CN114736106A - Lignan dimer compound and preparation method and application thereof - Google Patents
Lignan dimer compound and preparation method and application thereof Download PDFInfo
- Publication number
- CN114736106A CN114736106A CN202210457795.3A CN202210457795A CN114736106A CN 114736106 A CN114736106 A CN 114736106A CN 202210457795 A CN202210457795 A CN 202210457795A CN 114736106 A CN114736106 A CN 114736106A
- Authority
- CN
- China
- Prior art keywords
- lignan
- dimer compound
- compound
- silica gel
- methanol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/34—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/34—Separation; Purification; Stabilisation; Use of additives
- C07C41/36—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/34—Separation; Purification; Stabilisation; Use of additives
- C07C41/38—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention belongs to the technical field of medicines, and particularly discloses a lignan dimer compound, and a preparation method and application thereof. The separation preparation method of the compound is simple, and the pure compound can be obtained. Experiments show that the compound can obviously reduce the ALT and AST activities of the serum of a model mouse with liver injury caused by D-galactosamine and the MDA content of liver tissues, enhances the SOD activity of the liver, and has obvious protection effect on the liver injury.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a lignan dimer compound, a preparation method and application thereof, in particular to application in preparing a liver-protecting medicine.
Background
The liver is the largest gland and parenchymal organ of the human body and has various physiological functions of metabolism, detoxification, biotransformation, hematopoiesis, immunity and the like; meanwhile, the liver is also easily damaged by various exogenous and exogenous substances such as poison, medicine and toxic metabolites. Liver damage is a pathological condition common to many liver diseases. Liver diseases are common diseases and frequently encountered diseases in clinic, particularly the incidence of viral hepatitis, liver cirrhosis and liver cancer in China is high, and the health of people is seriously harmed, so the prevention and the treatment of liver injury are particularly important. At present, the drugs clinically used for treating liver injury mainly comprise reduced glutathione, compound glycyrrhizin, diammonium glycyrrhizinate, bicyclol, bifendate, polyene phosphatidylcholine, silymarin, tiopronin and the like, wherein the silymarin and the polyene phosphatidylcholine are extracted from plants, so that the finding of the drugs for treating liver injury from the plants is feasible.
LilacSyringa oblataLindl is deciduous tree of Syzygium of Oleaceae. The plant has abundant resources, is mainly distributed in northeast and inner Mongolia areas of China, and is a common interior-warming medicine. Warm in nature, pungent in flavor, entering spleen, stomach and lung, protecting liver and promoting function of gallbladderAnti-inflammatory and antibacterial effects. The pharmacological activities of treating acute icteric hepatitis and diarrhea and hepatitis are recorded in Xinhua Bencao gang Zhi and Changbai mountain botanical drug records, respectively. Lilac contains abundant chemical components, mainly including terpenes, lignans, phenylpropanoids, flavonoids and other chemical components. The invention intensively studies the chemical components of the lignans in the extract, and screens the lignans to obtain a novel lignans compound with the liver protection effect.
Disclosure of Invention
The invention aims to carry out deep research on chemical components of syringa oblata stems and provides a lignan dimer compound in syringa oblata and a preparation method and application thereof.
The technical scheme of the invention is as follows:
a lignan dimer compound extracted from Syringa oblata is named as disecoisolariciresinol, and has the following structural formula:
the invention also provides a preparation method of the lignan dimer compound, which comprises the following steps:
(1) adding ethanol solution into the lilac stems for extraction, collecting the extracting solution, filtering and concentrating to obtain extract concentrated solution;
(2) sequentially extracting the concentrated extract liquid obtained in the step (1) with dichloromethane and ethyl acetate to obtain dichloromethane part extract and ethyl acetate part extract;
(3) dissolving the ethyl acetate part extract obtained in the step (2) with methanol, adding silica gel, mixing the sample by a dry method, loading the sample into the silica gel column for column chromatography separation, performing gradient elution by dichloromethane-methanol with the volume ratio of 100:0, 90:10, 80:20, 70:30, 50:50, 30:70 and 0:100, and performing gradient elution by silica gel GF254Inspecting thin layer plate, spreading with petroleum ether-ethyl ester (volume ratio of 8:1, 4:1, 2:1, 1:1, 0: 1), respectively, mixing fractions containing approximate spots to obtain 14 fractions 1, 2, 3,4、5、6、7、8、9、10、11、12、13、14；
(4) Dissolving fraction 3 with methanol, separating by ODS reversed phase column chromatography, eluting with methanol-water at volume ratio of 1:10, 1:5, 2:5, 3:5, 4:5, 1:1, and 0:1, and detecting by HPLC with the following conditions: welchrom C18 reverse phase chromatography column, mobile phase: methanol-0.1% formic acid in water (40: 60 by volume), isocratic elution, full wavelength sweep, flow rate: 1mL/min, respectively analyzing spectra under the wavelengths of 254nm, 280nm and 300nm, and combining fractions with similar chemical compositions to obtain 7 fractions a, b, c, d, e, f and g;
(5) and taking the fraction d, and separating by using a preparative liquid chromatography with the volume ratio of 35: 65 taking methanol-water as mobile phase to elute, and keeping time for 28min, and separating to obtain pure compound.
Preferably, in the step (1), the specific extraction method is a cold soaking method, a percolation method, a microwave extraction method, an ultrasonic extraction method, a reflux extraction method or a continuous reflux extraction method, the volume fraction of the ethanol solution is 35-95%, more preferably 70% ethanol solution, and the addition amount of the ethanol solution is 4-20 times of the mass of the syringa oblata stem.
Preferably, in the step (2), the dosage of the dichloromethane and the ethyl acetate is 1/5-1/3 of the volume of the concentrated extract liquid each time, and the extraction times are 2-6 times.
Preferably, in the step (3), the mass ratio of the ethyl acetate part extract to the silica gel used for sample mixing is 1:2, the silica gel used for sample mixing is 100-200 meshes, and the silica gel used for the silica gel column is 100-200 meshes.
Preferably, in the step (4), the ODS reversed-phase column chromatography conditions are as follows: packing Daisogel Silica gel for HPLC (sp-120-40/60-ODS-RPS), column size 6 cm. times.80 cm, flow rate: 25mL/min, column temperature 25 ℃.
Preferably, in step (5), the chromatographic conditions of the preparative liquid chromatography are as follows: the size of a YMC-TriartC18 chromatographic column is 250 multiplied by 20mm, the particle size is 5 mu m, the flow rate is 10mL/min, and the column temperature is 25 ℃.
The invention also provides application of the lignan dimer compound in preparing a liver-protecting medicament.
Preferably, the lignan dimer compound specifically has a protective effect on liver damage caused by D-galactosamine.
The invention also provides a pharmaceutical preparation, which comprises a lignan dimer compound with effective treatment amount and a pharmaceutically acceptable carrier or auxiliary material, and the pharmaceutical preparation is an oral preparation or an injection preparation.
The lignan compound can be directly or indirectly added into various pharmaceutically acceptable common adjuvants such as filler, disintegrant, lubricant, and binder for preparing different dosage forms, and made into common oral preparation or injection by conventional method.
Preferably, the oral preparation can be tablets, capsules, granules, fat emulsion, microcapsules and dropping pills.
Preferably, the injection preparation can be injection or powder injection.
Has the advantages that: the lignan dimer compound has a simple preparation process, experiments show that the compound can obviously reduce the ALT and AST activities of serum and the MDA content of liver tissues of a model mouse with liver injury caused by D-galactosamine, enhance the activity of liver SOD, and have an obvious protective effect on liver injury, and toxicity experimental researches show that the compound with the liver protection effect has no obvious toxicity, and is expected to be developed into a new medicine with the liver protection effect.
Drawings
FIG. 1 is a chemical structural formula of a compound of the present invention;
FIG. 2 is a MS plot of a compound of the present invention;
FIG. 3 is a drawing of a compound of the present invention1H-NMR chart;
FIG. 4 is a drawing of a compound of the present invention13C-NMR chart;
FIG. 5 is a DEPT spectrum of a compound of the present invention;
FIG. 6 is an HSQC spectrum of a compound of the present invention;
FIG. 7 is an HMBC spectrum of a compound of the present invention;
FIG. 8 is a drawing of a compound of the present invention1H-1H-COSY spectrum;
FIG. 9 is a drawing of a compound of the present invention1H-1A schematic diagram of structural analysis of H-COSY and HMBC spectrums;
FIG. 10 is a graph showing the results of cytotoxicity experiments with the compounds of the present invention.
Detailed Description
In order to further understand the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Unless otherwise specified, the reagents involved in the examples of the present invention are all commercially available products, and all of them are commercially available.
Example 1
This example provides a lignan dimer compound having the following structural formula:
the embodiment also provides a preparation method of the lignan dimer compound, which specifically comprises the following steps:
(1) taking 10kg of lilac stem medicinal material, adding 70% ethanol solution with the weight of 8 times of the medicinal material, reflux-extracting for 2 times, each time for 2 hours, combining the extracting solutions, filtering, and concentrating until no alcohol smell exists to obtain an extract concentrated solution;
(2) extracting the concentrated extract obtained in the step (1) with 1/3 volumes of dichloromethane of the extract for 5 times, extracting with 1/3 volumes of ethyl acetate for 5 times, and concentrating the extracts under reduced pressure to obtain dichloromethane part extract and ethyl acetate part extract respectively;
(3) dissolving the ethyl acetate part extract obtained in the step (2) with methanol, adding silica gel (100-200 meshes, mass ratio: sample/silica gel = 1/2)) into the mixture, mixing the mixture by a dry method, and loading the mixture to a sample stationPerforming column chromatography on silica gel (100-200 mesh) column, performing gradient elution with dichloromethane-methanol at volume ratio of 100:0, 90:10, 80:20, 70:30, 50:50, 30:70, and 0:100, and eluting with silica gel GF254Inspecting thin layer plate, spreading with petroleum ether-ethyl ester (volume ratio of 8:1, 4:1, 2:1, 1:1, 0: 1), and mixing fractions containing similar spots to obtain 14 fractions 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14;
(4) dissolving fraction 3 with methanol, and separating by ODS reversed phase column chromatography under the following conditions: packing Daisogel Silica gel for HPLC (sp-120-40/60-ODS-RPS), column size 6 cm. times.80 cm, flow rate: 25mL/min, column temperature 25 ℃. Eluting with methanol-water gradient at volume ratio of 1:10, 1:5, 2:5, 3:5, 4:5, 1:1, 0:1, and detecting by HPLC under the following conditions: welchrom C18 reverse phase chromatography column, mobile phase: methanol-0.1% formic acid in water (40: 60 by volume), isocratic elution, full wavelength sweep, flow rate: 1mL/min, respectively analyzing spectra under the wavelengths of 254nm, 280nm and 300nm, and combining fractions with similar chemical compositions to obtain 7 fractions a, b, c, d, e, f and g;
(5) dissolving fraction d with 80% methanol water solution, and separating by preparative liquid chromatography under the following chromatographic conditions: YMC-TriartC18 chromatographic column, the size of the chromatographic column is 250X 20mm, the particle size is 5 μm, the flow rate is 10mL/min, and the column temperature is 25 ℃. The volume ratio is 35: and (5) eluting with 65% methanol-water as mobile phase, and keeping for 28min to obtain pure compound with purity of 99.7%.
Example 2
This example provides a method for preparing a lignan dimer compound:
(1) taking 10kg of syringa vulgaris stem, adding 95% ethanol solution with the amount of 4 times of the weight of the medicinal materials, performing cold soaking extraction for 3 times, performing cold soaking for 3 days each time, combining the extracting solutions, filtering, and concentrating until no alcohol smell exists to obtain an extract concentrated solution;
(2) extracting the concentrated extract obtained in the step (1) with 1/4 volumes of dichloromethane of the extract for 2 times each time, then extracting with 1/4 volumes of ethyl acetate for 2 times, and concentrating each extract under reduced pressure to obtain dichloromethane part extract and ethyl acetate part extract respectively;
the rest of the procedure was the same as in example 1.
Example 3
This example provides a method for preparing a lignan dimer compound:
(1) taking 10kg of syringa vulgaris stem, adding 35% ethanol solution 20 times the weight of the medicinal materials, performing reflux extraction for 4 times, 1 hour each time, combining the extracting solutions, filtering, and concentrating until no alcohol smell exists to obtain an extract concentrated solution;
(2) extracting the concentrated extract obtained in the step (1) with 1/5 volumes of dichloromethane of the extract for 6 times, extracting with 1/5 volumes of ethyl acetate for 6 times, and concentrating the extracts under reduced pressure to obtain dichloromethane part extract and ethyl acetate part extract respectively;
the rest of the procedure was the same as in example 1.
Structure analysis and identification of compound
Mainly uses the wave spectrum technology, including ultraviolet, infrared, mass spectrum, nuclear magnetic resonance (1H-NMR、13C-NMR, 2D-NMR), and the compound obtained in example 1 was subjected to structural analysis, and the specific spectrum is shown in fig. 2 to 8, and the spectral data and analysis process are as follows:
(1) white amorphous powder, high resolution mass spectrometry ESI-TOF-MS: 721.3269M-H.
The molecular formula of the compound is C40H50O12The exact molecular weight is 722.3302 and the unsaturation is 16.
By analysis of1H-NMR, it can be concluded that there are two ABX system signals in the structure of the compound, at δ H6.69 (4H, t, J =3.7, 7.9Hz), 6.58 (2H, d, J =8.0Hz), with 4 methoxy groups [ δ H3.78 (6H, s), 3.71 (6H, s)]Three methylene signals [ δ H3.61 (8H, m), 2.65 (8H, m) and 1.98 (4H, m)](ii) a By analysis of13C-NMR data, finding the pattern shows 20 carbon signals, 12 olefin proton signals; the compound is shown to be a highly symmetrical structure by fitting mass spectral data of the compound, and the compound is found to be related to the compound secoisolarici by nuclear magnetic resonance carbon spectral data analysisThe resinol has similarity, and then the compound is determined to be a dimer of the secoisolariciresol by combining two-dimensional nuclear magnetic resonance spectrum data such as HMBC, DEPT-135 and HSQC spectrums
The connection structure is shown in the attached figure 1, and the name is disciosololariciiresinol.
Wherein, the compound1H-1The structural analysis of H-COSY and HMBC spectra is shown in figure 9.
(2) The spectral data of this compound are summarized in the following table:
of the compounds of Table 11H-NMR and13C-NMR dataa
Note: a denotes the compound is dissolved in deuterated methanol1H-NMR（600MHz）、13C-NMR (150 MHz) spectrum.
Secondly, research on drug effect experiment of the compound
(I) test materials and animals
1. Drugs and agents
The lignan dimer compound prepared in example 1 of the present invention; human hepatocytes LO-2 (institute of basic medicine, national academy of medical sciences); CCK-8 (Dalian Meilun Biotech Co., Ltd.); PRMI-1640 medium (Beijing Soilebao Tech Co., Ltd.); fetal bovine serum (gemini); biological grade dimethyl sulfoxide (DMSO) (beijing solibao technologies ltd); AST (glutamic-oxalacetic transaminase), ALT (glutamic-pyruvic transaminase), MDA (malondialdehyde) and SOD (superoxide dismutase) kits are purchased from Nanjing institute of bioengineering; d-galactosamine (D-GalN, Sigma Co.) was diluted to a 70mg/mL solution with distilled water immediately before use; bifendate tablets (Beijing Taoyyo pharmaceutical Co., Ltd.), sodium carboxymethylcellulose (Gallery Senxuan cellulose Co., Ltd.) was prepared into a 0.5% solution with distilled water immediately before use.
2. Laboratory apparatus
Inverted electron microscope (OLYMPUS: CKX41, Japan), microplate reader (Molecular Devices: SpectraMax i3, USA), MCV-B161S (T) type superclean bench (SANYO, Japan), MCO-20ACI type CO2Thermostated incubator (Thermo company, usa), a ten thousandth balance model BS125S (mettler-toledo, switzerland), a desk top microcentrifuge model TDL-5C (Eppendorf, germany).
3. Animal(s) production
KM mice, clean grade, male and female halves, weight 20 + -2 g (Hunan Slek Jingda laboratory animals Co., Ltd.).
(II) Experimental method
1. Preparation of sample solution
Preparing a cell drug administration solution: after the compound prepared by the invention is dissolved in DMSO, 2, 5, 10, 20, 50 and 100 mu mol/L of drug-containing culture medium solutions are respectively obtained by diluting with PRMI-1640 culture medium, wherein the volume of the DMSO is controlled within three thousandth of the total volume.
Preparing a modeling agent solution: D-GalN was formulated into a solution of 70mg/mL with physiological saline according to a molding dose of 700mg/kg for animal administration.
Preparing an animal drug administration solution: an animal was dosed with a 0.5% sodium carboxymethylcellulose solution mixed with an accurately weighed amount of the compound prepared in example 1 to prepare a suspension of 4mg/mL in accordance with a dose of 40 mg/kg.
Preparing a positive medicine solution: according to the administration dose of 100mg/kg, 0.5% sodium carboxymethyl cellulose solution and accurately weighed bifendate are mixed to prepare 10mg/mL suspension for animal administration.
2. Investigating the toxicity of the Compounds of the invention
The toxicity of the compound prepared in example 1 to human hepatocyte LO-2 was examined by the CCK-8 method. Taking LO-2 cells in logarithmic growth phase, adjusting cell density to 5 × 10 with 1640 medium containing 10% fetal calf serum4cell/mL, inoculated in 96-well plates, and cell culture media containing compounds of different drug concentrations (2, 5, 10, 20, 50, 100 μmol/L) were inoculated in the culture media100 mu L/well is added into a 96-well plate, a normal cell control group and a blank group are additionally arranged, a cell culture solution without drugs is added into the control group, and a fresh 1640 culture medium containing 10% fetal bovine serum is added into the blank group. Each group had 6 multiple wells with 5% CO at 37 deg.C2After 24 hours of culture in an incubator, the supernatant was discarded, 10% CCK-8 solution was added thereto, 100 μ L was added to each well, and after 1 hour of incubation in an incubator at 37 ℃, absorbance (OD value) was measured at 450 nm in a microplate reader, and cell survival rate (%) = (OD value of administered group-blank OD value)/(OD value of control group-blank OD value) × 100% was calculated according to the formula. And calculating the cell survival rate.
3. Explore the influence of the compound on the D-GalN induced acute liver injury of mice
40 KM mice were selected and randomly divided into 4 groups of 10, namely a normal group, a model group, a compound group and a positive drug group. The normal group and the model group are administrated with 0.1mL/10g of 0.5 percent sodium carboxymethylcellulose solution by intragastric administration, the other groups are administrated with 40mg/kg/d of compound group and 100mg/kg/d of positive drug group respectively, and the administration is performed by intragastric administration according to the volume of 0.1mL/10g every day. After the continuous administration for 7 days and the last administration for 1h, the acute liver injury is caused by the intraperitoneal injection of 0.1mL/10g of D-GalN (700 mg/kg) in each group except the normal group which is intraperitoneally injected with 0.1mL/10g of physiological saline. After 16h, all mice were bled using the retroorbital venous plexus and sera were isolated for ALT and AST activity determination. The mice were sacrificed after blood collection, and then a part of liver was collected and prepared into 10% liver homogenate with physiological saline, and the MDA content and the SOD activity were measured according to the kit instructions.
4. Statistical method
Experimental data on
Shows that the SPSS 19.0 statistical software was used for the t-test comparison, P<0.05 is statistically significant.
(III) results of the experiment
1. The toxicity test results of the compounds of the present invention are shown in FIG. 10. The result shows that the cytotoxicity is not shown in the concentration range of 2-100 [ mu ] mol/L.
2. The results of the effects of the compounds of the present invention on D-GalN induced acute liver injury in mice are shown in Table 2 below.
TABLE 2 Effect of Compounds on D-GalN induced acute liver injury in mice: (
，n = 10）
Note: p < 0.05 compared to normal group; p < 0.01; a means P < 0.05 compared to model group; tangle-solidup means P < 0.01.
The experimental results in table 2 show that the compound can significantly reduce the ALT and AST activities of the serum of a model mouse with liver injury caused by D-galactosamine and the MDA content of liver tissues, enhance the SOD activity of the liver, and have obvious protection effect on the liver injury.
Finally, it should be noted that the above-mentioned embodiments are only preferred embodiments of the present invention, and not intended to limit the present invention, and although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications and equivalents can be made in the technical solutions described in the foregoing embodiments, or some technical features thereof can be replaced. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A lignan dimer compound, wherein: the structural formula of the compound is as follows:
2. a method for producing the lignan dimer compound of claim 1, wherein: the method specifically comprises the following steps:
(1) adding ethanol solution into the lilac stems for extraction, collecting the extracting solution, filtering and concentrating to obtain extract concentrated solution;
(2) sequentially extracting the concentrated extract liquid obtained in the step (1) with dichloromethane and ethyl acetate to obtain a dichloromethane part extract and an ethyl acetate part extract;
(3) dissolving the ethyl acetate part extract obtained in the step (2) with methanol, adding silica gel into the mixture, mixing the mixture by a dry method, loading the mixture into the silica gel column, performing column chromatography separation, and performing gradient elution by dichloromethane-methanol with volume ratios of 100:0, 90:10, 80:20, 70:30, 50:50, 30:70 and 0:100 to obtain 14 fractions 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 14;
(4) dissolving fraction 3 with methanol, separating by ODS reversed phase column chromatography, and gradient eluting with methanol-water at volume ratio of 1:10, 1:5, 2:5, 3:5, 4:5, 1:1, and 0:1 to obtain 7 fractions a, b, c, d, e, f, and g;
(5) and taking the fraction d, and separating by using a preparative liquid chromatography with the volume ratio of 35: 65 taking methanol-water as mobile phase to elute, and keeping time for 28min, and separating to obtain pure compound.
3. The method for producing a lignan dimer compound according to claim 2, wherein: in the step (1), the volume fraction of the ethanol solution is 35-95%, and the adding amount of the ethanol solution is 4-20 times of the mass of the syringa vulgaris stems.
4. The method for producing a lignan dimer compound according to claim 2, wherein: in the step (2), the dosage of dichloromethane and ethyl acetate is 1/5-1/3 of the volume of the concentrated solution of the extract each time, and the extraction times are 2-6 times.
5. The method for producing a lignan dimer compound according to claim 2, wherein: in the step (3), the silica gel used for sample mixing is 100-200 meshes, and the silica gel used in the silica gel column is 100-200 meshes.
6. The method for producing a lignan dimer compound according to claim 2, wherein:
in the step (4), the ODS reversed-phase column chromatography conditions are as follows: packing Daisogel Silica gel for HPLC, column size 6 cm. times.80 cm, flow rate: 25 mL/min.
7. The method for producing a lignan dimer compound according to claim 2, wherein:
in the step (5), the chromatographic conditions of the preparative liquid chromatography are as follows: and a YMC-TriartC18 chromatographic column, wherein the size of the chromatographic column is 250 multiplied by 20mm, the particle size is 5 mu m, and the flow rate is 10 mL/min.
8. Use of the lignan dimer compound of claim 1 in the preparation of a liver-protecting medicament.
9. The use of a lignan dimer compound of claim 8, wherein: in particular to the protective effect on the liver injury caused by D-galactosamine.
10. A pharmaceutical formulation characterized by: the lignan dimer compound of claim 1, wherein the pharmaceutical preparation is an oral preparation or an injectable preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210457795.3A CN114736106B (en) | 2022-04-28 | 2022-04-28 | Lignan dimer compound, and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210457795.3A CN114736106B (en) | 2022-04-28 | 2022-04-28 | Lignan dimer compound, and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114736106A true CN114736106A (en) | 2022-07-12 |
| CN114736106B CN114736106B (en) | 2023-06-09 |
Family
ID=82283913
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210457795.3A Active CN114736106B (en) | 2022-04-28 | 2022-04-28 | Lignan dimer compound, and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114736106B (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103169788A (en) * | 2013-04-16 | 2013-06-26 | 南京中医药大学 | Chinese date leaf extractive and application thereof in preparation of medicament or health food for preventing and treating liver injury |
| CN111925404A (en) * | 2020-09-09 | 2020-11-13 | 江西中医药大学 | Preparation method and application of lignan compound |
| CN113563172A (en) * | 2021-09-23 | 2021-10-29 | 江西中医药大学 | Azulene compound and preparation method and application thereof |
| CN113620912A (en) * | 2021-10-12 | 2021-11-09 | 江西省药品检验检测研究院 | Furanone compound and preparation method and application thereof |
| CN113845498A (en) * | 2021-09-15 | 2021-12-28 | 江西中医药大学 | Lignans compound and preparation method and application thereof |
| CN113956229A (en) * | 2021-12-20 | 2022-01-21 | 江西中医药大学 | Lignan compound in lilac and preparation method and application thereof |
| CN114105751A (en) * | 2022-01-25 | 2022-03-01 | 江西中医药大学 | Terpenoid and preparation method and application thereof |
| CN114105770A (en) * | 2022-01-25 | 2022-03-01 | 江西中医药大学 | Ester compound and preparation method and application thereof |
-
2022
- 2022-04-28 CN CN202210457795.3A patent/CN114736106B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103169788A (en) * | 2013-04-16 | 2013-06-26 | 南京中医药大学 | Chinese date leaf extractive and application thereof in preparation of medicament or health food for preventing and treating liver injury |
| CN111925404A (en) * | 2020-09-09 | 2020-11-13 | 江西中医药大学 | Preparation method and application of lignan compound |
| CN113845498A (en) * | 2021-09-15 | 2021-12-28 | 江西中医药大学 | Lignans compound and preparation method and application thereof |
| CN113563172A (en) * | 2021-09-23 | 2021-10-29 | 江西中医药大学 | Azulene compound and preparation method and application thereof |
| CN113620912A (en) * | 2021-10-12 | 2021-11-09 | 江西省药品检验检测研究院 | Furanone compound and preparation method and application thereof |
| CN113956229A (en) * | 2021-12-20 | 2022-01-21 | 江西中医药大学 | Lignan compound in lilac and preparation method and application thereof |
| CN114105751A (en) * | 2022-01-25 | 2022-03-01 | 江西中医药大学 | Terpenoid and preparation method and application thereof |
| CN114105770A (en) * | 2022-01-25 | 2022-03-01 | 江西中医药大学 | Ester compound and preparation method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| YASUDA, SEIICHI 等: "Chemical structures of sulfuric acid lignin. VIII. Reactions of 1,2-diaryl-1,3-propanediol and pinoresinol with sulfuric acid", MOKUZAI GAKKAISHI * |
| 姜月红 等: "紫丁香苷对大鼠肝缺血再灌注损伤保护作用的初步研究", 中国实验诊断学 * |
| 田雷 等: "紫丁香叶的化学成分研究", 中国实验方剂学杂志 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114736106B (en) | 2023-06-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2023045612A1 (en) | Azulene compound, and preparation method therefor and use thereof | |
| CN105294623B (en) | A kind of Sesquiterpene lactones compound, its preparation method and application | |
| US9278948B2 (en) | Line leaf inula flower lactone A and methods for preparing and using the same for treating multiple sclerosis | |
| CN103599144B (en) | The preparation method of jatamans valeriana rhizome epoxy iridoid ester active component | |
| CN101979366A (en) | Diarylheptanoid compounds in curcuma zedoary and medicinal application thereof | |
| CN107837301B (en) | Piper laetispicum extract and preparation method and application thereof | |
| CN107137434B (en) | Pharmaceutical composition, preparation method thereof and application thereof in preparation of coxsackie virus resistant medicine | |
| CN116606269B (en) | Renilla diterpenoid compound and extract L01 and application thereof in pharmacy | |
| CN109232491A (en) | The Preparation method and use of benzofuran compounds in a kind of Herba Serissae | |
| CN102875615B (en) | Extraction method and application of falcate dolichos root or leaf glucoside A and total saponins of falcate dolichos root or leaf | |
| CN113956229B (en) | Lignan compound in lilac and preparation method and application thereof | |
| CN109867649B (en) | Biflavonoid compound and preparation method and application thereof | |
| CN114736106A (en) | Lignan dimer compound and preparation method and application thereof | |
| JP5131855B2 (en) | Plant-derived malignant tumor therapeutic agent | |
| TW201109013A (en) | Cyclohexenone chemical compounds of Antrodia cinnamomea for suppressing the growth of the Lymphoma tumor cell | |
| CN106822071B (en) | Chinese medicinal effective component for treating coronary heart disease and hyperlipidemia, its preparation method and method for separating effective component from the same | |
| CN107485615A (en) | Purposes of the Ligustrum robust glycosides C and combinations thereof in treatment hyperlipidemia and slimming medicine is prepared | |
| CN108892657B (en) | Iridoid ester compound, preparation method and application thereof | |
| CN102675252B (en) | There is Cesong alkyl type diterpine compound and the application thereof of anti-tumor activity | |
| CN105753681A (en) | Drug composition of citicoline sodium and medical application of drug composition | |
| CN109111462A (en) | A kind of Salvia japonica A prime and preparation method thereof and the drug comprising Salvia japonica A prime | |
| CN108619179A (en) | Geranium extract and its medical usage | |
| CN116509921B (en) | Application of rice flower sesterterpene extract K01 in preparation of medicines for treating sepsis | |
| CN109575089B (en) | Acylated glucose compounds, pharmaceutical composition, preparation method and application thereof | |
| CN109206392A (en) | A kind of coumarin kind compound and the preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |