CN1247564C - Enrichment of ligusticum lactone and its preparations - Google Patents
Enrichment of ligusticum lactone and its preparations Download PDFInfo
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- CN1247564C CN1247564C CN 03153586 CN03153586A CN1247564C CN 1247564 C CN1247564 C CN 1247564C CN 03153586 CN03153586 CN 03153586 CN 03153586 A CN03153586 A CN 03153586A CN 1247564 C CN1247564 C CN 1247564C
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- ligustilide
- oil
- petroleum ether
- ligusticum wallichii
- enrichment
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Abstract
The present invention discloses a technology for enriching ligustilide, which comprises the following steps that (1) chuanxiong crude oil is prepared; (2) 5 times amount of petroleum ether with a boiling range of 30 to 60 DEG C or 60 to 90 DEG C is added to obtain a petroleum ether solution; (3) 80 to 200 meshes of silica gel of 1.6 times amount to 2 times amount of crude oil is put in a short column with the ratio of the diameter to the height of 1:1.3 to 1:1.5 and treats the petroleum ether solution; (4) after all the petroleum ether solution passes through the column, the column is washed by petroleum ether of 1 to 2 times of crude oil; (5) the column is washed by petroleum ether of 1 to 2 times of crude oil, and eluent is collected and concentrated to completely remove the petroleum ether to prepare ligustilide oil capable of preparing soft capsule preparations and liquid hard capsule preparations. The present invention has the advantages of low energy source consumption with 50 to 60% of content of the ligustilide in the enriched ligustilide oil, low cost with the recovered utilization of used solvent and the silica gel, high ligustilide yield, simple technical operation and simple required equipment and is suitable for large industrial production.
Description
Technical field
The present invention relates to a kind of technology and preparation thereof of enrichment Z-ligustilide, refer to especially a kind ofly from Ligusticum wallichii, to extract, the technology and the preparation thereof of enrichment Z-ligustilide, belong to modern Chinese traditional medicine field.
Background technology
Z-ligustilide is one of main effective constituent in the Ligusticum wallichii, has anti-cerebral ischemia and improves cerebral blood flow (CBF), is used for the treatment of the various symptoms that caused by cerebral ischemia.
Because the pure product of Z-ligustilide are unstable, all use at present with the form of Rhizoma Chuanxiong oil, the method of Rhizoma Chuanxiong oil used water steam distillation obtains, Z-ligustilide content can reach more than 50% in the Rhizoma Chuanxiong oil that obtains from Ligusticum wallichii, but because production process needs long steam heating (reaching several days) energy consumption very big, gained Rhizoma Chuanxiong oil collecting amount is very low, and the yield of Z-ligustilide is lower.The also available CO of Rhizoma Chuanxiong oil
2Supercritical extraction method extracts, but Z-ligustilide content in the gained Rhizoma Chuanxiong oil is used the HPLC internal mark method determination with Z-ligustilide reference substance (purity reaches more than 98%), and its content has only 5～9%, and slightly oily with the Ligusticum wallichii of 85% ethanol room temperature dipping gained, its Z-ligustilide content only is 14%～18%.Therefore, study a kind of simplely, the process of enriching that can make Z-ligustilide content reach the ligustilide oil more than 50% has Practical significance.
Summary of the invention
The technology that the purpose of this invention is to provide a kind of enrichment Z-ligustilide.
Another object of the present invention provides the pharmaceutical preparation that is rich in Z-ligustilide.
For achieving the above object, the present invention is by the following technical solutions:
A kind of technology of enrichment Z-ligustilide comprises the steps:
(1) the preparation Ligusticum wallichii is slightly oily;
(2) overstriking oil 5 times of amounts, boiling ranges are the sherwood oil 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 sherwood oil of 1～2 times of amount of thick oil in post;
(5) wash post with the sherwood oil of thick oily 12～16 times of amounts, collect elutriant, be concentrated into sherwood oil to the greatest extent, promptly get ligustilide oil.
The described method of the thick oil of Ligusticum wallichii for preparing of step (1) is for flooding Ligusticum wallichii or CO with 85% ethanol room temperature
2Supercritical extraction obtains slightly oil of Ligusticum wallichii.
Described 85% ethanol room temperature dipping is meant that the raw material that will contain Z-ligustilide floods 3 times through four times of amount 85% ethanol room temperatures, obtains slightly oil of Ligusticum wallichii.
Described CO
2Supercritical extraction is meant and will contains the raw material of Z-ligustilide through CO
2Supercritical extraction, extraction conditions is: pressure 34.5MPa, 60 ℃ of temperature, properties-correcting agent ethanol 0.3ml, 3 hours extraction time, the Rhizoma Chuanxiong oil that obtains.
Present method is utilized following principle enrichment Z-ligustilide: silica gel adsorption, the applied sample amount of overload.With common upper column quantity down can not the wash-out Z-ligustilide low polarity solvent, can separate eliminating than the more weak impurity of Z-ligustilide absorption, the wash-out Z-ligustilide, but can not adsorb stronger impurity than Z-ligustilide by wash-out, thus reach the purpose of purification enrichment Z-ligustilide.
With the ligustilide oil 25%～50% (its Z-ligustilide content 50%～60%) of enrichment processing back gained, plam oil 3%～6%, hydrogenated palm kernel oil 3%～6%, phosphatidase 12 %～4% and salad oil 42%～59%.Being mixed with soft capsule content, is rubber with glycerine-gelatin, is pressed into soft capsule, and every soft capsule contains Z-ligustilide and is not less than 25mg and every soft capsule and contains Z-ligustilide and be not less than 50mg.
With the ligustilide oil 20～80% (its Z-ligustilide content 50%～60%) of enrichment processing back gained, fat-soluble excipient such as salad oil 80～20%, can becomes liquid hard capsule, and every hard capsule contains Z-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 Z-ligustilide reference substance, HPLC measures, and the content of Z-ligustilide reaches 50～60% in the ligustilide oil.Energy low consumption, all technological 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; Z-ligustilide yield height; Technological operation is simple; Required equipment is simple, is suitable for industrialized production.
Be described further below in conjunction with preferable embodiment.
Embodiment
Embodiment 1, be the technology of raw material enrichment Z-ligustilide with the Ligusticum wallichii
One, material and method
1, material:
Ligusticum wallichii: purchase in Tianjin medicinal material company
Ethanol: purchase in Tianjin grain distillery
Silica gel: purchase in Haiyang Chemical Plant, Qingdao
Sherwood oil: purchase in Tianjin Milky Way chemical reagent work
The Z-ligustilide reference substance: Ligusticum wallichii by silicagel column, obtains oily matter through alcohol extracting, reaches Z-ligustilide reference substance more than 98% obtaining content on the preparation HPLC, meets the requirement of reference substance.
2, method:
(1) with Ligusticum wallichii through the 85% ethanol room temperature proofing 3 times of four times of amounts, obtain slightly oil of Ligusticum wallichii;
(2) overstriking oil 5 times of amounts, boiling ranges are 60～90 ℃ sherwood oil, 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 sherwood oil of 1.5 times of amounts of thick oil in post;
(5) wash post with the sherwood oil of thick oily 12 times of amounts, collect elutriant, be concentrated into sherwood oil to the greatest extent, promptly get ligustilide oil.
Two, detection and result:
Through being standard with the Z-ligustilide reference substance, HPLC measures, C
18Post; Moving phase is 64% methyl alcohol-1% Glacial acetic acid; The detection wavelength is 272nm.The content of Z-ligustilide reaches 15～17% in the thick oil of Ligusticum wallichii, Z-ligustilide yield 90～95%; The content of Z-ligustilide reaches 50～60% in the ligustilide oil, Z-ligustilide yield 85%.
Embodiment 2, be the technology of raw material enrichment Z-ligustilide with the Ligusticum wallichii
One, material and method
1, material: with embodiment 1.
2, method:
(1) Ligusticum wallichii is flooded 3 times through four times of amount 85% ethanol room temperatures, obtain slightly oil of Ligusticum wallichii;
(2) overstriking oil 5 times of amounts, boiling ranges are 30～60 ℃ sherwood oil, 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 sherwood oil of 2 times of amounts of thick oil in post;
(5) wash post with the sherwood oil of thick oily 16 times of amounts, collect elutriant, be concentrated into sherwood oil to the greatest extent, promptly get ligustilide oil.
Two, detection and result:
Through being standard with the Z-ligustilide reference substance, HPLC measures, and the content of Z-ligustilide reaches 17% in the thick oil of Ligusticum wallichii, Z-ligustilide yield 90～95%; The content of Z-ligustilide reaches 50～55% in the ligustilide oil, Z-ligustilide yield 85%.
Embodiment 3, with CO
2The thick oil of the Ligusticum wallichii of supercritical extraction method gained is the technology of raw material enrichment Z-ligustilide
One, material and method
1, material: with embodiment 1.
2, method
(1) with Ligusticum wallichii CO
2Supercritical extraction, CO
2The supercritical extraction condition is: pressure 34.5MPa, and 60 ℃ of temperature, properties-correcting agent ethanol 0.3ml, 3 hours extraction time, the Ligusticum wallichii that obtains is oil slightly;
(2) overstriking oil 5 times of amounts, boiling ranges are 60～90 ℃ of sherwood oils, 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 sherwood oil of 2 times of amounts of thick oil in post;
(5) wash post with the sherwood oil of thick oily 14 times of amounts, collect elutriant, be concentrated into sherwood oil to the greatest extent, promptly get ligustilide oil.
Two, detection and result:
Through being standard with the Z-ligustilide reference substance, HPLC measures, and the content of Z-ligustilide reaches 8.8% in the thick oil of Ligusticum wallichii: the content of Z-ligustilide reaches 58% in the ligustilide oil, Z-ligustilide yield 80%.
Embodiment 4, be rich in the preparation of Z-ligustilide
One, prescription: ligustilide oil 50%, plam oil 3%, hydrogenated palm kernel oil 3%, phosphatidase 12 % phosphatide and salad oil 42%.
Two, preparation method:
Being mixed with soft capsule content with formulation, is rubber with glycerine-gelatin, is pressed into soft capsule, and specification is every dress 0.2g content, and every soft capsule contains Z-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 Z-ligustilide
One, prescription: ligustilide oil 25%, plam oil 6%, hydrogenated palm kernel oil 6%, phosphatidase 14 % phosphatide and salad oil 59%.
Two, preparation method:
Being mixed with soft capsule content with formulation, is rubber with glycerine-gelatin, is pressed into soft capsule, and specification is every dress 0.2g content, and every soft capsule contains Z-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 Z-ligustilide
One, prescription: ligustilide oil 25%, plam oil 6%, hydrogenated palm kernel oil 6%, phosphatidase 14 % phosphatide and salad oil 59%.
Two, preparation method:
Being mixed with soft capsule content with formulation, is rubber with glycerine-gelatin, is pressed into soft capsule, and specification is every dress 0.4g content, and every soft capsule contains Z-ligustilide and is not less than 50mg.
Embodiment 7, be rich in the preparation of Z-ligustilide
One, prescription: ligustilide oil 40%, excipient 60%.
Two, preparation method:
Ligustilide oil and fat-soluble excipient are mixed, and can is in hard capsule case, and employing joint filling material (HPMC
5cp85%, PVA1%, ethanol 34%, water 60%) the capsule shell suit place is carried out once or secondary seals, be prepared into liquid hard capsule, every hard capsule contains Z-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 control group, ligustilide oil group.
2, method: nimodipine is selected intraperitoneal administration, each dosage group selection gastric infusion of Z-ligustilide, and blank group gives the water with volume.Each is organized the mouse administration and breaks end fast at the ear rear portion with clipper after 1 hour, and clocks immediately.Continue the time of breathing of dehiscing behind the record mouse broken end.
Two, result: can obviously prolong after nimodipine contrast, each dosage group mouse administration of Z-ligustilide and continue the time of breathing of dehiscing.
Claims (4)
1, a kind of technology of enrichment Z-ligustilide is characterized in that this technology comprises the steps:
(1) the preparation Ligusticum wallichii is slightly oily;
(2) overstriking oil 5 times of amounts, boiling ranges are the sherwood oil 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 sherwood oil of 1～2 times of amount of thick oil in post;
(5) wash post with the sherwood oil of thick oily 12～16 times of amounts, collect elutriant, be concentrated into sherwood oil to the greatest extent, promptly get ligustilide oil; Except that enrichment process, all operations at room temperature.
2, the technology of a kind of enrichment Z-ligustilide according to claim 1 is characterized in that: described step (1) prepares the method for the thick oil of Ligusticum wallichii for Ligusticum wallichii is flooded or CO with 85% ethanol room temperature
2Supercritical extraction obtains slightly oil of Ligusticum wallichii.
3, the technology of a kind of enrichment Z-ligustilide according to claim 2 is characterized in that: described 85% ethanol room temperature dipping is meant the Ligusticum wallichii raw material is flooded 3 times through four times of amount 85% ethanol room temperatures, obtains slightly oil of Ligusticum wallichii.
4, the technology of a kind of enrichment Z-ligustilide according to claim 2 is characterized in that: described CO
2Supercritical extraction is meant the Ligusticum wallichii raw material through CO
2Supercritical extraction, extraction conditions is: pressure 34.5MPa, 60 ℃ of temperature, properties-correcting agent ethanol 0.3ml, 3 hours extraction time, the Rhizoma Chuanxiong oil that obtains.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03153586 CN1247564C (en) | 2003-08-18 | 2003-08-18 | Enrichment of ligusticum lactone and its preparations |
| CNB200510105552XA CN1321638C (en) | 2003-08-18 | 2003-08-18 | Ligustilide oil and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03153586 CN1247564C (en) | 2003-08-18 | 2003-08-18 | Enrichment of ligusticum lactone and its preparations |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB200510105552XA Division CN1321638C (en) | 2003-08-18 | 2003-08-18 | Ligustilide oil and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1583735A CN1583735A (en) | 2005-02-23 |
| CN1247564C true CN1247564C (en) | 2006-03-29 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 03153586 Expired - Fee Related CN1247564C (en) | 2003-08-18 | 2003-08-18 | Enrichment of ligusticum lactone and its preparations |
| CNB200510105552XA Expired - Fee Related CN1321638C (en) | 2003-08-18 | 2003-08-18 | Ligustilide oil and its preparation |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB200510105552XA Expired - Fee Related CN1321638C (en) | 2003-08-18 | 2003-08-18 | Ligustilide oil and its preparation |
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1247564C (en) * | 2003-08-18 | 2006-03-29 | 天津药物研究院 | Enrichment of ligusticum lactone and its preparations |
| 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 |
| CN106138135B (en) * | 2016-08-18 | 2020-09-22 | 四川省中医药科学院 | Medicine for preventing and treating vascular cognitive disorder and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN1247564C (en) * | 2003-08-18 | 2006-03-29 | 天津药物研究院 | Enrichment of ligusticum lactone and its preparations |
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2003
- 2003-08-18 CN CN 03153586 patent/CN1247564C/en not_active Expired - Fee Related
- 2003-08-18 CN CNB200510105552XA patent/CN1321638C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1321638C (en) | 2007-06-20 |
| CN1583735A (en) | 2005-02-23 |
| CN1748676A (en) | 2006-03-22 |
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