CN1748676A - Ligustilide oil and its preparation - Google Patents

Ligustilide oil and its preparation Download PDF

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Publication number
CN1748676A
CN1748676A CN200510105552.XA CN200510105552A CN1748676A CN 1748676 A CN1748676 A CN 1748676A CN 200510105552 A CN200510105552 A CN 200510105552A CN 1748676 A CN1748676 A CN 1748676A
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Prior art keywords
ligustilide
oil
petroleum ether
preparation
rhizoma chuanxiong
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CN200510105552.XA
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CN1321638C (en
Inventor
吕沅珊
华伟义
任涛
郑雅楠
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Tianjin Institute of Pharmaceutical Research Co Ltd
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Tianjin Institute of Pharmaceutical Research Co Ltd
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Abstract

The ligustilide oil with ligustilide content of 50-60 wt% is prepared through the following steps: 1. preparing coarse canidium oil; 2. adding petroleum ether of boiling range 30-60 deg c or 60-90 deg.c in the amount of 5 times the canidium oil to obtain petroleum ether solution; 3. treating the petroleum ether solution in silicone gel column; 4. eluting with petroleum ether; and 5. collecting the eluted liquid and concentrating to eliminating petroleum ether to obtain the ligustilide oil. The ligustilide oil may be further prepared into capsule preparation. The present invention has the advantages of high ligustilide content, low power consumption, reusability of solvent and silicone gel, low cost, etc, and is suitable for industrial production.

Description

A kind of ligustilide oil and preparation thereof
The application is for dividing an application, and the application number of original application is 03153586.0, and the applying date is on August 18th, 2003.
Technical field
The present invention relates to a kind of ligustilide oil and preparation thereof, refer to especially a kind ofly from Rhizoma Chuanxiong, to extract, technology system, the ligustilide oil after the enrichment and the preparation thereof of enrichment ligustilide, belong to modern Chinese traditional medicine field.
Background technology
Ligustilide is one of main effective ingredient in the Rhizoma Chuanxiong, has anti-cerebral ischemia and improves cerebral blood flow, is used for the treatment of the various symptoms that caused by cerebral ischemia.
Because the pure product of ligustilide are unstable, all use at present with the form of Rhizoma Chuanxiong oil, the method of Rhizoma Chuanxiong oil available water steam distillation obtains, ligustilide content can reach more than 50% in the Rhizoma Chuanxiong oil that obtains from Rhizoma Chuanxiong, but because production process needs long Steam Heating (reaching several days) energy resource consumption very big, gained Rhizoma Chuanxiong oil collecting amount is very low, and the yield of ligustilide is lower.The also available CO of Rhizoma Chuanxiong oil 2Supercritical extraction method extracts, but ligustilide content in the gained Rhizoma Chuanxiong oil is used the HPLC internal mark method determination with ligustilide reference substance (purity reaches more than 98%), and its content has only 5~9%, and slightly oily with the Rhizoma Chuanxiong of 85% ethanol room temperature dipping gained, its ligustilide content only is 14%~18%.Therefore, study a kind of simplely, the process of enriching that can make ligustilide content reach the ligustilide oil more than 50% has Practical significance.
Summary of the invention
The purpose of this invention is to provide a kind of technology of enrichment ligustilide and the ligustilide oil that obtains.
Another object of the present invention provides the Rhizoma Ligustici pharmaceutical preparation of being rich in ligustilide.
For achieving the above object, the present invention is by the following technical solutions:
A kind of ligustilide oil, the content of ligustilide is 50~60% in the oil, is obtained by following prepared:
(1) the preparation Rhizoma Chuanxiong is slightly oily;
(2) overstriking oil 5 times of amounts, boiling ranges are the petroleum ether of 30~60 ℃ or 60 ℃~90 ℃, must petroleum ether solution;
(3) with 80~200 purpose silica gel of~2 times of amounts of thick oily 1.6 times of amounts, dress up short column, diameter and aspect ratio are 1: 1.3~1: the 1.5 above-mentioned petroleum ether solution of processing;
(4) after petroleum ether solution flows to end, wash post with the petroleum ether of 1~2 times of amount of thick oil in post;
(5) wash post with the petroleum ether of thick oily 12~16 times of amounts, collect eluent, be concentrated into petroleum ether to the greatest extent, promptly get ligustilide oil.
The described method of the thick oil of Rhizoma Chuanxiong for preparing of step (1) is for flooding Rhizoma Chuanxiong or CO with 85% ethanol room temperature 2Supercritical extraction obtains slightly oil of Rhizoma Chuanxiong.
Described 85% ethanol room temperature dipping is meant that the raw material that will contain ligustilide floods 3 times through four times of amount 85% ethanol room temperatures, obtains slightly oil of Rhizoma Chuanxiong.
Described CO 2Supercritical extraction is meant and will contains the raw material of ligustilide through CO 2Supercritical extraction, extraction conditions is: pressure 34.5MPa, 60 ℃ of temperature, modifier ethanol 0.3ml, 3 hours extraction time, the Rhizoma Chuanxiong oil that obtains.
This method is utilized following principle enrichment ligustilide: silica gel adsorption, the applied sample amount of overload.With common upper column quantity down can not the eluting ligustilide low polarity solvent, can separate eliminating than the more weak impurity of ligustilide absorption, the eluting ligustilide, but can not adsorb stronger impurity than ligustilide by eluting, thus reach the purpose of purification enrichment ligustilide.
With the ligustilide oil 25%~50% (its ligustilide content 50%~60%) of enrichment processing back gained, Petiolus Trachycarpi oil 3%~6%, hydrogenated palm oil 3%~6%, phosphatidase 12 %~4% and salad oil 42%~59%.Being mixed with soft capsule content, is rubber with glycerol-gelatin, is pressed into soft capsule, and every soft capsule contains ligustilide and is not less than 25mg and every soft capsule and contains ligustilide and be not less than 50mg.
With the ligustilide oil 20~80% (its ligustilide content 50%~60%) of enrichment processing back gained, fat-soluble excipient such as salad oil 80~20%, fill becomes liquid hard capsule, and every hard capsule contains ligustilide and is not less than 50mg.
The test of pesticide effectiveness shows that this product has anti-cerebral ischemia, is used for the treatment of the various symptoms that caused by cerebral ischemia.
Advantage of the present invention is: the ligustilide oil of back gained is handled in enrichment, and through being standard with the ligustilide reference substance, HPLC measures, and the content of ligustilide reaches 50~60% in the ligustilide oil.Energy low consumption, all technical process except that enrichment process, all is at room temperature to operate; Solvent for use and silica gel can be recycled, and cost is low; Ligustilide yield height; Technological operation is simple; Equipment needed thereby is simple, is suitable for industrialized great production.
Be described further below in conjunction with the preferable specific embodiment.
The specific embodiment
Embodiment 1, be the technology of raw material enrichment ligustilide with the Rhizoma Chuanxiong
One, material and method
1, material:
Rhizoma Chuanxiong: purchase in Tianjin medical material company
Ethanol: purchase in Tianjin Alcohol Plant
Silica gel: purchase in Haiyang Chemical Plant, Qingdao
Petroleum ether: purchase in Tianjin Milky Way chemical reagent work
The ligustilide reference substance: Rhizoma Chuanxiong by silicagel column, obtains grease through alcohol extraction, reaches ligustilide reference substance more than 98% obtaining content on the preparation HPLC, meets the requirement of reference substance.
2, method:
(1) Rhizoma Chuanxiong is flooded 3 times through four times of amount 85% ethanol room temperatures, obtain slightly oil of Rhizoma Chuanxiong;
(2) overstriking oil 5 times of amounts, boiling ranges are 60~90 ℃ petroleum ether, get petroleum ether solution;
(3) with 100~200 purpose silica gel of thick oily 1.8 times of amounts, dress up short column, diameter and aspect ratio are 1: 1.3 above-mentioned petroleum ether solution of processing;
(4) after petroleum ether solution flows to end, wash post with the petroleum ether of 1.5 times of amounts of thick oil in post;
(5) wash post with the petroleum ether of thick oily 12 times of amounts, collect eluent, be concentrated into petroleum ether to the greatest extent, promptly get ligustilide oil.
Two, detection and result:
Through being standard with the ligustilide reference substance, HPLC measures, C 18Post; Mobile phase is 64% methanol-1% glacial acetic acid; The detection wavelength is 272nm.The content of ligustilide reaches 15~17% in the thick oil of Rhizoma Chuanxiong, ligustilide yield 90~95%; The content of ligustilide reaches 50~60% in the ligustilide oil, ligustilide yield 85%.
Embodiment 2, be the technology of raw material enrichment ligustilide with the Rhizoma Chuanxiong
One, material and method
1, material: with embodiment 1.
2, method:
(1) Rhizoma Chuanxiong is flooded 3 times through four times of amount 85% ethanol room temperatures, obtain slightly oil of Rhizoma Chuanxiong;
(2) overstriking oil 5 times of amounts, boiling ranges are 30~60 ℃ petroleum ether, get petroleum ether solution;
(3) with 80~100 purpose silica gel of thick oily 2 times of amounts, dress up short column, diameter and aspect ratio are 1: 1.5 above-mentioned petroleum ether solution of processing;
(4) after petroleum ether solution flows to end, wash post with the petroleum ether of 2 times of amounts of thick oil in post;
(5) wash post with the petroleum ether of thick oily 16 times of amounts, collect eluent, be concentrated into petroleum ether to the greatest extent, promptly get ligustilide oil.
Two, detection and result:
Through being standard with the ligustilide reference substance, HPLC measures, and the content of ligustilide reaches 17% in the thick oil of Rhizoma Chuanxiong, ligustilide yield 90~95%; The content of ligustilide reaches 50~55% in the ligustilide oil, ligustilide yield 85%.
Embodiment 3, with CO 2The thick oil of the Rhizoma Chuanxiong of supercritical extraction method gained is the technology of raw material enrichment ligustilide
One, material and method
1, material: with embodiment 1.
2, method
(1) with Rhizoma Chuanxiong CO 2Supercritical extraction, CO 2The supercritical extraction condition is: pressure 34.5MPa, and 60 ℃ of temperature, modifier ethanol 0.3ml, 3 hours extraction time, the Rhizoma Chuanxiong that obtains is oil slightly;
(2) overstriking oil 5 times of amounts, boiling ranges are 60~90 ℃ of petroleum ether, get petroleum ether solution;
(3) with 100~200 purpose silica gel of thick oily 1.8 times of amounts, dress up short column, diameter and aspect ratio are 1: 1.4 above-mentioned petroleum ether solution of processing;
(4) after petroleum ether solution flows to end, wash post with the petroleum ether of 2 times of amounts of thick oil in post;
(5) wash post with the petroleum ether of thick oily 14 times of amounts, collect eluent, be concentrated into petroleum ether to the greatest extent, promptly get ligustilide oil.
Two, detection and result:
Through being standard with the ligustilide reference substance, HPLC measures, and the content of ligustilide reaches 8.8% in the thick oil of Rhizoma Chuanxiong; The content of ligustilide reaches 58% in the ligustilide oil, ligustilide yield 80%.
Embodiment 4, be rich in the preparation of ligustilide
One, prescription: ligustilide oil 50%, Petiolus Trachycarpi oil 3%, hydrogenated palm oil 3%, phosphatidase 12 % phospholipid and salad oil 42%.
Two, preparation method:
Being mixed with soft capsule content with formulation, is rubber with glycerol-gelatin, is pressed into soft capsule, and specification is every dress 0.2g content, and every soft capsule contains ligustilide and is not less than 50mg.
Consumption and usage: every day 2 times, each 1.(fixing tentatively)
Embodiment 5, be rich in the preparation of ligustilide
One, prescription: ligustilide oil 25%, Petiolus Trachycarpi oil 6%, hydrogenated palm oil 6%, phosphatidase 14 % phospholipid and salad oil 59%.
Two, preparation method:
Being mixed with soft capsule content with formulation, is rubber with glycerol-gelatin, is pressed into soft capsule, and specification is every dress 0.2g content, and every soft capsule contains ligustilide and is not less than 25mg.
Consumption and usage: every day 2 times, each 1.(fixing tentatively)
Embodiment 6, be rich in the preparation of ligustilide
One, prescription: ligustilide oil 25%, Petiolus Trachycarpi oil 6%, hydrogenated palm oil 6%, phosphatidase 14 % phospholipid and salad oil 59%.
Two, preparation method:
Being mixed with soft capsule content with formulation, is rubber with glycerol-gelatin, is pressed into soft capsule, and specification is every dress 0.4g content, and every soft capsule contains ligustilide and is not less than 50mg.
Embodiment 7, be rich in the preparation of ligustilide
One, prescription: ligustilide oil 40%, excipient 60%.
Two, preparation method:
With ligustilide oil and fat-soluble excipient mix homogeneously, fill is in hard capsule case, and employing joint filling material (HPMC 5cps5%, PVAl%, ethanol 34%, water 60%) the capsule shells suit place is carried out once or secondary seals, be prepared into liquid hard capsule, every hard capsule contains ligustilide and is not less than 50mg.
Embodiment 8, pharmacodynamic experiment
One, material and method:
1, animal: choose 51 of 22~27g kunming mices, male and female have concurrently, are divided into 5 groups at random, are respectively normal control group, nimodipine matched group, ligustilide line of oils.
2, method: nimodipine is selected intraperitoneal administration, each dosage group selection gastric infusion of ligustilide, and blank group gives the water with volume.Each is organized the mice administration and breaks end fast at the ear rear portion with shear after 1 hour, and clocks immediately.Continue the time of breathing of dehiscing behind the record mice broken end.
Two, result: can obviously prolong after nimodipine contrast, each dosage group mice administration of ligustilide and continue the time of breathing of dehiscing.

Claims (9)

1, a kind of ligustilide oil, the content of ligustilide is 50~60% in the oil, is obtained by following prepared:
(1) the preparation Rhizoma Chuanxiong is slightly oily;
(2) overstriking oil 5 times of amounts, boiling ranges are the petroleum ether of 30~60 ℃ or 60~90 ℃, must petroleum ether solution;
(3) with 80~200 purpose silica gel of~2 times of amounts of thick oily 1.6 times of amounts, dress up short column, diameter and aspect ratio are 1: 1.3~1: the 1.5 above-mentioned petroleum ether solution of processing;
(4) after petroleum ether solution flows to end, wash post with the petroleum ether of 1~2 times of amount of thick oil in post;
(5) wash post with the petroleum ether of thick oily 12~16 times of amounts, collect eluent, be concentrated into petroleum ether to the greatest extent, promptly get ligustilide oil.
2, a kind of ligustilide oil according to claim 1 is characterized in that: described step (1) prepares the method for the thick oil of Rhizoma Chuanxiong for Rhizoma Chuanxiong is flooded or CO with 85% ethanol room temperature 2Supercritical extraction obtains slightly oil of Rhizoma Chuanxiong.
3, a kind of ligustilide oil according to claim 2 is characterized in that: described 85% ethanol room temperature dipping is meant that the raw material that will contain ligustilide floods 3 times through four times of amount 85% ethanol room temperatures, obtains slightly oil of Rhizoma Chuanxiong.
4, a kind of ligustilide oil according to claim 2 is characterized in that: described CO 2Supercritical extraction is meant and will contains the raw material of ligustilide through CO 2Supercritical extraction, extraction conditions is: pressure 34.5MPa, 60 ℃ of temperature, modifier ethanol 0.3ml, 3 hours extraction time, the Rhizoma Chuanxiong oil that obtains.
5, a kind of preparation that is rich in ligustilide, it is characterized in that: said preparation is a soft capsule, with glycerol-gelatin is rubber, this soft capsule content contains the ligustilide oil 25~50% after the enrichment basically, Petiolus Trachycarpi oil 3%~6%, hydrogenated palm oil 3%~6%, phosphatidase 12 %~4% and salad oil 42%~59%.
6, a kind of preparation that is rich in ligustilide is characterized in that: said preparation is a liquid hard capsule, and this capsule 's content contains the ligustilide oil 20~80% after the enrichment basically, fat-soluble excipient 80~20%.
7, preparation according to claim 5 is characterized in that: every of described soft capsule contains ligustilide and is not less than 25mg.
8, preparation according to claim 5 is characterized in that: every of described soft capsule contains ligustilide and is not less than 50mg.
9, preparation according to claim 6 is characterized in that: every of described liquid hard capsule contains ligustilide and is not less than 50mg.
CNB200510105552XA 2003-08-18 2003-08-18 Ligustilide oil and its preparation Expired - Fee Related CN1321638C (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106138135A (en) * 2016-08-18 2016-11-23 四川省中医药科学院 Medicine for treatment of vascular cognitive disorder and preparation method thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1321638C (en) * 2003-08-18 2007-06-20 天津药物研究院 Ligustilide oil and its preparation
CN102872175A (en) * 2012-08-24 2013-01-16 天津中医药大学 Ligusticum chuanxiong hort extract and preparation method and application thereof
CN105079059B (en) * 2015-09-07 2020-03-31 宜诺(天津)医药工程有限公司 Angelica sinensis extract and extraction method thereof

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CN1035327C (en) * 1992-09-30 1997-07-02 兰州大学 Synthetic method for rhizoma ligustici internal ester
CN1102397C (en) * 2000-03-01 2003-03-05 山东绿叶制药股份有限公司 Chinese angelica root oil soft capsule and its preparing process
US20030165580A1 (en) * 2002-03-04 2003-09-04 Xinxian Zhao Safe pharmaceutical composition for treatment and prevention of gynecological disease
JP2003289827A (en) * 2002-04-02 2003-10-14 Osaka Yakuhin Kenkyusho:Kk Supplement containing japanese parsley extract
CN100391953C (en) * 2003-06-03 2008-06-04 北京九龙制药有限公司 Medicinal use and extraction of cis-ligusticum lactone
US20040247698A1 (en) * 2003-06-04 2004-12-09 Valenzuela Cortes Carmen Maria Erectile Dysfunction Treatment
CN1321638C (en) * 2003-08-18 2007-06-20 天津药物研究院 Ligustilide oil and its preparation

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106138135A (en) * 2016-08-18 2016-11-23 四川省中医药科学院 Medicine for treatment of vascular cognitive disorder and preparation method thereof

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CN1583735A (en) 2005-02-23
CN1247564C (en) 2006-03-29

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