.
In a preference, the hemorrhagic disease is platelet aggregation obstacle or coagulation disorders.
In another preference, the amenities is toothpaste.
The details of various aspects of the present invention will be able to detailed description in subsequent chapters and sections.By hereafter and claim
Description, the features of the present invention, purpose and advantage will become apparent from.
Brief description of the drawings
Fig. 1 embodies influences of the Ft1 to platelet aggregation rate；
Fig. 2 embodies dose-effect relationships of the Ft1 to platelet aggregation rate；
Fig. 3 embodies influences of the Ft1 to whole animal platelet aggregation rate；
Fig. 4 embodies Ft1 to be influenceed on the rat tail clotting time；
Fig. 5 embodies influences of the Ft1 to rat thrombin time test (TT)；
Fig. 6 embodies Ft1 to rat prothrombin time（PT）Influence；
Fig. 7 embodies influences of the Ft1 to rat activated partial thromboplastin time (APTT)；
Fig. 8 embodies influences of the Ft1 to mankind's blood coagulation four indices.
Embodiment
The appearance part of the present invention is had been surprisingly found that based on such a：Notoginsenoside Ft1 can be obviously promoted blood platelet
Aggregation, shorten prothrombin time and activated partial thromboplastin time.Therefore, notoginsenoside Ft1 is expected to exploitation into one kind
Promote platelet aggregation material be platelet aggregation accelerator and/or it is a kind of promote blood coagulation material i.e. blood coagulation accelerator, institute
It can be various forms of materials to state " platelet aggregation accelerator " and " blood coagulation accelerator ", included but is not limited to：Medicine, health care
Product, food, amenities etc..These " the platelet aggregation accelerator " and " blood coagulation accelerator " prepared with notoginsenoside Ft1
Available for preventing and treating various hemorrhagic diseases such as platelet aggregation obstacle, coagulation disorders etc..
And then the application the invention provides notoginsenoside Ft1 in blood coagulation accelerator is prepared.
Present invention also offers applications of the notoginsenoside Ft1 in platelet aggregation accelerator is prepared.
Present invention also offers a kind of pharmaceutical composition or food or amenities with hemorrhagic disease preventive and therapeutic effect,
It includes the notoginsenoside Ft1 of therapeutically effective amount.
More preferably, the hemorrhagic disease is platelet aggregation obstacle or coagulation disorders.
More preferably, the amenities is toothpaste.
The notoginsenoside Ft1 molecular formula of the present invention is：C47H80O17, molecular weight is：916.54 its structural formula is as follows：
R=H;R1=Xyl1-2Glc1-2Glc
The notoginsenoside Ft1 of the present invention can have by commercial sources from Sigma chemical companies, Chengdu Man Site biotechnologies
Limit company etc. purchase obtains, or is separated and obtained from notoginsenoside with the conventional method of this area.Its purity meets medicine
Use standard.
Exemplified by the notoginsenoside Ft1 of the present invention is made into medicine.The present invention notoginsenoside Ft1 can be used alone or
Used in the form of pharmaceutical composition.Pharmaceutical composition include as active component notoginsenoside Ft1 of the invention and can medicine
Use carrier.It is preferred that the pharmaceutical composition of the present invention contains the present invention as active component of 0.1-99.9% percentage by weights
Notoginsenoside Ft1." pharmaceutical acceptable carrier " will not destroy the notoginsenoside Ft1 of present invention pharmaceutical active, while its is effective
Amount, dosage when can play pharmaceutical carrier effect are nontoxic to human body.
Described pharmaceutical acceptable carrier includes but is not limited to：Soft phosphatide, aluminum stearate, aluminum oxide, ion exchange material, self-emulsifying
Drug delivery system, tween or other surfaces activator, haemocyanin, buffer substance for example phosphate, amion acetic acid, sorbic acid,
Water, salt, electrolyte such as sulfate protamine, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salt, magnesium silicate, saturated fatty acid
Partial glyceride mixtures etc..
Other conventional excipient substance such as adhesives（Such as microcrystalline cellulose）, filler（Such as starch, glucose, anhydrous lactitol
Sugar and lactose bead）, disintegrant（Such as cross-linked pvp, crosslinked carboxymethyl fecula sodium, Ac-Di-Sol, low-substituted hydroxypropyl
Base cellulose）, lubricant（Such as magnesium stearate）And sorbefacient, absorption carrier, flavouring agent, sweetener, excipient, dilution
Agent, wetting agent etc..
The notoginsenoside Ft1 of the present invention and its pharmaceutical composition can be prepared by this area conventional method and can pass through intestines
Road or non-bowel or topical routes.Oral formulations include capsule, tablet, oral liquid, granule, pill, powder, pellet
Agent, paste etc.；Non-intestinal drug delivery agent is including parenteral solution etc.；Local administration preparation includes creme, patch, ointment, spray
Deng.Preferably oral formulations.
The notoginsenoside Ft1 of the present invention and the method for administration of its pharmaceutical composition can be oral, sublingual, percutaneous, warp
Muscle or subcutaneous, mucocutaneous, vein, urethra, vagina etc..
In addition to medicine is made, antioxidant, pigment, enzyme preparation can be also added in the notoginsenoside Ft1 of the present invention
Etc. various food additives, health food is made by the conventional method of this area.Additionally can be by the notoginsenoside of the present invention
Ft1 is added in toothpaste and the health-care toothpaste that can prevent and treat bleeding gums is made.
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are merely to illustrate the present invention
Rather than limitation the scope of the present invention.The experimental method of unreceipted actual conditions in the following example, generally according to conventional strip
Part or according to the condition proposed by manufacturer.Unless otherwise indicated, otherwise all percentage, ratio, ratio or number is pressed
Weight meter.
Unless otherwise defined, anticipated known to all specialties used in text and scientific words and one skilled in the art
Justice is identical.In addition, any method similar or impartial to described content and material all can be applied in the inventive method.Wen Zhong
Described preferable implementation only presents a demonstration with material to be used.
The features described above that the present invention mentions, or the feature that embodiment is mentioned can be in any combination.Patent specification is taken off
All features shown can be used in combination with any combinations thing form, each feature disclosed in specification, can provide phase with any
The alternative characteristics substitution of same, impartial or similar purpose.Therefore except there is special instruction, disclosed feature is only impartial or similar
The general example of feature.
Embodiment 1：
Notoginsenoside Ft1 used is that Shanghai Univ. of Traditional Chinese Medicine's traditional Chinese medicine research is separated, prepared in the present embodiment,（Chlorine pyrrole
Gray is purchased from Products in China calibrating institute）.The purity of specimen in use meets medicinal standard.
1st, experiment material
1.1 medicinal material
Notoginsenoside Ft1（Molecular weight 1211.38 and 917.13, HPLC purity >=99%, institute of Chinese materia medica）；Clopidogrel
（Molecular weight 419.90, HPLC purity >=98%, institute is identified purchased from Products in China；Four human standard blood plasma, blood coagulation tests
Reagent（It is purchased from German SIEMENS companies）;Adenosine diphosphate (ADP)（ADP）（Purchased from Sigma companies）
1.2 experimental animal
230 ± 20g of body weight SD rats, are provided by Shanghai Univ. of Traditional Chinese Medicine's Experimental Animal Center, animal quality certification number：
SYXK (Shanghai) 2008-0016.It is placed in conventinal breeding environment, ad lib and drinking-water.
2nd, experimental method
2.1Ft1 the influence to platelet aggregation
2.1.1 extracorporeal platelet aggregation is tested：The blood of extraction adds sodium citrate anti-freezing.100g centrifuges 5min, takes
Clearly, rich platelet is produced（PRP）；Gained PRP is added into prostacyclin（2μg/ml）, centrifugation 5min (700g)；Add
0.9% physiological saline cleaning is twice；After cleaning by platelet suspension in Tyrodebuffered, and its concentration is set to be 4*
108, it is standby；Platelet aggregation measure is carried out by turbidimetry：Thrombocyte plasma is placed in colorimetric cylinder cup, adds induced polymerization inhibitor
（ADP：5- adenosine diphosphate disodium salts：1×10-4mol/L）.Afterwards, it is stirred with small magnetic grain, blood platelet is gradually assembled, blood plasma
Haze reduction, light transmittance increase.This change is recorded, forms the performance graph of platelet aggregation.With PRP PAR and light transmittance
For 0, using the PAR measured by suspension and light transmittance as 100%, automatically determined, recorded, described with platelet aggregation instrument
Curve of platelet aggregation.Judgement to suppressing or promoting aggregation, whether main detection occurs to act synergistically with derivant or antagonism
Effect.Generation synergy is to promote platelet aggregation, and antagonism occurs is to suppress platelet aggregation.
2.1.2 whole animal platelet aggregation test：Blood platelet in artery blood flow is when the rough surface of contact silk thread
Adhesion is with line, platelet thrombus is formed on its surface.When hematoblastic adhesion and aggregation function is suppressed, thrombus weight compared with
Gently.Therefore, the situation of platelet adhesion reaction aggregation capability can be predicted from thrombus weight.
2.1.2 whole animal coagulation function is evaluated
2.1.2.1 rat tail coagulation time test：Being cut with profit will be cross-section at rat tail point 0.5cm, treats that blood voluntarily overflows
Start to clock after going out, drop of blood is sucked 1 time with filter paper every 30s, until blood flow stops naturally（Without blood when filter paper is inhaled）Untill, it is
Bleeding time.
2.1.2.2 blood coagulation four indices determine：1) blood coagulation four indices：Prothrombin time（Prothrombintime,
PT）：Main reflection intrinsic coagulation system situation, is usually used in monitoring heparin dosage.Increase see blood plasma factor VIII, factor Ⅸ and
Factor XI, plasma thromboplastin antecedent reduced levels：Such as hemophilia A, hemophilia B and factor XI deficiency disease；Reduction sees hypercoagulative state：As coagulant enters
Enter situations such as activity of blood and clotting factor increases；Activated partial thromboplastin time (activated partial
thromboplatin time,APTT)：Main reflection intrinsic coagulation system situation, is usually used in monitoring heparin dosage.Increase and see
In blood plasma factor VIII, factor Ⅸ and factor XI, plasma thromboplastin antecedent reduced levels：Such as hemophilia A, hemophilia B and factor XI deficiency disease；Reduction is seen
Hypercoagulative state：Situations such as activity such as coagulant into blood and clotting factor increases；Thrombin time test（thrombin
Time, TT）：Main reflection fibrinogen switchs to the fibrinous time.Increase the DIC hyperfibrinolysis phases that see, it is low（Nothing）It is fine
Fibrillarin original mass formed by blood stasis, abnormal hemoglobinemia, fibrin in blood（It is former）Catabolite（FDPs）Increase；Reduce and anticipated without clinic
Justice；Fibrinogen（Fibrinogen, FIB）：The content of main reflection fibrinogen.Increase and see acute myocardial infarction AMI and subtract
It is low to see DIC expendables low solidifying breaking-in period, primary fibrinolytic disease, serious hepatitis, hepatic sclerosis；
2.2 packets and medication
Blank control：0.9% physiological saline（NS）.
Derivant group：Adenosine diphosphate (ADP)（ADP）（10mM）
Positive control drug：Clopidogrel (5mM).
Medication group：Every group six, after Ft1 is dissolved with DMSO, it is standby to be diluted to each concentration.
2.4 statistical analysis
All experimental datas are repeated 3 times, and are as a result represented with mean+SD, using SPSS13.0 statistical softwares pair
Experimental data is examined using One-way ANOVA (One-way ANOVA) and LSD, P<0.05 has significantly for statistically difference
Property.
3rd, result
Facilitations of the 3.1 notoginsenoside Ft1 to platelet aggregation.
3.1.1Ft1 to the influence of platelet aggregation rate
Fig. 1 and table 1 embody influences of the notoginsenoside Ft1 to platelet aggregation rate, as seen from Figure 1：Derivant (ADP) is single
It is 52.9% with group PAR, joint quotes Ft1（Dosage is 200 μM）PAR is respectively 79.5% afterwards；Ft1 groups are gathered
Collection rate is more than alone group of derivant（*P<0.05）.Ft1 has synergy with derivant.
In addition, as seen from Figure 1：Total extract group PAR is 40.1%, hence it is evident that less than Ft1 administration groups（52.9%）（**P<
0.01）, this illustrates that Ft1 monomers are better than total extract administration group in the drug effect for promoting platelet aggregation.
Table 1：Dose-effect relationships of the notoginsenoside Ft1 to platelet aggregation rate
3.1.2Ft1 to the dose-effect relationship to platelet aggregation rate
Influences of Fig. 2 notoginsenosides Ft1 to platelet aggregation rate, as seen from Figure 2：Ft1（10μM、20μM、40μM、55μM、
60μM）Promote the dose-effect relationship of platelet aggregation.From 10 μM --- 60 μM of platelet aggregation rates gradually increase, PAR from
13.3% increases to 54.3%, and amplification is up to 41%.Its IC50It is worth for 52.5 μM.
3.1.3Ft1 to the influence of whole animal platelet aggregation rate
Fig. 3 embodies influences of the Ft1 to whole animal platelet aggregation rate, as seen from Figure 3：Notoginsenoside Ft1 in body
The influence of platelet aggregation.By to weight in wet base thrombus weigh we have found that：Ft1 still has very strong work in the case of body
Property.We give 1.25mg/kg using the method being injected intravenously, Ft1.Administration starts Extracorporal collateral circulation after five minutes, circulates
Circulation is terminated after 15 minutes, removal of thromboses is heavy.Ft1 thrombus weight：41.2mg, hence it is evident that less than blank group：37.2mg
（*P<0.01）.
Influences of the 3.2 notoginsenoside Ft1 to blood coagulation function
3.2.1Ft1 to rat tail coagulation time test
Fig. 4 embodies Ft1 to be influenceed on the rat tail clotting time, as seen from Figure 4：Ft1 for the rat tail bleeding time,
Have a significant impact.
Influences of the 3.3Ft1 to rat and mankind's blood coagulation four indices
Fig. 5 embodies influences of the Ft1 to rat thrombin time test (TT), as seen from Figure 5：Ft1(15μg/ml、30μ
G/ml, 60 μ g/ml, 120 μ g/ml, 240 μ g/ml) various dose shows the gradual enhancing of effect, the Ft1 μ g/ml of dosage 15
The TT times are：40 seconds, 240 μ g/ml were 8 seconds.Amplitude of variation is 32 seconds.
Fig. 6 and table 2 embody Ft1 to rat prothrombin time（PT）Influence, as seen from Figure 6：Ft1(15μg/ml、
30 μ g/ml, 60 μ g/ml, 120 μ g/ml, 240 μ g/ml) various dose shows the gradual enhancing of effect, the Ft1 μ g/ of dosage 15
The ml PT times are：12 seconds, 240 μ g/ml were 8 seconds.Amplitude of variation is 4 seconds.
Dose-effect relationships of the notoginsenoside Ft1 of table 2 to P of Rats T time
Fig. 7 and table 3 embody Ft1 to rat activated partial thromboplastin time (activated
Partialthromboplatin time, APTT) influence, as seen from Figure 7：Ft1(15μg/ml、30μg/ml、60μg/ml、
120 μ g/ml, 240 μ g/ml) various dose shows the gradual enhancing of effect, and the Ft1 μ g/ml TT times of dosage 15 are：20
Second, 240 μ g/ml are 12 seconds.Amplitude of variation is 8 seconds.
Dose-effect relationships of the notoginsenoside Ft1 of table 3 to the rat APTT times
Fig. 8 embodies influences of the Ft1 to mankind's blood coagulation four indices, as seen from Figure 8：Ft1 240 μ g/ml dosage level,
The APTT times are only 82 seconds, hence it is evident that less than blank group（91 seconds）（**P<0.01）.The PT times are 17 seconds, hence it is evident that less than blank group
（20 seconds）（*P<0.05）.
Many aspects involved in the present invention have been explained as above.However, it should be understood that without departing from spirit of the invention
Under the premise of, those skilled in the art can carry out equivalent change and modification to it, and the change and modification equally fall into the application
The coverage of appended claims.
Claims (2)
1. applications of the notoginsenoside Ft1 in blood coagulation accelerator is prepared.
2. applications of the notoginsenoside Ft1 in platelet aggregation accelerator is prepared.
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| CN104771408B (en) * | 2014-01-15 | 2018-10-30 | 上海中医药大学 | The purposes of notoginsenoside Ft1 |
| CN105832753A (en) * | 2016-03-17 | 2016-08-10 | 云南普优生物科技有限公司 | Composition containing ginsenoside Rg3 and notoginsenoside ft1 |
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