CN102144998A - Application of senkyunolide I to medicaments for prevention and treatment of cerebral apoplexy and relevant treatment during convalescence - Google Patents
Application of senkyunolide I to medicaments for prevention and treatment of cerebral apoplexy and relevant treatment during convalescence Download PDFInfo
- Publication number
- CN102144998A CN102144998A CN2010101077657A CN201010107765A CN102144998A CN 102144998 A CN102144998 A CN 102144998A CN 2010101077657 A CN2010101077657 A CN 2010101077657A CN 201010107765 A CN201010107765 A CN 201010107765A CN 102144998 A CN102144998 A CN 102144998A
- Authority
- CN
- China
- Prior art keywords
- senkyunolide
- cerebral
- blood flow
- rats
- cerebral blood
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses new medicinal application of senkyunolide I shown in a structural formula (I). In the application, the influence of the senkyunolide I on the cerebral blood flow change of rats in a reperfusion model of local cerebral ischemia caused by middle cerebral artery occlusion (MCAO) of the rats and a kalium chloratum (KCL) induced rat cortical spreading depression model is studied by adopting an animal model, and pharmacological results prove that the senkyunolide I can improve the cerebral blood flow of the rats after MCAO molding obviously and can restore and exceed the original cerebral blood flow formed before modeling quickly after reperfusion so as to play a certain role in cerebral protection. In addition, the senkyunolide I can resist the condition that cerebral blood flow descends due to KCL-induced rat local cerebral vasoconstriction, so the senkyunolide I can be used for preparing medicaments for the prevention and treatment of cerebral apoplexy and relevant treatment during convalescence.
Description
Technical field
The present invention relates to Chemistry for Chinese Traditional Medicine and medical technical field, be specifically related to from Rhizoma Chuanxiong (Ligusticumchuanxiong Hort.), extract the new medical use of the senkyunolide I (senkyunolide I) of preparation.
Background technology
Rhizoma Chuanxiong (Ligusticum chuanxiong Hort.) is a Umbelliferae Ligustrum plant, and its medicinal part is a rhizome.Rhizoma Chuanxiong is China's Chinese medicine, has blood-activating and qi-promoting, the effect of wind-expelling pain-stopping, and Eastern Han Dynasty's Shennong's Herbal is classified it as top grade, is treatment depression and migrainous conventional Chinese medicine.
Phthalide analog compound is a compounds that is present in the Rhizoma Chuanxiong, and being proved to be is having activity aspect cardiovascular, blood and the smooth muscle.Wherein study more butylphthalide and have many activity such as anti-cerebral ischemia, protection cerebral trauma tissue, can be considered to one of material base of Rhizoma Chuanxiong drug effect.
Senkyunolide I (Senkynolide I, its chemical structural formula is seen (I)) is to separate a kind of phthalide analog compound that obtains in Rhizoma Chuanxiong, has well fat-soluble and water solublity, can enter blood and cerebrospinal fluid rapidly, has the potentiality of certain developing new drug.But at present still less to the report of its pharmacological action, only find that it can alleviate ConA and draw erythrocytic morphotropism damage, reduce its aggregation (time precious traditional Chinese medical science traditional Chinese medicines, 2003,14 (12): 738-739.); Flow in the calcium of inhibition guinea pig myocardium cell and human nerve cell tumor etc. (Clin ExpPharmacology Physion, 1999,26:845-846.).Do not see that as yet it has active report and patent in anti-cerebral ischemia, protection cerebral trauma organizational aspects.
Summary of the invention
Technical problem to be solved by this invention is the novel medical use that proposes senkyunolide I, i.e. application in preparation control apoplexy and convalescence associated treatment usefulness medicine thereof.
The present invention's extraction separation from Rhizoma Chuanxiong obtains the senkyunolide I [structural formula (I)] of q.s, by pharmacological evaluation, has confirmed that the senkyunolide I of following structural formula (I) expression can be used for preventing and treating apoplexy and convalescence treatment thereof.
The preparation method of senkyunolide I of the present invention adopts conventional alcohol extracting method, mainly comprises the steps:
(1) pre-treatment step: will be ground into powder behind the Rhizoma Chuanxiong decoction pieces removal impurity to be extracted;
(2) extraction step: with 70% ethanol serves as to extract solvent, makes the volume (liters) that extracts solvent and the ratio of the weight (kilogram) of medical material to be extracted reach 10: 1,90 ℃ of reflux, extract, 2 times, and each 2 hours, merge extractive liquid,, the recovery solvent gets extract A;
(3) purification by macroporous resin step: concentration is equivalent to crude drug 0.5gml
-1Extract A aqueous solution 5000rmin
-1Centrifugal 15min gets supernatant, last HPD-100 macroporous resin, and the absorption flow velocity is 2BVh
-1, distilled water be washed till near colourless after, with 50% ethanol elution 4BV, collect alcohol eluen, the recovery solvent gets extract B;
(4) abstraction purification step: concentration is equivalent to crude drug 10gml
-1The extract B aqueous solution colourless with ethyl acetate extraction to ethyl acetate layer, ethyl acetate extract; It is colourless substantially that the ethyl acetate extract water is extracted to water layer, discards ethyl acetate layer, and water layer concentrates; Colourless substantially with dichloromethane extraction again to water layer, discard water layer, keep dichloromethane layer; Reclaim solvent and get extract C;
(5) separation and purification step: adopt the method prepare thin layer, the developing solvent ratio of selection is: n-butyl alcohol: dehydrated alcohol: ammonia=20: 1: 1, Rf value is that 0.42 band is senkyunolide I under the uviol lamp 254nm.
The present invention adopts animal model; studied that senkyunolide I causes the local cerebral ischemia re-perfusion model to rat mesencephalic arteries blocking-up (MCAO) and potassium chloride (KCL) is induced the influence that the rat brain blood flow changes in the rat layer spreading depression model; pharmacology result confirms that senkyunolide I can significantly improve the cerebral blood flow of rat after the MCAO modeling; and can pour into the rapid recovery in back again and, demonstrate certain cerebral protection above original cerebral blood flow before the modeling.In addition, senkyunolide I can resist by the local cerebrovascular of the inductive rat of KCL and shrink the situation that cerebral blood flow descends that causes, and therefore, senkyunolide I can be used for preparation control apoplexy and convalescence associated treatment medicine thereof.
The specific embodiment
The reagent and the animal of adopting in following examples and the test example are described as follows:
1. reagent
HPD-100 macroporous resin (the grace chemical plant is protected in Cangzhou); Tlc silica gel (GF254, lot number 080130) is purchased in Qingdao Marine Chemical Co., Ltd.; Methanol (sigma company, chromatographically pure); Senkyunolide I (making purity 98.6% by embodiment 1 method); KCL injection (Chemical Reagent Co., Ltd., Sinopharm Group, lot number 20090928); Butyphthalide capsule (Enbipu Pharmacy Co., Ltd., Shiyao Group., lot number 09060211); Chloral hydrate (Chemical Reagent Co., Ltd., Sinopharm Group, lot number 20060220); Normal saline (the rich Pharmaceutical of Shanghai Hua Yuanchang Group Co.,Ltd, lot number 08032501); Laser Doppler flowmetry (PeriFlux System 5000, PERMED, USA); The Rhizoma Chuanxiong medical material is awarded the dry rhizome that is accredited as samphire Rhizoma Chuanxiong (Ligusticum chuanxiong Hort.) through the Shanghai Univ. of Traditional Chinese Medicine's Zhao Zhi of crude drug teaching and research room the Confucian or feudal ethical codes, available from Cambridge, Shanghai decoction pieces company (lot number 071215, Sichuan, the place of production).
2. animal
100 of SD rats, male, body weight (260 ± 20) g is provided by Shanghai Univ. of Traditional Chinese Medicine's Experimental Animal Center, the animal quality certification number: SCXK (Shanghai) 2008-0016S.
Embodiment 1, alcohol extracting method prepare senkyunolide I
Rhizoma Chuanxiong decoction pieces 1kg is ground into powder behind the removal impurity, 90 ℃ of reflux, extract, of 70% ethanol 10L 2 times, and each 2 hours, merge extractive liquid,, the about 8L of recovery solvent gets extract A 2L and (is equivalent to crude drug 0.5gml
-1).With extract A solution 5000rmin
-1Centrifugal 15min gets supernatant (the floating grease in upper strata discards).HPD-100 macroporous resin 240g (being equivalent to dried resin 80g) wet method dress post, sample on the extract A solution, the absorption flow velocity is about 0.7Lh
-1Behind the last sample with the 3.5L distilled water be washed till near colourless after, with 50%7 pure eluting 1.4L, collect alcohol eluen, the recovery solvent gets extract B.Extract B is dissolved in the 500ml distilled water gets the extract B aqueous solution, with the equal-volume ethyl acetate extraction, extract approximately 5～8 times colourless to ethyl acetate layer, ethyl acetate extract; With equal-volume distilled water extraction ethyl acetate extract, extract approximately 5～8 times colourless to water layer, discard ethyl acetate layer, water layer is concentrated into about 100ml; Again with the equal-volume dichloromethane extraction about 3 times colourless substantially to water layer, discard water layer, keep dichloromethane layer; Reclaim solvent and get the about 2～4ml of extract C.Adopt the method for preparing thin layer, GF254 silica gel bed board, the developing solvent ratio of selection is: n-butyl alcohol: dehydrated alcohol: ammonia=20: 1: 1, Rf value is 0.42 band under the uviol lamp 254nm, is the senkyunolide I of purification.
The preparation of embodiment 2. senkyunolide I tablets
Every consumption of composition
Senkyunolide I 100mg
Microcrystalline Cellulose 37.45mg
Micropowder silica gel 10.5mg
Stearic acid 17.5mg
Lactose 10.5mg
Magnesium stearate 1.05mg
By recipe quantity senkyunolide I (making by embodiment 1 method) is added microcrystalline Cellulose, micropowder silica gel, stearic acid, lactose mixing, make granule, add magnesium stearate, mixing, tabletting promptly gets (every contains senkyunolide I 0.1g).The oral consumption 1-4 sheet of adult's recommendation/time, every day 2-3 time.
The capsular preparation of embodiment 3. senkyunolide I
Every consumption of composition
Senkyunolide I 100mg
Microcrystalline Cellulose 37.45mg
Micropowder silica gel 10.5mg
Stearic acid 17.5mg
Lactose 10.5mg
By recipe quantity senkyunolide I (making by embodiment 1 method) is added microcrystalline Cellulose, micropowder silica gel, stearic acid, lactose mixing, make granule after, be filled into hard capsule case No. 0, polishing promptly makes (every capsules contains senkyunolide I 0.1g).The oral consumption 1-4 grain of adult's recommendation/time, every day 2-3 time.
Routine pharmacological activity test and result with senkyunolide I further specifies the present invention below by test.
The influence that test example 1. senkyunolide I change rat local cerebral ischemia re-perfusion model midbrain blood flow
50 of Sprague-Dawley (SD) rats, male, body weight (260 ± 20) g, be divided into 5 groups at random: sham operated rats, model group, the positive drug group (butyphthalide, 72mg/kg), senkyunolide I high dose group (72mg/kg), senkyunolide I low dose group (36mg/kg) (senkyunolide I makes by embodiment 1 method).Fasting 12h before the experiment freely drinks water.Modeling method: adopt Longa line bolt to send out and make the local cerebral ischemia re-perfusion model, cerebral ischemia 1h pours into 24h again.The every 100g lumbar injection of rat 0.35Ml 10% chloral hydrate anesthesia is made the epigastrium otch, reserves the duodenal administration window.It is fixing to lie on the back, conventional epidermis sterilization, the neck median incision, from separating exposure right carotid (CCA), external carotid artery (ECA) to the deep between muscle group, careful separation is avoided damaging vagus nerve, internal carotid artery (ICA), is upwards continued to separate arteria pterygopalatina (PPA) along ICA.Ligation ECA distal end, in ECA proximal part hanging wire, the temporary transient folder of arteriole folder closes CCA distal end and PPA, in the middle of the ligation of ECA two places, cut an osculum, with the line bolt for preparing along otch slow axis of thrust bolt of continuation after the ECA proximal part is advanced into the CCA folder place of closing and turns to the bottom right to be advanced into ICA, the power that is hampered stops, the about 16～18mm of insertion depth (deciding according to the weight of animals).Tighten up ECA proximal part hanging wire static line bolt, removing two place arteriole folder can inaccessible brain mesencephalic arteries blood flow, and ischemia reaches the careful about 1cm of outer pulling plug line behind the 1h, i.e. formation is poured into again.Sham operated rats line bolt only inserts 10mm, and all the other steps are with each group.1.5mm behind the rat bregma, the other drill diameter 1mm of the 5mm place aperture of opening in center line right side is inserted fibre-optical probe to brain cortex surface, before the continuous detecting MCAO behind basic value (pre), the duodenal administration, among the MCAO1h and pour into the interior cerebral blood flow value of (rep) 30min again.Every 5-10min writes down one group of data.During analysis, be basic blood flow value, calculate in the ischemia, after the administration and irritate the different time-histories local cerebral blood flow numerical value percentage ratios in back again with the cerebral blood flow value before the ischemia.
The influence that table 1. senkyunolide I changes rat local cerebral ischemia re-perfusion model midbrain blood flow
Annotate: compare with model group,
*P＜0.05,
*P＜0.01
Test example 2. senkyunolide I are induced the influence of rat layer spreading depression model to KCL
50 of SD rats, male, body weight (260 ± 20) g, be divided into 5 groups at random: sham operated rats, model group, the positive drug group (butyphthalide, 72mg/kg), senkyunolide I high dose group (72mg/kg), senkyunolide I low dose group (36mg/kg) (senkyunolide I makes by embodiment 1 method).Fasting 12h before the experiment freely drinks water.Modeling method: the every 100g lumbar injection of rat 0.35mL10% chloral hydrate anesthesia, make the epigastrium otch, reserve the duodenal administration window.1.5mm behind the rat bregma, the other drill diameter 1mm of the 5mm place aperture of opening in center line right side is inserted fibre-optical probe to brain cortex surface, behind the stable recording cerebral blood flow value 5min, in drill hole injection 1moL/L KCL 5 μ L, duodenal administrations immediately.The sham operated rats survey cerebral blood flow of only holing, normal saline is given in model group boring back.The interior cerebral blood flow value of 30min behind (basic value), the duodenal administration before the fibre-optical probe continuous detecting KCL injection.Every 5min writes down one group of data.During analysis, be basic blood flow value with the cerebral blood flow value before the KCL injection, different time-histories local cerebral blood flow numerical value percentage ratios behind the calculating injection KCL, after the administration.
Table 2. senkyunolide I is induced the influence of rat layer spreading depression model to KCL
Annotate: compare with model group,
*P＜0.05,
*P＜0.01
Above The pharmacological results shows, senkyunolide I can significantly improve the cerebral blood flow of rat after the MCAO modeling, and can be before perfusion back be again recovered rapidly and is surpassed modeling original cerebral blood flow, demonstrate certain cerebral protection.In addition, senkyunolide I can resist by the local cerebrovascular of the inductive rat of KCL and shrink the situation that cerebral blood flow descends that causes.
From the research data of present accumulation, senkyunolide I tentatively possesses as effectively preparing control apoplexy and convalescence associated treatment thereof the primary condition with medicine.Therefore, senkyunolide I can be used for preparation control apoplexy and convalescence associated treatment medicine thereof among the present invention.
Claims (1)
1. the application of the senkyunolide I of following structural formula (I) expression in preparation control apoplexy and convalescence associated treatment usefulness medicine thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101077657A CN102144998A (en) | 2010-02-09 | 2010-02-09 | Application of senkyunolide I to medicaments for prevention and treatment of cerebral apoplexy and relevant treatment during convalescence |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101077657A CN102144998A (en) | 2010-02-09 | 2010-02-09 | Application of senkyunolide I to medicaments for prevention and treatment of cerebral apoplexy and relevant treatment during convalescence |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102144998A true CN102144998A (en) | 2011-08-10 |
Family
ID=44419602
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010101077657A Pending CN102144998A (en) | 2010-02-09 | 2010-02-09 | Application of senkyunolide I to medicaments for prevention and treatment of cerebral apoplexy and relevant treatment during convalescence |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102144998A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111000886A (en) * | 2020-01-06 | 2020-04-14 | 南京中医药大学 | Pharmaceutical composition for treating cerebral arterial thrombosis and application thereof |
| CN114642669A (en) * | 2020-12-18 | 2022-06-21 | 正大青春宝药业有限公司 | A senkyunolide I compound and its application in preparing medicines for treating thrombosis |
| CN115837040A (en) * | 2022-12-06 | 2023-03-24 | 四川省中医药科学院 | Use of a chuanxiong extract in the preparation of drugs for preventing and treating cognitive impairment |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1989984A (en) * | 2005-12-31 | 2007-07-04 | 天津天士力现代中药研究开发有限公司 | Chuanxiong rhizome effective ingredient, preparing method, preparation and use thereof |
| CN101015552A (en) * | 2006-12-29 | 2007-08-15 | 天津大学 | Ligustilide extract and its preparing process and application |
-
2010
- 2010-02-09 CN CN2010101077657A patent/CN102144998A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1989984A (en) * | 2005-12-31 | 2007-07-04 | 天津天士力现代中药研究开发有限公司 | Chuanxiong rhizome effective ingredient, preparing method, preparation and use thereof |
| CN101015552A (en) * | 2006-12-29 | 2007-08-15 | 天津大学 | Ligustilide extract and its preparing process and application |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111000886A (en) * | 2020-01-06 | 2020-04-14 | 南京中医药大学 | Pharmaceutical composition for treating cerebral arterial thrombosis and application thereof |
| CN114642669A (en) * | 2020-12-18 | 2022-06-21 | 正大青春宝药业有限公司 | A senkyunolide I compound and its application in preparing medicines for treating thrombosis |
| CN114642669B (en) * | 2020-12-18 | 2023-10-10 | 正大青春宝药业有限公司 | Senkyunolide I compound and application thereof in preparation of medicines treating thrombus diseases |
| CN115837040A (en) * | 2022-12-06 | 2023-03-24 | 四川省中医药科学院 | Use of a chuanxiong extract in the preparation of drugs for preventing and treating cognitive impairment |
| CN115837040B (en) * | 2022-12-06 | 2024-03-08 | 四川省中医药科学院 | Application of ligusticum chuanxiong hort extract in preparation of medicine for preventing and treating cognitive dysfunction |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101554409A (en) | Long pepper alkaloid and preparation method, preparation and application thereof | |
| Du et al. | The potential of traditional Chinese medicine in the treatment and modulation of pain | |
| CN101102772A (en) | Compositions of huperzia serrata alkaloids comprising huperzine A and huperzine B and preparation thereof | |
| CN102144998A (en) | Application of senkyunolide I to medicaments for prevention and treatment of cerebral apoplexy and relevant treatment during convalescence | |
| CN104510853B (en) | A kind of Chinese medicinal effective-part composition for the treatment of dysmenorrhes and uses thereof | |
| CN103830374B (en) | The application in hyperuricemia clearly of three leaf glycolipids | |
| KR101223662B1 (en) | Composition for alalgesic comprising an extract of agrimonia | |
| CN102144997B (en) | Application of senkyunolide J in preparing medicaments for resisting cerebral apoplexy | |
| CN102144999B (en) | Application of senkyunolide H in preparing medicine for preventing and curing cerebral apoplexy | |
| CN110372591A (en) | The extraction separation method of corydaline and allopurine base in a kind of slenderstalk dicranostigma herb | |
| CN102178721A (en) | Application of fiveleaf gynostemma herb suspension and extract to preparation of drug for treating and resisting depression | |
| CN100551410C (en) | A kind of antidepressant drug and preparation method | |
| CN107041899B (en) | A kind of medicine for treating insulin resistance, preparation method and application | |
| CN104510854B (en) | A kind of Chinese medicine composition for the treatment of dysmenorrhes and uses thereof | |
| CN103432386B (en) | A kind of Chinese medicine preparation for the treatment of cough and preparation method thereof | |
| CN102670865A (en) | Process for extracting active ingredients of American eleutherine rhizome | |
| CN102309589A (en) | Zuojin gastric-floating tablet and preparation method thereof | |
| CN107753531A (en) | Literary king's one-pen extract and its application in cancer therapy drug is prepared | |
| CN103239618A (en) | Traditional Chinese medicine composition for treating chronic hepatitis and cirrhosis and preparation method thereof | |
| CN100528170C (en) | Mangiferin preparation and production thereof | |
| CN102048824B (en) | Traditional Chinese medicine composition for treating cerebrovascular disease and application thereof | |
| CN104069312B (en) | Treat Chinese medicine composition of apoplexy and preparation method thereof, pharmaceutical preparation and application | |
| CN104474040A (en) | Medicine composition for preventing and treating migraine disease, as well as preparation method and application thereof | |
| CN101780150B (en) | Plant extract and pharmaceutical composition for treating cough and preparation method thereof | |
| CN100457154C (en) | Compound longxuejie preparation, preparing technique and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20110810 |