CN102125576A - Application of liquiritin in preparing medicine for treating cardiovascular and cerebrovascular diseases - Google Patents
Application of liquiritin in preparing medicine for treating cardiovascular and cerebrovascular diseases Download PDFInfo
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Abstract
The invention belongs to the technical field of medicament, particularly relates to an application of liquiritin in preparing medicament for treating cardiovascular and cerebrovascular diseases, more specifically relates to an application of liquiritin in preparing medicine for treating cerebrovascular diseases. Pharmacological experiments reveal that liquiritin has distinct effects in resisting thrombosis, resisting cerebral ischemia, resisting cerebral anoxia and improving memory. The medicine with liquiritin as active ingredient has low medication dose and high safety, and has wide application prospect.
Description
Technical field
The invention belongs to medical technical field, be specifically related to the application of liquirtin in preparation treatment cardiovascular and cerebrovascular diseases medicament, particularly the application in the liquirtin preparation treatment cerebrovascular disease medicament.
Background technology
Along with the quickening of growth in the living standard and rhythm of life, cardiovascular and cerebrovascular disease has become the healthy and life-prolonging leading killer of threat middle-aged and elderly people.Wherein, cerebrovascular disease is one of human three big causes of death, and it causes the patient serious physical disabilities to occur, causes patient's speech disorder, more seriously causes patient vessel's dementia, has brought all constant for individual, family and society.Therefore, seek the focus that the cerebrovascular disease method of preventing and treating becomes current research.
Radix Glycyrrhizae is the root and rhizome of leguminous plant Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L..Radix Glycyrrhizae property is flat, and sweet in the mouth is returned 12 warps.On the traditional Chinese medical science, the Radix Glycyrrhizae invigorating the spleen and replenishing QI is grown and to be coughed lung moistening, and the emergency detoxifcation is in harmonious proportion hundred medicines.Liquirtin (Liquiritin) is the active ingredient in the Radix Glycyrrhizae rhizome; chemical structural formula is as shown below; be the white particulate crystallization; can be dissolved in methanol, ethanol and ethyl acetate; the characteristic ultraviolet absorption spike is long for 249nm, has antioxidation, antiinflammatory, neuroprotective, antidepressant and antitumor etc. and acts on widely.But the research of relevant liquirtin control cerebrovascular disease yet there are no the pertinent literature report (Rui Chunlan. domestic to Radix Glycyrrhizae The Chemical Constituents progress [J]. Chinese school physician, 2006,20 (1): 105-106; Yang Yun, Bian Guangxing, Lv Qiujun. liquirtin is to the protection and the Nutrition [J] of former generation hippocampal neurons. CHINA JOURNAL OF CHINESE MATERIA MEDICA, 2008,33 (8): 931-935; Zhao Zhiyu, Wang Weixing, Guo Hongzhu, etc. liquirtin is to depression model rat body weight and ethological influence [J]. Chinese psychohygiene magazine, 2006,20 (12): 787-790; Liu Ruiting, Bian Guangxing, Zou Libo, etc. the neuroprotective of liquirtin reaches degree of inhibition of AchE [J]. Chinese Journal of New Drugs, 2008,17 (7): 574-580; Wang Jianguo, Zhou Zhong, Liu Haifeng, etc. active component of Radix Glycyrrhizae and the application in cosmetics [J] thereof. daily chemical industry, 2004,34 ((4): 249-251).
Summary of the invention
The invention provides the new purposes of liquirtin, be the application of liquirtin in the medicine of preparation control cardiovascular and cerebrovascular disease, the particularly application of liquirtin in preparation control cerebrovascular disease medicament includes but not limited to cerebrovascular disease such as cerebral ischemia, cerebral anoxia, cerebral thrombosis, memory dysfunction.
The invention provides a kind of pharmaceutical composition that comprises liquirtin and conventional pharmaceutical carrier, it is characterized in that described pharmaceutical composition is the preparation that adopts the oral or non-oral route mode administration that routine or special preparation prepared form.
The invention provides the method for prevention or treatment cardiovascular and cerebrovascular disease, comprise to the cardiovascular and cerebrovascular disease patient giving liquirtin or pharmaceutical composition noted earlier.
Liquirtin provided by the invention can prolonged application, and have tangible prevention or improve the effect of heart and brain damage, no obvious adverse reaction, with low cost.
The specific embodiment
Cardiovascular and cerebrovascular disease is the general name of cardiovascular diseases and cerebrovascular.Common cardiovascular diseases includes but not limited to hypertension, hypertensive heart disease, coronary heart disease, angina pectoris, myocardial infarction, myocardial ischemia, arrhythmia, pulmonary heart disease and hyperlipemia etc.; Common cerebrovascular disease includes but not limited to cerebral thrombosis, cerebral embolism, apoplexy and cerebral hemorrhage etc.
The invention provides the application of liquirtin in the medicine of preparation control cardiovascular and cerebrovascular disease, the particularly application of liquirtin in preparation control cerebrovascular disease medicament includes but not limited to cerebrovascular disease such as cerebral ischemia, cerebral anoxia, cerebral thrombosis, memory dysfunction.
Liquirtin of the present invention can be according to clinical needs, add corresponding pharmaceutical carrier, exist with dosage forms such as tablet, pill, granule, capsule, suspension, solution, syrup, injection, cream, ointment, gel, spray, chewing agent or patches.
Liquirtin of the present invention can adopt oral or non-oral way medication, the preferred oral administering mode according to clinical needs.
When liquiritin preparation of the present invention adopted the oral way medication, the preferred 1-1000mg/ people of human dosage/day wherein 10-500mg/ people/day more preferably, most preferably was 50-100mg/ people/day.
Liquirtin of the present invention is that extraction separation obtains from the Chinese medicine Radix Glycyrrhizae, can adopt any open source literature or patented method extract preparation (Zhao's Yi radium, Shi Qingzhi, Tang Xing. the extraction and purification process of glycyrrhizic acid and liquirtin research [J] in the Radix Glycyrrhizae. China Dispensary, 2009,20 (6): 426-429).The liquirtin that adopts various distinct methods preparations is to not influence of purposes of the present invention.
The present invention will be described below in conjunction with experimental example, but the present invention is not limited to this embodiment.
Embodiment 1 liquirtin resists simple property cerebral ischemia effect
1. material and method
1.1 laboratory animal
The healthy adult male ICR mouse, the cleaning level, body weight 25～30g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., uses unity and coherence in writing health food Function detection center SPF level experimental animal room in the Beijing Union University before the experiment and conforms a week.
1.2 reagent
Liquirtin standard substance: Tianjin spike natural product company (purity 〉=98%); Edaravone: Nanjing Xianshengdongyuan Pharmaceutical Co., Ltd; Red tetrazolium (2,3,5-triphenyltetrazolium, TTC): Sigma company.
1.3 instrument
AR-2140 type ten thousand/electronic balance: prunus mume (sieb.) sieb.et zucc. Teller-Tuo benefit Instr Ltd.; Electric-heated thermostatic water bath: mayor of Beijing bearing instruments and meters company.
1.4 adopt line bolt legal system to be equipped with the permanent cerebral ischemic model of mice
The ICR mice is divided into six groups at random, sham operated rats, model group, Edaravone group, the high, medium and low dosage group of liquirtin, and 9 of every treated animals, dosage sees Table 1.Administration 3d before the art, once a day.Sham operated rats and model group are irritated stomach and are given solvent 0.5% carboxymethylcellulose sodium solution in contrast.
24h fasting before the ICR mice art is freely drunk water.With 4% chloral hydrate (400mg/kg, ip) anesthesia.It is fixing that postanesthetic mice is lain on the back, the cervical region preserved skin, and sterilization skin cuts skin along cervical midline, separates subcutaneous fascia and muscular tissue.Operating microscope separates left carotid (CCA) and internal carotid artery (ICA) and external carotid artery (ECA) branch down.Root ligation ECA.Folder closes CCA and ICA.On CCA, open an osculum, fishing line along CCA, is passed ICA and the ECA crotch enters ICA.Unclamp ICA, continue fishing line is inserted into the ICA intracranial segment.Insertion length from the ICA initial part is about 1.3cm, shows that the head end of line has passed the middle cerebral artery initial part.Ligation CCA and ICA.Electric filament lamp is heated in the art, keeps about 37 ℃ of mice anus temperature.The postoperative sew up wound, animal is steam again.The sham operated rats mice is only performed a surgical operation and is not inserted fishing line.
1.5 function of nervous system's defective scoring
Behind the cerebral ischemia 24h, carry out function of nervous system's defective scoring with reference to the five-grade marking system standards of grading of Longa: 0 minute: normal, impassivity damage symptom; 1 minute: can not full extension offside fore paw; 2 minutes: turn-take laterally after carrying tail; 3 minutes: topple over to offside during walking; 4 minutes: can not spontaneous walking or loss of consciousness.
1.6 the cerebral infarction scope is measured
Adopt the TTC staining to measure the cerebral infarction scope.Animal broken end back is taken out complete brain rapidly, and the crown brain sheet that is cut into 1.5mm is hatched 30min in (with the phosphate buffered saline(PBS) preparation) 37 ℃ of water-baths in 0.5%TTC solution.Infarction tissue is white in color, and normal surrounding tissue is rose.Fixing in 10% neutral formalin solution then.Every brain sheet tow sides are scanned, obtain infarcted region and non-infarcted region area with the image analysis software integration.
1.7 the mensuration of brain water content
Behind the ischemia 24h, the rapid broken end of mice is got brain, survey brain water content with dried wet method, on ice cube, get brain rapidly, the cerebral tissue that takes out is placed in the culture dish that the moistening qualitative filter paper of normal saline is arranged in, in case water evaporates, the while is removed the pia mater encephali and the sludged blood on brain cortex surface fast.Accurately take by weighing brain weight with dried/one day chessboard, place 100 ℃ of baking oven 24h then after, weigh once more, be relative water content with (1-dry weight/weight in wet base) * 100%.
1.8 statistical procedures
Experimental result is all represented with x ± s, adopts one factor analysis of variance to organize a significance relatively, relatively adopts the t check between sample average.
*Expression P＜0.05 shows that administration group and model group relatively have significant difference;
*Expression P＜0.01 shows that administration group and model group relatively have utmost point significant difference.
2 results
2.1 liquirtin is to the influence of mice function of nervous system defective, cerebral infarction scope, brain water content
Table 1 liquirtin to the influence of mice function of nervous system defective, cerebral infarction scope, brain water content (x ± s, n=9)
Compare with model group,
*Expression P＜0.05
*Expression P＜0.01
From the defective scoring of mice function of nervous system as seen, the defective scoring of sham operated rats mice function of nervous system is 0, illustrates that its brain function is normal fully, and brain sheet TTC dyeing also shows both sides cerebral hemisphere size homogeneous, no edema phenomenon.After mice was stood the 24h ischemia, tangible infarction appearred in ischemia side brain, and function of nervous system's defective scoring is 2.44 ± 0.53; The cerebral infarction scope is for reaching (33.92 ± 5.42) %; Brain water content reaches (82.90 ± 0.72) %.
Edaravone and liquirtin all have the function of nervous system's of improvement defective, dwindle brain infarction area and reduce the brain water content effect, compare with model group, have significant difference.Liquirtin high dose group and model group relatively have utmost point significant difference.Above-mentioned experiment shows liquirtin, and cerebral ischemia has obvious protective effect to simple property.
Embodiment 2 liquirtin anti-cerebral ischemia perfusion effects again
1. material and method
1.1 laboratory animal
The healthy adult male Wistar rat, the cleaning level, body weight 200～250g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., uses unity and coherence in writing health food Function detection center SPF level experimental animal room in the Beijing Union University before the experiment and conforms a week.
1.2 reagent
Liquirtin standard substance: Tianjin spike natural product company (purity 〉=98%); Edaravone: Nanjing Xianshengdongyuan Pharmaceutical Co., Ltd; MDA, MPO, SOD, Coomassie brilliant blue test kit: bio-engineering research institute is built up in Nanjing.
1.3 instrument
AR-2140 type ten thousand/electronic balance: prunus mume (sieb.) sieb.et zucc. Teller-Tuo benefit Instr Ltd.; Electric-heated thermostatic water bath: mayor of Beijing bearing instruments and meters company; TGL 16M centrifuge: the triumphant scientific instrument company limited that reaches in Hunan; MH-2 micro oscillator: its woods Bel instrument Manufacturing Co., Ltd of Haimen, Jiangsu; DY89-II type electric driven glass refiner: NingBo XinZhi Biology Science Co., Ltd; Microplate reader: U.S. Thermo company.
1.4 adopt line bolt legal system to be equipped with the cerebral ischemic reperfusion in rats model
The Wistar rat is divided into six groups at random, sham operated rats, model group, Edaravone group, the high, medium and low dosage group of liquirtin, and 9 of every treated animals, dosage sees Table 2.Administration 5d before the art, every day 1 time.Sham operated rats and model group are irritated stomach and are given solvent 0.5% carboxymethylcellulose sodium solution in contrast.
With 10% chloral hydrate (350mg/kg, ip) anesthesia Wistar rat.Animal heat is maintained 37 ℃.It is fixing to allow animal lie on the back, and cuts skin and subcutaneous tissue along cervical midline.Operating microscope separates in left carotid and the neck thereof down and the external carotid artery branch.The branchlet of ligation external carotid artery and last eventually branch.Folder closes neck summation internal carotid artery.With in advance with silicone rubber parcel, diameter is that the fishing line of 0.238mm inserts external carotid artery, passes in the neck and the external carotid artery crotch enters internal carotid artery.Unclamp internal carotid artery, continue fishing line is inserted into the internal carotid artery intracranial segment.When feeling significantly to insert resistance, this moment, the insertion length from the internal carotid artery initial part was about 1.8～2cm, showed that the head end of line has passed the middle cerebral artery initial part.With the silk thread ligation of external carotid artery stump, in case plug wire comes off.Extract fishing line behind the 2h out and pour into 22h again.About sham operated rats inlet wire degree of depth 10mm, do not block middle cerebral artery.
1.5 cerebral tissue MDA content, MPO and SOD determination of activity
Rat is sacrificed by decapitation after cerebral ischemia 2h pours into 22h again, gets brain on ice pan fast.Weigh, add ice-cold normal saline, make 10% brain tissue homogenate by 1: 9 (W/V).Homogenate with the centrifugal 10min of 3000r/min, is got supernatant, preserve to be measured at-70 ℃ of ultra cold storage freezers.Press the test kit description and measure MDA content, MPO activity and SOD activity.Protein content determination adopts the Coomassie brilliant blue method.
1.6 statistical procedures
Experimental result is all represented with x ± s, adopts one factor analysis of variance to organize a significance relatively, relatively adopts the t check between sample average.
*Expression P＜0.05 shows that administration group and model group relatively have significant difference;
*Expression P＜0.01 shows that administration group and model group relatively have utmost point significant difference.
2. result
2.1 liquirtin is to the influence of the MPO of rat cerebral tissue, SOD activity and MDA content
Table 2 liquirtin to the influence of the MPO of rat cerebral tissue, SOD activity and MDA content (x ± s, n=9)
Compare with model group,
*Expression P＜0.05
*Expression P＜0.01
Compare with sham operated rats, MPO of model group rat cerebral tissue and SOD enzymatic activity obviously reduce, and MDA content obviously raises.Liquirtin can strengthen MPO of cerebral ischemia re-pouring rat cerebral tissue and SOD enzymatic activity, reduces cerebral tissue MDA content, shows that liquirtin has the anti-cerebral ischemia reperfusion injury and protect, may be relevant with its antiinflammatory and antioxidant activity.
The anti-cerebral anoxia effect of embodiment 3 liquirtins
1. material and method
1.1 laboratory animal
The healthy adult male ICR mouse, the cleaning level, body weight 18～20g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., uses unity and coherence in writing health food Function detection center SPF level experimental animal room in the Beijing Union University before the experiment and conforms a week.
1.2 reagent
Liquirtin standard substance: Tianjin spike natural product company (purity 〉=98%); Edaravone: Nanjing Xianshengdongyuan Pharmaceutical Co., Ltd; Sodium nitrite, Xi'an chemical reagent factory.
1.3 instrument
AR-2140 type ten thousand/electronic balance: prunus mume (sieb.) sieb.et zucc. Teller-Tuo benefit Instr Ltd..
1.4 acute cerebral ischemia anoxia experiment
Get fasting 12h, tried 45 of ICR mices, be divided into negative control (0.5% sodium carboxymethyl cellulose) group, Edaravone, the high, medium and low dosage group of liquirtin at random, 9 every group.Behind the mouse peritoneal drug administration by injection 2h, each treated animal by broken end only, immediately by manual time-keeping, is noted down time and the mouth breathing number of times of each treated animal broken end back to the respiratory arrest from cervical region.
The survival experiment 1.5 sodium nitrite poisons
Get fasting 12h, tried 45 of ICR mices, be divided into negative control (0.5% sodium carboxymethyl cellulose) group, Edaravone group, the high, medium and low dosage group of liquirtin at random, 9 every group.Behind the mouse peritoneal drug administration by injection 2h, each organizes mice by 240mg/kg dosage lumbar injection sodium nitrite (concentration is 24mg/ml), is index with the respiratory arrest, writes down the mice time-to-live respectively.
1.6 statistical procedures
Experimental result is all represented with x ± s, adopts one factor analysis of variance to organize a significance relatively, relatively adopts the t check between sample average.
*Expression P＜0.05 shows that administration group and model group relatively have significant difference;
*Expression P＜0.01 shows that administration group and model group relatively have utmost point significant difference.
2 results
2.1 liquirtin is to the influence of chmice acute cerebral hypoxia ischemia time
Table 3 liquirtin to the influence of chmice acute cerebral hypoxia ischemia time (x ± s, n=9)
Compare with negative control group,
*Expression P＜0.05
*Expression P＜0.01
2.2 liquirtin is to the influence of poisoning time-to-live of mice sodium nitrite
Table 4 liquirtin to the mice sodium nitrite poison the time-to-live influence (x ± s, n=9)
Compare with negative control group,
*Expression P＜0.05
*Expression P＜0.01
The mouth breathing time of the global brain ischemia mice that data show liquirtin significant prolongation broken end causes in the table 3 increases the frequency of respiration after mice breaks end, and illustrates that liquirtin can reduce the brain oxygen consumption, improves the utilization rate of cerebral tissue to oxygen.The result shows that liquirtin can cause death the mice time-to-live by the significant prolongation sodium nitrite, shows that liquirtin can strengthen the cerebral tissue hypoxia-bearing capability in the table 4.
The anti-cerebral thrombosis effect of embodiment 4 liquirtins
1. material and method
1.1 laboratory animal
The male W istar of healthy adult rat, the cleaning level, body weight 250～300g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., uses unity and coherence in writing health food Function detection center SPF level experimental animal room in the Beijing Union University before the experiment and conforms a week.
1.2 reagent
Liquirtin standard substance: Tianjin spike natural product company (purity 〉=98%); Edaravone: Nanjing Xianshengdongyuan Pharmaceutical Co., Ltd.
1.3 instrument
AR-2140 type ten thousand/electronic balance: prunus mume (sieb.) sieb.et zucc. Teller-Tuo benefit Instr Ltd..
1.4 thrombosis experiment
The Wistar rat is divided into five groups at random, model group, Edaravone group, the high, medium and low dosage group of liquirtin, and 9 of every treated animals, dosage sees Table 5.Administration 14d before the art, every day 1 time.Sham operated rats and model group are irritated stomach and are given solvent 0.5% carboxymethylcellulose sodium solution in contrast.
With 10% chloral hydrate (350mg/kg, ip) anesthesia Wistar rat.Animal heat is maintained 37 ℃.It is fixing to allow animal lie on the back, and cuts skin and subcutaneous tissue along cervical midline.Operating microscope separates right carotid and left side external jugular vein down.Intubate is carried out at two ends, behind the formation rat neck artery-vein bypass 15min, takes out No. 4 silk thread, weighs after removing floating blood on the filter paper, promptly obtains wet weight of thrombus.The back thrombosis of will weighing places drying baker, at 60 ℃, takes out behind the dry 4h and weighs, and is the thrombosis dry weight.
1.5 statistical procedures
Experimental result is all represented with x ± s, adopts one factor analysis of variance to organize a significance relatively, relatively adopts the t check between sample average.
*Expression P＜0.05 shows that administration group and model group relatively have significant difference;
*Expression P＜0.01 shows that administration group and model group relatively have utmost point significant difference.
2. result
2.1 liquirtin is to the influence of rat neck arteriovenous thrombus weight
Table 5 liquirtin to the influence of rat neck arteriovenous thrombus weight (x ± s, n=9)
Annotate: compare with model group,
*Expression P＜0.05
*Expression P＜0.01
Compare with model group, liquirtin has the obvious suppression effect to rat neck artery-vein bypass thrombosis, shows that liquirtin has anti-cerebral thrombosis effect.
The anti-angiogenic dementia effect of embodiment 5 liquirtins
1. material and method
1.1 laboratory animal
The healthy adult male ICR mouse, the cleaning level, body weight 18～20g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., uses unity and coherence in writing health food Function detection center SPF level experimental animal room in the Beijing Union University before the experiment and conforms a week.
1.2 reagent
Liquirtin standard substance: Tianjin spike natural product company (purity 〉=98%); Edaravone: Nanjing Xianshengdongyuan Pharmaceutical Co., Ltd.
1.3 instrument
Water maze: Anhui Province Huaibei Zhenghua Biological Instrument Co., Ltd.; Mice is kept away dark instrument: institute of Materia Medica,Chinese Academy of Medical Sciences.
1.4 set up vascular dementia model
24h fasting before the ICR mice art is freely drunk water.With 4% chloral hydrate (400mg/kg, ip) anesthesia.It is fixing that postanesthetic mice is lain on the back, the cervical region preserved skin, and sterilization skin cuts skin along cervical midline, separates the left and right side common carotid artery, closes blood vessel with the bulldog clamp folder, blocking-up bilateral common carotid arteries blood flow 30min.Remove bulldog clamp and pour into again, skin suture.Sham operated rats will not be pressed from both sides and be closed blood vessel, and all the other steps are the same.After pouring into 2h again, gastric infusion under the mice waking state, continuous irrigation stomach 25d.
1.5 mice water maze laboratory
Before the experiment, give water filling in the water maze, the depth of water there was not 23～25 ℃ of platform 2cm water temperatures.The training the 1d mice be placed in 10s on the platform, make it be familiar with safety island, then with mice in order the head put into water from 4 quadrants successively towards tank, timing 2min, mice find platform and stop 10s thereon after, timing stops automatically.5d removes platform, and the swimming starting point of mice is 2 quadrantal points away from platform, and the platform number of times is worn in the incubation period of mice platform and record in the record 2min.
1.6 mice is kept away dark experiment
Mice is put into darkroom dorsad, bright chamber, can be shocked by electricity when mice enters into darkroom four-footed contact copper grid, its normal reaction is for withdrawing from the darkroom at once.During the 1st day adaptive training, the record mice enters the number of times in darkroom and the time that enters camera bellows the 1st time in 3min; Behind the adaptive training, open supply unit, mice is put into bright chamber and darkroom dorsad, mice enters darkroom contact copper grid and is shocked by electricity, and mice is taken out immediately.Experiment once more behind the 24h, the time that the interior mice of observation 3min enters camera bellows first is incubation period, the number of times that mice enters camera bellows is an errors number.
1.7 statistical procedures
Experimental result is all represented with x ± s, adopts one factor analysis of variance to organize a significance relatively, relatively adopts the t check between sample average.
*Expression P＜0.05 shows that administration group and model group relatively have significant difference;
*Expression P＜0.01 shows that administration group and model group relatively have utmost point significant difference.
2. result
2.1 liquirtin is to mice water maze laboratory escape latency and the influence of wearing the platform number of times
Table 6 liquirtin to mice water maze laboratory escape latency and wear the platform number of times influence (x ± s, n=9)
Compare with model group,
*Expression P＜0.05
*Expression P＜0.01
2.2 liquirtin is kept away the influence that dark experiment keeps away dark incubation period and wears the case number of times to mice
Table 7 liquirtin to mice keep away dark experiment keep away dark incubation period and wear the case number of times influence (x ± s, n=9)
Compare with model group,
*Expression P＜0.05
*Expression P＜0.01
Water maze laboratory as a result display model group mice 5d water maze escape latency time of undergoing training significantly increase, wear the platform number of times and significantly reduce, learning and memory function is impaired.Liquirtin significantly reduces the water maze escape latency time, increases to wear the platform number of times, relatively has significant difference with model group.
Compare with sham operated rats, passive the keeping away of model group mice significantly shortened dark incubation period, keeps away secretly to wear the case number of times and obviously increase.Liquirtin can increase significantly that mice is passive keeps away dark incubation period, reduces to keep away and secretly wears the case number of times, and have dose dependent.
The safety evaluatio of embodiment 6 liquirtins
1. material and method
1.1 laboratory animal
Healthy adult ICR mice, cleaning level, body weight 18～22g, male and female half and half; Healthy adult W istar rat, the cleaning level, body weight 250～300g, male and female half and half, provide by Beijing Vital River Experimental Animals Technology Co., Ltd., use unity and coherence in writing health food Function detection center SPF level experimental animal room in the Beijing Union University before the experiment and conform a week.
1.2 reagent
Liquirtin standard substance: Tianjin spike natural product company (purity 〉=98%).
1.3 method
20 of mices are got 10 at random as normal control, irritate stomach every day and give 0.5% sodium carboxymethyl cellulose; Surplus and irritate stomach 10 every days and give liquirtin 2g/kg body weight, 2 weeks of continuous irrigation stomach, observe the mice general state every day, food-intake is weighed.Took off cervical vertebra execution mice in 24 hours after the last administration, dissect its internal organs outward appearance of back perusal and change situation.
20 of rats are got 10 at random as normal control, irritate stomach every day and give 0.5% sodium carboxymethyl cellulose; Surplus and irritate stomach 10 every days and give liquirtin 1g/kg body weight, 2 weeks of continuous irrigation stomach, observe the rat general state every day, food-intake is weighed.Took off cervical vertebra execution animal in 24 hours after the last administration, dissect its internal organs outward appearance of back perusal and change situation.
2. result
The result shows, gives liquirtin 2g/kg (being equivalent to 10000 times of minimum effective doses) continuous two weeks of mice, the mice general state, and food ration, body weight and internal organs show no obvious abnormalities.Rat gives also to show no obvious abnormalities behind the liquirtin.Show that the liquirtin safety is higher.
Claims (10)
1. the application of liquirtin in preparation control cardiovascular and cerebrovascular diseases medicament.
2. purposes according to claim 1 is characterized in that the application of liquirtin in preparation control cerebrovascular disease medicament.
3. purposes according to claim 1 is characterized in that the application of liquirtin in preparation control cerebral ischemia disease medicament.
4. purposes according to claim 1 is characterized in that the application of liquirtin in preparation control cerebral anoxia disease medicament.
5. purposes according to claim 1 is characterized in that the application of liquirtin in preparation control cerebral thrombosis disease medicine.
6. purposes according to claim 1 is characterized in that the application of liquirtin in preparation control memory dysfunction disease medicament.
7. a pharmaceutical composition is characterized in that described pharmaceutical composition comprises liquirtin and conventional pharmaceutical carrier.
8. pharmaceutical composition according to claim 7 is characterized in that described pharmaceutical composition is the preparation that adopts the oral or non-oral route mode administration that routine or special preparation prepared form.
9. the method for preventing or treating cardiovascular and cerebrovascular disease comprises to the cardiovascular and cerebrovascular disease patient giving liquirtin.
10. the method for preventing or treating cardiovascular and cerebrovascular disease comprises to the cardiovascular and cerebrovascular disease patient giving claim 7 or 8 described pharmaceutical compositions.
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| CN2012101008035A Division CN102716141A (en) | 2010-01-14 | 2010-01-14 | Application of liquiritin in preparing medicine for preventing cerebral anoxia disease |
| CN2012101007812A Division CN102716139A (en) | 2010-01-14 | 2010-01-14 | Application of liquiritin in preparing medicine for preventing and treating cerebral ischemia disease |
| CN2012101008016A Division CN102716140A (en) | 2010-01-14 | 2010-01-14 | Application of liquiritin to preparation of drugs for preventing and treating cerebral thrombosis disease |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110693026A (en) * | 2019-04-22 | 2020-01-17 | 温州医科大学附属第一医院 | Fruit component composition for improving memory and application thereof |
| CN115054609A (en) * | 2022-03-30 | 2022-09-16 | 上海市皮肤病医院 | Application of liquiritin targeted SIRT7/H3K122 axis in preparation of anti-dandruff drugs |
| CN115317497A (en) * | 2022-01-13 | 2022-11-11 | 宁夏医科大学 | Application of liquiritin in preparing thoracic aorta vasodilation medicine |
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| CN110693026A (en) * | 2019-04-22 | 2020-01-17 | 温州医科大学附属第一医院 | Fruit component composition for improving memory and application thereof |
| CN110693026B (en) * | 2019-04-22 | 2023-02-17 | 温州医科大学附属第一医院 | Fruit component composition for improving memory and application thereof |
| CN115317497A (en) * | 2022-01-13 | 2022-11-11 | 宁夏医科大学 | Application of liquiritin in preparing thoracic aorta vasodilation medicine |
| CN115054609A (en) * | 2022-03-30 | 2022-09-16 | 上海市皮肤病医院 | Application of liquiritin targeted SIRT7/H3K122 axis in preparation of anti-dandruff drugs |
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Application publication date: 20110720 |