CN107569505A - A kind of pharmaceutical composition for treating myocardial ischemia and its application and the injection formed by its preparation - Google Patents
A kind of pharmaceutical composition for treating myocardial ischemia and its application and the injection formed by its preparation Download PDFInfo
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Abstract
The invention belongs to medical composition field, and in particular to a kind of pharmaceutical composition for treating myocardial ischemia and its application and the injection formed by its preparation.The pharmaceutical composition includes Quercetin 3 O β D glucosyl groups (1 2) α L rhamnosides, narcissin, O β D glucosyl groups (1 2) the α L rhamnosides of kaempferol 3 and Ginkgolide A. B. C, component contained by the pharmaceutical composition understands, quality controllable, under above-mentioned specific proportioning, each component cooperates, clinically it is applied to myocardial ischemia, its curative effect is substantially better than the indefinite ginkgo biloba p.e of component of prior art offer.The present invention also provides the preparation method of pharmaceutical composition, is extracted using 93~96% alcohol refluxs, and is handled using macroporous resin adsorption, can be effectively separated said components, and technique is simple, suitable for industrialized production.
Description
Technical field
The invention belongs to medical composition field, and in particular to a kind of pharmaceutical composition for treating myocardial ischemia and its application
With the injection formed by its preparation.
Background technology
Ginkgo (Ginkgo biloba L.), also known as gingko (seed), maidenhair tree, Gong Sunshu, moth leaf, duck bottom sediment, it is
Ginkgo (Ginkgo) deciduous tree under Ginkgoaceae (Ginkgoaceae), belongs to ancient few survivors's rare plant, there is " activation
Stone ", the laudatory title of " panda of plant kingdom ".Ginkgo leaf is the dried leaf of ginkgo, and autumn leaf harvests when not yet green, nature and flavor are sweet, it is bitter,
It is puckery, mild-natured, the thoughts of returning home, lung channel, have it is promoting blood circulation and removing blood stasis, remove obstruction in channels to relieve pain, astringe the lung and relieving asthma, change the effect of turbid lipid-loweringing, for treating hemostasis
Hinder the illnesss such as network, chest impediment and cardialgia, hemiplegia, deficiency syndrome of the lung cough and asthma, hyperlipemia.
External ginkgo leaf production development starts from the 1970s, German Schwabe companies utilize solvent extraction skill earliest
Art production standard ginkgo biloba p.e (EGb761), and develop Tebon in forte preparations.Subsequent French Beaufour-
Ipsen companies develop Rokan preparations, and Sobernheim drugmakers of West Germany produce the compound preparation containing ginkgo biloba extract
Hevert, Japan develop a series of ginkgo Leaves health care oral liquids.The processing of China's ginkgo biloba p.e and its preparation starts from 20
The nineties in century.In the past 30 years, China pays much attention to the development of ginkgo industry, and ginkgo cultivated area expands year by year, and yield is year by year
Rise, add up cultivated area more than 2000hm2, more than ginkgo leaf annual production 20000t, annual production ginkgo biloba p.e more than 200
Ton, accounts for the 1/6 of international market demand amount.According to statistics, the autonomic drug class cardiovascular drugs that can be monitored on retail market have more than 300
Kind, ginkgo class formulation products occupy nearly 30% market share.Therefore, the research and development of Bio-active Components From Ginkgo Biloba Leaves,
Turn into a huge industry in China.Research finds, main component is total flavonoids and ginkgolides in ginkgo leaf, always
Flavonol glycosides are the general name of variety classes flavonol glycosides monomer, and its structure is with Quercetin (querctin), Kaempferol
(kaempferol), Isorhamnetin (isorhamnetin) etc. is parent nucleus, and combines the monose structures such as glucose, rhamnose, polysaccharide
Into；Ginkgolides mainly has Ginkgolide A. B. C etc..Research finds, the total flavonoids and ginkgolides contained by ginkgo leaf because
With prominent pharmacological activity, usually as ginkgo biloba p.e and its quality control index composition of preparation；And ginkgo leaf
In also have sensitization containing ginkgo aldehydes matter (such as ginkgoic acid), be harmful components, its content should be controlled to ensure drug safety.
Therefore, Chinese patent literature CN100496518C discloses a kind of ginkgo biloba p.e, the note containing the extract
Agent and preparation method thereof is penetrated, the ginkgo biloba p.e mainly contains following weight percent composition：Flavonol glycosides 10-40%, silver
Apricot lactone 2.5-25%, content of beary metal are less than 9.4ppm；Wherein, ginkgolides by following weight ratio Ginkgolides a and B
Formed with C：7-27：3-20：4-40.Not only active constituent content is high for above-mentioned ginkgo biloba extract, and contained ginkgo phenolic material
The impurity such as matter (such as ginkgoic acid), protein, tannin, heat source substance are less than 20ppm, the pharmaceutical preparation thus prepared, especially note
Agent is penetrated, it is evident in efficacy for cardiovascular and cerebrovascular disease, Clinical practice safety, the side effects such as injection pain, heat source response will not be produced.
But as international market is more and more high to the quality requirement of ginkgo biloba p.e and its preparation, such as《European Pharmacopoeia》Regulation silver
Apricot leaf extract total flavonoids content between 22.0~27.0%, the total amount of Ginkgolide A. B. C 2.8~3.4% it
Between, ginkgo acid content is no more than 5ppm.It is apparent that existing ginkgo biloba p.e and its preparation are difficult to reach quality requirement, no
It can guarantee that good therapeutic effect and drug safety.In addition, what State Food and Drug Administration promulgated《Chinese medicine, natural drug note
Penetrate agent main technique requirements》It is required that " ingredient should be substantially clear in injection ", but in fact, ginkgo leaf kind, the place of production,
Growing environment and the time limit are different, and its chemical composition has differences, along with the effective extraction separation method of shortage and quality control
Method so that active component is complicated and indefinite in existing ginkgo biloba p.e and its formulation products, causes uncertain therapeutic efficacy to be cut, matter
Measure unstable.Therefore, according to the current situation of existing ginkgo industry, it is badly in need of breaking through prior art, further R and D silver
Active component and functional component in apricot leaf extract, will have great importance.
The content of the invention
Therefore, the technical problem to be solved in the present invention is the ginkgo biloba p.e and its preparation hardly possible for overcoming prior art to prepare
It cannot be guaranteed drug safety to reach quality requirement, and active component is indefinite causes uncertain therapeutic efficacy to cut this defect, enters
And a kind of new ginkgo biloba p.e formula and the injection formed by it are provided for treating myocardial ischemia.
Therefore, the technical scheme that the application takes is：
The present invention provides a kind of pharmaceutical composition for being used to treat myocardial ischemia, includes the component of following parts by weight：
Quercetin -3-O- β-D-Glucose base (1-2) -0.1~1 part of alpha-L-rhamnoside；
0.1~1 part of narcissin；
Kaempferol -3-O- β-D-Glucose base (1-2) -0.1~1 part of alpha-L-rhamnoside；
0.7~2 part of ginkalide A；
0.3~1 part of ginkolide B；
0.4~1 part of ginkalide C.
Optionally, the one or more in the narcissin, ginkalide A, ginkolide B, ginkalide C are by ginkgo leaf
Extraction is made.
The present invention provides the preparation for including aforementioned pharmaceutical compositions, and described pharmaceutical composition adds customary adjuvant, according to normal
Rule technique, clinically acceptable tablet, capsule, powder, mixture, pill, granule, oral liquid, syrup, cream is made
Agent, electuary, vina, injection, beverage, biscuit, candy, cake food or instant food.
The present invention provides aforementioned pharmaceutical compositions or the preparation comprising aforementioned pharmaceutical compositions is preparing treatment myocardial ischemia
Application in medicine.
The present invention provides a kind of method for preparing the injection comprising aforementioned pharmaceutical compositions, including, by the Quercetin-
3-O- β-D-Glucose base (1-2)-alpha-L-rhamnoside, narcissin, kaempferol -3-O- β-D-Glucose base (1-2)-α-L- mouse
Lee's glucosides, ginkalide A, ginkolide B, ginkalide C and water, auxiliary material are mixed and made into sterile solution；Wherein, the quercitrin
Element -3-O- β-D-Glucose base (1-2)-content of the alpha-L-rhamnoside in the sterile solution is 0.1~1mg/ml.
The present invention also provides the preparation method of aforementioned pharmaceutical compositions, comprises the following steps：
(1) after taking ginkgo leaf to crush, 93~96% alcohol refluxs is added and are extracted 1~3 time, each reflux extracting time is
0.3~0.5 hour, the quality for adding 93~96% ethanol every time was 10~12 times of the ginkgo leaf quality；Filtering, will
Gained filtrate decompression is concentrated into 0.1~0.2 times of the ginkgo leaf quality, refrigerates 47~52 hours；
(2) oil slick is scraped off, takes subnatant；
(3) water for injection is added into the subnatant to 0.45~0.65 times of the ginkgo leaf quality, refrigeration 47~
52 hours；Filter, concentrate filtrate to 0.1~0.2 times of the ginkgo leaf quality, put to room temperature, add 93~96%
Ethanol, make alcohol content that the solution after alcohol precipitation be refrigerated, filtered and concentrated successively, repeated 2~4 times to 79~83%；
(4) water for injection is added to 0.2~0.3 times of the ginkgo leaf quality to the filtrate after concentration, inhaled using macropore
Attached resin carries out absorption 4~8 times；Wherein, the positive macroreticular resin dosage is 0.5~5.0 times of the ginkgo leaf quality；
(5) auxiliary material and water are added to the decoction of adsorption treatment, is made sterile solution, Quercetin -3- in the sterile solution
The content of O- β-D-Glucose base (1-2)-alpha-L-rhamnoside is 0.1~1mg/mL.
Optionally, the macroporous absorbent resin granularity is 30~60 mesh.
Optionally, the pH value of the sterile solution is 4.0~7.0.
Optionally, in the sterile solution, ginkgoic acid≤20ng/ml, the μ g/ml of lead content≤0.6, the μ of cadmium content≤0.15
G/ml, the μ g/ml of arsenic content≤0.3, the μ g/ml of mercury content≤0.1, the μ g/ml of copper content≤7.5.
The present invention also provides the injection for being prepared and being formed by the above method.
Technical solution of the present invention, have the following advantages that：
1. the present invention provides a kind of pharmaceutical composition for being used to treat myocardial ischemia, including Quercetin -3-O- β-D- grapes
Glycosyl (1-2) -0.1~1 part of alpha-L-rhamnoside；0.1~1 part of narcissin；Kaempferol -3-O- β-D-Glucose base (1-2)-α -
0.1~1 part of L- rhamnosides；0.7~2 part of ginkalide A；0.3~1 part of ginkolide B, 0.4~1 part of ginkalide C.
Component contained by the pharmaceutical composition understands, quality controllable, and under above-mentioned specific proportioning, each component cooperates, and clinically should
For myocardial ischemia, its curative effect is substantially better than the indefinite ginkgo biloba p.e of component of prior art offer.Moreover, China is silver-colored
Apricot leaf aboundresources so that the pharmaceutical composition is cheap, and application prospect is wider.
2. the present invention provides aforementioned pharmaceutical compositions, the technique such as ginkgo leaf sinks by alcohol extracting, water successively, alcohol precipitation, absorption obtains
To pharmaceutical composition, the extraction of 93~96% alcohol refluxs and macroporous resin adsorption are used cooperatively, can be by the quercitrin in ginkgo leaf
Element -3-O- β-D-Glucose base (1-2)-alpha-L-rhamnoside, narcissin, kaempferol -3-O- β-D-Glucose base (1-2)-α -
L- rhamnosides and Ginkgolide A. B. C carry out effectively extraction and separated, into distinguishing one from the other, and the drug regimen prepared with this
Thing meets industry quality standard, ensures curative effect, drug safety.In addition, the extraction process cost that the present invention uses is low, operation letter
It is single, suitable for industrialized production.
3. the present invention is also provided using the injection being prepared by aforementioned pharmaceutical compositions, through animal experiment, can subtract
The peroxide injury of light Cell membrane lipids, strengthens the clear ability to oxygen radical, stabilizing cell membrane, reduces outside intracellular CK
Leakage, mitigate the cellular damage caused by free radical, protect ischemic myocardial cells；But also can significantly reduce rat whole blood viscosity,
Plasma concentration and red blood cell overstock, and are very beneficial for Clinical practice.
Embodiment
For the ease of understanding the purpose of the present invention, technical scheme and main points, embodiments of the present invention will be made below into
One step is described in detail.The present invention can be implemented with many different forms, and should not be construed as being limited to reality set forth herein
Apply example.Conversely, there is provided this embodiment so that the present invention will be thoroughly and completely, and will the design of the present invention is abundant
Those skilled in the art are communicated to, the present invention will only be defined by the appended claims.
Embodiment 1
The present invention provides a kind of preparation method of the injection of the pharmaceutical composition containing treatment myocardial ischemia, including following
Step：
(1) after taking ginkgo leaf to crush, adding 95% alcohol reflux and extract 3 times, each reflux extracting time is 0.5 hour,
The quality for adding 95% ethanol every time is 10 times of ginkgo leaf quality；Filtering, ginkgo leaf quality is concentrated into by gained filtrate decompression
0.2 times, refrigerate 48 hours；
(2) oil slick is scraped off, takes subnatant；
(3) water for injection is added into subnatant to 0.5 times of ginkgo leaf quality, is refrigerated 48 hours；Filtering, filtrate is subtracted
Pressure is concentrated into 0.2 times of ginkgo leaf quality, puts to room temperature, adds 95% ethanol, make alcohol content to 82%, by the solution after alcohol precipitation
Refrigerated, filtered and concentrated successively, repeated 2 times；
(4) to the filtrate addition water for injection after concentration to 0.2 times of ginkgo leaf quality, using 45 mesh macroporous absorbent resins
Carry out absorption 6 times；Wherein, positive macroreticular resin dosage is 2.8 times of ginkgo leaf quality；
(5) auxiliary material and water are added into the decoction of adsorption treatment, above-mentioned sterile solution, pH=7 is made.
Detected using high performance liquid chromatography, in above-mentioned sterile solution, its Quercetin -3-O- β-D-Glucose base (1-
2)-alpha-L-rhamnoside 0.37mg/ml；Narcissin 0.72mg/ml；Kaempferol -3-O- β-D-Glucose base (1-2)-α-L- mouse
Lee's glucosides 0.80mg/ml；Ginkalide A 2.00mg/ml；Ginkolide B 1.00mg/ml；Ginkalide C 0.40mg/ml.
Embodiment 2
The present invention provides a kind of preparation method of the injection of the pharmaceutical composition containing treatment myocardial ischemia, including following
Step：
(1) after taking ginkgo leaf to crush, adding 96% alcohol reflux and extract 1 time, each reflux extracting time is 0.4 hour,
The quality for adding 96% ethanol every time is 11 times of ginkgo leaf quality；Filtering, ginkgo leaf quality is concentrated into by gained filtrate decompression
0.15 times, refrigerate 52 hours；
(2) oil slick is scraped off, takes subnatant；
(3) water for injection is added into subnatant to 0.65 times of ginkgo leaf quality, is refrigerated 47 hours；Filtering, by filtrate
0.1 times of ginkgo leaf quality is concentrated under reduced pressure into, is put to room temperature, is added 96% ethanol, make alcohol content to 83%, will be molten after alcohol precipitation
Liquid is refrigerated, filtered and concentrated successively, is repeated 3 times；
(4) to the filtrate addition water for injection after concentration to 0.25 times of ginkgo leaf quality, using 30 mesh macroporous absorption trees
Fat carries out absorption 4 times；Wherein, positive macroreticular resin dosage is 5.0 times of ginkgo leaf quality；
(5) auxiliary material and water are added into the decoction of adsorption treatment, above-mentioned sterile solution, pH=4 is made.
Detected using high performance liquid chromatography, in above-mentioned sterile solution, its Quercetin -3-O- β-D-Glucose base (1-
2)-alpha-L-rhamnoside 1.00mg/ml；Narcissin 1.00mg/ml；Kaempferol -3-O- β-D-Glucose base (1-2)-α-L- mouse
Lee's glucosides 1.00mg/ml；Ginkalide A 1.57mg/ml；Ginkolide B 0.88mg/ml；Ginkalide C 0.68mg/ml.
Embodiment 3
The present invention provides a kind of preparation method of the injection of the pharmaceutical composition containing treatment myocardial ischemia, including following
Step：
(1) after taking ginkgo leaf to crush, adding 93% alcohol reflux and extract 2 times, each reflux extracting time is 0.3 hour,
The quality for adding 93% ethanol every time is 12 times of ginkgo leaf quality；Filtering, ginkgo leaf quality is concentrated into by gained filtrate decompression
0.1 times, refrigerate 47 hours；
(2) oil slick is scraped off, takes subnatant；
(3) water for injection is added into subnatant to 0.45 times of ginkgo leaf quality, is refrigerated 52 hours；Filtering, by filtrate
0.15 times of ginkgo leaf quality is concentrated under reduced pressure into, is put to room temperature, is added 93% ethanol, make alcohol content to 79%, after alcohol precipitation
Solution is refrigerated, filtered and concentrated successively, is repeated 4 times；
(4) to the filtrate addition water for injection after concentration to 0.3 times of ginkgo leaf quality, using 60 mesh macroporous absorbent resins
Carry out absorption 8 times；Wherein, positive macroreticular resin dosage is 0.5 times of ginkgo leaf quality；
(5) auxiliary material and water are added into the decoction of adsorption treatment, above-mentioned sterile solution, pH=5.5 is made.
Detected using high performance liquid chromatography, in above-mentioned sterile solution, its Quercetin -3-O- β-D-Glucose base (1-
2)-alpha-L-rhamnoside 0.10mg/ml；Narcissin 0.10mg/ml；Kaempferol -3-O- β-D-Glucose base (1-2)-α-L- mouse
Lee's glucosides 0.10mg/ml；Ginkalide A 0.70mg/ml；Ginkolide B 0.30mg/ml；Ginkalide C 1.00mg/ml.
Test example 1
Injection prepared by the sterile solution that embodiment 1-3 is provided is subjected to total flavonoids, ginkgoic acid, heavy metal respectively
Detection, its result are as follows：
The testing result of the sterile solution of table 1
As shown in Table 1, the pharmaceutical composition obtained using the embodiment 1-3 techniques provided, quality controllable, steady quality,
Harmful components meet professional standard, can ensure drug safety.
Test example 2
In order to further prove the performance of injection provided by the invention, the present invention is provided sterile using embodiment 1-3
Injection prepared by solution has been cooked following experiment：
1. the protective effect of pair ischemic myocardium
1.1 laboratory apparatus and reagent
Electrocardiograph ECG_106Ken2 (Japan)；
Automatic biochemistry analyzer Olympus Au560 (Japan)；
XW-80 swirl mixing devices (Shanghai instrument plant of the first medical college)；
NOS, MDA, SOD kit (Bioengineering Research Institute is built up in Nanjing)；
CK kits (factory of Beijing chemical industry two)；
Perhexiline injection (GXN) (martial prowess medicine company, lot number：160815, every 10ml)；
Injection prepared by the sterile solution that embodiment 1-3 is provided：ZHW-1、ZHW-2、ZHW-3.
1.2 perhexiline injection components detect
Perhexiline is process by Ligusticum wallichii, the red sage root, without with identical component of the present invention.
1.3 experimental animals and packet
Healthy Kunming mouse, male and female half and half, 25 ± 5g of body weight, by Tongji Medical College, Huazhong Science and Technology Univ. experimental animal
The heart provides.Mouse is randomly divided into physiological saline (NS) by its electrocardiogram negative patient as experimental subjects after adaptability is fed 3 days
Group, ischemia model (MI) group, perhexiline injection pretreated group (MI+GXN) group, ZHW-1 pretreated groups (MI+ZHW-1), ZHW-
2 pretreated groups (MI+ZHW-2), ZHW-3 pretreated groups (MI+ZHW-3), every group 6.
1.4MI group models replicate and each group processing method
Distilled water prepares 40% GXN, ZHW-1, ZHW-2, ZHW-3.NS groups and MI groups are with physiological saline gavage, gavage agent
Amount is according to 0.25ml/10 g, and 2 times/day, the time is 1 week.Control group mice intraperitoneal injection of saline 0.1ml/ is given after 1 week
10g, and perhexiline injection pretreated group (MI+GXN) group, ZHW-1 pretreated groups (MI+ZHW-1), ZHW-2 pretreated groups (MI
+ ZHW-2), ZHW-3 pretreated groups (MI+ZHW-3) mouse peritoneal equal injection of pituitrin (Pituitrin, Pit) 30U/kg_
2J, standard II lead connection limbs trace electrocardiogram, and terminal and the ST sections junction of QRS complex are referred to as J points, normal mouse J points
It may occur in which that J points rise or fall mostly on equipotential line, during myocardial ischemia, it is i.e. visual that J points rise or fall 0.1mV or more
For markers of cardiac ischemia, show modeling success.
1.5 sample collections and Biochemical Indexes
1.5.1CK detection
3h after administration, mouse femoral vein blood 1ml is taken to be transferred to immediately added with 20ul EDTA-Na2With the precooling of 10ul Aprotinins
Fully mixed in centrifuge tube, 3000r/min at 4 DEG C, centrifuge 5min, supernatant determines activity of serum CK in suction pipe.
1.5.2NOS, SOD, MDA are detected
Disconnected neck puts to death mouse after mouse takes blood, opens chest and takes out heart, draws bloodstain, ventricular muscles are weighed, with physiological saline system
Into 10% ventricular homogenate, centrifuging and taking supernatant, NOS, SOD activity and MDA are determined respectively according to the explanation of kit
Content.
1.6 statistical procedures
Experimental data is represented with mean ± standard deviation (± S), homogeneity test of variance is carried out, then respectively to each group mean
Difference carries out significance test with one-way analysis of variance, and the conspicuousness of more each group difference (uses SPSS11.0 statistical softwares
Analysis).
1.7 experimental result
1.7.1 to the influence of ischemic myocardium electrocardiogram J point displacement
In experiment, ischemia group mouse 5min after Pit is injected intraperitoneally, J points, which are raised, continues to 25min, and highest amplitude reaches
0.214mV；The electrocardiogram J point of ZHW-1, ZHW-2, ZHW-3 pretreated group and GXN pretreated group mouse is after Pit is injected intraperitoneally
Each period, raise that amplitude is small compared with MI groups, and its highest amplitude is 0.129mV, and ZHW-1, ZHW-2, ZHW-3 locate in advance
Reason group is superior to GXN pretreated group mouse.
1.7.2 the influence changed to cardiac muscular tissue's MDA contents and activity of serum CK
The MDA contents and CK activity of MI groups are obviously higher than physiological saline group, in significant difference (P ＜ 0.01), explanation
Model is established, and the MDA contents and CK of ZHW-1, ZHW-2, ZHW-3 pretreated group and GXN pretreated groups activity are substantially less than MI
Group (P ＜ 0.05), and ZHW-1, ZHW-2, ZHW-3 pretreated group are better than GXN pretreated groups.It is shown in Table 2.
Influence of the table 2 to MI mouse CK activity, cardiac muscular tissue's MDA contents
This experimental result shows that NS group serum CK concentrations are very low, and ZHW-1, ZHW-2, ZHW-3 pretreated group serum CK are lived
Property and myocardium MDA concentration are below MI groups.ZHW-1, ZHW-2, ZHW-3 pretreatment simultaneously can improve SOD in ischemic myocardial cells
Activity, prompt ZHW-1, ZHW-2, ZHW-3 that pretreatment can mitigate the peroxide injuries of Cell membrane lipids, strengthen to oxygen radical
Scavenging activity, stabilizing cell membrane, reduce intracellular CK leakage, mitigate the cellular damage caused by free radical, protection ischemic myocardium is thin
Born of the same parents, and it is superior to the GXN pretreated groups of control.
1.7.3 to the influence of ventricular homogenate NOS, SOD vigor
In MI groups cardiac muscular tissue NOS activity be substantially less than ZHW-1, ZHW-2, ZHW-3 pretreated group (P ＜ 0.01) and
GXN pretreated groups (P ＜ 0.05)；The SOD of MI groups is also significantly lower than other each groups, in significant difference (P ＜ 0.01), is shown in Table 3.
Influence of the table 3 to ventricular homogenate NOS, SOD vigor
This experiment shows MI group NOS activity decreases, gives ZHW-1, ZHW-2, ZHW-3 and GXN mouse ischemic of pretreatment
NOS activity is obvious afterwards strengthens, and ZHW-1, ZHW-2, ZHW-3 pretreated group are superior to GXN pretreated groups.With above-mentioned CK, S0D and
The change of the indexs such as MDA is consistent, shows the height of cardiac muscular tissue NOS activity and whether cardiac muscle damages relevant, i.e. NOS increased activities
(or decrease) causes the rise (or decline) that NO is horizontal in body, so as to mitigate (exacerbation) treating myocardial ischemia damage.
Influence of the composition to hemorheology in 2 present invention
2.1 given the test agent
Injection prepared by the sterile solution that embodiment 1-3 is provided：ZHW-1、ZHW-2、ZHW-3.
2.2 experimental animal：Regular grade Wistar big white mouse 70, male, body weight (200 ± 10) g.It is dynamic by Hebei province's experiment
Thing center provides, credit number：SCXK (Ji) 2008-1-003.
2.3 instrument reagent：
LBY-N6B Full-automatic self-cleanings lectin from hemolymph with, the micro blood plasma testers of LBY-N6B, LBY-BX red blood cell modification instrument
(Pulisheng Instruments Co., Ltd., Beijing)；
0.1% adrenalin hydrochloride, anesthetic chloraldurate, 0.5% Gansu anti-coagulants.
2.4 methods and result：
Animal is randomly divided into blank control group, model control group, perhexiline injection group, ZHW-1 injections group, ZHW-2
Injection group, ZHW-3 injection groups, every group ten.Intravenous injection gives corresponding dosage to above-mentioned four groups of injection groups respectively daily
By test product, the physiological saline for the capacity such as blank group control, model control group give, continuous 7 days.In addition to blank control group, remaining
0.1% adrenalin hydrochloride injection (0.6ml/kg) is subcutaneously injected in each group after being administered 2 hours, totally 2 times, is spaced 4 hours；The
After a shot 2 hours by rat chloral hydrate anesthesia (350mg/kg) arteria carotis communis talent and learning 5ml/ only, resisted with 0.5% heparin
It is solidifying, the index such as measure WBV, Plasma Viscosity, Plasma Viscosity.Measurement result is shown in Table 4.
Influence of the table 4 to hemorheology
From table 4, model control group blood viscosity, Plasma Viscosity and red blood cell compared with blank control group overstock notable
Rise, illustrate that model is established.ZHW-1 injections group, ZHW-2 injections group, ZHW-3 injections group and perhexiline are noted in the present invention
Penetrate agent control group to compare, can significantly reduce rat whole blood viscosity, Plasma Viscosity and red blood cell and overstock.
Test example 3
Toxicological evaluation is carried out to the present invention according to drug safety toxicological evaluation program and method, as a result such as
Under：
1. undue toxicity, checked according to four 1141 abnormal toxicity tests methods of Chinese Pharmacopoeia 2015 edition.
2. allergic reaction, checked according to four 1147 allergic reaction inspection techniques of Chinese Pharmacopoeia 2015 edition.
3. depressor, checked according to four 1145 test of depressor substance of Chinese Pharmacopoeia 2015 edition.
As a result regulation is met.
Obviously, above-described embodiment is only intended to clearly illustrate example, and is not the restriction to embodiment.It is right
For those of ordinary skill in the art, can also make on the basis of the above description it is other it is various forms of change or
Change.There is no necessity and possibility to exhaust all the enbodiments.And the obvious change thus extended out or
Among changing still in the protection domain of the invention.
Claims (10)
1. a kind of pharmaceutical composition for being used to treat myocardial ischemia, it is characterised in that include the component of following parts by weight：
Quercetin -3-O- β-D-Glucose base (1-2) -0.1~1 part of alpha-L-rhamnoside；
0.1~1 part of narcissin；
Kaempferol -3-O- β-D-Glucose base (1-2) -0.1~1 part of alpha-L-rhamnoside；
0.7~2 part of ginkalide A；
0.3~1 part of ginkolide B；
0.4~1 part of ginkalide C.
2. pharmaceutical composition according to claim 1, it is characterised in that the narcissin, ginkalide A, ginkgolides
B, one or more extracted by ginkgo leaf in ginkalide C is made.
3. a kind of include as the preparation of the pharmaceutical composition described in claim 1 or 2, it is characterised in that described pharmaceutical composition
Customary adjuvant is added, according to common process, clinically acceptable tablet, capsule, powder, mixture, pill, particle is made
Agent, oral liquid, syrup, paste, electuary, vina, injection, beverage, biscuit, candy, cake food or instant food.
4. the preparation of the pharmaceutical composition described in pharmaceutical composition or claim 3 described in claim 1 or 2 is preparing treatment
Application in myocardial ischemia medicine.
A kind of 5. method for preparing the injection comprising the pharmaceutical composition described in claim 1 or 2, it is characterised in that including,
By the Quercetin -3-O- β-D-Glucose base (1-2)-alpha-L-rhamnoside, narcissin, kaempferol -3-O- β-D-Glucose
Base (1-2)-alpha-L-rhamnoside, ginkalide A, ginkolide B, ginkalide C and water, auxiliary material are mixed and made into sterile solution；
Wherein, the Quercetin -3-O- β-D-Glucose base (1-2)-content of the alpha-L-rhamnoside in the sterile solution is 0.1
~1mg/ml.
6. a kind of preparation method of the pharmaceutical composition described in claim 1 or 2, comprises the following steps：
(1) take ginkgo leaf crush after, add 93~96% alcohol refluxs extract 1~3 time, each reflux extracting time be 0.3~
0.5 hour, the quality for adding 93~96% ethanol every time was 10~12 times of the ginkgo leaf quality；Filtering, by gained
Filtrate decompression is concentrated into 0.1~0.2 times of the ginkgo leaf quality, refrigerates 47~52 hours；
(2) oil slick is scraped off, takes subnatant；
(3) water for injection is added into the subnatant to 0.45~0.65 times of the ginkgo leaf quality, refrigeration 47~52 is small
When；Filter, concentrate filtrate to 0.1~0.2 times of the ginkgo leaf quality, put to room temperature, add 93~96% ethanol,
Make alcohol content that the solution after alcohol precipitation be refrigerated, filtered and concentrated successively, repeated 2~4 times to 79~83%；
(4) to the filtrate addition water for injection after concentration to 0.2~0.3 times of the ginkgo leaf quality, using macroporous absorption tree
Fat carries out absorption 4~8 times；Wherein, the positive macroreticular resin dosage is 0.5~5.0 times of the ginkgo leaf quality；
(5) auxiliary material and water are added to the decoction of adsorption treatment, is made sterile solution, Quercetin -3-O- β in the sterile solution -
The content of D-Glucose base (1-2)-alpha-L-rhamnoside is 0.1~1mg/mL.
7. the extracting method of ginkgo biloba p.e according to claim 6, it is characterised in that the macroporous absorbent resin grain
Spend for 30~60 mesh.
8. the preparation method of the injection according to claim 6 or 7, it is characterised in that the pH value of the sterile solution is
4.0~7.0.
9. according to the injection described in claim any one of 6-8, it is characterised in that in the sterile solution, ginkgoic acid≤
20ng/ml, the μ g/ml of lead content≤0.6, the μ g/ml of cadmium content≤0.15, the μ g/ml of arsenic content≤0.3, the μ g/ml of mercury content≤0.1,
The μ g/ml of copper content≤7.5.
10. a kind of method as described in claim 6-9 prepares the injection formed.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710705748.5A CN107569505A (en) | 2017-08-16 | 2017-08-16 | A kind of pharmaceutical composition for treating myocardial ischemia and its application and the injection formed by its preparation |
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|---|---|---|---|
| CN201710705748.5A CN107569505A (en) | 2017-08-16 | 2017-08-16 | A kind of pharmaceutical composition for treating myocardial ischemia and its application and the injection formed by its preparation |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114796196A (en) * | 2022-06-27 | 2022-07-29 | 山东省中医药研究院 | External medicine composition for treating vascular vertigo and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1899323A (en) * | 2005-07-18 | 2007-01-24 | 厦门国宇知识产权研究有限公司 | Ginkgo leaf extract, injection containing said extract and its preparing method |
-
2017
- 2017-08-16 CN CN201710705748.5A patent/CN107569505A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1899323A (en) * | 2005-07-18 | 2007-01-24 | 厦门国宇知识产权研究有限公司 | Ginkgo leaf extract, injection containing said extract and its preparing method |
Non-Patent Citations (1)
| Title |
|---|
| 徐芳等: "银杏叶提取物的研究进展", 《食品研究与开发》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114796196A (en) * | 2022-06-27 | 2022-07-29 | 山东省中医药研究院 | External medicine composition for treating vascular vertigo and application thereof |
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Effective date of registration: 20200803 Address after: No.8, Industrial Avenue, furniture base, Longling Industrial Park, Nankang District, Ganzhou City, Jiangxi Province Applicant after: LONCH GROUP JIANGXI PHARMACEUTICAL Co.,Ltd. Address before: 044200, No. 99, Xinjian South Road, Wanrong County, Yuncheng, Shanxi Applicant before: LONCH GROUP WANRONG PHARMACEUTICAL Co.,Ltd. |
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