CN101185661A - Technique for preparing liverwort extract and application of it in preparing medicine for treating liver cancer and hepatitis B - Google Patents
Technique for preparing liverwort extract and application of it in preparing medicine for treating liver cancer and hepatitis B Download PDFInfo
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- CN101185661A CN101185661A CNA2006100313247A CN200610031324A CN101185661A CN 101185661 A CN101185661 A CN 101185661A CN A2006100313247 A CNA2006100313247 A CN A2006100313247A CN 200610031324 A CN200610031324 A CN 200610031324A CN 101185661 A CN101185661 A CN 101185661A
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Abstract
The invention discloses two liverwort extracts: liverwort total flavonoids extract and liverwort terpene extract; the invention proves the liver cancer resistance and hepatitis B resistance effects of the two extract parts, and also discloses the application in preparations of the medicines used for treating hepatitis B and liver cancer. The extract method is shown as follows: liverwort raw material is pulverized and 10-20 folds dissolvent is added; the extraction is performed 2-3 times at 50-100 DEG C, 0.5-1.5 hours per time; the extract solution is filtered and concentrated to dry to obtain liverwort crude extract. The crude extract is extracted respectively by ligroin, acetidin and n-butanol. n -butanol extract is vacuum distilled, recovering solvent, condensed to dry; after dissolved by methanol, the crude extract passes through a chromatographic column (filled with silica gel or diatomite) which is firstly washed with chloroform and then with methanol, or passes through macroporous adsorptive resin column which is firstly washed with water, and then eluted with ethanol; methanol or ethanol is decompressed concentration at 40-50 DEG C; the concentrated solution is dried through vacuum drying, spray drying or freeze drying to get extract with total flavonoids content of 70-90%. Acetidin extract solution is decompressed and distilled, then the solvent is recovered and concentrated to dry; after being dissolved by methanol, the liquid passes through a silica gel chromatographic column which is eluted by dichloromethane; the dichloromethane eluent is decompressed and concentrated at 30-40 DEG C; the concentrated solution is dried through vacuum drying, spray drying or freeze drying to get extract with total terpenes content of 70-90%.
Description
Technical field
The present invention relates to plant extract and medical application thereof, especially the preparation technology of marchantia extract and the application in preparation treatment hepatocarcinoma and hepatitis B medicament thereof belong to the field of Chinese medicines.
Background technology
Marchantia (Marchantineae) belongs to Bryophyta (Bryophyta) Hepaticae (Hepaticae) Marchantiales (Marchantiales).Have another name called: pus crusts grass (Shaanxi), ground Herba Spirodelae, cloud, shuttle spinulose tree fern (Guizhou), Pheretima skin (Tibet), Marchantia polymorpha L. (Bashan Mountain, the Qinling Mountains), Ba Gulong, rice Nori (Shaanxi) (referring to Gao Qian etc. northeast noble liverwort will. Beijing: Science Press, 1981; 192).China's marchantia is except that having marchantia (Marchantia polymorpha L.) distribution, also have Marchantia convoluta (Marchantia convoluta Gao etChang), Marchantia paleacea (Marchantia paleacea Bert.)] and 3 kinds of Marchantia diptera (Marchantia dipteraMont.) etc., they mix and give birth to together, be difficult to distinguish (compile referring to Institute of Botany, Chinese Academy of Sciences. Chinese Higher plant illustrated handbook (first). Beijing: science tech publishing house, 1972; 27).Marchantia is the representative plant of Marchantiales, is that to have in the thallophytic noble liverwort form structure the most complicated, the more high kind of evolving; It is one of modal medical herbs in the bryophyte.The medicinal beginning of marchantia is stated from " Mingyi Bielu ", calls it " stone clothing " in Ming Dynasty's Li Shizhen (1518-1593 A.D.) Compendium of Material Medica, and is lightly seasoned, cool in nature, return Liver Channel, clearing away heat-damp and promoting diuresis is arranged, skin ulcer is held back in detoxifcation, clear away heart-fire the effect that makes eye bright (bright referring to the Notherna barbarin tribes in ancient China, muscology. Higher Education Publishing House, 1987; 2).Marchantia convoluta (Marchantia convoluta Gao Chang) is a Bryophyta Hepaticae marchantia, for Chinese endemic plant (referring to Zhu Hua etc., the former plant thallus of commodity medical material marchantia microstructure feature and retrieval, world health magazine, 2003; 3:110).The chemical constitution study of marchantia has been obtained many progress abroad, but be a blank extraction, separation and the structure identification research of the traditional herbal medicines marchantia effective ingredient of China.Pertinent literature and novelty assessment report show that the foreign scholar has carried out extensive studies to the Marchantiaceae plant of Japan, Germany, South Africa and India, and seldom relates to the marchantia that China produces.Plant studies show that marchantia mainly contains pertinent literature and novelty assessment report shows, the foreign scholar has carried out extensive studies to the Marchantiaceae plant of Japan, Germany, South Africa and India, and seldom relates to the marchantia that China produces.Plant studies show that, marchantia mainly contain flavone compound and volatile oil chemical compound (referring to [1] Xiao Jianbo, etc., reversed phase high-performance liquid chromatography is used for the separation and the mensuration of marchantia flavone compound, assay office, 2005; 4:17; [2] Xiao Jianbo, etc., the CO of volatile oil in the Marchantia convoluta
2Supercritical fluid extraction and GC-MS thereof analyze, new Chinese medicine and clinical pharmacology, 2005; 3:33; [3] Cao Hui, etc., the GC-MS of the different extract parts of Marchantia convoluta analyzes relatively and the part biological activity research. mass spectrum journal, 2005,1:1; [4] Zhu Hua, etc., apigenin-7-O-beta-D-glucuronide in the Marchantia convoluta, research and development of natural products, 2005,1:38 are identified in silica gel column chromatography/RP-HPLC/LC-ESI-MS separation and purification; [5] Zou Dengfeng, etc., the ultraviolet spectral line group method of marchantia, Marchantia convoluta and Marchantia paleacea is differentiated, research and development of natural products, 2005,4:463 and [6] Xiao Jianbo, etc., content of flavonoids is measured in the Marchantia convoluta, research and development of natural products, 2005,2:186).Therapeutical effect about marchantia is not seen relevant report.
Application facet, insight money and other marchantia be not as the patent and the document of medicine.
Hepatocarcinoma is one of global malignant tumor occurred frequently, occupies second of various malignant tumor in China's liver cancer mortality.Hepalobectomy or transplantation of liver that it is early hepatocarcinoma that present hepatocarcinoma has effective radical cure measure, but the concealment of hepatocarcinoma onset make a definite diagnosis chance and few in early days, and the transplantation of liver donor livers are limited, and is costly, is difficult to popularize.Other treatment is worn dehydrated alcohol or acetic acid injection, radio frequency or cold therapy, ultrasonic therapy etc. in the tumor such as transcatheter hepatic arterial chemoembolization, percutaneous liver, all can suppress growth of tumor to a certain extent, but all belongs to palliative therapy.Therefore, oneself made a definite diagnosis back its mean survival time (MST) less than 1 year a lot of liver cancer patients, and the toxic and side effects of postoperative recurrence and transfer, chemotherapeutics, liver failure etc. are the principal elements that influences patient's prognosis and life cycle.Now generally acknowledged, curing the most promising means of hepatocarcinoma is the Comprehensive Treatments that comprise operation, embolism chemical therapeutic, immunity and Biotherapeutics etc., and wherein the Biotherapeutics development in recent years has prospect especially.
Hepatitis B (Hepatitis B) is that (disease of harm humans health in the Hepatitis B virus, a kind of serious world wide that HBV) causes, its infectiousness is strong, sickness rate is high by hepatitis B virus.According to the statistics of WHO, at present, the whole world has 3.5 hundred million chronic viral hepatitis B virus carrier approximately, and wherein the infection rate of HBV can be in any more in the population of China.The chronic asymptomatic HBV carrier (ASC) of China is considerably beyond 1.2 hundred million people.Now suffering from the hepatitis B people is 2,800 ten thousand people, and existing prevalence is about 27,70/,100,000, annual morbidity about 2,30/,100,000.The prevalence rate of chronic hepatitis B (CHB) is 0.1%～1.0%.15%～25% chronic hepatitis B patient will be died from liver cirrhosis and hepatocarcinoma prematurely.HBV infects has become one of topmost infectious disease of the China and even the whole world.
Summary of the invention
The object of the present invention is to provide two kinds of two kinds of marchantia extracts and extractive of general flavone and terpenes extract.
The present invention also aims to confirm that the marchantia extract has the effect of anti-hepatocarcinoma and anti-hepatitis B virus.
The said marchantia extractive of general flavone of the present invention obtains by following method:
With the marchantia raw material pulverizing, add solvent 10-20 and doubly measure, under 50-100 ℃ of condition, extract 2-3 time, each 0.5-1.5 hour, extracting liquid filtering, be concentrated into dried, the marchantia crude extract.Crude extract is used petroleum ether, ethyl acetate and n-butanol extraction successively respectively, and solvent is reclaimed in the butanol extraction liquid distilling under reduced pressure, be concentrated into dried, behind the dissolve with methanol,, wash post with chloroform earlier by chromatographic column (is filler with silica gel or kieselguhr etc.), wash post through methanol again, or, wash the reuse ethanol elution earlier with water by macroporous adsorptive resins, methanol or ethanol liquid is in 40-50 ℃ of concentrating under reduced pressure, and concentrated solution obtains the extract that general flavone content is 70-90% through vacuum drying or spray drying or lyophilization.
The said marchantia terpenes of the present invention extract obtains by following method:
With the marchantia raw material pulverizing, add solvent 10-20 and doubly measure, under 50-100 ℃ of condition, extract 2-3 time, each 0.5-1.5 hour, extracting liquid filtering, be concentrated into dried, the marchantia crude extract.Crude extract is used petroleum ether, ethyl acetate and n-butanol extraction successively respectively, the acetic acid ethyl acetate extract distilling under reduced pressure, reclaim solvent, be concentrated into dried, behind the dissolve with methanol,, use the dichloromethane eluting by silica gel column chromatography, the dichloromethane eluent is in 30-40 ℃ of concentrating under reduced pressure, and concentrated solution obtains the extract that terpene content is 70-90% through vacuum drying or spray drying or lyophilization.
The said marchantia raw material of the present invention is meant and any in the marchantia comprises marchantia (Marchantia polymorpha), Marchantia convoluta (Marchantia convoluta), Marchantia paleacea (Marchantia paleacea) and Marchantia diptera (Marchantia diptera) etc.
With marchantia total flavones or terpenes extract, or contain the compositions of marchantia total flavones or terpenes extract, and can mix by received auxiliary adding ingredient in the pharmacy, preparation process routinely promptly can be made into oral type pharmaceutical preparation or injection-type pharmaceutical preparation.As with oral formulations in can received disintegrating agent, after auxiliary adding ingredient that excipient, lubricant, binding agent, filler etc. are commonly used mixes, promptly may be made in oral solid pharmaceutical formulations such as tablet, capsule, soft capsule, granule and pill according to a conventional method; Mix with the surfactants of using always such as solubilizing agent, emulsifying agent, wetting agent, foaming or defoamer, diluent, antiseptic, stabilizing agent, thickening agent etc.,, promptly may be made in oral liquid medicine preparations such as water preparation, syrup by corresponding conventional method; Cooperate with appropriate solvent commonly used in the injection and additives and operate, can also be prepared into intramuscular injection pharmaceutical preparatioies such as corresponding freeze-dried powder, liquid drugs injection.
Following test cell line confirms that marchantia extract and extractive of general flavone and terpenes extract have the effect of anti-hepatitis B virus and inhibition hepatoma carcinoma cell respectively
Experimental example 1
(1) cytotoxicity of marchantia extractive of general flavone in hepatitis B virus 2.2.15 cell culture
Annotate: compare between 1) medication group and cell matched group
*P＜0.01; Compare between the medication group
2) going up table is twice parallel laboratory test result
(2) the marchantia extractive of general flavone behind 2.2.15 cell culture 3d to the inhibitory action of HBeAg
The maximal non-toxic concentration of marchantia extractive of general flavone is 40 μ g/mL, the 3 batches of result of the tests of 4 diluted concentration 40 μ g/mL, 20 μ g/mL, 10 μ g/mL and 5 μ g/mL show: each concentration marchantia extractive of general flavone to 2.2.15 cell culture 3d after in the supernatant HBeAg inhibitory action is all arranged, its average suppression ratio is respectively 28.68%, 27.92%, 15.30%, 13.38%, and the positive drug contrast is 23.52%, suppresses antigen medium effective concentration IC
50Be 35.48 μ g/mL.
(3) the marchantia extractive of general flavone behind 2.2.15 cell culture 3d to the effect of HBsAg
The marchantia extractive of general flavone of 40 μ g/mL, 20 μ g/mL, 10 μ g/mL, 4 dosage groups of 5 μ g/mL is respectively 28.53%, 26.94%, 26.31% and 18.86% to 2.2.15 cell culture 3d supernatant to the average suppression ratio of HBsAg.And the positive drug contrast is 14.58%, suppresses antigen medium effective concentration IC
50Be 24.45 μ g/mL.
(4) the marchantia extractive of general flavone is to the change of 2.2.15 cellular morphology
After the 2.2.15 cell is handled 3 days with 40 μ g/mL, 20 μ g/mL, 10 μ g/mL, 5 μ g/mL marchantia extractive of general flavone, on cellular morphology, take place obviously to change, cell shrinks.(accompanying drawing 1)
(5) marchantia extractive of general flavone inhibitory action of HBV-DNA in the pair cell in the 2.2.15 cell culture
4 diluted concentrations, 40 μ g/mL, the 20 μ g/mL of marchantia extractive of general flavone, 10 μ g/mL and 5 μ g/mL handle the 2.2.15 cell, 4d extracts DNA respectively, put respectively on nitrocellulose filter, make dot blot hybridization with the HBV-DNA probe, autoradiography is developed a film and (is measured each point OD with microplate reader
570Be worth as seen, the HBV-DNA of marchantia extractive of general flavone 40 μ g/mL group and cell contrast HBV-DNA compare, and average suppression ratio reaches 31.52%; 20 μ g/mL group suppression ratio reaches 27.60%; L0 μ g/mL group suppression ratio is 19.36%; 5 μ g/mL group suppression ratio is 11.60%.(accompanying drawing 2)
Experimental example 2
Marchantia terpenes extract suppresses the cancer cell activity in cell culture
(1) marchantia terpenes extract is to the inhibition of people HepG2 hepatoma carcinoma cell
(2) investigate of the effect of marchantia terpenes extract simultaneously to the H1299 small cell lung cancer cell, find that marchantia terpenes extract is not obvious to the toxic inhibition of people H1299 small cell lung cancer cell, can prove the specific effect of marchantia terpenes extract people HepG2 hepatoma carcinoma cell.
Description of drawings
Accompanying drawing 1:40 μ g/mL, 20 μ g/mL, 10 μ g/mL, 5 μ g/mL marchantia extractive of general flavone were handled the 2.2.15 cell after 3 days, and HBsAg, HBeAg are had appreciable impact, and cell shrinks.
Accompanying drawing 2: the marchantia extractive of general flavone of variable concentrations is to the inhibitory action of HBV-DNA.
The specific embodiment
Below in conjunction with the specific embodiment the present invention is done explanation in further detail.
Embodiment 1 is marchantia (Marchantia polymorpha) raw material 300g, suitably pulverizes, and adds 20 times of amounts of ethanol (being solvent), under 100 ℃ of conditions, extracts 3 times, each 0.5 hour, extracting liquid filtering, after filtrate merges, be concentrated into dried, must crude extract.Crude extract is used petroleum ether, ethyl acetate and n-butanol extraction successively respectively, the butanol extraction liquid distilling under reduced pressure, reclaim solvent, be concentrated into dried, behind the dissolve with methanol, by silica gel (Haiyang Chemical Plant, Qingdao) chromatographic column, earlier with chloroform 400ml eluting, reuse 500ml methanol-eluted fractions, meoh eluate be in 48 ℃ of concentrating under reduced pressure, and it is 86% extract that concentrated solution obtains general flavone content through vacuum drying.Solvent is reclaimed in the acetic acid ethyl acetate extract distilling under reduced pressure, is concentrated into dried, behind the dissolve with methanol,, use 3000ml dichloromethane eluting successively by silica gel column chromatography, the dichloromethane eluent is in 38 ℃ of concentrating under reduced pressure, and it is 78% extract that concentrated solution obtains terpene content through vacuum drying.
Embodiment 2 is Marchantia convoluta (Marchantia convoluta) raw material 300g, suitably pulverizes, and adds 13 times of amounts of ethanol (being solvent), under 70 ℃ of conditions, extracts 3 times, each 1.5 hours, extracting liquid filtering, after filtrate merges, be concentrated into dried, must crude extract.Crude extract is used petroleum ether, ethyl acetate and n-butanol extraction successively respectively, the butanol extraction liquid distilling under reduced pressure, reclaim solvent, be concentrated into dried, behind the dissolve with methanol, by AB-8 macroporous adsorptive resins (Chemical Plant of Nankai Univ.) chromatographic column, wash post earlier with water, reuse 1000ml ethanol is washed post, and ethanol elution is in 46 ℃ of concentrating under reduced pressure, and concentrated solution is spray-dried, and to obtain general flavone content be 90% extract.Solvent is reclaimed in the acetic acid ethyl acetate extract distilling under reduced pressure, is concentrated into dried, behind the dissolve with methanol,, use 3000ml dichloromethane eluting successively by silica gel column chromatography, the dichloromethane eluent is in 30-40 ℃ of concentrating under reduced pressure, and it is 84% extract that concentrated solution obtains terpene content through vacuum drying.
Embodiment 3 suitably pulverizes Marchantia paleacea (Marchantia paleacea) raw material 300g, adds 16 times of amounts of 80% ethanol water (being solvent), under 80 ℃ of conditions, extract 3 times, each 1.0 hours, extracting liquid filtering, after filtrate merges, be concentrated into dried, crude extract.Crude extract is used petroleum ether, ethyl acetate and n-butanol extraction successively respectively, the butanol extraction liquid distilling under reduced pressure, reclaim solvent, be concentrated into dried, behind the dissolve with methanol, by S-8 macroporous adsorptive resins (Chemical Plant of Nankai Univ.) chromatographic column, wash post earlier with water, reuse 1000ml ethanol is washed post, and ethanol elution is in 49 ℃ of concentrating under reduced pressure, and concentrated solution is spray-dried, and to obtain general flavone content be 71% extract.Solvent is reclaimed in the acetic acid ethyl acetate extract distilling under reduced pressure, is concentrated into dried, behind the dissolve with methanol,, use 3000ml dichloromethane eluting successively by silica gel column chromatography, the dichloromethane eluent is in 35 ℃ of concentrating under reduced pressure, and it is 75% extract that concentrated solution obtains terpene content through vacuum drying.
Embodiment 4 suitably pulverizes Marchantia diptera (Marchantia diptera) raw material 300g, adds 10 times of amounts of 70% ethanol water (being solvent), under 70 ℃ of conditions, extract 3 times, each 1.5 hours, extracting liquid filtering, after filtrate merges, be concentrated into dried, crude extract.Crude extract is used petroleum ether, ethyl acetate and n-butanol extraction successively respectively, the butanol extraction liquid distilling under reduced pressure, reclaim solvent, be concentrated into dried, behind the dissolve with methanol, by A# macroporous adsorptive resins (Chemical Plant of Nankai Univ.) chromatographic column, wash post earlier with water, reuse 1000ml ethanol is washed post, and ethanol elution is in 50 ℃ of concentrating under reduced pressure, and it is 82% extract that concentrated solution obtains general flavone content through lyophilization.Solvent is reclaimed in the acetic acid ethyl acetate extract distilling under reduced pressure, is concentrated into dried, behind the dissolve with methanol,, use 3000ml dichloromethane eluting successively by silica gel column chromatography, the dichloromethane eluent is in 37 ℃ of concentrating under reduced pressure, and it is 86% extract that concentrated solution obtains terpene content through vacuum drying.
Claims (6)
1. marchantia extractive of general flavone, it obtains by following method: with the marchantia raw material pulverizing, add solvent 10-20 and doubly measure, under 50-100 ℃ of condition, extract 2-3 time, each 0.5-1.5 hour, extracting liquid filtering, be concentrated into dried, the marchantia crude extract.Crude extract is used petroleum ether, ethyl acetate and n-butanol extraction successively respectively, and solvent is reclaimed in the butanol extraction liquid distilling under reduced pressure, be concentrated into dried, behind the dissolve with methanol,, wash post with chloroform by chromatographic column (is filler with silica gel or kieselguhr etc.), wash post through methanol again, or, wash the reuse ethanol elution earlier with water by macroporous adsorptive resins, methanol or ethanol elution be in 40-50 ℃ of concentrating under reduced pressure, obtains the extract that general flavone content is 70-90% through vacuum drying or lyophilization or spray drying.
2. marchantia terpenes extract, it obtains by following method: with the marchantia raw material pulverizing, add solvent 10-20 and doubly measure, under 50-100 ℃ of condition, extract 2-3 time, each 0.5-1.5 hour, extracting liquid filtering, be concentrated into dried, the marchantia crude extract.Crude extract is used petroleum ether, ethyl acetate and n-butanol extraction successively respectively, the acetic acid ethyl acetate extract distilling under reduced pressure, reclaim solvent, be concentrated into dried, behind the dissolve with methanol,, use the dichloromethane eluting by silica gel column chromatography, the dichloromethane eluent is in 30-40 ℃ of concentrating under reduced pressure, and concentrated solution obtains the extract that terpene content is 70-90% through vacuum drying.
3. according to claim 1 and 2 described marchantia extracts, it is characterized in that: described marchantia raw material is meant and any in hepatica (Marchantineae) plant comprises marchantia (Marchantia polymorpha), Marchantia convoluta (Marchantia convoluta), Marchantia paleacea (Marchantia paleacea) and Marchantia diptera (Marchantia diptera) etc.
4. the application of the described marchantia extractive of general flavone of claim 1 in preparation treatment hepatitis B medicament.
5. the application of the described marchantia terpenes of claim 2 extract in preparation treatment liver-cancer medicine.
6. according to claim 4 and 5 described marchantia total flavones and the application of terpenes extract in preparation treatment hepatitis B and liver-cancer medicine, it is characterized in that: described pharmaceutical dosage form is peroral dosage form or injection types such as freeze-dried powder, liquid drugs injection such as tablet, capsule, soft capsule, granule, pill, water preparation, syrup.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103030615A (en) * | 2012-12-13 | 2013-04-10 | 大兴安岭林格贝有机食品有限责任公司 | Method for preparing aureusidin in liverwort by superhigh pressure technique |
| CN103211873A (en) * | 2013-05-03 | 2013-07-24 | 广西中医药大学 | Medicinal composition for treating hepatic fibrosis and preparation method thereof |
| CN103230420A (en) * | 2013-05-03 | 2013-08-07 | 广西中医药大学 | Preparation method of total flavones from liverwort |
| CN104382962A (en) * | 2014-10-24 | 2015-03-04 | 徐�明 | Liver cancer resistant medicine containing liverwort extractives and preparation method of liver cancer resistant medicine |
| CN104840761A (en) * | 2015-06-08 | 2015-08-19 | 李晓杰 | Novel sandwiched moxibustion medicine cake |
| CN109692190A (en) * | 2019-01-28 | 2019-04-30 | 新疆前进荣耀投资有限公司 | Marchantia alcohol extract is in the application for preparing medicines resistant to liver cancer |
| CN114027324A (en) * | 2021-11-24 | 2022-02-11 | 中国科学院成都生物研究所 | Application of liverwort in preventing and treating root rot |
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- 2006-03-10 CN CNA2006100313247A patent/CN101185661A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103030615A (en) * | 2012-12-13 | 2013-04-10 | 大兴安岭林格贝有机食品有限责任公司 | Method for preparing aureusidin in liverwort by superhigh pressure technique |
| CN103030615B (en) * | 2012-12-13 | 2016-01-20 | 大兴安岭林格贝寒带生物科技股份有限公司 | A kind of method utilizing superhighpressure technology to prepare aureusidin in marchantia |
| CN103211873A (en) * | 2013-05-03 | 2013-07-24 | 广西中医药大学 | Medicinal composition for treating hepatic fibrosis and preparation method thereof |
| CN103230420A (en) * | 2013-05-03 | 2013-08-07 | 广西中医药大学 | Preparation method of total flavones from liverwort |
| CN103211873B (en) * | 2013-05-03 | 2015-01-07 | 广西中医药大学 | Medicinal composition for treating hepatic fibrosis and preparation method thereof |
| CN104382962A (en) * | 2014-10-24 | 2015-03-04 | 徐�明 | Liver cancer resistant medicine containing liverwort extractives and preparation method of liver cancer resistant medicine |
| CN104840761A (en) * | 2015-06-08 | 2015-08-19 | 李晓杰 | Novel sandwiched moxibustion medicine cake |
| CN109692190A (en) * | 2019-01-28 | 2019-04-30 | 新疆前进荣耀投资有限公司 | Marchantia alcohol extract is in the application for preparing medicines resistant to liver cancer |
| CN114027324A (en) * | 2021-11-24 | 2022-02-11 | 中国科学院成都生物研究所 | Application of liverwort in preventing and treating root rot |
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