CN1089846A - A kind of anticarcinogen and preparation method thereof - Google Patents
A kind of anticarcinogen and preparation method thereof Download PDFInfo
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- CN1089846A CN1089846A CN 93100881 CN93100881A CN1089846A CN 1089846 A CN1089846 A CN 1089846A CN 93100881 CN93100881 CN 93100881 CN 93100881 A CN93100881 A CN 93100881A CN 1089846 A CN1089846 A CN 1089846A
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- sophoridine
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Abstract
The invention discloses a kind of PTS and preparation method thereof, it is characterized in that the sophoridine that will extract is mixed and made into injection, tablet, capsule and other preparations as active component and pharmaceutical carrier and additive from the Chinese medicine Herba Sophorae alopecuroidis.Its preparation method be get the Herba Sophorae alopecuroidis aerial parts through immersion, diafiltration, ion exchange, alkalization, eluting, once change that salt, free, extraction, secondary change salt, free, extraction, change salt for three times, free, extraction, coarse crystallization, refiningly obtain sophoridine, add hydrochloric acid then and make injection.Add excipient and make tablet, capsule etc., the anticarcinogen that the present invention makes is obviously stablized choriocarcinoma, evil Portugal, pulmonary carcinoma, digestive tract cancer antitumaous effect, and toxicity is low.And the Herba Sophorae alopecuroidis aboundresources, sophoridine content height, the cost of extraction is low, is a kind of of great value PTS.
Description
The present invention relates to a kind of anticarcinogen, particularly from Chinese herbal medicine, extract the anticarcinogen and the preparation method thereof of active ingredient.
Tumor is present world the world of medicine difficult problem anxious to be captured.Anticancer chemotherapy poison of drug and the side effect of using now is big, how to find that the higher and lower PTS of toxicity of curative effect is the needs that people closely cut.From there not being right product, from Chinese herbal medicine, obtain active anticancer component, be important directions and the approach of seeking PTS now in the world.
Contain multiple alkaloid in the Chinese medicine Herba Sophorae alopecuroidis, isolated 27 kinds of sophoridine, matrine, sophocarpine etc. so far.1972, the good equality of the island of Japan found that matrine wherein has active anticancer (" Medical Biology " Japanese 1972 84,65 phases) to animal-transplanted tumor.1984, people such as LI XUEMEI reported that sophocarpine has inhibitory action to animal tumor.But these several alkaloidal active anticancers are lower, and the content in Herba Sophorae alopecuroidis is also low, the extraction cost height.
The objective of the invention is to overcome the deficiency of above-mentioned prior art and a kind of new type anticancer medicine that extracts active ingredient from Chinese medicine is provided, require its active anticancer high and to produce cost lower.
The object of the present invention is achieved like this: a kind of to curative effect height such as choriocarcinoma, malignant mole, pulmonary carcinoma, digestive tract cancer, cancer therapy drug that toxicity is low, it is characterized in that the sophoridine that will extract mixes with pharmaceutical carrier and additive as active ingredient from the Chinese medicine Herba Sophorae alopecuroidis, make injection, tablet, capsule.
The preparation method of described anticarcinogen comprises the steps:
(1) get the Herba Sophorae alopecuroidis aerial parts, pulverize and be coarse powder, moistening with 1% sulfuric acid solution, soaked diafiltration routinely, the inventory of collecting 11 times of percolates 12 hours.
(2) ion exchange, alkalization, eluting, once change salt.
Percolate is filtered, and filtrate is adsorbed by styrene sulfonic acid h type resin post, gets saturated resin, resin is washed till colourless with distilled water, bleed off water, continue, put clean alkali liquor with 8% soaking with sodium hydroxide 4 hours, the alkali liquor methylbenzene extraction, resin merges with 70 ℃ of eluting of toluene, extract and eluent, again through 10% sulphuric acid extraction, promptly once change salt 10% sulphuric acid extraction, promptly once change salt;
(3) free, extraction, secondary change salt
Get and once change the total alkali of salt saline solution, add concentrated sodium hydroxide and transfer to PH111～12, with the toluene extraction, toluene extract (mobile phase) carries out extraction separation through 5% hydrochloric acid (immobile phase) with countercurrent distribution, obtains the alkaloid neutralizer through thin layer chromatography evaluation, merging;
(4) dissociate, extract, change salt three times.
Get the alkaloid neutralizer, it is free to add concentrated sodium hydroxide, with 60～90 ℃ of Petroleum ether extraction aloperines (otherwise processed), alkali liquor methylbenzene extraction then, methylbenzene extraction liquid separates through countercurrent distribution, promptly change salt (with 5% hydrochloric acid is immobile phase, and toluene is mobile phase) alkaloid neutralizer again for three times;
(5) free, extraction, coarse crystallization
Get the alkaloid neutralizer, it is free to add concentrated sodium hydroxide, and alkali liquor discards, and educt adds anhydrous sodium sulfate dehydration with 60～90 ℃ of petroleum ether extractiones of oily, adds the neutral alumina decolouring, reclaims small size, and cooling makes it crystallization, and the mother solution branch draws the sophoridine of coarse crystallization.
(6) dissolving, dehydration, decolouring, sucking filtration, refining
Get the sophoridine coarse crystallization, use 30-60 ℃ of petroleum ether dissolution, add and anhydrous sodium sulfate dehydration, the neutral alumina decolouring, the buchner funnel sucking filtration reclaims filtrate to small size, and cooling makes its crystallization, and mother solution is told, and gets the pure crystallization of sophoridine.Yield 0.45%.
(7) get sophoridine 12.5 gram and add about 600 milliliters of injection water, stirring and dissolving adds the hydrochloric acid solution (1 More/liter) of amount of calculation gradually, adds injection and is diluted with water to 1000 milliliters, stir evenly, filter to solution clarification, fill, sealing by fusing was sterilized 30 minutes, and system is carried injection.
The present invention can also make oral and capsule, and its method is as follows:
Make the method for oral tablet:
Get sophoridine 25 grams, add mixed with excipients, be pressed into tablet, every contains 25 milligrams of sophoridine.
Make capsular method:
Get sophoridine 25 grams, add mixed with excipients, incapsulate, every capsule contains 25 milligrams of sophoridine.
Anticancer pharmacology medicineization and clinical experiment that the present invention makes are as follows:
(1) to the anticancer experiment of animal
1, to the curative effect (in vivo test) of animal-transplanted tumor:
Laboratory animal hybrid and mouse inbred lines C57BL/6, DBA, 615, and animal tumor strain mice LLC, U14, S180, EAC, leukemia L1210, L615 is provided by Shanghai Pharmaceutical Inst., Chinese Academy of Sciences or Chinese Academy of Medical Sciences's institute.
Anticancer experiment reaches 1989 Nanning conference methods and carries out according to " national screening anticancer medicine rules " (1978), establishes 10.15.20mg/kg(30, and 45,60mg/m
2High, normal, basic three dosage (ip, ig).
To mouse entity tumor lewis lung tumor (LLC), U14, the cancer suppressing ratio of S180 etc. are 30-60%(P ∠ 0.05-0.01), the show dose relation.Increase in life span to ehrlich carcinoma EC oral administration is 25-50%(P＜0.05), to S-180(A) increase in life span be 26-38%(P＜0.05).But it is invalid to L1210.In used tumor spectrum, better to the effect of solid tumor, wherein better with LLC car U14 effect.
Compare with known anticarcinogen cyclophosphamide, body weight does not descend in the sophoridine administration process, and animal is not dead, toxicity low (see Table 1, table 2)
Compare with matrine, oxymatrine in the Herba Sophorae alopecuroidis, consumption is few and cancer suppressing ratio is high.(table 3)
2, to EC cancerous cell concentration, sum, the influence of doubling time
Ip in mice EC1 * 10
724h divides matched group and administration group, ip * 8d at random behind/the 0.2ml.
The result: 0-3d cancerous cell quantity is the growth of index sample behind the inoculation cancerous cell, and growth curve gradually departs from logarithm value behind the 3d; The 4-7d doubling time is: sophoridine 53h, and sophocarpine 59h, cyclophosphamide 70h, and matched group is 36h; Extract d3 cancerous cell liquid counting cancerous cell concentration, sum obviously reduces, and the cancerous cell caryomitosis descends.Above presentation of results sophoridine has inhibitory action to EC.
3, external to cancerous cell killing experiments (trypan blue staining)
Sophoridine dilution back adds 3 * 10
6/ 0.1mlEAC ascites cells is put in 37 ℃ of water-baths and is hatched, and counting cancerous cell indigo plant is dyed rate.The result proves: the indigo plant of the sophoridine group rate of dying increases with drug level and prolongs action time and increases, and cancerous cell enlargement distortion, karyopyknosis, dissolving, even disappear alleviate but change with the drug level reduction.
4, to the influence of animal-transplanted tumor and normal structure amplifying nucleic acid content
(1) sophoridine influences administration behind 40 inoculations of mice oncocyte 24h to mice U14 and S180 tumor tissues and normal mouse spleen tissue core acid content, press literature method and extracts nucleic acid, press diphenylamines method survey RNA, orcin method survey DNA.The result proves that spleen tissue core acid content: RNA descends 36% behind the normal mouse ig sophoridine, and DNA descends 19%; S180 and U14 be tumor tissues nucleic acid suppression ratio after the sophoridine treatment: U14, DNA28.4%, RNA14.1%; S180DNA50.8%, RNA55.6%, only take temperature from containing (P＞0.05), and sophoridine is not obvious to the nucleic acid metabolism influence.
(2) micro-spectral degree method is measured the influence of sophoridine to oncocyte DNA
EAC, the S-180 of treatment, with content decline 26.6-40%(P＞0.05 of U14 oncocyte DNA), the oncocyte nuclear fluorescence is dim before the treatment, karyon is more loose, nuclear morphology is irregular slightly.
(2) clinical experiment
With this anticancer drug therapy malignant trophoblastic disease (choriocarcinoma malignant mole) 20 examples certain curative effect is arranged through Jiangxi Province's health care of women institute.In 20 examples, clinical cure 15 examples, effective 3 examples, invalid 2 examples, total effective percentage reaches 90%(and sees Table 4).Not because of side effect drug withdrawal and bad complication, most patient appetite increases after the medication among the 20 routine patients.
Also effective in cure and have no side effect to pulmonary carcinoma and digestive tract tumor.
6, general pharmacology experiment:
Show that through zoopery and clinical trial this anticarcinogen does not all have tangible influence to nervous system, blood pressure, heart rate, electrocardiogram, breathing and the body's immunological function of animal.
7, toxicological experiment:
Show that through mutagenicity test and tertogenicity test this anticarcinogen does not have mutagenesis and teratogenesis.
Show that in vivo toxicity is low and do not have the savings phenomenon through acute toxicity test and long term toxicity test and clinic trial result.
More than experiment shows that the anticarcinogen that the present invention makes has active anticancer to multiple animal-transplanted tumor, clinical choriocarcinoma malignant mole, pulmonary carcinoma, digestive tract cancer antitumaous effect is obviously stablized.Its toxicity is low, does not reduce the body cell immunologic function, and no mutagenesis and do not have teratogenesis does not have the phenomenon of accumulating in vivo, with clinical anticancer chemotherapeutic agent commonly used at present tangible advantage is arranged relatively.The Herba Sophorae alopecuroidis resource is very abundant.Sophoridine is the alkaloid that wherein content is the highest (0.45%), and than matrine, sophocarpine height, it is lower that anticancer effective dose then is lower than matrine, sophocarpine, extraction cost, is a kind of of great value PTS.
Claims (4)
1, a kind of to curative effect height such as choriocarcinoma, malignant mole, pulmonary carcinoma, digestive tract cancer, cancer therapy drug that toxicity is low, its feature: be that the sophoridine that will extract from the Chinese medicine Herba Sophorae alopecuroidis mixes with pharmaceutical carrier and additive as active ingredient, make injection, oral tablet and capsule.
2, the preparation method of anticarcinogen according to claim 1 is characterized in that it may further comprise the steps:
(1) gets the Herba Sophorae alopecuroidis aerial parts, pulverize and be coarse powder,, immersion moistening, diafiltration with 1% sulfuric acid solution;
(2) percolate is adsorbed by styrene sulfonic acid h type resin post, get saturated resin, resin is washed with distilled water, continue with the alkalization of 8% soaking with sodium hydroxide, put clean alkali liquor, the alkali liquor methylbenzene extraction, resin is with 70 ℃ of toluene eluting, extract and eluent merge, and again through 10% sulphuric acid extraction, promptly once change salt;
(3) get and once change the total alkali of salt saline solution, add concentrated sodium hydroxide and transfer to PH11～12, with the toluene extraction, toluene extract (mobile phase) carries out extraction separation through 5% hydrochloric acid (immobile phase) with countercurrent distribution, identifies, merges the alkaloid neutralizer through thin layer chromatography;
(4) get the alkaloid neutralizer, it is free to add concentrated sodium hydroxide, with 60～90 ℃ of Petroleum ether extraction aloperines, alkali liquor methylbenzene extraction then, methylbenzene extraction liquid separates through countercurrent distribution, promptly changes salt (with 5% hydrochloric acid is immobile phase, and toluene is mobile phase) alkaloid neutralizer again for three times;
(5) get the alkaloid neutralizer, add concentrated sodium hydroxide and dissociate, educt adds anhydrous sodium sulfate dehydration with 60～90 ℃ of petroleum ether extractiones, adds the neutral alumina decolouring, reclaims small size, and cooling makes it crystallization, and mother solution is told, and gets the sophoridine of coarse crystallization;
(6) get the sophoridine coarse crystallization,, add anhydrous sodium sulfate dehydration with 30～60 ℃ of petroleum ether dissolutions, the neutral alumina decolouring, the buchner funnel sucking filtration, other receives filtrate to small size, and cooling makes its crystallization, and mother solution is told, and proposes the pure crystallization of sophoridine;
(7) get sophoridine 12.5 gram and add about 600 milliliters of injection water, stirring and dissolving adds the hydrochloric acid solution (1 More/liter) of amount of calculation gradually, adds injection and is diluted with water to 1000 milliliters, stir evenly, filter to solution clarification, fill, sealing by fusing was sterilized 30 minutes, made injection.
3, the preparation method of anticarcinogen according to claim 2 is characterized in that getting sophoridine 25 grams, adds mixed with excipients, is pressed into tablet, and every contains 25 milligrams of sophoridine.
4, the preparation method of anticarcinogen according to claim 2 is characterized in that getting sophoridine 25 grams, adds mixed with excipients, incapsulates 25 milligrams of every capsule sophoridine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN93100881A CN1052405C (en) | 1993-01-18 | 1993-01-18 | Anti-cancer medicine and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN93100881A CN1052405C (en) | 1993-01-18 | 1993-01-18 | Anti-cancer medicine and preparation method thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 99124918 Division CN1295076A (en) | 1999-12-01 | 1999-12-01 | Sophorine extracting process |
Publications (2)
| Publication Number | Publication Date |
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| CN1089846A true CN1089846A (en) | 1994-07-27 |
| CN1052405C CN1052405C (en) | 2000-05-17 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN93100881A Expired - Fee Related CN1052405C (en) | 1993-01-18 | 1993-01-18 | Anti-cancer medicine and preparation method thereof |
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Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002102379A1 (en) * | 2001-06-14 | 2002-12-27 | Tonghua Fangda Pharmaceuticals, Ltd. | Sophoridine and use thereof as an analgesic |
| CN1110339C (en) * | 2000-06-19 | 2003-06-04 | 宁夏药物研究所 | Process for preparing total allooerine liquid |
| CN1111532C (en) * | 2000-11-25 | 2003-06-18 | 宁夏药物研究所 | The preparation technology of sophocarpine |
| WO2004087186A1 (en) * | 2003-04-03 | 2004-10-14 | Medigreen Biotechnology Corporation | Composition and method for supporting cancer treatments |
| CN1305471C (en) * | 2005-04-20 | 2007-03-21 | 刘平 | Use of sophoridine oxide in preparing anticancer medicine |
| CN1325496C (en) * | 2000-11-18 | 2007-07-11 | 宁夏药物研究所（有限公司） | Preparation process of sophora alopecuroides series alkaloid salts substances |
| CN1325495C (en) * | 2000-11-18 | 2007-07-11 | 宁夏药物研究所（有限公司） | Preparation process of sophoridine |
| CN100335075C (en) * | 2004-01-02 | 2007-09-05 | 中国科学院新疆理化技术研究所 | Method for extracting effective component from sophora alopecuroide for reducing blood fat and its medicinal use |
| CN100390171C (en) * | 2004-02-10 | 2008-05-28 | 上海佳谷药业有限公司 | Method for extracting dophoridine from residual solution of matrine extracting solution from fenugreek |
| CN102659784A (en) * | 2012-05-11 | 2012-09-12 | 宁夏紫荆花制药有限公司 | Method for preparing high-purity aloperine |
| CN104937069A (en) * | 2013-01-25 | 2015-09-23 | 温特沙尔控股有限公司 | Method for recovering oil |
| CN106389546A (en) * | 2016-10-18 | 2017-02-15 | 漯河医学高等专科学校 | Traditional Chinese medicine for postoperative treatment of colorectal cancer and preparation method of traditional Chinese medicine |
| CN107488187A (en) * | 2017-03-21 | 2017-12-19 | 南方医科大学 | Applications of the Sophora alopecuroide alkali dimer A ~ D in anti-inflammatory or anti-tumor medicinal preparation is prepared |
| CN113288896A (en) * | 2021-05-28 | 2021-08-24 | 成都中医药大学 | Application of sophoridine in preparation of anti-herpes virus medicine |
-
1993
- 1993-01-18 CN CN93100881A patent/CN1052405C/en not_active Expired - Fee Related
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1110339C (en) * | 2000-06-19 | 2003-06-04 | 宁夏药物研究所 | Process for preparing total allooerine liquid |
| CN1325496C (en) * | 2000-11-18 | 2007-07-11 | 宁夏药物研究所（有限公司） | Preparation process of sophora alopecuroides series alkaloid salts substances |
| CN1325495C (en) * | 2000-11-18 | 2007-07-11 | 宁夏药物研究所（有限公司） | Preparation process of sophoridine |
| CN1111532C (en) * | 2000-11-25 | 2003-06-18 | 宁夏药物研究所 | The preparation technology of sophocarpine |
| WO2002102379A1 (en) * | 2001-06-14 | 2002-12-27 | Tonghua Fangda Pharmaceuticals, Ltd. | Sophoridine and use thereof as an analgesic |
| WO2004087186A1 (en) * | 2003-04-03 | 2004-10-14 | Medigreen Biotechnology Corporation | Composition and method for supporting cancer treatments |
| CN100335075C (en) * | 2004-01-02 | 2007-09-05 | 中国科学院新疆理化技术研究所 | Method for extracting effective component from sophora alopecuroide for reducing blood fat and its medicinal use |
| CN100390171C (en) * | 2004-02-10 | 2008-05-28 | 上海佳谷药业有限公司 | Method for extracting dophoridine from residual solution of matrine extracting solution from fenugreek |
| CN1305471C (en) * | 2005-04-20 | 2007-03-21 | 刘平 | Use of sophoridine oxide in preparing anticancer medicine |
| CN102659784A (en) * | 2012-05-11 | 2012-09-12 | 宁夏紫荆花制药有限公司 | Method for preparing high-purity aloperine |
| CN104937069A (en) * | 2013-01-25 | 2015-09-23 | 温特沙尔控股有限公司 | Method for recovering oil |
| CN106389546A (en) * | 2016-10-18 | 2017-02-15 | 漯河医学高等专科学校 | Traditional Chinese medicine for postoperative treatment of colorectal cancer and preparation method of traditional Chinese medicine |
| CN107488187A (en) * | 2017-03-21 | 2017-12-19 | 南方医科大学 | Applications of the Sophora alopecuroide alkali dimer A ~ D in anti-inflammatory or anti-tumor medicinal preparation is prepared |
| CN113288896A (en) * | 2021-05-28 | 2021-08-24 | 成都中医药大学 | Application of sophoridine in preparation of anti-herpes virus medicine |
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| Publication number | Publication date |
|---|---|
| CN1052405C (en) | 2000-05-17 |
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