CN1417208A - Prepn and application in preparing cancer-treating medicine of mistletoe alkaloid - Google Patents
Prepn and application in preparing cancer-treating medicine of mistletoe alkaloid Download PDFInfo
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- CN1417208A CN1417208A CN 02148404 CN02148404A CN1417208A CN 1417208 A CN1417208 A CN 1417208A CN 02148404 CN02148404 CN 02148404 CN 02148404 A CN02148404 A CN 02148404A CN 1417208 A CN1417208 A CN 1417208A
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Abstract
The present invention relates to an anticarcinogen prepared through extraction from mistletoe. The extraction process of mistletoe alkaloid includes the steps of: drying and crushing raw material, ethanol reflux extraction, reduced pressure recovering ethanol in extractive liquid, concentration to obtain extract, hydrochloric acid dissolution of alkaloid, still standing, extracting supernatant liquid, sucking filtering, adding dropwise concentrated ammonia water to free alkaloid, chloroform extraction, water washing chloroform liquid, drying with anhydrous sodium sulfate, recovering chloroform, and still standing to separate mistletoe alkaloid crystal. The medicine mistletoe alkaloid has obvious inhibiting effect on liver cancer, stomach cancer oesophagus cancer and mammary cancer, and has high anticancer activity, wide anticancer spectrum and less toxicity.
Description
One, technical field:
The present invention relates to a kind of method for making and application thereof of cancer therapy drug, specifically is alkaloid and the application aspect the medicine of preparation treatment cancer thereof that raw material extracts with the herbal medicine.
Two, background technology:
Cancer is the formidable enemy of harm humans health.The annual New Development cases of cancer of China has 1,600,000 people approximately, and that dies from cancer every year has 1,300,000 people approximately.Rise year by year because of the dead number of cancer in the whole nation.China is cancer districts occurred frequently such as liver cancer, cancer of the stomach, the esophageal carcinoma, mammary cancer, lung cancer, and cancer mortality is high.
Still there are not the most of cancer patientss of effective cured substance at present.Though chemotherapeutics has certain curative effect to cancer, toxic side effect is big.Chinese patent medicine is generally lower to the curative effect of cancer, is 3.5% as ginseng lotus capsule to the cancer kitchen range remission rate of lung cancer of the stomach, and curative effect is also undesirable.
Mistletoe is the Loranthaceae mistletoe.China's Viscum distribution 11 kinds and 1 mutation, medicinal part is dry stem and branch with leaf.Mistletoe is a traditional Chinese medicine simply, and its property is flat, and bitter has functions such as strengthening the bones and muscles, antiabortive, wind-damp dispelling, beneficial blood, invigorating the liver and kidney.At present, the extract of existing bibliographical information vicum album and Korea's mistletoe has anti-tumor activity.Domestic report adopts total alkaloids that dilute acetic acid extraction or dilute hydrochloric acid extraction extract from mistletoe Viscum coloratum (Kom.) Nakai 50, during 75mg/kg to mice transplanted tumor S
180, S
37, EAC, ARS and L
1210Leukemia all has obvious restraining effect ((1) Wang Qingduan, Liu Meijun, Wang Dongyang etc., the antitumor action CHINA JOURNAL OF CHINESE MATERIA MEDICA of mistletoe total alkaloids, 1994,19 (1) 45; (2) Hu Jiahui, Zhang Yongzhong, Guo Shanli etc., antitumor and anti-inflammatory action research teachers college, Liaocheng journal of mistletoe total alkali, 2001,14 (2) 64; (3) Chen Shiwei, Li Junfeng, Hu Jiahui etc., the extraction purifying of Gums,Phoradendron californicum and antitumor research Shandong Traditional Chinese Medicine University journal, 2001,25 (5) 373), 50, the tumour inhibiting rate to Lewis lung cancer during 75mg/kg is 59.0% and 65.2%, and transfer has restraining effect (1) to the Lewis lung cancer lung.
Three, summary of the invention
1, goal of the invention: the purpose of this invention is to provide a kind of high-efficiency low-toxicity, the wide cancer therapy drug of anticancer spectrum, is the alkaloid that extracts of raw material and in the application aspect the medicine of preparation treatment liver cancer, cancer of the stomach, the esophageal carcinoma, mammary cancer with Herba Visci, Visc, mistletoe specifically.
2, technical scheme: also do not have the bibliographical information Gums,Phoradendron californicum to be used for treatment for cancer such as anti-liver cancer, cancer of the stomach, the esophageal carcinoma, mammary cancer at present through data consultation.The alkaloid (Gums,Phoradendron californicum) that the present invention extracts from Herba Visci Viscum album L.var.meridianum Danser, Visc Viscum articulatum Burm.f., mistletoe Viscum coloratum (Kom.) Nakai, the step of extraction is:
1. with Herba Visci, or Visc, or the stem and branch with leaf of mistletoe, behind natural air drying, pulverize.2. added 6～10 times of refluxing extraction of 70%-95% ethanol 3～5 hours with the mistletoe meal 2-5kg after pulverizing, the ethanol in the reclaim under reduced pressure extracting solution is concentrated into medicinal extract.3. add 1%～2% hydrochloric acid, 700～1000ml, fully stir and make the alkaloid dissolving, leave standstill, inclining supernatant liquor, suction filtration, and filtrate places the 1000ml separating funnel, drips strong aqua and transfers to PH9, makes alkaloid free.4. add chloroform 150-300ml, shaking out divides and to get chloroform layer, and upper strata alkaline water liquid is again with chloroform extraction 4～8 times.5. combined chloroform liquid is washed, and with reclaiming chloroform behind the anhydrous sodium sulfate drying, leaves standstill, and separates out crystallization and is Gums,Phoradendron californicum.
The present invention relates to the application of anticarcinogen Gums,Phoradendron californicum aspect the medicine of preparation treatment liver cancer.
Experimental technique is to get the liver cancer H of inoculation after 7 days
22Ascites, the suspension that is diluted to 1:3 with physiological saline is standby.With liver cancer H
22It is subcutaneous that suspension is inoculated in mouse right fore armpit with 0.2ml/ amount only, after 24 hours vaccinated mouse is divided into 5 groups at random, 10 every group, establishes control group, 5-FU group, the big small dose group of Gums,Phoradendron californicum.The Gums,Phoradendron californicum group is given mouse stomach administration 1 time every day; The 5-FU group is intraperitoneal injection, every day 1 time, each 0.2ml/20g body weight; Control group is irritated stomach equivalent 1%CMC-Na liquid every day.Each organizes equal successive administration 7 days.Drew neck to put to death in 1～3 day after the mouse drug withdrawal, strip the knurl piece and weigh, by " tumour inhibiting rate=(1-T/C) * 100% " formula calculating tumour inhibiting rate.
When experimental result shows that consumption when Gums,Phoradendron californicum is at 60mg/kg-120mg/kg, to the inhibitory rate 41.5%～68.9% of rat liver cancer cell.
The present invention relates to the application of anticarcinogen Gums,Phoradendron californicum aspect the medicine of preparation treatment cancer of the stomach.
Experimental technique is under aseptic condition, gets the lotus knurl mouse of going down to posterity, the sterilization skin of abdomen, with aseptic empty syringe pump ascites, do 1: 2 times dilution with stroke-physiological saline solution, get 50 of female mices, every mouse inoculation 0.2ml, the inoculation back is divided into 5 groups, 10 every group next day at random, 3 dosage gastric infusions by size, every day 1 time, 10d writes down the mouse survival time continuously, calculate increase in life span, experiment repeats 3 times.
Experimental result shows when the consumption of Gums,Phoradendron californicum during at 60mg/kg～120mg/kg, to the inhibitory rate 33.6%～71.9% of Mouse Gastric Cancer cell
The present invention relates to the application of anticarcinogen Gums,Phoradendron californicum aspect the medicine of preparation treatment mammary cancer.
Experimental technique is to adopt mtt assay to measure Gums,Phoradendron californicum to the effect of human breast cancer cell growth-inhibiting.The breast cancer cell of taking the logarithm vegetative period is adjusted to 1 * 10
5/ ml, 0.2ml are inoculated on 96 orifice plates, put 37 ℃, 5%CO
2Abandon original fluid after cultivating 24h, add and contain each 0.2ml of different concns Gums,Phoradendron californicum nutrient solution (establishing 0.125mg/ml, 0.0625mg/ml, a 0.03125mg/ml3 concentration), each concentration is established 9 multiple holes (dividing 3 repetitions), and establishes no medicine (ethanol that contains compounding pharmaceutical) nutrient solution and blank hole (making 3 plates simultaneously).Supernatant liquor is removed in effect 24h hypsokinesis, and each hole adds MTT0.1ml, inhales behind 37 ℃ of 4h and removes supernatant liquor, adds DMSO0.1ml in each hole, goes up microplate reader 570nm place behind the 30min and surveys the OD value.Inhibiting rate (%)=(control wells OD value-experimental group OD value)/control wells OD value * 100%.
Experimental result shows the rising with Gums,Phoradendron californicum concentration, and the inhibiting rate of breast cancer cell is also raise.Growth all has obvious restraining effect to breast cancer cell at the above dosage of 0.03125mg/ml.
The invention still further relates to the application of anticarcinogen Gums,Phoradendron californicum aspect the medicine of the preparation treatment esophageal carcinoma.
Experimental technique is to adopt mtt assay to measure Gums,Phoradendron californicum to the effect of esophageal cancer cell growth-inhibiting.The esophageal cancer cell of taking the logarithm vegetative period is adjusted to 1 * 10
5/ ml, 0.2ml are inoculated on 96 orifice plates, put 37 ℃, 5%CO
2Abandon original fluid after cultivating 24h, add and contain each 0.2ml of different concns Gums,Phoradendron californicum nutrient solution (establishing 0.125mg/ml, 0.0625mg/ml, a 0.03125mg/ml3 concentration), each concentration is established 9 multiple holes (dividing 3 repetitions), and establishes no medicine (ethanol that contains compounding pharmaceutical) nutrient solution and blank hole (making 3 plates simultaneously).Supernatant liquor is removed in effect 24h hypsokinesis, and each hole adds MTT0.1ml, inhales behind 37 ℃ of 4h and removes supernatant liquor, adds DMSO0.1ml in each hole, goes up microplate reader 570nm place behind the 30min and surveys the OD value.Inhibiting rate (%)=(control wells OD value-experimental group OD value)/control wells OD value * 100%.
Experimental result shows, with the rising of Gums,Phoradendron californicum concentration, the inhibiting rate of esophageal cancer cell also raise, and growth all has obvious restraining effect to esophageal cancer cell at the above dosage of 0.03125mg/ml.
3, beneficial effect: medicine of the present invention-individual important feature is the antitumour activity height, and anticancer spectrum is wide, and toxicity is low.
Medicine of the present invention shows that through anticancer pharmacological research and zooperal result following advantage is arranged:
1. cancer is active high.Consumption is when 60mg/kg～120mg/kg, to rat liver cancer H
22Inhibitory rate 41.5%～68.9%, mouse is transplanted the inhibitory rate 33.6%～71.9% of cancer of the stomach.
2. anticancer spectrum is wide.Liver cancer, cancer of the stomach, the esophageal carcinoma, mammary cancer all there is the obvious suppression effect.
3. toxicity is low.In the anticancer in animal body experiment, do not find that it has tangible toxic side effects.
4. the medicine material source is abundant, and extraction process is simple.
Four, embodiment:
Embodiment 1:
The stem and branch with leaf of Herba Visci is pulverized behind natural air drying.Mistletoe meal 5kg after the pulverizing was with 10 times of refluxing extraction of 95% ethanol 5 hours, and the ethanol in the reclaim under reduced pressure extracting solution is concentrated into medicinal extract.Add 2% hydrochloric acid 1000ml, fully stir and make the alkaloid dissolving, leave standstill, inclining supernatant liquor, suction filtration, and filtrate places the 1000ml separating funnel, drips strong aqua and transfers to PH9, makes alkaloid free.Add chloroform 300ml, shaking out divides and gets chloroform layer, and upper strata alkaline water liquid is again with chloroform extraction 8 times.Combined chloroform liquid, washing with reclaiming chloroform behind the anhydrous sodium sulfate drying, is left standstill, and separates out crystallization and is Gums,Phoradendron californicum.
Embodiment 2:
The stem and branch with leaf of Herba Visci is pulverized behind natural air drying.Mistletoe meal 2kg after the pulverizing was with 6 times of refluxing extraction of 70% ethanol 3 hours, and the ethanol in the reclaim under reduced pressure extracting solution is concentrated into medicinal extract.Add 1% hydrochloric acid 700ml, fully stir and make the alkaloid dissolving, leave standstill, inclining supernatant liquor, suction filtration, and filtrate places the 1000ml separating funnel, drips strong aqua and transfers to PH9, makes alkaloid free.Add chloroform 150ml, shaking out divides and gets chloroform layer, and upper strata alkaline water liquid is again with chloroform extraction 4 times.Combined chloroform liquid, washing with reclaiming chloroform behind the anhydrous sodium sulfate drying, is left standstill, and separates out crystallization and is Gums,Phoradendron californicum.。
Embodiment 3:
Stem and branch with leaf with Visc is a raw material, and extracting method is identical with embodiment 1 with step.
Embodiment 4:
Stem and branch with leaf with mistletoe is a raw material, and extracting method is identical with embodiment 2 with step.
Embodiment 5:
Gums,Phoradendron californicum is to rat liver cancer H
22Restraining effect.
1, experiment material:
Knurl strain: liver cancer H
22, the Shanghai zooscopy provides.Laboratory animal: Kunming mouse, male and female half and half, body weight 18g～22g, Nanjing University of Traditional Chinese Medicine's Experimental Animal Center provides.The contrast medicine: 5 FU 5 fluorouracil (5-FU), lot number: 010104, Shanghai Xudong Hipu Medicine Co., Ltd produces.
2, experimental technique:
Get the liver cancer H of inoculation after 7 days
22Ascites, the suspension that is diluted to 1: 3 with physiological saline is standby.With liver cancer H
22It is subcutaneous that suspension is inoculated in mouse right fore armpit with 0.2ml/ amount only, after 24 hours vaccinated mouse is divided into 5 groups at random, 10 every group, establishes control group, 5-FU group, the big small dose group of Gums,Phoradendron californicum.The Gums,Phoradendron californicum group is given mouse stomach administration 1 time every day; The 5-FU group is intraperitoneal injection, every day 1 time, each 0.2ml/20g body weight; Control group is irritated stomach equivalent 1%CMC-Na liquid every day.Each organizes equal successive administration 7 days.Drew neck to put to death in 1～3 day after the mouse drug withdrawal, strip the knurl piece and weigh, by " tumour inhibiting rate=(1-T/C) * 100% " formula calculating tumour inhibiting rate.
3, experimental result: see Table 1.
Table 1 Gums,Phoradendron californicum is to rat liver cancer H
22The influence of knurl bulk-growth
Dosage number of animals the weight of animals (g) knurl body weight (g) tumour inhibiting rate group (mg/kg * (beginning/knot (beginning/end) (X ± SD) (%)
D) control group 10/10 19.6/26.1 1.29 ± 0.335-FU 20 * 7 10/9 19.9/21.7 0.38 ± 0.29** 70.54 Gums,Phoradendron californicums 120 * 7 10/10 20.0/21.6,0.35 ± 0.42** 72.87 bundle)
90×7 10/10 20.4/26.8 0.49±0.31** 62.02
60 * 7 10/10 20.7/26.2 0.73 ± 0.36**, 43.41 control groups, 10/10 19.5/26.9,1.30 ± 0.415-FU, 20 * 7 10/10 20.3/21.6 0.41 ± 0.23**, 68.46 Gums,Phoradendron californicums 120 * 7 10/9 20.0/26.8,0.34 ± 0.36** 73.85
90×7 10/10 19.9/27.1 0.51±0.33** 60.77
60 * 7 10/10 20.1/26.5 0.76 ± 0.33* 41.54 annotate:
*P＜0.05,
*Compare with control group P＜0.01
The control group medication is a 5 FU 5 fluorouracil in the experiment, and its toxic side effect has: bone marrow depression; Gastrointestinal reaction; Nervous system damage; Liver and kidney dysfunction.
Embodiment 6:
Gums,Phoradendron californicum is transplanted the restraining effect of cancer of the stomach to mouse.
1, experiment material:
Laboratory animal: Kunming mouse, male and female half and half, body weight 18g～22g, Nanjing University of Traditional Chinese Medicine's Experimental Animal Center provides.The contrast medicine: endoxan, produce lot number: 010304 by Hualian Pharmaceutical Co., Ltd., Shanghai.The knurl strain: the strain of cancer of the stomach knurl is available from province tumour hospital institute of oncology.
2, experimental technique:
Under aseptic condition, get the lotus knurl mouse of going down to posterity, the sterilization skin of abdomen, with aseptic empty syringe pump ascites, do 1: 2 times dilution with stroke-physiological saline solution, get 50 of female mices, every mouse inoculation 0.2ml, the inoculation back is divided into 5 groups, 10 every group next day at random, 3 dosage gastric infusions by size, every day 1 time, 10d writes down the mouse survival time continuously, calculate increase in life span, experiment repeats 3 times.
3, experimental result: see Table 2
Table 2 Gums,Phoradendron californicum is transplanted restraining effect (X soil S) the group dosage n survival time increase in life span of cancer of the stomach to mouse
(mg/kg) (d) % lotus knurl control group 10 11.2 ± 2.90 endoxan 50 10 15.9 ± 3.01** 41.96 Gums,Phoradendron californicums 120 10 18.9 ± 2.57** 68.75
90 10 17.0±2.23** 51.79
60 10 15.4 ± 2.16*, 37.50 lotus knurl control groups, 10 10.7 ± 2.10 endoxan, 50 10 16.3 ± 2.90**, 52.34 Gums,Phoradendron californicums, 120 10 18.4 ± 2.65** 71.96
90 10 16.6±2.47** 55.14
60 10 14.3 ± 2.83*, 33.64 lotus knurl control groups, 10 11.8 ± 1.90 endoxan, 50 10 15.9 ± 2.57*, 34.75 Gums,Phoradendron californicums, 120 10 18.3 ± 2.80** 55.08
90 10 16.7±2.07** 41.52
60 10 14.8 ± 2.28 25.42 annotate:
*P＜0.05,
*Compare with control group P＜0.01
The control group medication is an endoxan in the experiment, and its toxic side effect has: bone marrow depression; Gastrointestinal reaction; Hemorrhagic cystitis; Hepar damnification.
Embodiment 7:
Gums,Phoradendron californicum is to the restraining effect of human breast cancer cell.
1, experiment material:
The knurl strain: human breast carcinoma MCF-7 cell strain is available from province tumour hospital institute of oncology.RPMI
1640Nutrient solution (GIBCO company product) includes 10% calf serum, L-glutaminate 2nM, penicillin 100IU/ml and Streptomycin sulphate 100ug/ml.Human breast cancer cell is incubated at RPMI
1640In the nutrient solution, cultivate at 37 ℃, 5%CO
2In the incubator.Compound is the alkaloid that extracts from mistletoe.
2, experimental technique:
Adopt mtt assay to measure Gums,Phoradendron californicum to the effect of breast cancer cell growth-inhibiting.The breast cancer cell of taking the logarithm vegetative period is adjusted to 1 * 10
5/ ml, 0.2ml are inoculated on 96 orifice plates, put 37 ℃, 5%CO
2Abandon original fluid after cultivating 24h, add and contain each 0.2ml of different concns Gums,Phoradendron californicum nutrient solution (establishing 3 concentration), each concentration is established 9 multiple holes (dividing 3 repetitions), and establishes no medicine (ethanol that contains compounding pharmaceutical) nutrient solution and blank hole (making 3 plates simultaneously).
Supernatant liquor is removed in effect 24h hypsokinesis, and each hole adds MTT0.1ml, inhales behind 37 ℃ of 4h and removes supernatant liquor, adds DMSO0.1ml in each hole, goes up microplate reader 570nm place behind the 30min and surveys the OD value.Inhibiting rate (%)=(control wells OD value-experimental group OD value)/control wells OD value * 100%.
3, experimental result:
The result with the rising of Gums,Phoradendron californicum concentration, also raises to the inhibiting rate of breast cancer cell as shown in Table 3.Growth all has obvious restraining effect to breast cancer cell at the above dosage of 0.03125mg/ml.
Table 3 Gums,Phoradendron californicum is to breast cancer cell growth-inhibiting effect (n=9) drug level (mg/ml) OD value (inhibiting rate (%) of A ± S)
0 0.346 ± 0.0210 0.0 Gums,Phoradendron californicums 0.125 0.103 ± 0.017
*70.23
0.0625 0.152±0.015
** 56.07
0.03125 0.198±0.020
* 42.77
Annotate:
*P＜0.05,
*Compare with control group P＜0.01
Embodiment 8:
Gums,Phoradendron californicum is to the restraining effect of esophageal cancer cell.
1, experiment material:
Esophageal cancer cell strain (Eca-109) is provided by microorganism teaching and research room of Nanjing University of Traditional Chinese Medicine.Cell cultures in 199 nutrient solutions, in add 10% calf serum, cultivate at 37 ℃, 5%CO
2In the incubator.Compound is the alkaloid that extracts from mistletoe.
2, experimental technique:
Adopt mtt assay to measure Gums,Phoradendron californicum to the effect of esophageal cancer cell growth-inhibiting.The esophageal cancer cell of taking the logarithm vegetative period is adjusted to 1 * 10
5/ ml, 0.2ml are inoculated on 96 orifice plates, put 37 ℃, 5%CO
2Abandon original fluid after cultivating 24h, add and contain each 0.2ml of different concns Gums,Phoradendron californicum nutrient solution (establishing 3 concentration), each concentration is established 9 multiple holes (dividing 3 repetitions), and establishes no medicine (ethanol that contains compounding pharmaceutical) nutrient solution and blank hole (making 3 plates simultaneously).
Supernatant liquor is removed in effect 24h hypsokinesis, and each hole adds MTT0.1ml, inhales behind 37 ℃ of 4h and removes supernatant liquor, adds DMSO0.1ml in each hole, goes up microplate reader 570nm place behind the 30min and surveys the OD value.Inhibiting rate (%)=(control wells OD value-experimental group OD value)/control wells OD value * 100%.
3, experimental result:
The result with the rising of Gums,Phoradendron californicum concentration, also raises to the inhibiting rate of esophageal cancer cell as shown in Table 4, and growth all has obvious restraining effect to esophageal cancer cell at the above dosage of 0.03125mg/ml.
Table 4 Gums,Phoradendron californicum is to restraining effect (n=9) drug level (mg/ml) the OD value of the esophageal cancer cell growth (inhibiting rate (%) of A ± S)
0 0.349 ± 0.016 0.0 Gums,Phoradendron californicums 0.125 0.115 ± 0.019
*67.05
0.0625 0.187±0.012
** 46.42
0.03125 0.210 ± 0.011
*39.83 annotate:
*P＜0.05,
*Compare with control group P＜0.01
Claims (8)
1, a kind of preparation method of cancer therapy drug Gums,Phoradendron californicum is characterized in that preparation process is:
1. with the stem and branch with leaf of Herba Visci or Visc or mistletoe, behind natural air drying, pulverize;
2. add the ethanol in the alcohol reflux reclaim under reduced pressure extracting solution in the mistletoe meal after pulverizing, be concentrated into medicinal extract;
3. add hydrochloric acid, fully stir and make the alkaloid dissolving, leave standstill, inclining supernatant liquor, and suction filtration places separating funnel with filtrate, drips strong aqua, makes alkaloid free;
4. add the chloroform shaking out, divide and get chloroform layer, the upper strata alkaline aqueous solution is again with chloroform extraction;
5. with chloroform solution, washing, reclaim chloroform with anhydrous sodium sulfate drying, leave standstill, the crystallization of separating out is Gums,Phoradendron californicum.
2, the preparation method of Gums,Phoradendron californicum according to claim 1 is characterized in that the mistletoe meal consumption in 2. is 2-5kg, and alcohol concn is 70%-95%, and consumption is 6-10 a times of mistletoe meal, refluxing extraction 3-5 hour.
3, the preparation method of Gums,Phoradendron californicum according to claim 1, the concentration that it is characterized in that hydrochloric acid in 3. is 1%-2%, consumption is 700-1000ml, drips strong aqua and transfers to PH9.
4, the preparation method of Gums,Phoradendron californicum according to claim 1 is characterized in that adding chloroform 150-300ml in 4., extracts 4-8 time.
5, the application of anticarcinogen Gums,Phoradendron californicum aspect the medicine of preparation treatment liver cancer.
6, the application of anticarcinogen Gums,Phoradendron californicum aspect the medicine of preparation treatment cancer of the stomach.
7, the application of anticarcinogen Gums,Phoradendron californicum aspect the medicine of preparation treatment mammary cancer.
8, the application of anticarcinogen Gums,Phoradendron californicum aspect the medicine of the preparation treatment esophageal carcinoma.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100431557C (en) * | 2005-03-22 | 2008-11-12 | 山西大学 | Medicine for treating and preventing tumour, and its prepn. method |
| CN104415573A (en) * | 2013-09-10 | 2015-03-18 | 中国科学院大连化学物理研究所 | Method for classifying and preparing tertiary amine alkaloid and quaternary ammonium alkaloid from corydalis extract |
-
2002
- 2002-12-02 CN CN 02148404 patent/CN1417208A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100431557C (en) * | 2005-03-22 | 2008-11-12 | 山西大学 | Medicine for treating and preventing tumour, and its prepn. method |
| CN104415573A (en) * | 2013-09-10 | 2015-03-18 | 中国科学院大连化学物理研究所 | Method for classifying and preparing tertiary amine alkaloid and quaternary ammonium alkaloid from corydalis extract |
| CN104415573B (en) * | 2013-09-10 | 2017-03-22 | 中国科学院大连化学物理研究所 | Method for classifying and preparing tertiary amine alkaloid and quaternary ammonium alkaloid from corydalis extract |
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