CN105412136B - It is a kind of to be used to treat the composition of ischemic angiocardiopathy and cerebrovascular disease and its medicine of preparation and application - Google Patents
It is a kind of to be used to treat the composition of ischemic angiocardiopathy and cerebrovascular disease and its medicine of preparation and application Download PDFInfo
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- CN105412136B CN105412136B CN201510937664.5A CN201510937664A CN105412136B CN 105412136 B CN105412136 B CN 105412136B CN 201510937664 A CN201510937664 A CN 201510937664A CN 105412136 B CN105412136 B CN 105412136B
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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Abstract
It is used to treat the composition of ischemic angiocardiopathy and cerebrovascular disease and its medicine of preparation and application the present invention relates to a kind of; the composition by percentage by weight be 1 60% 3; 5 two-caffeoyl quinic acid and 30% scutellarin and the 4 of 10 69%; 5 two-caffeoyl quinic acid+1,5 two-caffeoyl quinic acid+Erigeroster B mixture composition.The medicine includes the composition and pharmaceutically acceptable pharmaceutical carrier or excipient, for treating ischemic angiocardiopathy and cerebrovascular disease.Composition and medicine provided by the invention, compared with prior art, its inhibition thrombosis and suppress onset time of platelet aggregation and are obviously shortened, and inhibiting rate significantly improves, in clinical practice can more fast onset drug effect, make patient obtain more timely giving treatment to.
Description
Technical field
It is used to treat the composition of ischemic angiocardiopathy and cerebrovascular disease and its medicine of preparation and application the present invention relates to a kind of,
Belong to medicinal application field.
Background technology
In recent years, the incidence of the cardiovascular and cerebrovascular disease in China is constantly soaring, and age of onset has also shifted to an earlier date, cardiovascular and cerebrovascular
The prevention of disease becomes important public health problem.
Ischemic angiocardiopathy and cerebrovascular disease refers to the heart caused by a variety of causes, brain blood supply obstacle, lacks the heart, brain tissue
Blood, Hypoxic necrosis, cause local heart and brain tissues that a kind of disease of irreversibility infringement occurs, acute attack endangers pole to body
Greatly.It such as cannot in time treat, the sequelae such as hemiplegia, physical handicaps, facial paralysis may be left, seriously affect minimal invasive treatment
Quality.
For ischemic angiocardiopathy and cerebrovascular disease since therapeutic time window is narrow, timely diagnosis and treatment are most important, during Clinical Processing, especially by force
Adjust early diagnosis, early treatment.After morbidity, there are 1,900,000 nerve cell deaths since anoxic is per minute, but within a certain period of time, necrosis
It is still reversible that the surrounding tissue of lesion, which is damaged, if can be immediately subjected to treat, will significantly reduce the risk of deformity.Cause
This, in addition to it should just be controlled as early as possible after morbidity, the onset time speed of the medicine for treating such disease is also to influence therapeutic effect
Key factor.The drug effect time is shorter, and therapeutic effect is better, and irreversible degree of injury is lighter caused by disease, sequelae
Less or degree is lighter.
In ischemic angiocardiopathy and cerebrovascular disease clinical treatment, inhibition thrombosis and platelet aggregation-against are most common control
Treatment measure.
Patent document CN1173707C discloses a kind of scutellarin and 45~95% caffeoyl quinine by 5~25%
The pharmaceutical composition of acid or its officinal salt composition；Patent document CN100374120C discloses a kind of erigeron breviscapus active component
Erigeron breviscapus, mainly by active ingredient scutellarin, 3,5- two-caffeoyl quinic acid, 1,5- two-caffeoyl quinic acid,
Erigeroster B and 4,5- two-caffeoyl quinic acid composition, wherein scutellarin content 10-40%, four caffeic acid ester contents it
With in 40-60%.Both of which can be used for treating cardiovascular and cerebrovascular disease, and provided pharmaceutical composition is also disclosed in two parts of documents
Or active component can suppress thrombus generation, suppress platelet aggregation.
Composition provided by the invention, is made of three parts, is respectively：(1) 3,5- two-caffeoyl quinic acid, (2) lamp
Small cup B prime and (3) 4,5- two-caffeoyl quinic acid+1,5- two-caffeoyl quinic acid+Erigeroster B mixture.By 3,5- bis-
Caffeoyl quinic acid, scutellarin and 4,5- two-caffeoyl quinic acid+1,5- two-caffeoyl quinic acid+Erigeroster B mix
Compound combines in specific proportions, and compared with prior art, the onset time of its inhibition thrombosis and suppression platelet aggregation is bright
Aobvious to shorten, inhibiting rate significantly improves, in clinical practice can more fast onset drug effect, make patient obtain more timely giving treatment to.
The content of the invention
The object of the present invention is to provide a kind of composition for being used to treat ischemic angiocardiopathy and cerebrovascular disease.
It is a further object of the present invention to provide it is a kind of by the composition prepare be used for treat ischemic angiocardiopathy and cerebrovascular disease
The medicine of disease.
Present invention also offers the use that the composition and its medicine of preparation are used to treat ischemic angiocardiopathy and cerebrovascular disease
On the way.
Technical scheme is as follows：
On the one hand, the present invention provide it is a kind of be used to treating the composition of ischemic angiocardiopathy and cerebrovascular disease, the composition by
Percentage by weight is the 3,5- two-caffeoyl quinic acid and bis- coffees of 4,5- of 30% scutellarin and 10-69% of 1-60%
Acyl group quininic acid+1,5- two-caffeoyl quinic acid+Erigeroster B mixture composition, total amount 100%.
Preferably, the composition is by 3,5- two-caffeoyl quinic acid and 30% that percentage by weight is 10-50%
4,5- two-caffeoyl quinic acid+1,5- two-caffeoyl quinic acid+Erigeroster B mixture group of scutellarin and 20-60%
Into total amount 100%.
It is highly preferred that 3,5- two-caffeoyl quinic acid and 30% of the composition by percentage by weight for 20-40%
Scutellarin and 30-50% 4,5- two-caffeoyl quinic acid+1,5- two-caffeoyl quinic acid+Erigeroster B mixture
Composition, total amount 100%.
On the other hand, the present invention provides a kind of medicine for being used to treat ischemic angiocardiopathy and cerebrovascular disease, and the medicine contains
The composition of the invention described above and pharmaceutically acceptable pharmaceutical carrier or excipient.
Preferably, the medicine is oral formulations or injection.
Composition and medicine provided by the present invention for treating ischemic angiocardiopathy and cerebrovascular disease, by 3,5-, bis- coffee acyls
Quininic acid, scutellarin and 4,5- two-caffeoyl quinic acid+1,5- two-caffeoyl quinic acid+Erigeroster B mixture are by spy
Certainty ratio combines, and compared with prior art, the onset time of its inhibition thrombosis and suppression platelet aggregation is obviously shortened, and presses down
Rate processed significantly improves, and generates unexpected effect.
Specific embodiment
Embodiment 1
1% 3,5- two-caffeoyl quinic acid and 30% scutellarin and 69% 4,5- two-caffeoyl quinic acid
+ 1,5- two-caffeoyl quinic acid+Erigeroster B mixture, are uniformly mixed, to obtain the final product.
Embodiment 2
10% 3,5- two-caffeoyl quinic acid and 30% scutellarin and 60% bis- coffee acyl quinines of 4,5-
+ 1,5- of acid two-caffeoyl quinic acid+Erigeroster B mixture, is uniformly mixed, to obtain the final product.
Embodiment 3
20% 3,5- two-caffeoyl quinic acid and 30% scutellarin and 50% bis- coffee acyl quinines of 4,5-
+ 1,5- of acid two-caffeoyl quinic acid+Erigeroster B mixture, is uniformly mixed, to obtain the final product.
Embodiment 4
30% 3,5- two-caffeoyl quinic acid and 30% scutellarin and 40% bis- coffee acyl quinines of 4,5-
+ 1,5- of acid two-caffeoyl quinic acid+Erigeroster B mixture, is uniformly mixed, to obtain the final product.
Embodiment 5
40% 3,5- two-caffeoyl quinic acid and 30% scutellarin and 30% bis- coffee acyl quinines of 4,5-
+ 1,5- of acid two-caffeoyl quinic acid+Erigeroster B mixture, is uniformly mixed, to obtain the final product.
Embodiment 6
50% 3,5- two-caffeoyl quinic acid and 30% scutellarin and 20% bis- coffee acyl quinines of 4,5-
+ 1,5- of acid two-caffeoyl quinic acid+Erigeroster B mixture, is uniformly mixed, to obtain the final product.
Embodiment 7
60% 3,5- two-caffeoyl quinic acid and 30% scutellarin and 10% bis- coffee acyl quinines of 4,5-
+ 1,5- of acid two-caffeoyl quinic acid+Erigeroster B mixture, is uniformly mixed, to obtain the final product.
Embodiment 8
Pharmaceutical carrier and the excipient such as arbitrary composition in Example 1-7, addition lactose, starch, magnesium stearate, are made
Tablet, capsule, granule etc. are used for the drug oral preparation for treating ischemic angiocardiopathy and cerebrovascular disease.
Embodiment 9
Pharmaceutical carrier and the tax such as arbitrary composition in Example 1-7, addition mannitol, sodium acid carbonate, hydrochloric acid, sodium chloride
Shape agent, is made the drug injection liquid formulation for treating ischemic angiocardiopathy and cerebrovascular disease.
Embodiment 10
The pharmaceutic adjuvant such as arbitrary composition in Example 1-7, addition mannitol, sodium acid carbonate, hydrochloric acid, sodium chloride, matches somebody with somebody
Solution is made, it is freeze-dried after aseptic filtration, the drug injection powder pin for treating ischemic angiocardiopathy and cerebrovascular disease is made
Agent.
Specific test example
1st, test material
(1) experimental animal
SD rats, the western Poole-Bi Kai experimental animals Co., Ltd in Shanghai provide, Shanghai dynamic circuit connector lattice word 152.
(2) test specimen
Totally 3, the sample being for experiment, is numbered with A, B, C.
A：(any one composition or medicine are attained by identical effect to the composition that embodiment 4 provides in embodiment 1-10
Fruit).
B：Preparing the composition of gained according to CN1173707C patent documents contents, (content of wherein scutellarin is
5%, the content of caffeoylquinic acids is 95%, total amount 100%)；
C：Preparing the composition of gained according to CN100374120C patent documents contents, (wherein scutellarin content is
40%, total coffee acid ester's content is 60%, total amount 100%)；
2nd, test method
(1) rat arteriovenous shunt thrombosis generation experiment
Healthy male SD rat 200, is randomly divided into solvent control group, sample A, sample B, sample C totally four groups, every group
50, each administration group dosage is 30mg/kg, the dosage blank solvents such as solvent control group is given, single intravenous injection administration, point
3 not after 0min, the administration, 6,9, thrombus of the 12min after totally 5 different time points observation rat arteriovenous shunt thrombosis are formed it is wet
Weight, 10 rats of every group of each time point.Rat arteriovenous shunt thrombosis forms test method：SD rats by intraperitoneal injection fiber crops
Liquor-saturated, dorsal position fixes promoting the circulation of qi cannula, and separates right common carotid artery and left vena jugularis externa.By built-in long 6cm silk threads, full of heparin
Left vena jugularis externa, other end insertion right common carotid artery are inserted into polyethylene pipe one end of normal saline solution.After intravenous injection administration
At corresponding time point, artery clamp is opened, makes blood from right common carotid artery through returning to left vena jugularis externa in polyethylene pipe.Open blood
Stream middle clinopodium polycephalum after 15 minutes, the rapid silk thread that takes out are weighed, and gross weight subtracts silk thread weight, up to thrombus growing amount.Inhibiting rate=
(sample group ﹣ solvent control groups)/solvent control group
Result of the test is shown in Table 1.
1 rat arteriovenous shunt thrombosis of table generation experiment (N=10)
* P ＜ 0.05vs solvent control groups；* P ＜ 0.01vs solvent control groups
According to experimental result, 3min can substantially suppress blood to composition (sample A) provided by the present invention upon administration
Bolt generates, and inhibiting rate reaches 23.58%, the composition (sample B) and patent document that patent document CN1173707C is provided
The composition (sample C) that CN100374120C is provided, just produces the effect for suppressing thrombus generation when being 9min after being administered, suppresses
Rate is respectively 21.55%, 20.26%.At same time point, sample B and sample C are below the inhibiting rate of thrombus institute of the present invention
Composition (sample A) is provided.
(2) rat platelet aggregation function test
Healthy male SD rat 200, is randomly divided into solvent control group, sample A, sample B, sample C totally four groups, every group
50, each administration group dosage is 30mg/kg, the dosage blank solvents such as solvent control group is given, single intravenous injection administration, point
Not in 0min, administration after 1,3,5, adopt by totally 5 different time points yellow Jackets intraperitoneal injection of anesthesia rats, abdominal aorta by 7min
Blood, anticoagulant heparin, prepares platelet rich plasma (PRP) and platelet poor plasma (PPP).By turbidimetry for Determination platelet aggregation journey
Degree, adds to PPP with the buffer solution or liquid of equivalent and opposes and look after zeroising, and liquid is added in PRP, 37 DEG C of incubations, then with
4 μm of ol/L induced platelet aggregations of ADP.Optical density curve is traced, peak is risen as maximum aggregation rate using curve, asks each
Group average aggregate rate, reduces amplitude with curve and calculates medicine to hematoblastic inhibitory action.
L-Arginine=(solvent control group average aggregate rate ﹣ investigational agent average aggregates rate)/solvent control group
Average aggregate rate.
Result of the test is shown in Table 2.
Table 2 to ADP induced rat platelet aggregations influence (N=10)
* P ＜ 0.05vs solvent control groups；* P ＜ 0.01vs solvent control groups
According to experimental result, 1min can substantially suppress blood to composition (sample A) provided by the present invention upon administration
Platelet is assembled, and aggregation inhibiting rate reaches 19.4%, after the composition that patent document CN1173707C (sample B) is provided is administration
The effect for suppressing platelet aggregation, the composition that patent document CN100374120C (sample C) is provided just are produced during 7min
The effect for suppressing platelet aggregation is just produced when being 5min after being administered, inhibiting rate is respectively 20.4%, 18.6%.In the same time
Point, sample B and sample C are significantly lower than composition (sample A) provided by the present invention to the inhibiting rate of platelet aggregation.
3rd, conclusion (of pressure testing)
(1) rat arteriovenous shunt thrombosis generation result of the test shows that composition and medicine provided by the invention have bright
The aobvious effect for suppressing thrombus generation, compared with prior art, onset time is obviously shortened, and inhibiting rate significantly improves.
(2) the influence result of the test of ADP induced rat platelet aggregations is shown, composition provided by the invention and
Medicine has the function that the platelet aggregation for substantially suppressing ADP inductions, and compared with prior art, onset time is obviously shortened, and
Inhibiting rate significantly improves.
Claims (6)
1. a kind of composition for being used to treat ischemic angiocardiopathy and cerebrovascular disease, it is characterised in that the composition is by weight percent
Than the 3,5- two-caffeoyl quinic acid for 20-40% and the 4,5- two-caffeoyl quinic acid of 30% scutellarin and 30-50%
+ 1,5- two-caffeoyl quinic acid+Erigeroster B mixture composition, total amount 100%.
2. medicine prepared by composition according to claim 1, it is characterised in that the medicine contains claim 1 institute
The composition and pharmaceutically acceptable pharmaceutical carrier stated.
3. medicine prepared by composition according to claim 1, it is characterised in that the medicine contains claim 1 institute
The composition and pharmaceutically acceptable excipient stated.
4. the medicine according to Claims 2 or 3, it is characterised in that the medicine is oral formulations.
5. the medicine according to Claims 2 or 3, it is characterised in that the medicine is injection.
6. the composition or medicine in claim 1 to 5 described in any one are preparing treatment ischemic angiocardiopathy and cerebrovascular disease
Purposes in medicine.
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| CN201510937664.5A CN105412136B (en) | 2015-12-16 | 2015-12-16 | It is a kind of to be used to treat the composition of ischemic angiocardiopathy and cerebrovascular disease and its medicine of preparation and application |
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| CN201510937664.5A CN105412136B (en) | 2015-12-16 | 2015-12-16 | It is a kind of to be used to treat the composition of ischemic angiocardiopathy and cerebrovascular disease and its medicine of preparation and application |
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| Publication Number | Publication Date |
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| CN105412136A CN105412136A (en) | 2016-03-23 |
| CN105412136B true CN105412136B (en) | 2018-05-04 |
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| CN114699437B (en) * | 2020-12-29 | 2022-12-20 | 云南生物谷药业股份有限公司 | Oral preparation containing herba Erigerontis extract and its preparation method |
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| CN1462620A (en) * | 2003-04-22 | 2003-12-24 | 中国科学院昆明植物研究所 | Powder of flenabane and its preparation method as well as application in making drugs |
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| CN1462620A (en) * | 2003-04-22 | 2003-12-24 | 中国科学院昆明植物研究所 | Powder of flenabane and its preparation method as well as application in making drugs |
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