CN115429790B - Application of isoflavone compound in preparing medicament for preventing or treating alcoholic liver injury or dispelling alcohol effect and protecting liver - Google Patents
Application of isoflavone compound in preparing medicament for preventing or treating alcoholic liver injury or dispelling alcohol effect and protecting liver Download PDFInfo
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- CN115429790B CN115429790B CN202110620348.0A CN202110620348A CN115429790B CN 115429790 B CN115429790 B CN 115429790B CN 202110620348 A CN202110620348 A CN 202110620348A CN 115429790 B CN115429790 B CN 115429790B
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- alcoholic
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- liver injury
- methanol
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- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
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- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 241000894007 species Species 0.000 description 1
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- 238000006467 substitution reaction Methods 0.000 description 1
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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Abstract
The invention provides application of isoflavone compounds in preparing medicines for preventing or treating alcoholic liver injury or relieving alcohol and protecting liver. The invention provides application of 6, 7-position ring-formed isoflavone compounds shown in a formula (I) in preparation of medicines for preventing or treating alcoholic liver injury or relieving alcohol and protecting liver for the first time. The activity of 6, 7-position ring-forming isoflavone compounds (compounds 1-21) for treating alcoholic liver injury and relieving alcoholic liver injury is verified through animal experiments, and compared with tectorigenin, the 6, 7-position ring-forming isoflavone compounds have better repairing effect on alcoholic liver injury, and the 6, 7-position ring-forming isoflavone compounds have obvious anti-alcoholic effect through observing the behaviors of alcohol rats before and after administration. Therefore, the invention expands the application field of the isoflavone compound with the 6, 7-position ring.
Description
Technical Field
The invention relates to the field of medicines, in particular to application of an isoflavone compound in preparing a medicine for preventing or treating alcoholic liver injury or relieving alcohol and protecting liver.
Background
Alcoholic liver injury, i.e., alcoholic liver disease (alcoholic liver disease, ALD), is a disease that causes toxic damage to the liver and related health problems after long-term consumption of alcohol, and the incidence of ALD has been on an increasing trend year by year worldwide, and is therefore of great concern. ALD is clinically classified into alcoholic fatty liver (alcoholic fatty liver, AFL), alcoholic hepatitis (alcoholic hepatitis, AH), alcoholic liver fibrosis (alcoholic liver fibrosis, ALF) and alcoholic cirrhosis (alcoholic cirrhosis, AC).
Alcohol is a neurotropic substance that can cause irreversible damage to central and peripheral nerves, and the burden of drinking on public health is 5.1% of the burden of global disease. Alcohol use disorders, including alcohol abuse and alcohol dependence, are one of the major risk factors for premature death, and can cause over 200 diseases, including neuropsychiatric diseases, chronic diseases, cancer, and disabling trauma. Alcohol use disorders are the most common cause of alcoholic liver injury, and can cause a range of liver diseases such as fatty liver, steatohepatitis, liver fibrosis, cirrhosis, liver cancer, and the like.
Various flavonoid compounds are reported to have certain anti-hangover and liver-protecting effects, such as flavonoids derived from chrysanthemum, flavonoids derived from mung beans, flavonoids derived from red bayberry, and the like. Studies have shown that isoflavones derived from kudzuvine flower, such as tectoridin and tectorigenin (tectorigenin), have good liver protecting activity, and that the ethanol dehydrogenase activation effect of tectorigenin is superior to that of tectorigenin.
Tectorigenin
Chinese patent document (CN 1986556A) discloses a 6, 7-position ring-forming isoflavone compound (5, 3',5' -trimethoxy-6, 7-methylenedioxy isoflavone-4 ' -O-beta-D-glucose), and discloses application of the isoflavone compound in preventing and treating estrogen low level and female climacteric syndrome. Regarding the 6, 7-position ring-formed isoflavone compound, no report on the aspects of treating alcoholic liver injury or dispelling alcohol and protecting liver is currently seen.
Disclosure of Invention
Therefore, the technical problem to be solved by the invention is to provide a new application of the isoflavone compound with 6, 7-position ring formation.
The invention provides an application of isoflavone compound shown in a formula (I) and pharmaceutically acceptable salt thereof in preparing medicines for preventing or treating alcoholic liver injury or relieving alcohol and protecting liver,
wherein:
R 1 、R 2 、R 3 、R 4 independently of each other selected from hydrogen, hydroxy, C 1 -C 8 Alkyl, C of (2) 3 -C 10 Cycloalkyl, C 1 -C 8 Alkoxy or C of (2) 4 -C 20 Is a glycosyl residue of (a).
Further, the method comprises the steps of,
R 1 、R 2 、R 3 、R 4 independently of each other, selected from hydrogen, hydroxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-propoxy, isopropoxy or from substituted or unsubstitutedWherein the substitution is such that hydrogen in a hydroxyl group on the above group is replaced with another substituent.
Further, the method comprises the steps of,
R 1 、R 2 、R 3 、R 4 independently of each other selected from hydrogen, hydroxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-propoxy, isopropoxy or from At least one formed glycosyl residue, wherein R 1 、R 2 、R 3 、R 4 Independently of each other, selected from any one of the above-mentioned glycosyl residues, or from a combination of two or more glycosyl residues of the same kind or different kinds.
Further, the method comprises the steps of,
R 1 selected from hydroxy, methoxy or fromA glycosyl residue formed;
R 2 、R 3 、R 4 independently of one another, from hydrogen, hydroxy, methoxy or from At least one formed glycosyl residue, wherein R 2 、R 3 、R 4 Independently of each other, selected from any one of the above-mentioned glycosyl residues, or from a combination of two or more glycosyl residues of the same kind or different kinds.
Further, the method comprises the steps of,
R 1 selected from hydroxyl or methoxy;
R 2 selected from hydrogen, hydroxy or methoxy;
R 3 selected from hydroxy, methoxy or from At least one formed glycosyl residue, wherein R 3 Any one of the above glycosyl residues, or a combination of two or more glycosyl residues of the same kind or different kinds;
R 4 selected from hydrogen, hydroxy, methoxy or fromThe glycosyl residue formed.
Further, the method comprises the steps of,
the isoflavone compound has a structure shown as follows:
further, the medicament also comprises a pharmaceutically acceptable carrier.
Further, the medicine is added with conventional auxiliary materials and is prepared into clinically acceptable tablets, capsules, oral liquid, powder, dripping pills, granules or injections according to a conventional process.
Further, the alcoholic liver injury includes: alcoholic fatty liver, alcoholic liver fibrosis, alcoholic hepatitis, and alcoholic cirrhosis.
The technical scheme of the invention has the following advantages:
the invention provides application of 6, 7-position ring-forming isoflavone compounds shown in a formula (I) in preparation of medicines for preventing or treating alcoholic liver injury or relieving alcohol and protecting liver for the first time. The activity of 6, 7-position ring-forming isoflavone compounds (compounds 1-21) for treating alcoholic liver injury and relieving alcoholic liver injury is verified through animal experiments, an alcoholic rat model is constructed through experimental rat alcohol lavage, and the compounds 1-21 and tectorigenin are respectively used for administration, so that compared with tectorigenin, the 6, 7-position ring-forming isoflavone compounds have better repairing effect on alcoholic liver injury, and the behavior of an alcoholic rat before and after administration is observed, so that the 6, 7-position ring-forming isoflavone compounds have obvious anti-alcoholic effect. Therefore, the invention expands the application field of the isoflavone compound with the 6, 7-position ring.
Detailed Description
The following examples are provided for a better understanding of the present invention and are not limited to the preferred embodiments described herein, but are not intended to limit the scope of the invention, any product which is the same or similar to the present invention, whether in light of the present teachings or in combination with other prior art features, falls within the scope of the present invention.
The specific experimental procedures or conditions are not noted in the examples and may be followed by the operations or conditions of conventional experimental procedures described in the literature in this field. The materials or instruments used are all conventional products commercially available, including but not limited to those used in the examples of the present application.
The percentages of solutions in the examples and experimental examples represent the volume fraction (v/v).
Example 1
Crushing 5kg of commercially available fresh blackberry lily, extracting with 4 times of ethanol at room temperature for 5 days, extracting twice, combining the extracting solutions, concentrating under reduced pressure to obtain an extract, subjecting the extract to column chromatography by using AB-8 macroporous resin, eluting by sequentially using pure water, 30% ethanol aqueous solution, 60% ethanol aqueous solution and 95% ethanol aqueous solution, eluting by each gradient for 3BV, collecting 30% and 60% ethanol aqueous solution eluents respectively, and concentrating under reduced pressure to obtain Fr30 and Fr60.
Fr30 was treated with reverse phase C 18 The column chromatography was performed using 10%,20%,25%,30%,70%,95% aqueous methanol (containing 0.2% formic acid) for elution with each gradient of 3BV to obtain 6 fractions Fr30-1 to Fr30-6, wherein Fr30-2 was subjected to preparative chromatography (20% aqueous methanol elution) to obtain Compound 1.
Fr60 was treated with reverse phase C 18 The column was subjected to column chromatography, eluting with 15%,25%,35%,45%,55%,70%,95% aqueous methanol (containing 0.2% formic acid), each gradient eluting 3BV to give 7 fractions Fr60-1 to Fr60-7, wherein Fr60-3 preparative chromatography (20% aqueous methanol elution) gave compound 2 and compound 4, fr60-5 preparative chromatography (40% aqueous methanol elution) gave compound 3, and Fr60-6 preparative chromatography (60% aqueous methanol elution) gave compound 5.
The compounds prepared above were each subjected to structure confirmation by HPLC-MS, and the structure confirmation data were as follows: chen Y J, liang Z T, zhu Y, et al tissue-specific metabolites profiling and quantitative analyses of flavonoids in the rhizome of Belamcanda chinensis by combining laser-microdissection with UHPLC-Q/TOF-MS and UHPLC-QqQ-MS [ J ]. Talanta,2014,130:585-597.
Example 2
5kg of commercial medicinal material iris (dried) is taken, crushed, extracted for 5 days at room temperature by 8 times of methanol, extracted twice, the extracting solutions are combined and concentrated under reduced pressure to obtain extract, the obtained extract is subjected to column chromatography by HP-20 macroporous resin, 10% methanol aqueous solution, 50% methanol aqueous solution and 90% methanol aqueous solution are used for eluting, 50% methanol eluting component and 90% methanol eluting component are respectively collected, and the extract is obtained through reduced pressure concentration.
Separating the 50% aqueous methanol solution eluting component extract by using silica gel column chromatography, eluting by using chloroform/methanol (100:1; 50:1;20:1;10:1;5:1;3:1;2:1; 1:1) and pure methanol sequentially, eluting three column volumes by each gradient, combining the eluents at the same spot position according to the detection result of Thin Layer Chromatography (TLC), and concentrating under reduced pressure to remove the solvent to obtain Fr 1-Fr 8.
Fr3 was subjected to column chromatography using reverse phase silica gel, followed by elution with 15% aqueous methanol, 25% aqueous methanol, 30% aqueous methanol, 40% aqueous methanol, 60% aqueous methanol, 95% aqueous methanol to give 6 components Fr3-1 to Fr3-6, wherein Fr3-2 was subjected to preparative chromatography (elution with 20% aqueous methanol) to give compound 7 and compound 10, and Fr3-3 was subjected to preparative chromatography (elution with 20% aqueous methanol) to give compound 6.
Fr5 is subjected to column chromatography by using reverse phase silica gel, and is eluted by using 20% methanol aqueous solution, 30% methanol aqueous solution, 35% methanol aqueous solution, 40% methanol aqueous solution, 60% methanol aqueous solution and 95% methanol aqueous solution to obtain 6 components Fr5-1 to Fr5-6, wherein Fr5-1 is subjected to preparative chromatography (20% methanol aqueous solution elution) to obtain a compound 11, fr5-3 is subjected to preparative chromatography (30% methanol aqueous solution elution) to obtain a compound 21, and Fr5-4 is subjected to preparative chromatography (30% methanol aqueous solution elution) to obtain a compound 12.
Separating the extract of the eluting component of the 90% aqueous methanol solution by silica gel column chromatography, eluting with chloroform/methanol/water (90:10:1; 45:10:1;30:10:1;20:10:1; 10:10:1) and pure methanol sequentially, eluting three column volumes with each gradient, combining the eluents at the same spot position according to TLC detection results, concentrating under reduced pressure to remove the solvent to obtain Fr 11-Fr 16,
fr12 is subjected to column chromatography by using reverse phase silica gel, 20% methanol aqueous solution, 35% methanol aqueous solution, 40% methanol aqueous solution, 45% methanol aqueous solution, 70% methanol aqueous solution and 95% methanol aqueous solution are sequentially used for elution, 6 components Fr12-1 to Fr12-6 are obtained, wherein Fr12-2 is subjected to preparative chromatography (elution with 20% methanol aqueous solution) to obtain a compound 17, fr12-4 is subjected to preparative chromatography (elution with 40% methanol aqueous solution) to obtain a compound 9, fr12-5 is subjected to preparative chromatography (elution with 60% methanol aqueous solution) to obtain a compound 19 and a compound 20.
Fr14 was subjected to column chromatography using reverse phase silica gel, followed by elution with 30% aqueous methanol, 45% aqueous methanol, 55% aqueous methanol, 70% aqueous methanol, 95% aqueous methanol to give 5 components Fr14-1 to Fr14-5, wherein Fr14-2 was subjected to preparative chromatography (elution with 20% aqueous methanol) to give compound 13, fr14-3 was subjected to preparative chromatography (elution with 40% aqueous methanol) to give compound 14 and compound 15, and Fr14-4 was subjected to preparative chromatography (elution with 60% aqueous methanol) to give compound 8.
Fr15 was subjected to column chromatography using reverse phase silica gel, eluting with 35% aqueous methanol, 45% aqueous methanol, 70% aqueous methanol, and 95% aqueous methanol successively to give 4 components Fr15-1 to Fr15-4, wherein Fr15-3 was subjected to preparative chromatography (eluting with 60% aqueous methanol) to give compound 16 and compound 18.
Subjecting the above prepared compounds to HPLC-MS respectively 1 H-NMR、 13 C-NMR structure confirmation, structure confirmation dataThe following documents are considered:
Arisawa M,Morita N,Kondo Y,et al.Studies on Constituents of Iris Genus Plants.IV.The Constituents of Iris florentina L.(2)[J].CHEMICAL&PHARMACEUTICAL BULLETIN,1973,21(10):2323-2328.
Wollenweber E,et al.Cancer chemopreventive in vitro activities of isoflavones isolated from Iris germanica.[J].Planta Med 2003,69:15-20.
yang Yang, dong Xiaofang, shen Meilun, et al, chinese herbal medicine, 2018,49 (23): 24-30, for inhibiting lipopolysaccharide-induced NO production by mouse RAW264.7 cells in iris membranaceus and iris.
BukvicKi D,Novakovic M,Ab Ghani N,et al.Secondary metabolites from endemic species\r,Iris adriatica,Trinajstic ex Mitic(Iridaceae)[J].Natural Product Research,2017:1-4.
Yokosuka A,Koyama Y,Mimaki Y.Chemical Constituents of the Underground Parts of Iris florentina and their Cytotoxic Activity[J].Natural Product Communications,2015,10(6):955-958.
Qin M J, li R, wang X, et al New Isoflavonoid Glycosides from the Rhizomes of Iris leptophylla Lingelsh [ J ]. Proprietary plant (English edition), 2007,49 (2): 213-217.
Experimental example
1. Main reagent
Compounds 1 to 21 prepared in examples 1 to 2;
compound glycyrrhizin tablet (Le Pu pharmaceutical company, national drug standard H20073723); ALT, AST, TC, TG kit (Beckmann coulter Co., ltd., U.S.A.);
MDA kit (Nanjing institute of biological engineering) adopts thiobarbituric acid colorimetric method (TBA) and detects according to the requirement of the kit.
2. Pharmaceutical formulation
Test drug solution: preparing the compounds 1-21 into a tested drug solution with the drug concentration of 50mg/mL by adopting an aqueous solution of sodium carboxymethylcellulose (CMC-Na) with the mass percentage of 0.5%;
tectorigenin solution: preparing tectorigenin into tectorigenin solution with concentration of 50mg/mL by adopting CMC-Na water solution with mass percent of 0.5%;
compound glycyrrhizin solution: the compound glycyrrhizin is prepared into a compound glycyrrhizin solution with the concentration of 6mg/mL by adopting a CMC-Na aqueous solution with the mass percentage of 0.5 percent.
3. Experimental animals and raising
250 SPF-class SD rats with 8 weeks of age, weight of 180-220 g, animal laboratory temperature of 22-25 ℃ and relative humidity of 55-70%.
4. Grouping, modeling and administration of animals
After the SD rats were fed adaptively for 7 days, they were randomly divided into 25 groups according to body weight, 10 groups each, which were a blank control group, an alcohol model group, an experimental group (containing the compounds 1 to 21 prepared in examples 1 and 2 of the present invention), an tectorigenin control group and a compound glycyrrhizin positive control group, respectively. Wherein 10 blank groups are administered with physiological saline in the morning, the dosage of 8mL/kg is given in the first 2 weeks, and the dosage of 12mL/kg is given in the last 4 weeks; the remaining 24 groups (240) were model mice, and 50% alcohol was administered daily at noon, 8mL/kg for the first 2 weeks and 12mL/kg for the second 4 weeks.
After molding for 2 weeks (i.e. 4 weeks later), the treatment drug was administered daily in afternoon at a dose of 10mL/kg, wherein the blank control group and the alcohol model group were administered with physiological saline, and the test group (compound group 1-21), tectorigenin control group and compound glycyrrhizin positive control group were respectively administered with the test drug solution (compound group 1-21), tectorigenin solution and compound glycyrrhizin solution, and the specific administration modes were as shown in table 1:
table 1 experimental treatment modes of each group
Note that: the gastric lavage time interval between morning and afternoon is about 6 hours.
5. Index detection and method
5.1 observations after dosing
Observation is carried out before daily administration, and mental state, exercise cleaning, hair color, stool and other conditions are carried out.
5.2 Biochemical index
After the last gastric lavage, the patients are fasted and not forbidden for 12 hours, after weighing, isoflurane anesthesia is performed, abdominal aorta blood is taken, whole blood is separated, and a full-automatic biochemical analyzer (AU 480) is used for detecting serum glutamic-oxaloacetic transaminase (AST), alanine Aminotransferase (ALT), triglyceride (TG) and Total Cholesterol (TC); malondialdehyde (MDA) was measured by 10% liver tissue homogenization.
5.3 organ coefficients
After blood sampling is completed, the liver is rapidly dissected and separated, the liver is rinsed by cold normal saline, and the liver coefficient is calculated by weighing after the filter paper is wiped dry.
6. Experimental results
6.1 test results of biochemical indicators and organ coefficients of each group are shown in Table 2.
TABLE 2 detection results of Biochemical index and organ coefficients
Note that: * Represents P <0.05 compared to model control group (t-test);
* P <0.01 compared to model control group (t-test);
* P <0.001 (t-test) compared to model control group.
As shown in table 2, each biochemical index observation of the alcohol model group rats: serum glutamic-oxaloacetic transaminase (AST), alanine transaminase (ALT), triglyceride (TG), total Cholesterol (TC), malondialdehyde (MDA) are all significantly increased compared to the blank, and liver index is also significantly increased. The serum glutamic-oxaloacetic transaminase (AST), alanine transaminase (ALT), triglyceride (TG), total Cholesterol (TC), malondialdehyde (MDA) and liver index of the rats in the group 1-21 are obviously different from those in the alcohol model group, so that the improvement effect is improved to different degrees, and the improvement effect is superior to that of tectorigenin (each index of tectorigenin Huang Suzu is P <0.05 compared with that of the model control group); especially, the compound 1, 2, 3, 5, 6,7, 8, 10, 13, 14, 15 groups of rats have better improvement effect compared with the alcohol model group with P <0.01 or P < 0.001. In addition, the improvement degree of each index of the compounds 5, 7 and 13 is better than that of the compound glycyrrhizin positive control group. The above proves that the 6, 7-position cyclo-isoflavone compound provided by the invention has good activity of treating alcoholic liver injury and has good liver protection effect.
6.2 observations after dosing
6.2.1 observations of results in rats in alcohol model group
Rats in the alcohol model group showed different levels of listlessness; the ingestion and water intake are reduced, and the stool is loose; the haircolor of the rat is not glossy, a little standing condition occurs, and the rat is generally represented by scratching the mouth with the front paws and drunk: the light person walks unstably, acts hard, the heavy person overturns, the reflection disappears, and the individual rats have shortness of breath.
6.2.2 observations of the results from rats of the experimental group
Compared with the alcohol model group, the compound feed has the advantages that the listlessness degree is relieved, the ingestion water intake is reduced compared with the model group, and loose stool is improved; the frequency of the front paw scratching mouth is greatly reduced compared with the model group under the condition of partial hair color and non-gloss, and the drunk person almost has no overturning condition.
The 6, 7-position cyclic isoflavone compound provided by the invention has obvious anti-alcohol effect through observing and comparing the behaviors of rats in an alcohol model group and an experimental group.
It is apparent that the above examples are given by way of illustration only and are not limiting of the embodiments. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. While still being apparent from variations or modifications that may be made by those skilled in the art are within the scope of the invention.
Claims (4)
1. An application of isoflavone compounds and pharmaceutically acceptable salts thereof in preparing medicines for preventing or treating alcoholic liver injury or relieving or protecting liver, wherein the isoflavone compounds have the following structures:
2. the use according to claim 1, wherein the medicament further comprises a pharmaceutically acceptable carrier.
3. The use according to claim 1 or 2, wherein the medicament is formulated into clinically acceptable tablets, capsules, oral liquid, powder, drop pills, granules or injections by adding conventional excipients according to conventional processes.
4. The use according to claim 1 or 2, wherein the alcoholic liver injury comprises: alcoholic fatty liver, alcoholic liver fibrosis, alcoholic hepatitis, and alcoholic cirrhosis.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105582003A (en) * | 2016-02-26 | 2016-05-18 | 桂林医学院 | Application of methyl ferulic acid in preparation of medicine for preventing and treating alcoholic liver disease |
| CN109078011A (en) * | 2018-10-01 | 2018-12-25 | 东北师范大学 | The application of iris aglycone and its derivative in prevention and treatment insulin resistance disease medicament |
| CN112353792A (en) * | 2020-10-29 | 2021-02-12 | 南通大学 | Application of eupatilin in preparing medicament for preventing or treating alcoholic liver disease |
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|---|---|---|---|---|
| CN105582003A (en) * | 2016-02-26 | 2016-05-18 | 桂林医学院 | Application of methyl ferulic acid in preparation of medicine for preventing and treating alcoholic liver disease |
| CN109078011A (en) * | 2018-10-01 | 2018-12-25 | 东北师范大学 | The application of iris aglycone and its derivative in prevention and treatment insulin resistance disease medicament |
| CN112353792A (en) * | 2020-10-29 | 2021-02-12 | 南通大学 | Application of eupatilin in preparing medicament for preventing or treating alcoholic liver disease |
Non-Patent Citations (3)
| Title |
|---|
| "Protective Effects of Irisflorentin on PC12 Cells Against the Injury Induced by OGD/R Via Inhibiting Oxidative Stress and Apoptosis";Xiangwei XU et al.;《Lat. Am. J. Pharm.》;第38卷(第9期);第1879页 * |
| "葛花鸢尾苷醒酒作用及其醒酒机理研究";张巧芸;《CNKI优秀硕士学位论文全文库 工程科技Ⅰ辑》;第1-73页 * |
| 李钦等主编.《生药学》.中国医药科技出版社,2016,第395页. * |
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