CN106562961B - A kind of pharmaceutical composition for treating cerebral infarction - Google Patents
A kind of pharmaceutical composition for treating cerebral infarction Download PDFInfo
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- CN106562961B CN106562961B CN201611137199.8A CN201611137199A CN106562961B CN 106562961 B CN106562961 B CN 106562961B CN 201611137199 A CN201611137199 A CN 201611137199A CN 106562961 B CN106562961 B CN 106562961B
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- cerebral infarction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
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Abstract
The present invention relates to a kind of pharmaceutical composition for treating cerebral infarction, described pharmaceutical composition is made up of bulk drug described herein, egg yolk lecithin, cholesterol, NaGC and Tween 80 of following method：The bulk drug, egg yolk lecithin, cholesterol, NaGC, Tween 80 are dissolved in solvent, are well mixed, removes and immobilized artificial membrane is made after solvent；Adding buffer salt solution makes the complete aquation of immobilized artificial membrane, and liposome is obtained after suspension is freeze-dried or is spray-dried into liposome turbid liquor.
Description
Technical field
The present invention relates to field of medicaments, specifically, the present invention relates to a kind of pharmaceutical composition for treating cerebral infarction.
Background technology
Cerebral infarction is also known as cerebral arterial thrombosis, refers to because brain blood supplies obstacle, limitation caused by ischemic, anoxic
The ischemic necrosis or cerebromalacia of brain tissue, including cerebral thrombosis (atherosclerotic infarct of brain), lacunar infarction and cerebral embolism.
Clinic is mainly shown as that the focal neurologicals such as hemiplegia, hemidysesthesia, aphasia, hemianopsia, incoordination are lacked.Cerebrovascular disease
It is common disease, the frequently-occurring disease in senescence phase, is to threaten one of three big diseases of human health, with the incidence of disease is high, the death rate is high, cause
The characteristics of residual rate height, high recurrence rate.Epidemiological study shows, cerebrovascular disease have become the big underlying cause of death of the elderly three it
One, wherein acute ischemic cerebrovascular disease accounts for 43%~65%, and case fatality rate is 15%~25%, and cerebral thrombosis is accounted for beyond bleeding
More than 70% something lost has different degrees of dysfunction in the 9/10 of cerebrovascular disease, survivor, and disability rate is higher, has a strong impact on patient
Quality of life.In recent years ischemic cerebrovascular disease morbidity has the trend of rejuvenation, and its clinical manifestation is not quite similar with gerontal patient,
Common with initial property, solitary, lacunar infarction, dyskinesia is more than sensory disturbance.Cerebral Infarction Patients are by treatment, depolarization
It is a small number of outer in acute stage recovery from illness, it is most of to undergo this process of convalescence.Therefore, the preventing and treating of cerebral infarction at restoration stage turns into society
The important topic that can be paid close attention to medical field.
The reason for modern medicine thinks cerebral infarction mainly has two major classes：First, more due to elderly brain atherosclerosis,
Blood vessel is caused to thicken, lumen of vessels is narrow, slow blood flow, the visible component in blood is gathered in intravascular, itself formation
Thrombus, occlusion, and there is the brain tissue ischemia necrosis of blood vessel domination, and then there are corresponding clinical symptoms, i.e. " cerebral thrombus shape
Into ".Young man, cerebral thrombosis is then more due to cerebral arteritis, such as CTD and bacterium, virus, spirochaete infection, cigarette
Mist disease (multiple progressive intracranial vessel narrow or occlusion), fibromuscular dysplasia, Drug and disease in the blood system, it is such as red
Blood cell increase disease, piastrenemia, thrombotic thrombocytopenic purpura etc. cause.Second, due to various external emboluses, with
Blood flow enters entocranial artery, makes the cerebrovascular acute occlusion, and causes corresponding clinical sign, i.e., " cerebral embolism ".Cardiogenic embolus,
The embolus produced such as atrial fibrillation；Non-cardiogenic embolus, the fat embolus such as fractured, performed the operation, air embolus, bacterium and parasite
Embolus etc..After cerebral infarction, the brain regional blood flow in the inaccessible artery cloth area can be caused to reduce or blood supply interruption, then the local group of brain
Ischemic, anoxic are knitted, causes brain tissue softening necrosis, local nerve systemic symptom and sign occurs.Such as：Extremity numbness, it is weak or
Paralysis, dispute tiltedly or aphasis, or has dysopia, incoordination or spirit, the disturbance of consciousness etc..
At present, western medical treatment cerebral infarction is with thrombolysis, reduction encephaledema, control blood pressure, reduction blood viscosity and platelet aggregation
Based on collection, the hypercoagulative state for improving blood, improvement Brain circlulation and protection brain cell, limbs, linguistic function rehabilitation are equipped with.
(1) thromboembolism treatment：Domestic to select streptokinase, urokinase, tissue-type plasminogen activator, general curative effect very well, can make to close more
Plug blood leads to again, and maximum side reaction is secondary cerebral hemorrhage；(2) brain safeguard measure：It is many from free radical scavenger (such as according to up to
La Feng, vitamin E etc.), opiate receptor retarding agent (Allylnoroxymorphone), calcium channel blocker (such as Nimodipine, Flunarizine) and emerging
Put forth energy acidic amino acid ARBs；(3) anticoagulant therapy：Inaccessible patient again after progressive Ischemic Stroke or thrombolysis, can be using early
Phase, short application use anticoagulant therapy, extend to prevent tampon, are now typically injected with LMWHs, a few patients also have Secondary cases
The side reaction of cerebral hemorrhage；(4) anti-platelet aggregation is treated：Conventional enteric coated aspirin, persantine or clopidogrel, it is possible to decrease brain
The recurrence rate of infraction, is a kind of preventive usage, but can not simultaneously be applied with thrombolysis or anticoagulant therapy, to peptic ulcer, is gone out
Blood patient should not also apply；(5) application Pimobendane, brain cell nutritional drugs：1~2 kind of Pimobendane application is can select, with
Alleviate and improve clinical sign, but acute stage has and should not applied during encephaledema, stand-by mannitol is alleviated after encephaledema, then with expanding
Blood vessel drug eluting；(6) Hemodilution Therapy：Typically multi-purpose D-40；(7) encephaledema is prevented and treated：For Early stage of cerebral infarction,
When especially infraction face is larger, the state of an illness is heavier, 20% mannitol dead point is commonly used, the bad person of cardiorenal function should use with caution；(8) suit the medicine to the illness and control
Treat and rehabilitation；Concrete condition depending on patient is instructed to carry out by the doctor in charge.
The content of the invention
It is an object of the invention to provide a kind of pharmaceutical composition for treating cerebral infarction.
In order to realize the purpose of the present invention, the present invention provides a kind of pharmaceutical composition for treating cerebral infarction, the medicine group
Compound is made up of following bulk drugs, egg yolk lecithin, cholesterol, NaGC and Tween 80 of following method：
The bulk drug, egg yolk lecithin, cholesterol, NaGC, Tween 80 are dissolved in solvent, are well mixed,
Remove and immobilized artificial membrane is made after solvent；Adding buffer salt solution makes the complete aquation of immobilized artificial membrane, into liposome turbid liquor that suspension is cold
Liposome is obtained after lyophilized dry or spray drying.
Preferably, described buffer salt solution is the pharmaceutically acceptable buffer salt solution of pH value 4.5~6.0, for example
Buffer salt solution is selected from phosphate buffer, citrate buffer, carbonate buffer solution, borate buffer solution, acetate and delayed
One or more in fliud flushing.
Preferably, described solvent is organic solvent, is selected from ethanol, methanol, the tert-butyl alcohol, n-butanol, isopropanol, third
One or more in ketone, ether, phenmethylol, n-hexane, preferred solvent is isopropanol.
Preferably, adding buffer salt solution makes the complete aquation of immobilized artificial membrane, then with the homogeneous emulsification of tissue mashing machine, into liposome
Suspension.
The present invention also provides purposes of the compound in the medicine for preparing treatment cerebral infarction, and the compound has following knot
Structure：
Medicine of the present invention has good curative effect in zoopery for cerebral infarction, is expected to continual exploitation into clinically having
The new drug of effect.
Embodiment
Further detailed description is done to the present invention with reference to embodiment, but the present invention is not limited with this.
Therapeutic effect of the embodiment medicine of the present invention for cerebral infarction
For reagent thing
LC-MS:(ES,m/z):[M+H]+445.H-NMR:(300Hz,CD3OD,ppm):δ7.74(2H,m),7.76(1H,
D, J=8.4Hz), 7.75 (3H, m), 7.74 (1H, d, J=8.1Hz), 4.83 (1H, m), 4.43 (1H, m), 4.33 (1H, m),
4.23(2H,m),4.15(1H,m),4.06(1H,m),3.82(2H,m),3.62(2H,m),2.31(3H,s),1.83(3H,s),
1.24(3H,t)。
Choose male Wistar rat, 280-320 grams of body weight, in 23 DEG C of ad libs and drinking-water.By 10% water of rat
Close after chloral 3.5ml/kg intraperitoneal injection (ip) anesthesia, neck median incision, separation, ligation right carotid, external carotid artery and
Its bifurcated artery.Artery clamp is placed for line, distal end in internal carotid near-end, arteria carotis communis crotch otch inserts 4~0 nylon
Line, its depth is 17~20mm, and bolt line enters internal carotid, enters cranium to arteria cerebri anterior, blocks all blood flows of arteria cerebri media
Source.Artery clamp is removed, standby line is tightened, cuts off unnecessary the end of a thread, wound is with iodophor disinfection, last skin suture, operation is finished back
Cage is raised.Sham-operation group is in addition to not plug wire, and remaining step is ibid.Remaining each group rat presses above-mentioned operation method modeling.Modeling into
The standard of work(：Have after postoperative animal is clear-headed substantially operation side (on the left of i.e.) Horner diseases (left side ptosis, enophthalmos,enophthalmus) and
Operation side (i.e. left side) hemiplegia Signs (being unable to full extension left fore, topple over or turn-take to the left during walking).According to above-mentioned standard
The rat for being possible to survival 24h is defined as last experimental subjects, and carries out neurological deficit score and quickly break end to take brain.
Rat is divided into 6 groups, every group 20, is respectively：Sham-operation group (physiological saline), model group (physiological saline), sun
Property control group (nimotop vial, 0.3mg/kg) basic, normal, high dosage group of medicine of the present invention (for reagent composition injection 10mg/
kg、20mg/kg、40mg/kg).Medicine normal saline is into corresponding concentration, and it is 0.2ml/100g big to make administered volume
Mouse.0.5h is first injected intravenously and is administered once before modeling；After modeling 6h and 12h carry out the 2nd respectively, 3 administrations, i.e., 3 are administered altogether
It is secondary.Model group and rats in sham-operated group give physiological saline, and administration time and volume are ibid.
Take half brain latter half of left side to claim weight in wet base respectively, put 120 DEG C of baking boxs and dry to constant weight, brain group is calculated as follows
Knit water content.
Brain water content (%)=(weight in wet base-dry weight)/weight in wet base × 100%.
The brain water content (%) of sham-operation group is 73.6 ± 0.6, and the brain water content (%) of model group is 80.3
± 0.8, the brain water content (%) of positive controls is 75.2 ± 0.5, the brain group of the basic, normal, high dosage group of medicine of the present invention
It is respectively 77.4 ± 0.7,75.8 ± 0.6,74.8 ± 0.5 to knit water content (%).Rats in sham-operated group brain water content is relatively low, model
Group rat brain water content is significantly higher than sham-operation group (P ＜ 0.01).The brain water content of positive controls and medicine group of the present invention is equal
Substantially less than model group rats (P ＜ 0.05).
Every group of 24h takes 10 rats after modeling, quickly takes full brain, removes olfactory bulb, cerebellum and low brain stem, freezes 25 points
Clock.Then it is coronal to cut four knives, full brain is cut into five.First cutter spacing is in pole before brain and optic chiasma line midpoint, the second cutter spacing
In optic chiasma, the 3rd arrives in pars infundibularis, and the 4th arrives between infundibular stalk and leaf tail pole.Then brain piece is put into 2% red four nitrogen rapidly
In azoles (TTC), lucifuge, 37 DEG C of temperature are incubated 30 minutes, are stirred once every 7~8min therebetween, solid with 4% paraformaldehyde after dyeing
It is fixed.Coloration result：Normal structure takes on a red color, and blocking tissue is white.Take pictures and use BI2000 medical images analysis system to calculate
Cerebral infarct size percentage.
The cerebral infarct size ratio (%) of sham-operation group is 2.37 ± 1.16, and the cerebral infarct size ratio (%) of model group is
42.61 ± 6.28, the cerebral infarct size ratio (%) of positive controls is 25.39 ± 3.47, the basic, normal, high dosage of medicine of the present invention
The cerebral infarct size ratio (%) of group is respectively 31.55 ± 3.82,26.75 ± 3.07,21.53 ± 2.86.
Claims (1)
1. purposes of the compound in the medicine for preparing treatment cerebral infarction, it is characterised in that the compound has having structure：
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611137199.8A CN106562961B (en) | 2016-12-12 | 2016-12-12 | A kind of pharmaceutical composition for treating cerebral infarction |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611137199.8A CN106562961B (en) | 2016-12-12 | 2016-12-12 | A kind of pharmaceutical composition for treating cerebral infarction |
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| Publication Number | Publication Date |
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| CN106562961A CN106562961A (en) | 2017-04-19 |
| CN106562961B true CN106562961B (en) | 2017-09-01 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101623259A (en) * | 2009-07-23 | 2010-01-13 | 海南美大制药有限公司 | Amoxicillin lipidosome solid preparation and new application thereof |
| CN103705521A (en) * | 2012-09-28 | 2014-04-09 | 韩冰 | Compound for treating cerebral infarction and application thereof |
| CN105980376A (en) * | 2014-01-07 | 2016-09-28 | 3-V生物科学股份有限公司 | Heterocyclic modulators of lipid synthesis for use against cancer and viral infections |
-
2016
- 2016-12-12 CN CN201611137199.8A patent/CN106562961B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101623259A (en) * | 2009-07-23 | 2010-01-13 | 海南美大制药有限公司 | Amoxicillin lipidosome solid preparation and new application thereof |
| CN103705521A (en) * | 2012-09-28 | 2014-04-09 | 韩冰 | Compound for treating cerebral infarction and application thereof |
| CN105980376A (en) * | 2014-01-07 | 2016-09-28 | 3-V生物科学股份有限公司 | Heterocyclic modulators of lipid synthesis for use against cancer and viral infections |
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| CN106562961A (en) | 2017-04-19 |
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| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Yan Yawei Inventor after: Zhao Hailan Inventor before: Qu Shenghuan |
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| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20170808 Address after: Pingshan Pingshan street Shenzhen City, Guangdong Province Jinniu Road 518118 No. 16 Huahan science and Technology Industrial Park, No. 2 building 345 room Applicant after: Shenzhen Acer Huihao Medical Technology Co Ltd Address before: 075000 No. 18 Xingye Road, industrial agglomeration area, Hebei, Zhangjiakou, China Applicant before: Qu Shenghuan |
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| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170901 Termination date: 20191212 |