CN101380318A - Use of isochlorogenic acid compound and different combinations in hepatitis treatment - Google Patents
Use of isochlorogenic acid compound and different combinations in hepatitis treatment Download PDFInfo
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Abstract
The invention relates to the application of a compound to treating hepatitis and aims at providing an isochlorogenic acid compound which has stronger effects of anti-HBV, anti-inflammation and liver protection, and has wide and rich sources, and simple and convenient extraction process. The technical proposal is as follows: the isochlorogenic acid compound is made from one or more than one of isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C according to any mixture ratio; in addition, the technical proposal further comprises the application of the compound to preparing drugs for resisting hepatitis B virus, and resisting inflammation and protecting liver.
Description
Technical field
The present invention relates to the application of a kind of chemical compound on treating hepatitis, especially isochlorogenic acid compounds and the various combination application on treating hepatitis.
Background technology
Hepatitis is the general name of liver generation inflammatory lesion, can be divided into viral, ethanol, medicine source property and autoimmune hepatitis etc. according to the cause of disease, and for seeing, wherein based on hepatitis B, hepatitis C is taken second place more with viral hepatitis.According to statistics, the whole world has 300,000,000 hepatitis B virus carrierss approximately at present, and the infection rate of hepatitis C in some special crowd is up to 70%.China is one of higher country of hepatopathy incidence rate, has every year 300000 people to die from hepatopathy approximately.Present about 100,000,000 people of the hepatitis B infected person of China, the virus carrier accounts for 10% of total population up to 1.3 hundred million.Hepatitis B propagation approach complexity, the sickness rate height, the course of disease is long, easily repeatedly, has quite a few to develop to chronicity, and severe patient develops into liver cirrhosis, hepatocarcinoma very then, serious harm people ' s health.
At present mechanism and the pathological process to hepatitis still lacks enough understanding, and this has brought difficulty for treating hepatitis and new drug development, so the Antihepatitis medicament great majority only play auxiliary or symptomatic treatment effect, still do not have the specific treatment medicine so far and comes out.Clinical Antihepatitis medicament commonly used is divided three classes substantially at present: (1) antiviral agents, as interferon (IFN), lamivudine (Lamivudine, 3TC), famciclovir (famciclovir), lamivudine (adefovir), En Takawei (entacavir, BMS-200475) etc. can suppress hepatitis B virus duplication, be used for the treatment of chronic viral hepatitis B; (2) immunomodulator, but as thymosin, levamisole and immune ribonucleic acid human body immunity improving, adrenocortical hormone has non-special antiinflammatory action and immunosuppressive action, can be used for treating the autoimmunity active hepatitis; (3) hepatoprotective is promptly protected the medicine of hepatocyte function (or anti-hepatocyte injury), as silymarin, glycyrrhizin, Malotilate etc.Hepatocyte injury is the common pathologic basis of various hepatopathy, and treatment is one of major measure of various liver disease with correcting hepatocyte injury, so hepatoprotective is the most frequently used medicines of the various hepatitis of treatment.
Hepatitis B is a kind of very harmful worldwide popular infectious disease that is caused by hepatitis B virus (HBV), the whole world has 3.5 hundred million HBV carriers approximately at present according to statistics, and the China high infected zone that is HBV, the HBV carrier accounts for the total population ratio up to 10%～15%, wherein about 3,000 ten thousand examples of chronic viral hepatitis B patient have 350,000 people to die from the chronic viral hepatitis B relevant disease every year approximately.From the data that Ministry of Public Health is announced, the hepatitis B sickness rate still keeps occupying height and growth at present.HBV is mainly by blood and transmission through sex, and mother and baby's vertical transmission is also very common.The adult infects HBV and shows as symptomless infection or acute hepatitis more, has 15%～20% patient to transfer chronic carrier and chronic patients to approximately, and part chronic viral hepatitis B patient further is converted into liver cirrhosis and primary hepatocellular carcinoma (hcc).Though what HBV genetic engineering subunit vaccine may command infected at present is popular, the carrier and the chronic patients that have infected HBV in a large number still exist.Although scientist has developed the to a certain degree disease controlling development of some new anti-hbv drugs both at home and abroad, its curative effect still has very long distance apart from the target of removing viral infection, the most hepatitis B patients of healing and virus carrier.Therefore, the anti-hbv drug of continuation development high-efficiency low-toxicity is still the task of top priority.
Chlorogenic acid (Chlorogenic acid, be called for short CA), being by caffeic acid (Caffeic acid) and the depside that quinic acid (Quinic acid, 1-hydroxyl six hydrogen gallic acids) generates, is a kind of phenylpropyl alcohol chlorins compound that plant produces through shikimic acid pathway in the aerobic respiration process.3-caffeoyl guinic acid structural formula wherein is as shown in the formula expression:
Different according to the binding site of caffeoyl on quinic acid with number, at present from plant isolation identification 4 kinds of single caffeoyl guinic acids: 1-caffeoyl guinic acid, 3-caffeoyl guinic acid, 4-caffeoyl guinic acid and 5-caffeoyl guinic acid; 6 kinds of dicaffeoyl quinic acid: 1,3-dicaffeoyl quinic acid, 1,4-dicaffeoyl quinic acid, 1,5-dicaffeoyl quinic acid, 3,4-dicaffeoyl quinic acid, 3,5-dicaffeoyl quinic acid and 4,5-dicaffeoyl quinic acid; 3 kind of three caffeoyl guinic acid: 1,3,5-three caffeoyl guinic acids, 1,4,5-three caffeoyl guinic acids and 3,4,5-three caffeoyl guinic acids; And a kind of four caffeoyl guinic acid: 1,3,4,5-four caffeoyl guinic acids.Studies show that in the various isomers of chlorogenic acid, pharmacologically active with the dicaffeoylquinic acid chemical compound is the most remarkable, have multiple pharmacological effect such as antioxidation, antiinflammatory, antiviral (herpesvirus and HIV (human immunodeficiency virus)), fibrosis, inhibition smooth muscle contraction, blood fat reducing, have drug development and clinical value.The chlorogenic acid chemical compound extensively is present in the Chinese medicines such as plant kingdom such as Flos Lonicerae, Flos Inulae, Herba Xanthii, aboundresources.All kinds of caffeoyl guinic acid structural representations are as follows:
Isochlorogenic acid compounds (3,4-dicaffeoyl quinic acid, 3,5-dicaffeoyl quinic acid and 4,5-dicaffeoyl quinic acid) does not exist only in the Laggera alata (Roxb.) Sch.-Bip., also extensively is present in the Chinese medicines such as Flos Lonicerae, Flos Inulae, Herba Xanthii aboundresources.Literature search shows still do not have the research report of this 3 phenols component anti-hepatitis Bs effect both at home and abroad.
Summary of the invention
The objective of the invention is to overcome the deficiency of above-mentioned background technology, a kind of application of isochlorogenic acid compounds is provided, this chemical compound should have stronger anti-hepatitis virus and antiinflammatory hepatoprotective effect, and wide material sources, aboundresources, and extraction process is easy.
Technical scheme provided by the invention is: following one or more isochlorogenic acid compounds by any proportioning combination are used in the medicine that preparation anti-hepatitis virus, antiinflammatory protect the liver:
1) isochlorogenic acid A (Isochlorogenic acid A): promptly 3,5-dicaffeoylquinic acid (3,5-Dicaffeoylquinic acid), molecular formula C
25H
24O
12, molecular weight 516.45,
2) isochlorogenic acid B (Isochlorogenic acid B): promptly 3,4-dicaffeoylquinic acid (3,4-Dicaffeoylquinic acid), molecular formula C
25H
24O
12, molecular weight 516.45,
3) isochlorogenic acid C (Isochlorogenic acid C): promptly 4,5-dicaffeoylquinic acid (4,5-Dicaffeoylquinic acid).Molecular formula C
25H
24O
12, molecular weight 516.45,
Ratio between described isochlorogenic acid A, isochlorogenic acid B, the isochlorogenic acid C is 26:19:31.
The extracting method of described isochlorogenic acid compounds extracts in any Chinese crude drug the Laggera alata (Roxb.) Sch.-Bip. that this isochlorogenic acid compounds can obtain from outsourcing, Flos Lonicerae, Flos Inulae, the Herba Xanthii.
The extracting method of described isochlorogenic acid compounds, this isochlorogenic acid compounds prepares (is example with the dry medical material of Laggera alata (Roxb.) Sch.-Bip.) according to following steps:
1) getting the dry medical material 20kg of Laggera alata (Roxb.) Sch.-Bip., is that 95% ethanol atmospheric pressure reflux is extracted three times through concentration, and after extracting solution merged, concentrating under reduced pressure reclaimed ethanol, makes blackish green extractum;
2) with the blackish green extractum weighing that makes be 915 the gram after, behind water dissolution, extract repeatedly, up to removing low-polarity component with ethyl acetate;
3) aqueous solution that will remove low-polarity component is cut apart with n-butyl alcohol after the dilute hydrochloric acid acidify, and reacted n-butyl alcohol partly is being washed to neutrality, and concentrating under reduced pressure gets brown-black powder 320g, is the Laggera alata (Roxb.) Sch.-Bip. extract.
4) get the freeze dried Laggera alata (Roxb.) Sch.-Bip. extract of 2.0g, be dissolved in the distilled water,, produce 8 different positions of climbing gradient with 30% methanol-eluted fractions by Sephadex LH-20 column chromatography.
5) to the climbing gradient at the solution on the 6th repeatedly behind the chromatography, using 30% methanol-eluted fractions through Sephadex LH-20 post, isolate 3 chemical compounds, that is: 3,4-dicaffeoyl quinic acid (26mg), 3,5-dicaffeoyl quinic acid (19mg) and 4,5-dicaffeoyl quinic acid (31mg).
The extracting method of described Flos Lonicerae, Flos Inulae, Herba Xanthii is identical with the extracting method of Laggera alata (Roxb.) Sch.-Bip..
Pharmacological evaluation proves: isochlorogenic acid compounds single component and different components thereof have significant anti-hepatitis B effect (suppressing HBV-DNA duplicate, especially suppress duplicating of HBV-cccDNA, improve the pathologic damage that HBV causes), hepatoprotective effect (comprise and improve D-GalN, the hepatic injury that CCI4 and acetaminophen etc. cause) and immunoregulation effect (comprise and improve the inductive immunologic liver injury of BCG-LPS etc.).
Isochlorogenic acid compounds provided by the invention has great anti-hepatitis virus and antiinflammatory hepatoprotective effect, especially the application on treatment hepatitis, comprise protect the liver, antiinflammatory and immunoregulation effect, particularly external enwergy significantly suppresses duplicating of hepatitis B virus in vivo, and significantly improve hepatitis B virus, the rational damage of poisonous substance and drug-induced hepatopathy; Can be used for treating hepatitis (comprising anti-hbv drug or hepatic) drug development utilization.And the isochlorogenic acid compounds is present in the plant medicines such as Laggera alata (Roxb.) Sch.-Bip., Flos Lonicerae, Flos Inulae, Herba Xanthii widely, aboundresources; And extraction process is simple and easy to do.
The specific embodiment
The present invention finds isochlorogenic acid compounds (3, the 4-dicaffeoyl quinic acid, 3,5-dicaffeoyl quinic acid and 4, the 5-dicaffeoyl quinic acid) single component, different components and as the plant extract of main pharmacodynamics composition, all having the anti-hepatitis B activity (comprises and suppresses the HBV dna replication dna, reduce hepatitis B surface antigen etc.) and liver-protecting activity, show that this compounds has the anti-hepatitis B surface antigen of making, the function that suppresses hepatitis B virus duplication, thereby can develop the medicine of treatment hepatitis B, isochlorogenic acid optimal set compound drug effect the strongest (anti-HBV effect is better than lamivudine, and hepatoprotective effect is better than the Herba Silybi mariani kneecap) wherein.
The isochlorogenic acid chemical compound (comprises 3,4-dicaffeoyl quinic acid, 3,5-dicaffeoyl quinic acid and 4,5-dicaffeoyl quinic acid) can be from medicinal plants such as Laggera alata (Roxb.) Sch.-Bip., Flos Lonicerae, Flos Inulae, Herba Xanthii extraction separation, also can be by chemical method preparation such as complete synthesis or semi-synthetic.
The isochlorogenic acid compounds can be applied to treating hepatitis with following dosage forms:
1. isochlorogenic acid compounds (3,4-dicaffeoyl quinic acid, 3,5-dicaffeoyl quinic acid and 4,5-dicaffeoyl quinic acid) is made dosage forms such as capsule, injection with single component, as the medicine of treatment hepatitis (comprise the treatment hepatitis B and protect the liver etc.).
2. isochlorogenic acid compounds (3,4-dicaffeoyl quinic acid, 3,5-dicaffeoyl quinic acid and 4,5-dicaffeoyl quinic acid) different components is made dosage forms such as capsule, injection, as the medicine of treatment hepatitis (comprise the treatment hepatitis B and protect the liver etc.).
3. with isochlorogenic acid compounds (3,4-dicaffeoyl quinic acid, 3,5-dicaffeoyl quinic acid and 4,5-dicaffeoyl quinic acid) be main pharmacodynamics composition plant extract, make dosage forms such as capsule, injection, as the medicine of treatment hepatitis (comprise the treatment hepatitis B and protect the liver etc.).
Isochlorogenic acid compounds (3,4-dicaffeoyl quinic acid, 3,5-dicaffeoyl quinic acid and 4,5-dicaffeoyl quinic acid) compositions best proportion (26:19:31).
Below further specify beneficial effect of the present invention by the animal effect experiment.
Embodiment 1
The isochlorogenic acid compositions is to changeing HBV (hepatitis B virus) gene HepG2.2.15 (transfection has the cell strain of HBV DNA) emiocytosis HBsAg (hepatitis B virus surface antigen), the inhibitory action of HBeAg (hepatitis B virus E antigen) and HBV-DNA (the virus replication number of hepatitis B virus).
Working sample is to the inhibitory action of HepG2.2.15 cell growth: cell is digested with trypsin-EDTA and be diluted to 1 * 10
5/ mL is added in the 96 porocyte culture plates, and every hole 100uL puts CO
2Cultivate in the incubator.Behind the inoculation 24h, the culture medium of inclining, the sample that adding is diluted with culture medium, every hole 200ul, each concentration adds 3 holes, the MTT that in the cell culture hole, adds 5mg/ml behind the cultivation 72h, every hole 10ul puts 37 ℃ and hatches 3h, adds DMSO 150ul Shi Jia Za and dissolves fully, with microplate reader colorimetric under the 570nm wavelength.Calculation sample is to the median toxic concentration of HepG2.2.15 cell growth.Working sample is to the inhibitory action of HBV: changed the culture medium that contains the non-toxic concn sample in per 4 days, with the culture medium equal-volume mixing that swaps out of the same concentration of same sample, as testing sample.With HBsAg and HBeAg concentration in the ELISA kit measurement culture medium; Measure HBV-DNA concentration in the culture medium with the HBV-DNA quantitative PCR kit.
Anti-HBV evaluation of effect: with transfection HBV DNA cell strain (HepG2.2.15) being arranged is model, by the HBsAg in the sample pair cell culture supernatant, and HBeAg, the situation that influences of HBV-DNA, the effect that comes the anti-HBV of assess sample.
Table 1 isochlorogenic acid compositions is to HepG2.2.15 emiocytosis HBsAg, HBeAg and HBV-DNA inhibitory action
The result shows that the isochlorogenic acid compositions is to changeing HBV gene HepG2.2.15 emiocytosis HBsAg, and HBeAg has very strong inhibitory action, HBV-DNA is duplicated also have very strong inhibitory action, and its effect is better than positive control medicine lamivudine.
Embodiment 2 isochlorogenic acid compositionss cause the influence of hepatocyte injury to D-GalN (aminogalactose)
People's normal liver cell strain HL-7702 puts 37 ℃ of following CO
2Cultivate in the incubator; After treating that hepatocyte is adherent, change culture fluid, add the D-GalN of 20mmol/l, effect 8h; Discard culture fluid then, add each 200 μ l of test medicinal liquid of variable concentrations respectively, each concentration is established 6 multiple holes, establishes solvent and positive control simultaneously; Continue to cultivate 48h, every hole adds 10 μ l MTT (5mg/ml), and effect 4h inhales and abandons supernatant, adds 150 μ l DMSO, the vibration mixing; Under the 570nm wavelength, measure the A value with microplate reader.Protective effect is estimated: calculate protective rate (%) and hypertrophy index.
Annotate 2: hypertrophy index=sample sets (A)/damage group (A)
Table 2 isochlorogenic acid compositions causes the influence of people's normal liver cell damage to D-GalN
The result shows that the isochlorogenic acid compositions has significant protective effect to the inductive hepatocyte injury of D-GalN, and its effect is better than positive control medicine silymarin.
Embodiment 3 isochlorogenic acid compositionss cause the protective effect of chmice acute liver injury model to D-GalN
Draw materials: get 20-25g, male, the ICR mice, by the body weight random packet, 10 every group.If normal control group, damage matched group, positive controls and the high, medium and low dosage group of reagent.Medicine treated animal prevention administration, every day 1 time, continuous 7 days.Normal control group and damage matched group give isopyknic solvent, and positive controls gives silymarin 50mg/kg.1h after the last administration, except that normal group, each treated animal lumbar injection 650mg/kg aminogalactose (D-GalN) intoxicating.Behind the last administration 24h, separation of serum is surveyed AST and ALT.Get hepatic tissue simultaneously and be used to make pathological section.
Therapeutic evaluation: the significance of AST and ALT difference between relatively treatment group and damage matched group, and the improvement of pathology variation.
The influence of the chmice acute hepatic injury that table 3 isochlorogenic acid compositions is brought out D-GalN (x ± s)
Compare with model,
*P＜0.05,
*P＜0.01 and
* *P＜C.001 promptly compares with model control group and has significant difference.
The result shows that the isochlorogenic acid compositions is better than positive control medicine silymarin to the protective effect of D-GalN acute liver damage mice, and can significantly improve D-GalN acute liver damage histologic lesion.
Embodiment 4 isochlorogenic acid compositionss are to CCl
4(carbon tetrachloride) causes the protective effect of chmice acute liver injury model
Draw materials: get 20-25g, male, the ICR mice, by the body weight random packet, 10 every group.If normal control group, damage matched group, positive controls and the high, medium and low dosage group of reagent.Medicine treated animal prevention administration, every day 1 time, continuous 7 days.Normal control group and damage matched group give isopyknic solvent, and positive controls gives silymarin 50mg/kg.1h after the last administration, except that normal group, the CCl of each treated animal lumbar injection 1%
4Olive oil solution (10ml/kg) intoxicating.Behind the last administration 24h, separation of serum is surveyed AST and ALT.Get hepatic tissue simultaneously and be used to make pathological section.
Therapeutic evaluation: the significance of AST and ALT difference between relatively treatment group and damage matched group, and the improvement of pathology variation.
Table 4 isochlorogenic acid compositions is to CCl
4The influence of the chmice acute hepatic injury of bringing out (x ± s)
Compare with model,
*P＜0.05,
*P＜0.01 and
* *P＜0.001 is promptly compared with model control group and is had significant difference.
The result shows that the isochlorogenic acid compositions is to CCl
4The protective effect of acute liver damage mice is better than positive control medicine silymarin, and can significantly improve CCl
4The acute liver damage histologic lesion.
Embodiment 5 isochlorogenic acid compounds and different components thereof are to CCl
4(carbon tetrachloride) causes the protective effect of rat chronic liver injury model
Draw materials: get 160 ± 20g, male, SD or Wistar rat, by the body weight random packet, during on-test 20 every group, during off-test, every treated animal must not be less than 8.If normal control group, damage matched group, positive controls and the high, medium and low dosage group of reagent.Except that normal group, the CCl of each treated animal abdominal part or back subcutaneous injection 10%
4Olive oil solution (5ml/kg) intoxicating is injected weekly 2 times, continuous 3 months.Behind the intoxicating 2 months, carry out Drug therapy, every day 1 time, 5 days weekly, successive administration two months.Normal control group and damage matched group give isopyknic solvent, and positive controls gives silymarin 50mg/kg.Behind the last administration 24h, separation of serum detects AST, ALT level.Get hepatic tissue simultaneously and be used to make pathological section.
Therapeutic evaluation: the significance of every index difference between relatively treatment group and damage matched group, and the improvement of pathology variation.
Table 5 isochlorogenic acid compositions is to CCl
4The influence of chronic hepatic injury rat AST (glutamic oxaloacetic transaminase, GOT) and ALT (serum glutamic pyruvic transminase) (x ± s)
Compare with model,
*P＜0.05,
*P＜0.01 and
* *P＜0.001 is promptly compared with model control group and is had significant difference.
The result shows that the isochlorogenic acid compositions is to CCl
4The protective effect of chronic hepatic injury rat is better than positive control medicine silymarin, and can significantly improve CCl
4The chronic hepatic injury histologic lesion.
Portfolio ratio among the above embodiment between the different components is a weight ratio.
Claims (4)
1, following one or more isochlorogenic acid compounds by any proportioning combination are used in the medicine that preparation anti-hepatitis virus, antiinflammatory protect the liver:
1) isochlorogenic acid A (Isochlorogenic acid A): promptly 3,5-dicaffeoylquinic acid (3,5-Dicaffeoylquinic acid), molecular formula C
25H
24O
12, molecular weight 516.45,
2) isochlorogenic acid B (Isochlorogenic acid B): promptly 3,4-dicaffeoylquinic acid (3,4-Dicaffeoylquinic acid), molecular formula C
25H
24O
12, molecular weight 516.45,
3) isochlorogenic acid C (Isochlorogenic acid C): promptly 4,5-dicaffeoylquinic acid (4,5-Dicaffeoylquinic acid).Molecular formula C
25H
24O
12, molecular weight 516.45,
2, the extracting method of the described a kind of isochlorogenic acid compounds of claim 1 is characterized in that the ratio between described isochlorogenic acid A, isochlorogenic acid B, the isochlorogenic acid C is 26:19:31.
3, the extracting method of the described a kind of isochlorogenic acid compounds of claim 1 is characterized in that extracting in this isochlorogenic acid compounds any Chinese crude drug from Laggera alata (Roxb.) Sch.-Bip., Flos Lonicerae, Flos Inulae, Herba Xanthii.
4, the extracting method of a kind of isochlorogenic acid compounds according to claim 2 is characterized in that this isochlorogenic acid compounds prepares according to following steps:
1) get dry medical material, extract three times through the ethanol atmospheric pressure reflux, after extracting solution merged, concentrating under reduced pressure reclaimed ethanol, makes blackish green extractum;
2) with the blackish green extractum that makes with water dissolution after, extract repeatedly with ethyl acetate, up to removing low-polarity component;
3) aqueous solution that will remove low-polarity component is cut apart with n-butyl alcohol after the dilute hydrochloric acid acidify, and reacted n-butyl alcohol partly is being washed to neutrality, and concentrating under reduced pressure gets extract.
4) extract is dissolved in the distilled water, by Sephadex LH-20 column chromatography, produces 8 different positions of climbing gradient with 30% methanol-eluted fractions.
5) to the climbing gradient at the solution on the 6th repeatedly behind the chromatography, using 30% methanol-eluted fractions through Sephadex LH-20 post, isolate 3 chemical compounds, that is: 3,4-dicaffeoyl quinic acid (26mg), 3,5-dicaffeoyl quinic acid (19mg) and 4,5-dicaffeoyl quinic acid (31mg).
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101774921A (en) * | 2010-03-04 | 2010-07-14 | 中国人民解放军第三○二医院 | Method for preparing dicaffeoylquinic acid methyl compound and composition thereof |
| CN101774920A (en) * | 2010-03-04 | 2010-07-14 | 中国人民解放军第三○二医院 | Preparation method of 3,5-cynarin methyl ester and medicament composition thereof |
| CN102942483A (en) * | 2012-10-19 | 2013-02-27 | 湖北楚天舒药业有限公司 | Method for preparing a plurality of caffeoylquinic acid monomers from honeysuckle |
| CN108403682A (en) * | 2018-05-14 | 2018-08-17 | 杨真慧 | It is a kind of to be used to substitute composition and its assay method that the achene of Siberian cocklebur prepares drugs for prostate cancer |
| CN108752208A (en) * | 2018-07-17 | 2018-11-06 | 深圳市人民医院 | The extracting method and its product of coffee mesitoyl quinine acid compounds and application |
| CN110548022A (en) * | 2019-09-20 | 2019-12-10 | 广西科学院 | Organic acid inhibitor for resisting fish diseases and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101774921A (en) * | 2010-03-04 | 2010-07-14 | 中国人民解放军第三○二医院 | Method for preparing dicaffeoylquinic acid methyl compound and composition thereof |
| CN101774920A (en) * | 2010-03-04 | 2010-07-14 | 中国人民解放军第三○二医院 | Preparation method of 3,5-cynarin methyl ester and medicament composition thereof |
| CN102942483A (en) * | 2012-10-19 | 2013-02-27 | 湖北楚天舒药业有限公司 | Method for preparing a plurality of caffeoylquinic acid monomers from honeysuckle |
| CN108403682A (en) * | 2018-05-14 | 2018-08-17 | 杨真慧 | It is a kind of to be used to substitute composition and its assay method that the achene of Siberian cocklebur prepares drugs for prostate cancer |
| CN108403682B (en) * | 2018-05-14 | 2018-12-25 | 绍兴市逸晨医疗科技有限公司 | A kind of composition and its measuring method preparing drugs for prostate cancer for substituting the achene of Siberian cocklebur |
| CN108752208A (en) * | 2018-07-17 | 2018-11-06 | 深圳市人民医院 | The extracting method and its product of coffee mesitoyl quinine acid compounds and application |
| CN108752208B (en) * | 2018-07-17 | 2021-03-16 | 深圳市人民医院 | Extraction method of caffeoylquinic acid compounds, and product and application thereof |
| CN110548022A (en) * | 2019-09-20 | 2019-12-10 | 广西科学院 | Organic acid inhibitor for resisting fish diseases and preparation method and application thereof |
| CN110548022B (en) * | 2019-09-20 | 2023-06-23 | 广西科学院 | Organic acid inhibitor for resisting fish diseases and preparation method and application thereof |
| CN112353719A (en) * | 2020-11-02 | 2021-02-12 | 郭光波 | Anti-aging lucid ganoderma face cream and preparation method thereof |
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