CN106562961A - Pharmaceutical composition for treating cerebral infarction - Google Patents
Pharmaceutical composition for treating cerebral infarction Download PDFInfo
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- CN106562961A CN106562961A CN201611137199.8A CN201611137199A CN106562961A CN 106562961 A CN106562961 A CN 106562961A CN 201611137199 A CN201611137199 A CN 201611137199A CN 106562961 A CN106562961 A CN 106562961A
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- pharmaceutical composition
- cerebral infarction
- buffer
- salt solution
- solvent
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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
-
- 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
-
- 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—Liposomes
Abstract
The invention relates to a pharmaceutical composition for treating cerebral infarction. The pharmaceutical composition is composed of a bulk drug, egg yolk lecithin, cholesterol, sodium glycocholate, and tween 80. The pharmaceutical composition is prepared by the following steps: dissolving the bulk drug, egg yolk lecithin, cholesterol, sodium glycocholate, and tween 80 into a solvent, evenly mixing, removing the solvent to obtain a phospholipid membrane, adding a buffer salt solution to completely hydrate the phospholipid membrane to obtain liposome suspension, and finally freeze-drying or spray-drying the liposome suspension to obtain liposome.
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 referred to and supply obstacle, the limitation that ischemia, anoxia cause due to brain blood also known as cerebral infarction
The ischemic necrosiss or cerebral malacia of cerebral tissue, including cerebral thrombosiss (atherosclerotic infarct of brain), lacunar infarction and cerebral embolism.
Clinic is mainly shown as that the focal neurologicals such as hemiplegia, hemidysesthesia, aphasia, hemianopsia, ataxia are lacked.Cerebrovascular
It is senile commonly encountered diseases, frequently-occurring disease, is to threaten one of three big diseases of human health, with sickness rate height, mortality rate height, causes
The characteristics of residual rate height, high recurrence rate.Epidemiological study shows, cerebrovascular have become three big underlying cause of death of old people it
One, wherein acute ischemic cerebrovascular disease accounts for 43%～65%, and case fatality rate is 15%～25%, and cerebral thrombosiss are accounted for beyond bleeding
The 9/10 of cerebrovascular, in survivor, more than 70% something lost has different degrees of dysfunction, and disability rate is higher, has a strong impact on patient
Quality of life.In recent years ischemic cerebrovascular morbidity has the trend of rejuvenation, and its clinical manifestation is not quite similar with gerontal patient,
Common with initial property, solitary, lacunar infarction, the dyskinesia is more than sensory disturbance.Cerebral Infarction Patients are through treatment, depolarization
Minority is outer in acute stage recovery from illness, and great majority will experience this process of convalescent period.Therefore, the preventing and treating of cerebral infarction at restoration stage has become society
Can be with the important topic of medical circle concern.
The reason for modern medicine thinks cerebral infarction mainly has two big class：First, more due to elderly brain atherosclerosiss,
Blood vessel is caused to thicken, lumen of vessels is narrow, slow blood flow, the visible component in blood is gathered in the Ink vessel transfusing, itself forms
Thrombosis, obturation, and there is the brain tissue ischemia necrosis of the blood vessel domination, and then there are corresponding clinical symptoms, i.e. " cerebral thrombosiss shape
Into ".Adolescent, cerebral thrombosiss are then more due to cerebral arteritises, such as connective tissue disease and antibacterial, virus, spirochaete infection etc., cigarette
Mist disease (multiple progressive intracranial vessel is narrow or inaccessible), fibromuscular dysplasia, Drug and disease in the blood system, it is such as red
Blood cell increase disease, thrombocytosiss, 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,
Such as the embolus that atrial fibrillation is produced；Non-cardiogenic embolus, such as fracture, the fat emboluses of operation, air embolus, antibacterial and parasite
Embolus etc..After due to cerebral infarction, the brain regional blood flow in the inaccessible tremulous pulse cloth area can be caused to reduce or blood supply interruption, then brain local group
Ischemia, anoxia are knitted, is caused cerebral tissue to soften necrosis, local nerve systemic symptom and sign is occurred.Such as：Numb limbs and tense tendons, it is weak or
Paralysis, dispute tiltedly or aphasis, or have visual disorder, ataxia or spirit, disturbance of consciousness etc..
At present, western medical treatment cerebral infarction is with thrombolytic, reduction cerebral edema, control blood pressure, reduction blood viscosity and platelet aggregation
Collect, improve the hypercoagulability of blood, improve based on cerebral circulation and protection brain cell, be equipped with limbs, language function rehabilitation.
(1) thromboembolism treatment：It is domestic to select streptokinase, urokinase, tissue-type plasminogen activator, general curative effect very well, make to close more
Plug blood leads to again, and maximum side reaction is secondary cerebral hemorrhage；(2) brain protective measure：More from free radical scavenger (such as according to reaching
La Feng, Vitamin E etc.), opiate receptor blocker (Allylnoroxymorphone), calcium channel blocker (such as nimodipine, flunarizine etc.) and emerging
Put forth energy acidic amino acid receptor blocking agent；(3) anticoagulant therapy：Inaccessible patient again after progressive Ischemic Stroke or thrombolytic, can be using early
Phase, short application use anticoagulant therapy, in case tampon extension, is now typically injected with Low molecular heparin, a few patients also have Secondary cases
The side reaction of cerebral hemorrhage；(4) anti-platelet aggregation treatment：Conventional enteric coated aspirin, persantin or clopidogrel, it is possible to decrease brain
The relapse rate of infraction, is a kind of preventive usage, but can not be applied with thrombolytic or anticoagulant therapy simultaneously, to peptic ulcer, is gone out
Disorders of blood people should not also apply；(5) using Pimobendane, brain cell nutritional drugs：1～2 kind of Pimobendane application is can select, with
Alleviate and improve clinical sign, but acute stage should not be applied when having cerebral edema, after stand-by Mannitol alleviates cerebral edema, then with expanding
Blood vessel drug eluting；(6) Hemodilution Therapy：General multiplex low molecular dextran；(7) prevent and treat cerebral edema：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, cardiorenal function bad person should use with caution；(8) suit the medicine to the illness and control
Treat and rehabilitation；Concrete condition depending on patient is carried out by doctor in charge's guidance.
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 by following method of following bulk drugs, Egg Yolk Lecithin (PC-98T), cholesterol, NaGC and Tween 80：
The crude drug, Egg Yolk Lecithin (PC-98T), cholesterol, NaGC, Tween 80 are dissolved in solvent, mix homogeneously,
Immobilized artificial membrane is obtained after removing solvent；Buffer salt solution is added to make the complete aquation of immobilized artificial membrane, it is suspension is cold into liposome turbid liquor
Lyophilizing it is dry or be spray-dried after liposome.
Preferably, pharmaceutically acceptable buffer salt solution of the described buffer salt solution for pH value 4.5～6.0, for example
Buffer salt solution delays selected from phosphate buffer, citrate buffer, carbonate buffer solution, borate buffer solution, acetate
Rush one or more in liquid.
Preferably, described solvent be organic solvent, be selected from ethanol, methanol, the tert-butyl alcohol, n-butyl alcohol, isopropanol, third
One or more in ketone, ether, benzyl alcohol, normal hexane, preferred solvent are isopropanol.
Preferably, buffer salt solution is added to make the complete aquation of immobilized artificial membrane, then with the homogeneous emulsifying 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 for cerebral infarction has good curative effect, is expected to continual exploitation into clinically having in zoopery
The new drug of effect.
Specific embodiment
Further detailed description is done to the present invention with reference to embodiment, but the present invention is not limited with this.
Embodiment medicine of the present invention is for the therapeutic effect of 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, body weight 280-320 gram, in 23 DEG C of ad libs and drinking-water.By 10% water of rat
Close chloral 3.5ml/kg lumbar injections (ip) anesthesia after, neck median incision, separate, ligation right carotid, external carotid artery and
Its bifurcated artery.Bulldog clamp is placed for line, distal end in internal carotid artery near-end, common carotid artery crotch otch inserts 4～0 nylon
Line, its depth are 17～20mm, and bolt line enters internal carotid artery, enter cranium to anterior cerebral artery, all blood flows of blocking middle cerebral artery
Source.Bulldog clamp is removed, standby line is tightened, is cut off unnecessary the end of a thread, with iodophor disinfection, last skin suture, operation are finished back wound
Cage is raised., in addition to not plug wire, remaining step is ibid for sham operated rats.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 (i.e. left side) Horner diseases (left side blepharoptosiss, enophthalmos,enophthalmuses) and
Operation side (i.e. left side) hemiplegia Signs (being unable to full extension left fore, toppled over during walking to the left or turn-taked).According to above-mentioned standard
The rat for being possible to survival 24h is defined as last experimental subject, and carries out neurological deficit score and quickly break end taking brain.
Rat is divided into into 6 groups, 20 per group, respectively：Sham operated rats (normal saline), model group (normal saline), sun
Property the basic, normal, high dosage group of matched group (Nimodipine Injection, 0.3mg/kg) medicine of the present invention (supply reagent composition injection 10mg/
kg、20mg/kg、40mg/kg).Medicine normal saline makes administered volume be 0.2ml/100g big into corresponding concentration
Mus.0.5h elder generations intravenous injection before modeling is administered once；After modeling, 6h and 12h carry out the 2nd, 3 administrations respectively, i.e., be administered altogether 3
It is secondary.Model group and rats in sham-operated group give normal saline, and administration time and volume are ibid.
Take half brain latter half of left side and claim weight in wet base respectively, put 120 DEG C of baking boxs and dry to constant weight, calculate brain group 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 operated rats 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
Knit water content (%) and be respectively 77.4 ± 0.7,75.8 ± 0.6,74.8 ± 0.5.Rats in sham-operated group brain water content is relatively low, model
Group rat brain water content is significantly higher than sham operated rats (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).
After modeling, 24h takes 10 rats per group, 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 into five.First cutter spacing pole and optic chiasma line midpoint, second cutter spacing before brain
In optic chiasma, the 3rd in infundibulum, and the 4th 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 ratio.
Cerebral infarct size ratio (%) of sham operated rats is 2.37 ± 1.16, and cerebral infarct size ratio (%) of model group is
42.61 ± 6.28, cerebral infarct size ratio (%) of positive controls is 25.39 ± 3.47, the basic, normal, high dosage of medicine of the present invention
Cerebral infarct size ratio (%) of group is respectively 31.55 ± 3.82,26.75 ± 3.07,21.53 ± 2.86.
Claims (5)
1. a kind of pharmaceutical composition for treating cerebral infarction, it is characterised in that described pharmaceutical composition is by following bulk drugs, egg yolk ovum
Phospholipid, cholesterol, NaGC and Tween 80 are made by following method：
The crude drug, Egg Yolk Lecithin (PC-98T), cholesterol, NaGC, Tween 80 are dissolved in solvent, mix homogeneously, are removed
Immobilized artificial membrane is obtained after solvent；Buffer salt solution is added to make the complete aquation of immobilized artificial membrane, will be suspension freezing dry into liposome turbid liquor
Liposome is obtained after dry or spray drying.
2. the pharmaceutical composition for the treatment of cerebral infarction according to claim 1, it is characterised in that described buffer salt solution is
The pharmaceutically acceptable buffer salt solution of pH value 4.5～6.0, such as buffer salt solution are selected from phosphate buffer, citric acid
One or more in salt buffer, carbonate buffer solution, borate buffer solution, acetate buffer.
3. the pharmaceutical composition for the treatment of cerebral infarction according to claim 2, it is characterised in that described solvent is for organic molten
Agent, one kind being selected from ethanol, methanol, the tert-butyl alcohol, n-butyl alcohol, isopropanol, acetone, ether, benzyl alcohol, normal hexane or several
Kind, preferred solvent is isopropanol.
4. it is according to claim 3 treatment cerebral infarction pharmaceutical composition, it is characterised in that add buffer salt solution make phosphorus
The complete aquation of adipose membrane, then with the homogeneous emulsifying of tissue mashing machine, into liposome turbid liquor.
5. compound prepare treatment cerebral infarction medicine in purposes, it is characterised in that the compound has having structure：
Priority Applications (1)
| 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 |
Applications Claiming Priority (1)
| 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 true CN106562961A (en) | 2017-04-19 |
| CN106562961B CN106562961B (en) | 2017-09-01 |
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| CN201611137199.8A Expired - Fee Related CN106562961B (en) | 2016-12-12 | 2016-12-12 | A kind of pharmaceutical composition for treating cerebral infarction |
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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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| CN106562961B (en) | 2017-09-01 |
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| Date | Code | Title | Description |
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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 |
Inventor after: Yan Yawei Inventor after: Zhao Hailan Inventor before: Qu Shenghuan |
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| CB03 | Change of inventor or designer information | ||
| 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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| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170901 Termination date: 20191212 |
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| CF01 | Termination of patent right due to non-payment of annual fee |