CN109498637A - Application of the Quzhazhigan or derivatives thereof in preparation prevention and treatment brain edema drug - Google Patents
Application of the Quzhazhigan or derivatives thereof in preparation prevention and treatment brain edema drug Download PDFInfo
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Abstract
The present invention relates to the application of pharmaceutical technology field more particularly to Quzhazhigan or derivatives thereof in preparation prevention and treatment brain edema drug.The present invention is found through experiments that Quzhazhigan can be substantially reduced the brain water content that the focal permanent cerebral ischemia model of mouse, cerebral inschemia-reperfusion injury model type, lipopolysaccharides cause four kinds of infection model, Rat Cerebral hemorrhage Model model mices, and injection Quzhazhigan is prompted to all have potential therapeutic effect to brain edema caused by above-mentioned many reasons.Effective component of the invention can be extracted from plants, and drug price used is cheap, is easy to get, and market prospects are good.
Description
Technical field
The present invention relates to pharmaceutical technology fields more particularly to Quzhazhigan or derivatives thereof to prevent and treat brain edema drug in preparation
In application.
Background technique
Brain edema refers to the pathological phenomenon that intracerebral moisture increases, brain volume is caused to increase, be brain tissue to it is various it is pathogenic because
The reaction of element.It is the final pathological phenomenon secondary to a variety of cerebral diseases, is to form hernia cerebri and lethal principal element, for many years one
It is directly that (1 applies happy, and Yang Xiping, Shang Chongzhi Xingnaojing is in protective effect [J] of craniocerebral trauma for the hot spot [1] of brain science research
State's applied physiology magazine, 2014,30 (3): 230-232.).It is clinically common in the nervous system disease, many factors can draw
Play brain edema, such as ischemic, anoxic, bleeding, intracranial injury, inflammation, dysbolism of brain, brain tumor and poisoning.Brain edema rises
Sick anxious, rapid onset, can not only lead to brain tissue cell (neuron, Deiter's cells) interior environmental disruption, cause nerve
Dysfunction, and intracranial hypertension can be caused, the blood perfusion of brain is influenced, brain tissue oedema is further aggravated, forms hernia cerebri very
To leading to death.Currently, mostly using dehydration therapy to the treatment of brain edema, however it cannot but obtain satisfied effect.Study carefully
Its reason is because people's Central nervous system water, the mechanism of electrolyte transportation balance so far is unclear.Therefore,
Research is carried out around this problem to have a very important significance.
It is still not very clear to the molecular mechanism of brain edema formation at present, generally brain edema is divided into according to its pathogenesis
Two classes, i.e. cytotoxic brain edema and vasogenic brain edema.Cytotoxic brain edema is mainly shown as that moisture is stagnant in the cell
It stays, cellular swelling, but blood-brain barrier (blood-brain barrier, BBB) still keeps complete；Vasogenic edema is then main
Increased by the impaired caused capillary permeability of BBB, moisture exudation increases, and lodges in around blood vessel and caused by cytoplasm.
Clinical treatment brain edema is only symptomatic treatment at present, without specific treatment medicine, easily makes interior environment disturbance, therefore needs further
The pathogenesis of brain edema is studied, and provides theoretical foundation for further medicament research and development.Many Clinical and experimental studies show
Cerebral ischemia, anoxic, bleeding equivalent damage can cause to divide in energy exhaustion, free radical generation, calcium overload, inflammatory reaction and nerve
Change such as excitatory amino acid, slow sharp skin isoreactivity substance release increase are secreted, all multiple-factors such as Neuron Apoptosis participate in, and promote brain
Oedema.Clinically common drug has dehydrating agent, diuretics and glucocorticoid three categories, but has more toxic side effect.Closely
There is cell calcium oscillations, free radical scavenger, cytokine antagonist, blood-brain barrier protecting agent, NO synthase and inhibits in Nian Lai
Agent, etc., but there is no a kind of specific medicament that can reverse brain edema pathologic process well at present, and fundamentally solve the change of its pathology
Change, reaches therapeutic purposes.Therefore, the drug for exploring good effect and the treatment brain edema of Small side effects is the hot spot studied.
Quzhazhigan ((E) -1- (3,5- dihydroxyphenyl) -2- (3- hydroxyl -4-O- β-D- glucopyranose phenyl) ethylene or
3,5,3', 4'- tetrahydroxy Stilbene -3'-O- beta-glucosidase), plant origin is Lhasa rhubarb rhizome, and piceatannol is bent letter Stilbene
The aglycon of glycosides.A kind of Chinese patent (application number: 2011110371198.0) " height for measuring Quzhazhigan content in Lhasa rhubarb
Effect liquid phase chromatogram method "；Chinese patent (application number: 201110253242.8) " a method of prepare piceatannol " it discloses
The extraction process of Quzhazhigan, detection method and prepare Quzhazhigan aglycon piceatannol method.It has no in the prior art
The purposes report in brain edema drug is being treated and/or prevented to Quzhazhigan.
Summary of the invention
In view of this, preventing and treating brain in preparation the technical problem to be solved in the present invention is that providing Quzhazhigan or derivatives thereof
Application in edema drugs, studies have shown that Quzhazhigan or derivatives thereof can be used in brain edema caused by preventing and treating many factors.
The present invention provides application of the Quzhazhigan or derivatives thereof in the drug of preparation prevention and treatment brain edema.
The present invention is found through experiments that Quzhazhigan can be substantially reduced the focal permanent cerebral ischemia model of mouse, global cerebral ischemia
Re-perfusion model, lipopolysaccharides cause the brain water content of four kinds of infection model, Rat Cerebral hemorrhage Model model mices, prompt injection bent
Letter Stilbene glycosides all has potential therapeutic effect to brain edema caused by above-mentioned many reasons.
In the present invention, the brain edema is stroke brain edema and/or infectious brain edema.In some specific embodiments,
The stroke brain edema includes: hemorrhagic brain edema or ischemic brain edema.
The hemorrhagic brain edema refers to secondary brain edema after cerebral hemorrhage.The ischemic brain edema includes focal permanent
The secondary brain edema of cerebral ischemia and/or the secondary brain edema of global cerebral ischemic-reperfusion.In some specific embodiments, the infectivity
Brain edema is the brain edema that lipopolysaccharides causes infection.
In the present invention, the prevention and treatment includes the prevention and/or treatment to brain edema.In embodiments of the present invention, described anti-
The effect controlled includes: reduction brain water content, inhibition blood vessel and cell peripheral gap are broadening, inhibit nerve cell oedema, inhibit thin
Born of the same parents' vacuolation and/or inhibition neuron pyknosis.
Carry out histopathological examination to experimental animal to show: sham-operation group cerebral morphology has no obvious pathological change；
Model group Mice brain tissues visible vessels and cell peripheral gap are broadening, nerve cell oedema, a large amount of obvious vacuolation (gas of cell
Ball sample becomes), it is seen that the pathological changes such as acidophilia neuron and its pyknotic nucleus；Each administration group is compared with model group, histopathology
Form has different degrees of improvement.
The detection of brain water content is carried out to experimental animal, test result is shown: model group mouse brain water content is significantly higher than
Sham-operation group (P < 0.01) shows that modeling animal brain edema is obvious；And each administration group can reduce model mice in various degree
Brain water content.
The present invention also provides application of the Quzhazhigan or derivatives thereof in preparation prevention and treatment cephalophyma drug.Cerebral hemorrhage
After animal model, model group animal intracerebral hematoma, i.e. Hb level obviously increase after surgery, and vein gives injection simultaneously for modeling
Quzhazhigan, and model group ratio, three dosage groups to the Hb level after modeling for 24 hours have significant decrease (P < 0.01 or P <
0.05)；The Hb level of the 72h after modeling, each group rat are declined, and model group ratio, after giving injection Quzhazhigan
Hb level has decreasing trend, but no difference of science of statistics.
In the present invention, the Quzhazhigan derivative is piceatannol.
The present invention also provides a kind of drugs for preventing and treating brain edema, contain Quzhazhigan or derivatives thereof.
In the present invention, the drug further includes the drug that other are used to treat brain edema.
In some specific embodiments, other described drugs for being used to treat brain edema are selected from Edaravone, butylphenyl phthaleine, Buddhist nun not
Horizon, mannitol.
The dosage form of drug of the present invention is injection liquor or powder-injection.
In the embodiment of the present invention, the pharmaceutical dosage form used is injection.Wherein, Quzhazhigan mass fraction in prescription is
9%~20%
The present invention also provides a kind of methods for preventing and treating brain edema, are to give the medicine containing Quzhazhigan or derivatives thereof
Object.
The prevention and treatment includes prevention and/or treatment.The prevention effect, which refers to, gives institute of the present invention before brain edema generation
The drug stated.In the embodiment of the present invention, occurs first 3 days in brain edema, give drug of the present invention for three days on end.It is described to give
The mode given is intraperitoneal injection or intravenous injection.The treatment, which refers to, gives drug of the present invention after brain edema generation.
In embodiments of the present invention, 1h gives drug of the present invention after brain edema generation, and the mode given is abdominal cavity note
It penetrates or is injected intravenously.In the present invention, the dosage given is 5~20mgkg-1·d-1。
The present invention is found through experiments that Quzhazhigan can be substantially reduced the focal permanent cerebral ischemia model of mouse, global cerebral ischemia
Re-perfusion model, lipopolysaccharides cause the brain water content of four kinds of infection model, Rat Cerebral hemorrhage Model model mices, prompt injection bent
Letter Stilbene glycosides all has potential therapeutic effect to brain edema caused by above-mentioned many reasons.Effective component of the invention can be from plant
It is extracted in object, drug price used is cheap, is easy to get, and market prospects are good.
Detailed description of the invention
Fig. 1 influence (× 100) morphologic on focal permanent cerebral ischemia mouse brain histopathology；Wherein, Fig. 1-a shows
Sham-operation (giving sodium chloride injection) group, has no obvious pathological change；Fig. 1-b representation model (giving sodium chloride injection) organizes blood
Pipe and cell peripheral gap are broadening obvious, and nerve cell oedema is obvious, a large amount of obvious vacuolations of cell (change of balloon sample), a large amount of minds
Through first pyknosis；Fig. 1-c shows the experimental group for giving Edaravone 10mg/kg, and blood vessel and cell peripheral gap are broadening, nerve cell water
It is swollen, part Vacuole formation (change of balloon sample), a small amount of neuron pyknosis；Fig. 1-d shows the experimental group for giving butylphenyl phthaleine 8.3mg/kg,
Blood vessel and cell peripheral gap are broadening, nerve cell oedema, a small amount of neuron pyknosis；Fig. 1-e, which shows, gives mannitol 2.0g/kg's
Experimental group, blood vessel and cell peripheral gap are broadening, nerve cell oedema, individual vacuolations, a small amount of neuron pyknosis；Fig. 1-f shows
The experimental group of Quzhazhigan 16mg/kg is given, blood vessel and cell peripheral gap are broadening, nerve cell oedema, a small amount of vacuolation, few
Measure neuron pyknosis；Fig. 1-g shows the experimental group for giving Quzhazhigan 8mg/kg, and blood vessel and cell peripheral gap are broadening, and nerve is thin
Born of the same parents' oedema, a small amount of vacuolation, individual neuron pyknosis；Fig. 1-h shows the experimental group for giving Quzhazhigan 4mg/kg, blood vessel and cell
Peripheral clearance is broadening, nerve cell oedema, a small amount of vacuolation, a small amount of neuron pyknosis；
Fig. 2 shows to the influence of global cerebral ischemia/Reperfu- sion mouse brain water content, wherein compared with sham-operation group, a:P <
0.05, b:P < 0.01；Compared with model group, c:P < 0.05, d:P < 0.01；
Fig. 3 shows the influence that infectious mouse brain water content is caused to LPS, wherein compared with sham-operation group, a:P < 0.05, b:P
<0.01；Compared with model group, c:P < 0.05, d:P < 0.01.
Specific embodiment
The present invention provides application of the Quzhazhigan or derivatives thereof in preparation prevention and treatment brain edema drug, art technologies
Personnel can use for reference present disclosure, be suitably modified realization of process parameters.In particular, it should be pointed out that all similar replacements and changing
Move apparent to those skilled in the art, they are considered as being included in the present invention.It method of the invention and answers
With being described by preferred embodiment, related personnel can obviously not depart from the content of present invention, in spirit and scope
To methods herein and application is modified or appropriate changes and combinations, carrys out implementation and application the technology of the present invention.
The instrument that the present invention uses is all common commercially available product, can all be bought in market.
Below with reference to embodiment, the present invention is further explained:
Embodiment:
1. test material
1.1 SPF grades of animal ICR mouse (20~30g of weight), SD rat (weight: 200-250 grams) all-male, by Kun Yaoji
Laboratory animal room, limited liability company, group provides, production licence: SCXK (Yunnan) K2014-0001；It raises in IVC zoopery
Room, 20~26 DEG C of temperature, humidity 40%~70%, illumination 12h:12h light and shade alternating, 150~300lx of illumination, noise≤60dB,
Experimental animal uses licensing: SYXK (Yunnan) K2014-0001, issuing unit: Kunming Office of Science and Technology.
1.2 drugs and reagent injector with Quzhazhigan (lot number: 170101, specification: 20mg/ branch is ground by Kun Yao group drug
Institute's offer is provided): Edaravone Injection (lot number: 170406, Kunming Jida Pharmaceutical Co., Ltd.)；Formula mannitol injection liquid
(lot number: S1704007, Shanghai Baxter Healthcare Ltd.)；Butylphenyl phthaleine sodium chloride injection (lot number: 20170109, stone
TU & P Pharmaceutical Co., Ltd, medicine group)；Protease inhibitors, sigma, lot number: 031M7030V；Chloraldurate (lot number:
119957, No. Cas: 302-17-0, Shandong West Asia chemical industry Co., Ltd produces)；Lipopolysaccharides (LPS) (Exp2019/04,
Sigma company)；Sodium chloride injection (lot number: A160301D1, Cologne medicine company Zhejiang Guo Jing pharmaceutcal corporation, Ltd)；
1.3 instrument AR224 type electronic balances (weigh reagent and brain weight), Ohaus Instrument (Shanghai) Co., Ltd.；BL-
2000 type electronic balances (weigh animal), Xiamen Bai Lunsi Electronic Science and Technology Co., Ltd.；HG-9245A type electric heating constant temperature air blast is dry
Dry case, Shanghai Yiheng Scientific Instruments Co., Ltd；Dental burr: STRONG 90SAESHIN PRECISION IND.CO.SXP-
1B；Surgical operation microscope, the production of Shanghai medical optical instrument factory；Electrophoresis apparatus: Beijing Baijing Biotechnology Co., Ltd.；
Varioskan Flash all-wave length multi-function microplate reader: Thermo Fisher Scientific；Centrifuge: Shanghai Medical device
Tool Co., Ltd；Imager: Cell Biosciences；Volumetric flask, scissors, curved tweezer, haemostatic clamp, artery clamp, stopwatch, it is domestic；
Diameter 0.128mm nylon wire, Japan.
1.4 statistical procedures use SPSS17.0 software, experimental data average ± standard deviationIt indicates, side
Comparison among groups are examined using LSD when poor neat, and comparison among groups are using Dunnett ' s T3 inspection when heterogeneity of variance.There is statistics in P < 0.05
Meaning is learned, P < 0.01 is statistically significant.
2. test method
The line brush for influencing to refer to Huang etc. of 2.1 pairs of focal permanent cerebral ischemia mouse brain water contents, selection 26~
30g male ICR mouse, with 4% chloraldurate intraperitoneal injection of anesthesia (400mgkg-1.bw after), right neck skin is cut,
Separation, ligation right carotid proximal part and external carotid artery, the notch at 2~3mm of proximal end of arteria carotis communis crotch, insertion
Diameter is 8~10mm of nylon wire of 0.125mm, and line bolt is dynamic before entering ICA, passing through the starting point to brain arteria cerebri media (MCA)
Arteries and veins proximal end blocks all blood flow sources of MCA, ligatures standby line and skin suture, sham-operation group remaining same mould in addition to not plug wire
Type group.Animal pattern circulation is divided into 8 groups: sham-operation group；Model control group；Positive control Edaravone 10mgkg-1, butylphenyl phthaleine
Group 8.3mgkg-1And mannitol 2.0gkg-1Group；The high, medium and low dosage of Quzhazhigan (16,8,4mgkg-1) group.In modeling
1h afterwards, groups of animals press 20mLkg respectively-1The administration of weight tail vein injection, model group and sham-operation group give isometric chlorination
Sodium injection.Guarantee that being included in qualified number of animals for every group is 14, after administration for 24 hours, every group of 1-11 animal takes brain to weigh, and in 80
DEG C dry constant weight, by dry and wet mass method calculating brain moisture content；Every group of 12-14 animal quickly takes brain, is placed in 10% formalin
Histopathological examination is carried out after middle fixation.For the systematic error for reducing test, modeling grouping, is administered, takes brain and weigh flat
Row operation.
Brain moisture content=(wet brain weight-dry brain constant weight)/brain wet weight × 100%
The influence of 2.2 pairs of global cerebral ischemias/Reperfu- sion mouse brain water content selects 24~28g male mice 96, by weight
It is randomly divided into 8 groups: sham-operation group；Model group；Positive control Edaravone 12mgkg-1, butylphenyl phthaleine 10mgkg-1Group and sweet
Reveal alcohol 2.0gkg-1Group；Quzhazhigan 20,10,5mgkg-1Group；Every group 12.Groups of animals presses 20mLkg daily-1Body
Weight intraperitoneal injection 1 time, continuous 3d；Control group and model group give isometric sodium chloride injection.Before last dose, mouse
With 400mgkg-1After chloraldurate intraperitoneal injection of anesthesia, to face upward position and fix, row neck median incision separates bilateral common carotid arteries,
It is pressed from both sides simultaneously with micro-arterial clamp and closes bilateral common carotid arteries blocking blood flow 5min, unclamping artery clamp makes blood flow answer filling 10min, then again
Block 5min, 3 times repeatedly；Sham-operation group only separates bilateral common carotid arteries, not blocking blood flow.Modeling is completed, and is sewed up a wound,
Mouse is steam again and is raised.Row last dose is according to dosage injected intraperitoneally for every group of 1h after modeling, rear cervical dislocation puts to death mouse for 24 hours, takes
Brain weighing measures brain water content by 2.1 test methods.To reduce systematic error, modeling is administered, takes brain and weigh parallel behaviour
Make.
2.3 pairs of lipopolysaccharides cause the influence of infectious mouse brain water content with reference to the methods of Alexander and are improved.Choosing
20-24g male mice 96,8 groups are randomly divided by weight: blank control group；Model group；Positive control Edaravone 12mg
kg-1, butylphenyl phthaleine 10mgkg-1Group and mannitol 2.0gkg-1Group；Quzhazhigan 20,10,5mgkg-1Group；Every group 12.
Groups of animals presses 20mLkg daily-1Weight intraperitoneal injection 1 time, continuous 3d；Blank control group and model group give equal bodies
Product sodium chloride injection.1h before last dose, in addition to sodium chloride injection is injected intraperitoneally in blank control group, remaining each group is pressed
10mL·kg-1LPS is injected intraperitoneally in weight；Row last dose after modeling 1h.The 6h after modeling, cervical dislocation put to death mouse, brain are taken to claim
Weight measures brain moisture content by 2.1 test methods.To reduce systematic error, modeling, last dose take brain, drying and weigh flat
Row operation.
The influence of 2.4 pairs of cerebral hemorrhage rats brain water contents
200-250g health male SD rat is selected, is anaesthetized with the intraperitoneal injection of 10% chloraldurate, head skin preservation is simultaneously
After Iodophor routine disinfection, prone position is fixed on direction finder, and bregma raises 1mm, and taking length is about that the vertical shape in the center 2cm is cut
Mouthful, small-sized expansion skin device retracts notch, takes side on the right side of bregma middle line to open 3.0mm, 1.5mm, dental drill drill through cranium backward along sagittal plane
Bone, depth and periosteum.A stringer notch is done in rat-tail veutro center after disinfection, arteria caudalis is extracted and the arterial blood of anti-coagulants is not added about
60~70 μ L.By syringe needle perpendicular to the direction of skull bone hole, inserting needle about 6mm is slowly injected into 50 μ L Autologous arterial blood liquid, the time with
It is advisable within two minutes；To prevent mouse blood reflux, by needle indwelling 10min.The slow withdraw of the needle, bone wax close skull bone hole, suture operation wound
Mouthful.Animal pattern is randomly divided into 7 groups by weight: blank control group (for 24 hours, 72h)；Model group (for 24 hours, 72h)；Positive control Buddhist nun is not
Horizon 0.5mg/kg group (for 24 hours, 72h) and mannitol 2.0gkg-1Group (for 24 hours, 72h)；Quzhazhigan 20,10,5mgkg-1Group
(24h,72h)；Groups of animals presses 20mLkg respectively-1The administration of weight tail vein injection, model group and sham-operation group, which are given, waits bodies
Product sodium chloride injection.Guarantee that being included in qualified number of animals for every group is 12, respectively after administration for 24 hours, 72h, cervical dislocation is put to death big
Mouse, 6 take brain to weigh, and measure brain moisture content by 2.1 test methods；It is another 6 big by the sick side region hemotoncus of Hb quantitative response evaluation
It is small.
3. test result
The influence test result of 3.1 pairs of focal permanent cerebral ischemia mouse brain water contents is shown: model group mouse brain is aqueous
Amount is significantly higher than sham-operation group (P < 0.01), and 25h mouse brain edema is obvious after showing middle cerebral artery occlusion；Each administration group is in brain
1h single intravenous injection is administered after stalk, can reduce the brain water content of model mice in various degree, removes Quzhazhigan low dose group
Effect close to statistical difference (P=0.0541) outside, remaining all administration group all had compared with model group statistical difference (P <
0.05/0.01)；It the results are shown in Table 1.
Histopathological examination is shown: sham-operation group cerebral morphology has no obvious pathological change；Model group mouse brain group
It knits visible vessels and cell peripheral gap is broadening, nerve cell oedema, a large amount of obvious vacuolations of cell (change of balloon sample), it is seen that thermophilic
The pathological changes such as acid neuron and its pyknotic nucleus；For each administration group compared with model group, histopathology form has different journeys
The improvement of degree.The result is shown in Figure 1.
Influence of the table 1 to focal permanent cerebral ischemia mouse brain water content
Note: compared with sham-operation group, a:P < 0.05, b:P < 0.01；
Compared with model group, c:P < 0.05, d:P < 0.01
3.2 pairs of global cerebral ischemias/Reperfu- sion mouse brain water content influence test result is shown: model group mouse brain water content
It is significantly higher than sham-operation group (P < 0.01), shows that global cerebral ischemia/Reperfu- sion mouse brain edema is obvious；Each continuous abdominal cavity note of administration group
Penetrate administration 3 days, can be substantially reduced the brain water content of model mice, all had compared with model group statistical difference (P <
0.05).As a result see Fig. 2.
3.3 pairs of lipopolysaccharides cause the influence test result of infectious mouse brain water content to show: model group mouse brain water content
It is significantly higher than sham-operation group (P < 0.01), shows that LPS causes infection model mouse brain edema obvious；Each administration group is continuously injected intraperitoneally
Administration 3 days, can be substantially reduced the brain water content of model mice, statistical difference (P < 0.05/ is all had compared with model group
0.01).As a result see Fig. 3.
The influence of 3.4 pairs of cerebral hemorrhage rats brain water contents
After after cerebral hemorrhage mold foundation for 24 hours, with sham-operation group ratio, the raising of model group rats brain water content is obvious, has
Statistical significance (P < 0.01).With model group ratio, positive controls, Quzhazhigan height, middle dose group rat cerebral tissue water content
It is substantially reduced, it is statistically significant (P < 0.05).72h after cerebral hemorrhage mold is established, each group rat cerebral tissue water content is
It reduces, and model group ratio, rat cerebral tissue, treatment group water content is in there is different degrees of decline.It is shown in Table 2.
After cerebral hemorrhage mold foundation for 24 hours, model group rats brain water content reaches peak, just decreases after 72h.24h
With model group ratio, treatment group rat Hb decline has significant difference；72h also has certain decline, treatment group rat because of model group Hb
Hb has different degrees of decline, but there was no significant difference, this is related with the time.
Influence of the table 2 to cerebral hemorrhage rats brain water content
Note: with sham-operation group ratio ##P < 0.01；
With P < 0.05 model group ratio * * P < 0.01, *.
Influence of 3 Quzhazhigan of table to cerebral hemorrhage rats disease lateral areas Hb
With sham-operation group ratio ##P < 0.01；With P < 0.05 model group ratio * * P < 0.01, *.
To sum up, Quzhazhigan causes sense to the focal permanent cerebral ischemia model of mouse, cerebral inschemia-reperfusion injury model type, lipopolysaccharides
The brain water content of four kinds of model, Rat Cerebral hemorrhage Model model mices is contaminated, prompts injection Quzhazhigan to above-mentioned many reasons
The brain edema of initiation all has potential therapeutic effect, has good potential applicability in clinical practice.
The above is only the preferred embodiment of the present invention, it is noted that those skilled in the art are come
It says, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications also should be regarded as
Protection scope of the present invention.
Claims (10)
1. application of the Quzhazhigan or derivatives thereof in the drug of preparation prevention and treatment brain edema.
2. application according to claim 1, which is characterized in that the brain edema is infectious brain edema, hemorrhagic brain water
Swollen and/or ischemic brain edema.
3. application according to claim 2, which is characterized in that the ischemic brain edema includes: that focal permanent brain lacks
Hemorrhagic brain edema or global cerebral ischemic-reperfusion brain edema；
The infectious brain edema is that lipopolysaccharides causes infectious brain edema.
4. application according to claim 1, which is characterized in that the effect of the prevention and treatment includes: to reduce brain water content, inhibit
Blood vessel and cell peripheral gap are broadening, inhibit nerve cell oedema, inhibit Vacuole formation and/or inhibit neuron pyknosis.
5. application of the Quzhazhigan or derivatives thereof in preparation prevention and treatment cephalophyma drug.
6. described in any item applications according to claim 1~5, which is characterized in that the Quzhazhigan derivative is white Pi Shan
Alcohol.
7. a kind of prevention and treatment brain edema and/or the drug of cerebral hemorrhage, which is characterized in that contain Quzhazhigan or derivatives thereof.
8. drug according to claim 7, which is characterized in that further include the drug that other are used to treat brain edema.
9. drug according to claim 8, which is characterized in that other described drugs for being used to treat brain edema are selected from according to reaching
La Feng, butylphenyl phthaleine, Nimodipine, mannitol.
10. according to any one of claim 7~9 drug, which is characterized in that it is injection liquor or powder-injection.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201811591673.3A CN109498637B (en) | 2018-12-25 | 2018-12-25 | Application of Quzhazhigan or derivatives thereof in preparation of medicines for preventing and treating cerebral edema |
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| CN201811591673.3A CN109498637B (en) | 2018-12-25 | 2018-12-25 | Application of Quzhazhigan or derivatives thereof in preparation of medicines for preventing and treating cerebral edema |
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| CN109498637A true CN109498637A (en) | 2019-03-22 |
| CN109498637B CN109498637B (en) | 2020-11-03 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104586866A (en) * | 2013-10-31 | 2015-05-06 | 昆明制药集团股份有限公司 | A pharmaceutical composition for treating cerebrovascular diseases |
| CN107648243A (en) * | 2017-10-23 | 2018-02-02 | 昆药集团股份有限公司 | Purposes of the Quzhazhigan in the medicine of cerebral hemorrhage caused by rtPA thromboembolism treatments after preparing treatment cerebral hemorrhage or reduction cerebral ischemia |
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2018
- 2018-12-25 CN CN201811591673.3A patent/CN109498637B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104586866A (en) * | 2013-10-31 | 2015-05-06 | 昆明制药集团股份有限公司 | A pharmaceutical composition for treating cerebrovascular diseases |
| CN107648243A (en) * | 2017-10-23 | 2018-02-02 | 昆药集团股份有限公司 | Purposes of the Quzhazhigan in the medicine of cerebral hemorrhage caused by rtPA thromboembolism treatments after preparing treatment cerebral hemorrhage or reduction cerebral ischemia |
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| CN109498637B (en) | 2020-11-03 |
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Effective date of registration: 20210520 Address after: 650106 No. 166, medical Road, hi tech Industrial Development Zone, Yunnan, Kunming Patentee after: Kunming Pharmaceutical Corp. Patentee after: Shanghai kunheng Medical Technology Co.,Ltd. Address before: 650106 No. 166, medical Road, hi tech Industrial Development Zone, Yunnan, Kunming Patentee before: Kunming Pharmaceutical Corp. |