CN102144999B - Application of senkyunolide H in preparing medicine for preventing and curing cerebral apoplexy - Google Patents
Application of senkyunolide H in preparing medicine for preventing and curing cerebral apoplexy Download PDFInfo
- Publication number
- CN102144999B CN102144999B CN 201010107770 CN201010107770A CN102144999B CN 102144999 B CN102144999 B CN 102144999B CN 201010107770 CN201010107770 CN 201010107770 CN 201010107770 A CN201010107770 A CN 201010107770A CN 102144999 B CN102144999 B CN 102144999B
- Authority
- CN
- China
- Prior art keywords
- senkyunolide
- cerebral
- blood flow
- senkynolide
- rat
- 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.)
- Expired - Fee Related
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a novel pharmaceutical application of senkyunolide H (represented by formula I). The invention adopts an animal model to study the influence of the senkyunolide H on the cerebral blood flow change in an MCAO (middle cerebral artery occlusion)-caused local cerebral ischemia reperfusion rat model and a KCl (potassium chloride)-induced cortical spreading depression rat model. Pharmacological results prove that senkyunolide H can remarkably increase the cerebral blood flow of a rat after MCAO modeling, and rapidly restore or even exceed the original cerebral blood flow before modeling after filling is performed, and show a certain brain protection effect. In addition, senkyunolide H can resist the cerebral blood flow decrease caused by KCl-induced rat local cerebral vasoconstriction, Therefore, senkyunolide H can be used for preparing a medicine for preventing and curing cerebral apoplexy.
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 Senkynolide H (senkyunolide H) of preparation.
Background technology
Rhizoma Chuanxiong (Ligusticum chuanxiong Hort.) is Umbelliferae Ligustrum plant, and its medicinal part is 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 Cure of 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.
Senkynolide H (Senkynolide H, its chemical structural formula is seen (I)) be in Rhizoma Chuanxiong, to separate a kind of phthalide analog compound that obtains, have well fat-soluble and water solublity, can enter rapidly blood and cerebrospinal fluid, have 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. (ClinExp Pharmacology Physion, 1999,26:845-846.).There is not yet it in anti-cerebral ischemia, the protection cerebral trauma activated report of organizational aspects tool and patent.
Summary of the invention
Technical problem to be solved by this invention is the novel medical use that proposes Senkynolide H, i.e. application in preparation control apoplexy medicine.
The present invention extracts from Rhizoma Chuanxiong and separates the Senkynolide H (structural formula (I)) that obtains q.s, by pharmacological evaluation, has confirmed that the Senkynolide H of following structural formula (I) expression can be used for preventing and treating apoplexy and convalescence treatment thereof.
The extraction of Senkynolide H of the present invention separates adopts conventional alcohol extraction chromatography, 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: take 70% ethanol as extracting solvent, make the ratio of the weight (kilogram) of the volume (liters) that extracts solvent and medical material to be extracted reach 10: 1,90 ℃ of reflux, extract, 2 times, each 2 hours, merge extractive liquid, reclaims solvent and gets extract A;
(3) chromatographic purification step: extractum separates with normal phase silica gel column chromatography, and carries out eluting as 100: 1 take the chloroform-methanol volume ratio, with eluent thin-layer silicon offset plate (GF
254) under uviol lamp 254nm, observe behind the point sample, collect the part that contains Senkynolide H, and decompression and solvent recovery, the extractum through the silica gel chromatography purification got; Again utilize C
18Reversed-phase silica gel column chromatography separates, and the 30%-50% methanol-eluted fractions is with eluent thin-layer silicon offset plate (GF
254) under uviol lamp 254nm, observe behind the point sample, collect the part that contains Senkynolide H, and decompression and solvent recovery, namely get the Senkynolide H of purification.
The present invention adopts animal model; studied that Senkynolide H causes the focal cerebral ischemia model to Midbrain In The Rat artery occlusion (MCAO) and potassium chloride (KCL) is induced the impact that the rat brain blood flow changes in the rat layer spreading depression model; pharmacology result confirms that Senkynolide H can significantly improve the cerebral blood flow of rat after the MCAO modeling; and can pour into again rear rapidly recovery and above original cerebral blood flow before the modeling, demonstrate certain cerebral protection.In addition, Senkynolide H can resist the rat local cerebral vasoconstriction of being induced by KCL and cause the situation that cerebral blood flow descends, and therefore, Senkynolide H can be used for preparation control apoplexy and convalescence associated treatment medicine thereof.
The specific embodiment
Reagent and the animal of adopting in following examples and the test example are described as follows:
1. reagent
Tlc silica gel (GF254, lot number 080130) is purchased from Qingdao Marine Chemical Co., Ltd.; Methanol (sigma company, chromatographically pure); Senkynolide H (making purity 98.2% 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); Ligusticum chuanxiong Hort 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 chromatographs prepare Senkynolide H
Rhizoma Chuanxiong decoction pieces 1kg is ground into powder behind the removal impurity, 70% ethanol 10L reflux, extract, 2 times, and each 2 hours, merge extractive liquid, reclaimed solvent and gets the about 100g of extractum A.Extractum is separated (silica gel is 100-200 order or 200-300 order column chromatography silica gel, and extractum sample and silica gel weight ratio are 1: 30) with silica gel column chromatography, and carried out eluting as 20: 1 take the chloroform-methanol volume ratio, with eluent thin-layer silicon offset plate (GF
254) under uviol lamp 254nm, observe behind the point sample, collect the part that contains Senkynolide H, and decompression and solvent recovery; The anti-phase C of gained extractum
18Silica gel column chromatography separates (extractum sample and C
18The reverse phase silica gel weight ratio is=1: 30), and to discard eluent behind the methanol-water volume ratio 30% eluting 5BV, be 50% eluting 5BV with the methanol-water volume ratio again, with eluent thin-layer silicon offset plate (GF
254) under uviol lamp 254nm, observe behind the point sample, collect the part that contains Senkynolide H, and decompression and solvent recovery, namely get the about 0.3g of Senkynolide H of purification.
The preparation of embodiment 2. Senkynolide H tablets
Every consumption of composition
Senkynolide H 100mg
Lactose 37.45mg
Microcrystalline Cellulose 17.5mg
Starch 21.0mg
Magnesium stearate 1.05mg
By recipe quantity Senkynolide H (making by embodiment 1 method) is added mixing behind lactose, microcrystalline Cellulose, the starch, granulation adds magnesium stearate, mixing, and tabletting namely gets (every contains Senkynolide H 0.1g).The adult recommends oral consumption 1-4 piece/times, every day 2-3 time.
The preparation of embodiment 3. Senkynolide H capsules
Every consumption of composition
Senkynolide H 100mg
Microcrystalline Cellulose 37.45mg
Micropowder silica gel 10.5mg
Stearic acid 17.5mg
Lactose 10.5mg
By recipe quantity Senkynolide H (making by embodiment 1 method) is added mixing behind lactose, microcrystalline Cellulose, micropowder silica gel, the stearic acid, behind the granulation, be filled into hard capsule case No. 0, polishing namely makes (every capsules contains Senkynolide H 0.1g).The adult recommends oral consumption 1-4 tablets/time, every day 2-3 time.
Further specify the present invention below by test example with pharmacological activity test and the result of Senkynolide H.
The impact that test example 1. Senkynolide Hs change cerebral blood flow in the focal cerebral ischemia in rats re-perfusion model
50 of Sprague-Dawley (SD) rats, male, body weight (260 ± 20) g, be divided at random 5 groups: sham operated rats, model group, the positive drug group (butyphthalide, 72mg/kg), senkyunolide H (Senkynolide H) high dose group (72mg/kg), senkyunolide H low dose group (36mg/kg) (Senkynolide H 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 focal cerebral ischemia model, cerebral ischemia 1h pours into 24h again.The every 100g lumbar injection of rat 0.35mL10% 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, the line bolt for preparing is advanced into the CCA folder place of closing along otch to the ECA proximal part turn to the bottom right to be advanced into the slow axis of thrust bolt of continuation behind the 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, insert fibre-optical probe to brain cortex surface, before the continuous detecting MCAO behind basic value (pre), the duodenal administration, among the MCAO1h and the interior cerebral blood flow value of perfusion (rep) 30min.Every 5-10min records one group of data.During analysis, the cerebral blood flow value before the ischemia is as basic Blood Flow Value, calculate in the ischemia, after the administration and fill with again after different time course local cerebral blood flow numerical value percentage ratio.
The impact that table 1. Senkynolide H changes cerebral blood flow in the focal cerebral ischemia in rats re-perfusion model
Annotate: compare with model group,
*P＜0.05,
*P＜0.01
Test example 2. Senkynolide Hs are induced the impact of rat layer spreading depression model on KCL
50 of SD rats, male, body weight (260 ± 20) g, be divided at random 5 groups: sham operated rats, model group, the positive drug group (butyphthalide, 72mg/kg), senkyunolide H (Senkynolide H) high dose group (72mg/kg), senkyunolide H low dose group (36mg/kg) (Senkynolide H 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/LKCL5 μ L, immediately duodenal administration.The sham operated rats survey cerebral blood flow of only holing is given normal saline after the model group boring.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 records one group of data.During analysis, inject front cerebral blood flow value as basic Blood Flow Value take KCL, different time course local cerebral blood flow numerical value percentage ratio behind the calculating injection KCL, after the administration.
Table 2. Senkynolide H is induced the impact of rat layer spreading depression model on KCL
Annotate: compare with model group,
*P＜0.05,
*P＜0.01
Above the pharmacological results shows, Senkynolide H can significantly improve the cerebral blood flow of rat after the MCAO modeling, and can after perfusion again, recover rapidly and surpass modeling before original cerebral blood flow, demonstrate certain cerebral protection.In addition, Senkynolide H can resist the rat local cerebral vasoconstriction of being induced by KCL and cause the situation that cerebral blood flow descends.
From the research data of present accumulation, Senkynolide H tentatively possesses as effectively preparing the primary condition that control apoplexy and convalescence associated treatment thereof are used medicine.Therefore, Senkynolide H can be used for preparation control apoplexy and convalescence associated treatment medicine thereof among the present invention.
Claims (1)
1. the application of the Senkynolide H of following structural formula (I) expression in preparation control apoplexy medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010107770 CN102144999B (en) | 2010-02-09 | 2010-02-09 | Application of senkyunolide H in preparing medicine for preventing and curing cerebral apoplexy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010107770 CN102144999B (en) | 2010-02-09 | 2010-02-09 | Application of senkyunolide H in preparing medicine for preventing and curing cerebral apoplexy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102144999A CN102144999A (en) | 2011-08-10 |
| CN102144999B true CN102144999B (en) | 2013-05-01 |
Family
ID=44419603
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010107770 Expired - Fee Related CN102144999B (en) | 2010-02-09 | 2010-02-09 | Application of senkyunolide H in preparing medicine for preventing and curing cerebral apoplexy |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102144999B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101015552A (en) * | 2006-12-29 | 2007-08-15 | 天津大学 | Ligustilide extract and its preparing process and application |
| CN101563080A (en) * | 2006-08-11 | 2009-10-21 | 帝斯曼知识产权资产管理有限公司 | Ligustilide derivatives for the treatment of disorders of the central nervous system |
-
2010
- 2010-02-09 CN CN 201010107770 patent/CN102144999B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101563080A (en) * | 2006-08-11 | 2009-10-21 | 帝斯曼知识产权资产管理有限公司 | Ligustilide derivatives for the treatment of disorders of the central nervous system |
| CN101015552A (en) * | 2006-12-29 | 2007-08-15 | 天津大学 | Ligustilide extract and its preparing process and application |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102144999A (en) | 2011-08-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2004200624B2 (en) | Medicinal preparation containing phenylethanoid glycosides extracted from herbaceous plant, cistanche tubulosa (schenk.) wight, process of making the same, and uses of the same | |
| CN101554409B (en) | Long pepper alkaloid and preparation method, preparation and application thereof | |
| CN103877244B (en) | A kind of pharmaceutical composition and preparation method thereof for treating headache | |
| CA2589994A1 (en) | A pharmaceutical composition for the treatment and/or prevention of hyperlipidemia, processes for producing the same and the use thereof | |
| CN1931270B (en) | Sobering up and liver protecting Chinese medicine preparation and its preparation process | |
| Du et al. | The potential of traditional Chinese medicine in the treatment and modulation of pain | |
| CN101816723B (en) | Sobering up and liver protecting Chinese medicinal preparation and preparation method thereof | |
| KR100700065B1 (en) | A composition of chinese drugs having neuro-protecting activity | |
| CN103816150A (en) | Use of beggarweed alkaloid monomer component | |
| CN104510853B (en) | A kind of Chinese medicinal effective-part composition for the treatment of dysmenorrhes and uses thereof | |
| CN102144999B (en) | Application of senkyunolide H in preparing medicine for preventing and curing cerebral apoplexy | |
| CN102144997B (en) | Application of senkyunolide J in preparing medicaments for resisting cerebral apoplexy | |
| KR100876440B1 (en) | Antistress or antidepressant composition comprising water lily extract | |
| CN108434399A (en) | A kind of Chinese medicine composition and preparation method of anti-curing oncoma | |
| CN102144998A (en) | Application of senkyunolide I to medicaments for prevention and treatment of cerebral apoplexy and relevant treatment during convalescence | |
| KR101223662B1 (en) | Composition for alalgesic comprising an extract of agrimonia | |
| CN104892419B (en) | A kind of total coffee acid ester extract of multiradiate fleabane | |
| CN101933962B (en) | Ligusticum wallichii formulation granule and preparation method thereof | |
| CN101085802A (en) | Method for preparing Notoginsen triterpenes | |
| CN103239618B (en) | Traditional Chinese medicine composition for treating chronic hepatitis and cirrhosis and preparation method thereof | |
| CN103520235A (en) | Plant composition with lipid-lowering function and preparation method and application thereof | |
| CN101084954A (en) | Method for preparing American ginseng total saponins | |
| CN100551410C (en) | A kind of antidepressant drug and preparation method | |
| CN102670865A (en) | Process for extracting active ingredients of American eleutherine rhizome | |
| CN101928325A (en) | Method for preparing natural 18-alpha glycyrrhizinic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130501 Termination date: 20200209 |