CN1608616A - Application of coniferyl ferulate in anticancer medicine - Google Patents
Application of coniferyl ferulate in anticancer medicine Download PDFInfo
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- CN1608616A CN1608616A CN 200310104929 CN200310104929A CN1608616A CN 1608616 A CN1608616 A CN 1608616A CN 200310104929 CN200310104929 CN 200310104929 CN 200310104929 A CN200310104929 A CN 200310104929A CN 1608616 A CN1608616 A CN 1608616A
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Abstract
The present invention relates to the development of active anticancer component in Chuanxiong rhizome, and is especially the application of coniferyl ferulate in anticancer medicine. The present invention separates coniferyl ferulate from Chuanxiong rhizome as one traditional Chinese medicine and provides new precursor compound for designing new medicine with effective Chinese medicine component. The present invention establishes the liquid chromatographic purification method of the compound with simple operation, high repeatability and mild condition, and suitable for the preparation of Chinese medicinal components with inferior chemical stability.
Description
Technical field
The present invention relates to the research and development of active anticancer component in the Rhizoma Chuanxiong, the application of coniferyl ferulate in cancer therapy drug specifically.
Background technology
Because Chinese medicine is the precious legacy of motherland's medicine and pharmacology, have the clinical practice in thousands of years so far, and formed the Traditional Chinese medical theory system of system, in China application foundation is extremely widely arranged.With favorable factors such as Chinese medicine are with clearly defined objective for this developing new drug has, toxic and side effects is little, raw material sources are many.
Rhizoma Chuanxiong Rhizoma Chuanxiong is the dry rhizome of samphire Rhizoma Chuanxiong Ligusticum chuanxiongHort., has promoting flow of QI and blood, and the effect of wind-expelling pain-stopping is the blood circulation promoting and blood stasis dispelling conventional Chinese medicine.It is reported that it contains lactone, alkaloid, organic acid or plurality of active ingredients such as phenols and neutral oils.The main pharmacological about the Rhizoma Chuanxiong effective ingredient of report has at present: ligustrazine has the increase coronary flow, reduces coronary resistance, promotes the tremulous pulse microcirculation, and platelet aggregation is had depolymerisation; Rhizoma Chuanxiong extractum can suppress small intestinal and shrink and all contractions in uterus of gestation, and alkaloid, ferulic acid, cnidium lactone have spasmolysis; Water decoction can suppress the excitation of caffeine; Rhizoma Chuanxiong volatile oil has sedation; Rhizoma Chuanxiong extract has inhibitory action to antibacterial and fungus; The compound recipe that contains Rhizoma Chuanxiong can be used for auxiliary oncotherapy, and [document 1. Yan De sea .CN 1109337A, 1995 antitumor Chinese medicines regulate and recover soup; The clear .CN 1092972C of document 2. Shen Han, the medicine of 2,002 one kinds of antitumor and anticancer transfer; Document 3. Zhao Jinhuas, Zhao Yun .CN 1362064A such as Yao Qian, 2,002 one kinds of anti-tumor compositions and its production and use; Document 4. Xu repaiies gift, Zhang Jianfang, Liu Baorui etc. tumor .22 (2), 107-108,2002 Rhizoma Chuanxiong elements to the influence of colorectal cancer cells moser and with the synergism of chemotherapeutics].
Up to the present, the report that relevant Rhizoma Chuanxiong effective ingredient can suppress tumor cell have only ligustrazine [5. spring tinkling of pieces of jade of document, Xiao Wei, Wang Yingnian. Chinese practical medical science .4 (9), 26-29, the regulating action that 2002 Radixs Astragali, ligustrazine are secreted IL-4, IL-6 to intestinal cancer patient sun PMBC; Document 6. woodss floods is given birth to, and Japanese plum is strange, Pei Yingxia etc. and Chinese Journal of New Drugs .8 (6), 384-386,1999 ligustrazine, matrine adhere to cancerous cell and endotheliocyte and the influence of adhesion factor expression; Document 7. woodss flood is given birth to, and Japanese plum is strange, PiaoBing Kui etc. Chinese tumor .8 (12), and 574-576,1,999 three ginseng electuaries are to the influence of endotheliocyte in the lung cancer metastasis and adhesion factor; Document 8. is lofty, Xu Shijie, rattan is quiet to be eaten etc. Chinese TCM basis medical journal .3 (1), 27-28,31,1997 blood-activating and stasis-removing suppress tumor cell---the experimentation of platelet aggregation], but the content of ligustrazine in Rhizoma Chuanxiong is extremely low, simultaneously ligustrazine easily distils, and therefore extracts ligustrazine and be used for antitumor research and do not appear in the newspapers from Rhizoma Chuanxiong.
Summary of the invention
The objective of the invention is to for new lead compound-promptly the research and develop application of 4-hydroxy-3-methoxycinnamic alcohol ferulic acid ester in cancer therapy drug is provided based on the design of the new drug of middle pharmaceutically active ingredient.
For achieving the above object, the technical solution used in the present invention is:
By chromatographic separation technology and the outer pharmacological experiment method of coalition, from Chinese medicine---filter out effective ingredient-coniferyl ferulate the Rhizoma Chuanxiong with physiologically active.
The present invention adopts the separation and purification from Rhizoma Chuanxiong of preparation scale chromatograph to go out a kind of ester type compound, and by liquid chromatograph and mass spectrometry, gas chromatogram and mass spectrometry, infrared spectrum, ultraviolet spectra, nuclear magnetic resonance, NMR this chemical compound has been carried out the structure evaluation.Find that in antineoplastic MTT experiment this chemical compound has the physiologically active that suppresses growth of tumour cell.
Be specially: from Chinese medicine---prepare 3-(4-hydroxyl-3-methoxyl group-phenyl)-acrylic acid 3-(4-hydroxyl-3-methoxyl group-phenyl)-allyl ester the Rhizoma Chuanxiong, and structure is identified;
A certain amount of Szechwan Lovage Rhizome of weighing is inserted in the flask, adds the dehydrated alcohol reflux, obtains extracting solution after filtration, vapors away that solvent gets paste in the extracting solution; Under certain drip washing condition (is mobile phase with the acetonitrile/water), so that being housed, C18 SPE (Solid-Phase Extraction) post separates the said extracted thing, collect the fraction of eluting; After LC-MS is analyzed, will contain 3-(4-hydroxyl-3-methoxyl group-phenyl)-acrylic acid 3-(4-hydroxyl-3-methoxyl group-phenyl)-allyl ester fraction and vapor away solvent and get paste.With the paste of preparation HPLC C18 column purification, collect the peak of 3-(4-hydroxyl-3-methoxyl group-phenyl)-acrylic acid 3-(4-hydroxyl-3-methoxyl group-phenyl)-allyl ester through preliminary purification.Vapor away solvent through distilling under reduced pressure, obtain purity at the pure product more than 98%.Finally carry out structure and identify that molecular formula is C by RP-HPLC, ultraviolet spectra, mass spectrum, infrared spectrum
20H
20O
6Structural formula following (also claiming coniferyl ferulate):
The present invention has following advantage:
1. provide new lead compound for new drug design based on middle pharmaceutically active ingredient.The present invention is first from Chinese medicine---separation and purification goes out a kind of chemical compound of esters the Rhizoma Chuanxiong---3-(4-hydroxyl-3-methoxyl group-phenyl)-acrylic acid 3-(4-hydroxyl-3-methoxyl group-phenyl)-allyl ester is also referred to as coniferyl ferulate.
2. set up the liquid chromatograph isolation and purification method of this chemical compound, easy to operation.Adopt the preparation method among the present invention, can separate fastly, be purified into 3-(4-hydroxyl-3-methoxyl group-phenyl)-acrylic acid 3-(4-hydroxyl-3-methoxyl group-phenyl)-allyl ester, purity is more than 98%.Owing to adopt the HPLC technology, this method also has good reproducibility simultaneously, and mild condition is highly suitable for the preparation of the middle pharmaceutically active ingredient of poor chemical stability.
3. the chemical compound of the present invention's application has the activity of certain antitumor cell (s), and has no side effect.Because present antitumor drug ubiquity obvious toxic and side effects, and this chemical compound derives from Chinese medicine commonly used, therefore have more the value of carrying out structure of modification and research, for exploitation of new anti-cancer drug thing and industrialization based on Chinese medicine lay the first stone.
The specific embodiment
Embodiment 1
Weighing is inserted in the flask through pulverizing (35 order) Szechwan Lovage Rhizome 120g, adds the 700mL dehydrated alcohol, soaks 30min, and reflux 1h filters (0.5 μ m) preparation extracting solution.Distilling under reduced pressure vapors away that solvent gets paste in the extracting solution.SPE post with 40 μ m C18 fillers that 30g is housed separates the said extracted thing, uses acetonitrile/water solution and the pure acetonitrile drip washing of 30/70,50/50 (v/v) respectively, collects the fraction of eluting.Through the LC-MS analysis, 3-(4-hydroxyl-3-methoxyl group-phenyl)-acrylic acid 3-(4-hydroxyl-3-methoxyl group-phenyl)-allyl ester is in the fraction of 50% acetonitrile solution eluting.Distilling under reduced pressure vapors away solvent and gets paste.With the paste of the above-mentioned preliminary purification of preparation HPLC C18 column purification, mobile phase is the acetonitrile/water solution of 37/63 (v/v), collects the peak of 3-(4-hydroxyl-3-methoxyl group-phenyl)-acrylic acid 3-(4-hydroxyl-3-methoxyl group-phenyl)-allyl ester.Vapor away solvent through distilling under reduced pressure, obtain purity at the pure product more than 98%.To the suppression ratio of s is that 50% o'clock concentration is about 3.7 μ g/ μ L.
In the present invention, also can extract Rhizoma Chuanxiong with other solvents, such as: methanol, 95% ethanol, water etc., but be higher than other solvents through experiment ethanol in the efficient that leaches 3-(4-hydroxyl-3-methoxyl group-phenyl)-acrylic acid 3-(4-hydroxyl-3-methoxyl group-phenyl)-allyl ester.
Application examples
External MTT (tetrazolium salts) method is measured the suppression ratio of 3-(4-hydroxyl-3-methoxyl group-phenyl)-acrylic acid 3-(4-hydroxyl-3-methoxyl group-phenyl)-allyl ester to s;
Get the 90mg coniferyl ferulate and be dissolved in the 250 μ L dehydrated alcohol, add 250 μ L PBS dilution, add 4,6,8,10,12 μ L (parallel assay 8 holes) to 96 orifice plates of cultivating s respectively.After the cultivation, utilize the ELISA detector to measure optical density at 570nm; Suppression ratio is respectively 47.7%, 79.4%, 79.4%, 82.1%, 83.2%.Experimental result shows that 3-(4-hydroxyl-3-methoxyl group-phenyl)-acrylic acid 3-(4-hydroxyl-3-methoxyl group-phenyl)-allyl ester has certain anti-tumor activity.
The detection method of MTT
1 with every hole 103---104 density inoculating cell on 96 orifice plates.
After 2 cell culture finished, every hole added MTT (5mg/ml), hatched 3-4 hour for 37 ℃, stopped cultivating, and careful the suction abandoned supernatant.Every hole adds 0.1-.0.2mlDMSO, vibrates 10 minutes, makes the crystal dissolving.
3 colorimetrics are measured its trap with enzyme-linked immunosorbent assay instrument at the 570nm place.
Claims (6)
1. the application of coniferyl ferulate in cancer therapy drug.
2. according to the application of the described coniferyl ferulate of claim 1 in cancer therapy drug, it is characterized in that: described coniferyl ferulate separates from Rhizoma Chuanxiong and obtains.
3. according to the application of the described coniferyl ferulate of claim 2 in cancer therapy drug, it is characterized in that: the separation acquisition process of described coniferyl ferulate is as follows,
Szechwan Lovage Rhizome places the solution reflux, filters to obtain extracting solution, vapors away that solvent gets paste in the extracting solution; In acetonitrile/water is under the drip washing condition of mobile phase, separates the said extracted thing so that C18 SPE post to be housed, and collects the fraction of eluting; After liquid chromatograph and mass spectrometry analysis, will contain 3-(4-hydroxyl-3-methoxyl group-phenyl)-acrylic acid 3-(4-hydroxyl-3-methoxyl group-phenyl)-allyl ester fraction and vapor away solvent and get paste; With the paste of preparation HPLC C18 column purification through preliminary purification, collect the peak of 3-(4-hydroxyl-3-methoxyl group-phenyl)-acrylic acid 3-(4-hydroxyl-3-methoxyl group-phenyl)-allyl ester, vapor away solvent through distilling under reduced pressure, obtain product.
4. according to the application of the described coniferyl ferulate of claim 3 in cancer therapy drug, it is characterized in that: described solution is methanol, 95% ethanol, ethanol or water.
5. according to the application of the described coniferyl ferulate of claim 3 in cancer therapy drug, it is characterized in that: described solution is ethanol.
6. according to the application of the described coniferyl ferulate of claim 3 in cancer therapy drug, it is characterized in that: the volume ratio of described acetonitrile/water is 30～100: 0～70.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200310104929 CN1278679C (en) | 2003-10-24 | 2003-10-24 | Application of coniferyl ferulate in anticancer medicine |
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| CN 200310104929 CN1278679C (en) | 2003-10-24 | 2003-10-24 | Application of coniferyl ferulate in anticancer medicine |
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| CN1608616A true CN1608616A (en) | 2005-04-27 |
| CN1278679C CN1278679C (en) | 2006-10-11 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101543488B (en) * | 2006-05-17 | 2011-03-02 | 连晓媛 | A medicine containing caffeic acid 3,4-dihydroxyl phenethyl ester and its uses |
| CN102791125A (en) * | 2009-08-20 | 2012-11-21 | 比奥卡卜可变资本股份公司 | Phytoceutical compositions for pets |
| CN101639470B (en) * | 2008-07-29 | 2013-03-20 | 江苏康缘药业股份有限公司 | Checking method of Chinese medicinal composition standard fingerprint, and use thereof |
| CN101246176B (en) * | 2007-02-13 | 2013-06-05 | 许洋 | Mass spectrum kit for detecting squamous-cell carcinoma antigen feminine cervical carcinoma serum protein and preparation method thereof |
-
2003
- 2003-10-24 CN CN 200310104929 patent/CN1278679C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101543488B (en) * | 2006-05-17 | 2011-03-02 | 连晓媛 | A medicine containing caffeic acid 3,4-dihydroxyl phenethyl ester and its uses |
| CN101246176B (en) * | 2007-02-13 | 2013-06-05 | 许洋 | Mass spectrum kit for detecting squamous-cell carcinoma antigen feminine cervical carcinoma serum protein and preparation method thereof |
| CN101639470B (en) * | 2008-07-29 | 2013-03-20 | 江苏康缘药业股份有限公司 | Checking method of Chinese medicinal composition standard fingerprint, and use thereof |
| CN102791125A (en) * | 2009-08-20 | 2012-11-21 | 比奥卡卜可变资本股份公司 | Phytoceutical compositions for pets |
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| Publication number | Publication date |
|---|---|
| CN1278679C (en) | 2006-10-11 |
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