CN109810154B - Sabia parviflora Wall.ex Roxb alkaloid compound, preparation method, using and combinations thereof - Google Patents

Sabia parviflora Wall.ex Roxb alkaloid compound, preparation method, using and combinations thereof Download PDF

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CN109810154B
CN109810154B CN201810335263.6A CN201810335263A CN109810154B CN 109810154 B CN109810154 B CN 109810154B CN 201810335263 A CN201810335263 A CN 201810335263A CN 109810154 B CN109810154 B CN 109810154B
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parviflora wall
sabia parviflora
alkaloid compound
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CN109810154A (en
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李志峰
冯育林
王�琦
欧阳辉
何明珍
杨世林
樊东辉
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Jiangxi University of Traditional Chinese Medicine
Jiangxi Bencao Tiangong Technology Co Ltd
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Jiangxi Bencao Tiangong Technology Co Ltd
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Abstract

The present invention relates to pharmaceutical technology fields, and in particular to Sabia parviflora Wall.ex Roxb alkaloid compound, preparation method and its application.The structure of Sabia parviflora Wall.ex Roxb alkaloid compound of the present invention is shown in specification;The present invention also provides the preparation methods of the QFTA compound and the QFTA compound to prevent and treat the application in fatty liver injury medicament or health care product in preparation.Show that QFTA compound provided by the invention can significantly reduce fat drips content in LO2 Human normal hepatocyte caused by fatty acid and increase through pharmacological research.LDL-C/HDL-C, ALT, AST level for reducing mouse high fat diet (HFD) induction increase, and illustrating to accumulate liver cell inner lipid has obvious inhibiting effect.It is expected to develop into the new drug or health care product with the fatty liver damage disease of prevention and treatment.

Description

Sabia parviflora Wall.ex Roxb alkaloid compound, preparation method, using and combinations thereof
Technical field
The present invention relates to pharmaceutical technology fields, and in particular to Sabia parviflora Wall.ex Roxb alkaloid compound, preparation method, application And combinations thereof.
Background technique
Sabia parviflora Wall.ex Roxb is Sabiaceae fresh breeze Calamus liana Sabia parviflora Wall.ex Roxb Sabia parviflora The drying stem and leaf of Wall.ex Roxb..Guizhou produces the Folk medicine that Sabia parviflora Wall.ex Roxb is the Bouyei, Miao ethnic group, is mainly distributed on expensive The ground such as Xingyi City, Anlong County, Ceheng County, the Wangmo County in state, rhizome, Ye Junke are used as medicine, and have the work of dispelling wind and eliminating dampness, anti-inflammatory analgetic With treatment A type and virus B hepatitis are significant in efficacy, and Small side effects.Its related kind, clinic are chiefly used in liver region Related disease, however, main active is unknown in Sabia parviflora Wall.ex Roxb at present, the working substance of liver disease is still unclear Chu.
Non-alcohol fatty liver (NAFLD) refers to except alcohol and liver cell caused by other specific liver damage factor Interior fat over-deposit is the clinical pathology syndrome of main symptom, and insulin resistance and genetic predisposition are closely related obtains Obtain property metabolic stress hepatic injury.With the fashion trend of fat and its associated metabolic syndrome globalization, non-alcoholic fatty Property hepatopathy become the Important cause of disease of the developed countries such as America and Europe and China areas of well-being chronic liver disease, average adult NAFLD suffers from Sick rate 10%~30%, wherein cirrhosis incidence is up to 25% in nonalcoholic fatty liver disease 10 years.Non-alcoholic fatty Property hepatopathy in addition to it can directly result in decompensated liver cirrhosis, hepatocellular carcinoma and liver transplantation recur, can also influence other chronic liver diseases Progress, and participate in the morbidity of type II diabetes and atherosclerosis.Metabolic syndrome associated malignancies, arteriosclerotic Cardiovascular and cerebrovascular disease and cirrhosis be influence patients with nonalcoholic fatty liver disease quality of life and life expectancy it is important because Element.For this purpose, non-alcohol fatty liver is the new challenge in contemporary medical science field, the research of therapeutic agent is still that the mankind are strong The necessary direction of health cause and task.
Summary of the invention
The present invention furthers investigate the chemical component of Sabia parviflora Wall.ex Roxb, extracts from Sabia parviflora Wall.ex Roxb a kind of new Alkaloid compound (abbreviation QFTA) proves that the QFTA compound has the function for the treatment of fatty liver damage through pharmacodynamic test.
The object of the present invention is to provide a kind of Sabia parviflora Wall.ex Roxb alkaloid compound or its pharmaceutical salt, chemistry knots Structure is as follows:
Chemical name: 1- (N, N- dimethyl amine base -2-) -3- hydroxyl phenanthrene -4-O- glucoside;For white-amorphous powder End;Molecular formula is C24H29NO7
Pharmaceutical salt of the present invention refers to that above compound is able to maintain original bioactivity and is suitable for pharmaceutical Certain salts on way, the pharmaceutical salt of the compounds of this invention can be hydrochloride, sulfate, phosphate, hydrobromate, nitric acid Salt, acetate, maleate, fumarate or succinate etc..
The present invention also provides the preparation methods of the Sabia parviflora Wall.ex Roxb alkaloid compound, comprising the following steps:
(1) it takes dry Sabia parviflora Wall.ex Roxb medicinal material as raw material, 10~14 times of quality of medicinal material of ethanol solution is added and carries out It repeatedly extracts, filtering, combined extract is concentrated under reduced pressure into no alcohol taste, obtains extract;
(2) taking the extract of step (1) that ethyl alcohol solubilising to concentration of alcohol is added is 15%~25%, and filtering removes insoluble Object obtains supernatant;
(3) macroporous resin column on the supernatant for taking step (2) to obtain, successively with water, 25%~35% ethyl alcohol, 45%~ 55% ethyl alcohol, 65%~75% ethyl alcohol, 95% or more ethanol elution, 4~6 column volumes of each gradient elution;Take 25%~ 35% alcohol elution affords 20 fractions through LH-20 gel filtration chromatography, with 15%~25% methanol, takes fraction 20 Through preparative high-performance liquid chromatographic, it is finally separating to obtain the compound.
In embodiments of the invention, the method for step (1) described extraction includes cold-maceration, percolation, Microwave Extraction Method, ultrasonic extraction, reflux extraction and continuous circumfluence extraction method.
Preferably, extracting method described in step (1) is reflux extraction, and the number of the extraction is 3 times, extraction time Respectively 2.5~3.5 hours, 1.5~2.5 hours and 1.5~3.5 hours.
Preferably, step (1) concentration of alcohol is 50%~80%.
Preferably, step (2) concentration of alcohol is 50%~95%.
Preferably, step (3) macroporous resin column use following models one of resin column: HP-20, D101, AB-8,732 cation exchange resins, HPD400, HPD100.
Preferably, it is C that efficient liquid-phase chromatography method described in step (3), which is column model,18Chromatographic column, mobile phase are The aqueous solution of 10%~80% methanol or 10%~40% acetonitrile solution, flow velocity are 4~50ml/min;It is highly preferred that described Mobile phase is the aqueous solution of 25%~35% methanol, 10~20ml/min of flow velocity, retention time 35min.
The present invention also provides the Sabia parviflora Wall.ex Roxb alkaloid compounds to prevent and treat fatty liver damage in preparation Application in medicinal health-care food and drug.
It is normal to show that QFTA compound provided by the present invention can significantly reduce LO2 people caused by fatty acid through pharmacological research Fat drips content increases in liver cell.LDL-C/HDL-C, ALT, AST level for reducing mouse high fat diet (HFD) induction increase, Illustrate to accumulate liver cell inner lipid and has obvious inhibiting effect.Therefore QFTA compound can develop into new having and prevent and control Treat the drug or health care product of fatty liver damage disease.
The present invention also provides a kind of pharmaceutical compositions, and the Sabia parviflora Wall.ex Roxb of the present invention containing therapeutically effective amount is raw Object alkaloid compound and pharmaceutically acceptable carrier.The present invention also provides this pharmaceutical compositions to prepare tablet, capsule, soft Answering in capsule, suppository, granule, transdermal absorption formulation, dripping pill, oral rapidly disintegrating formulation, sustained-release preparation, freeze-dried powder etc. With.
QFTA compound provided by the invention can significantly reduce fat drips content in LO2 Human normal hepatocyte caused by fatty acid It increases.LDL-C/HDL-C, ALT, AST level for reducing mouse high fat diet (HFD) induction increase, and illustrate to liver cell lactones Matter accumulation has obvious inhibiting effect.It is expected to develop into drug or health care that new having prevents and treats fatty liver damage disease Product.
Detailed description of the invention
Influence quantitative analysis figure of Fig. 1: the QFTA compound to the intracellular fat drips content of LO2
Influence quantitative analysis figure of Fig. 2: the QFTA compound to LO2 intracellular triglyceride content
Specific embodiment
The present invention is further described with reference to embodiments, it should be appreciated that these embodiments are not constituted to this hair Bright limitation.
Experimental method in following embodiments, unless otherwise specified, involved raw materials and reagents are common commercially available product, all It can be bought and be obtained by market, unless otherwise specified, related solution is aqueous solution.
Embodiment 1: preparation embodiment
A kind of preparation method of neoformation alkaloid compound in Sabia parviflora Wall.ex Roxb, comprising the following steps:
(1) dry Sabia parviflora Wall.ex Roxb medicinal material is taken, 70% alcohol reflux of concentration that 12 times of amounts are added every time extracts, extraction time Number is three times, extraction time is respectively 3 hours, 2 hours, 2 hours three times, is filtered, and combined extract is concentrated under reduced pressure into no alcohol Taste obtains extract;
(2) it takes the extract of step (1) that 95% ethyl alcohol is added and adjusts determining alcohol to 20%, filtration removes insoluble matter, obtains Supernatant.
(3) supernatant for taking step (2) to obtain be splined on HP-20 type macroporous resin column (sample: resin according to 1:3 body Product filling), successively with water, 30% ethyl alcohol, 50% ethyl alcohol, 70% ethyl alcohol, the elution of 95% ethanol solution, each gradient elution 5 Column volume.It takes 30% alcohol elution through LH-20 gel filtration chromatography, affords 20 fractions with 20% methanol-water.Take stream Part 20 is through preparative high-performance liquid chromatographic, chromatographic condition are as follows: C18- ODS chromatographic column (30mm × 250mm, 10 μm), methanol-water 30:70 For mobile phase, flow velocity 16ml/min, retention time 35min are finally separating to obtain the Sabia parviflora Wall.ex Roxb alkaloids chemical combination Object (QFTA), purity 99.6%.
Embodiment 2: preparation embodiment
A kind of preparation method of neoformation alkaloid compound in Sabia parviflora Wall.ex Roxb, comprising the following steps:
(1) dry Sabia parviflora Wall.ex Roxb medicinal material is taken, 50% ethyl alcohol of concentration that 14 times of amounts are added extracts under conditions of ultrasound Three times, extraction time is respectively 2.5 hours, 1.5 hours, 1.5 hours, is filtered, and combined extract is concentrated under reduced pressure into no alcohol taste, Obtain extract;
(2) it takes the extract of step (1) that 50% ethyl alcohol is added and adjusts determining alcohol to 15%, filtration removes insoluble matter, obtains Supernatant.
(3) supernatant for taking step (2) to obtain be splined on D101 type macroporous resin column (sample: resin according to 1:3 volume Filling), successively with water, 25% ethyl alcohol, 45% ethyl alcohol, 65% ethyl alcohol, the elution of 95% ethanol solution, 4 columns of each gradient elution Volume.It takes 25% alcohol elution through LH-20 gel filtration chromatography, affords 20 fractions with 15% methanol-water.Take fraction 20 through preparative high-performance liquid chromatographic, chromatographic condition are as follows: C18- ODS chromatographic column (30mm × 250mm, 10 μm), methanol-water 25:75 is Mobile phase, flow velocity 16ml/min, retention time 35min are finally separating to obtain the Sabia parviflora Wall.ex Roxb alkaloid compound (QFTA), purity 99.3%.
Embodiment 3: preparation embodiment
A kind of preparation method of neoformation alkaloid compound in Sabia parviflora Wall.ex Roxb, comprising the following steps:
(1) dry Sabia parviflora Wall.ex Roxb medicinal material is taken, 50% ethyl alcohol of concentration that 10 times of amounts are added extracts under conditions of ultrasound Three times, extraction time is respectively 3.5 hours, 2.5 hours, 2.5 hours, is filtered, and combined extract is concentrated under reduced pressure into no alcohol taste, Obtain extract;
(2) it takes the extract of step (1) that 75% ethyl alcohol is added and adjusts determining alcohol to 25%, filtration removes insoluble matter, obtains Supernatant.
(3) supernatant for taking step (2) to obtain be splined on HP-20 type macroporous resin column (sample: resin according to 1:3 body Product filling), successively use water, 35% ethyl alcohol, 55% ethyl alcohol, 75% ethyl alcohol, anhydrous ethanol elution, 6 cylinders of each gradient elution Product.It takes 35% alcohol elution through LH-20 gel filtration chromatography, affords 20 fractions with 25% methanol-water.Take fraction 20 Through preparative high-performance liquid chromatographic, chromatographic condition are as follows: C18- ODS chromatographic column (30mm × 250mm, 10 μm), methanol-water 35:65 are stream Dynamic phase, flow velocity 25ml/min, retention time 35min are finally separating to obtain the Sabia parviflora Wall.ex Roxb alkaloid compound (QFTA), purity 99.5%.
Embodiment 4: Structural Identification
The QFTA compound that Example 1 is prepared utilizes spectral technique, including ultraviolet, infrared, mass spectrum, nuclear magnetic resonance (UV、IR、MS、1H-NMR、13C-NMR, 2D-NMR) identify its structure, then through TOF high resolution mass spectrum accurately determine its molecular weight and Molecular formula.
Its spectral data is as follows:
(1) white amorphous powder, high resolution mass spec ESI-TOF-MS:444.2010 [M+H]+., determine that molecular formula is C24H29NO7, δ in H NMR spectroscopyC: 45.0 be two azine methyl signals, δC:134.3(C-1),119.4(C-2),148.0(C-3), 140.1(C-4),124.4(C-4a),127.4(C-5),129.1(C-5a),125.0(C-6),126.4(C-7),129.6(C- 8), 132.3 (C-8a), 124.5 (C-9), 122.3 (C-10), 125.3 (C-10a), 30.6 (C-11), 60.2 (C-12) show Structure is a luxuriant and rich with fragrance type alkaloid, δC: 105.8,77.2,76.2,74.3,69.7,61.0 show there is a glucose in structure Group.Then in conjunction with HMBC, the 2D nuclear magnetic resonance spectroscopies data such as HSQC determine the final structure of compound, as follows.
1H NMR(600MHz,DMSO-d6)δ:2.27(6H,s,2×N-CH3),7.20(1H,s,H-2),9.84(1H,d,J =8.6Hz, H-5), 7.85 (1H, d, J=8.9Hz, H-6), 7.56 (1H, m, H-7), 7.51 (1H, m, H-8), 7.64 (1H, d, J=9.1Hz, H-9), 7.85 (1H, d, J=8.9Hz, H-10), 3.16 (2H, m, H-11), 2.58 (2H, t, J=7.5Hz, H- 12), 4.86 (1H, d, J=7.0Hz, H-1 '), 3.61 (1H, m, H-2 '), 3.29 (1H, m, H-3 '), 3.25 (1H, m, H-4 '), 3.04(1H,m,H-5′),3.41(1H,m,H-6′a),3.30(1H,m,H-6′b);
13C NMR(150MHz,DMSO-d6)δ:134.3(C-1),119.4(C-2),148.0(C-3),140.1(C-4), 125.3(C-4a),129.6(C-5),129.1(C-5a),127.4(C-6),126.4(C-7),125.0(C-8),132.3(C- 8a),124.4(C-9),122.3(C-10),124.5(C-10a),30.6(C-11),60.2(C-12),45.0(C-NCH3), 105.8(C-1′),74.3(C-2′),76.2(C-3′),69.7(C-4′),77.2(C-5′),61.0(C-6′)。
Embodiment 5: effect experiment research
One, experimental material
1. drug, reagent, animal, cell
Human normal hepatocyte strain (LO2 cell, Shanghai Hui Ying Biotechnology Co., Ltd), fetal calf serum (Hangzhou Chinese holly Biological engineering material Co., Ltd), 1640 culture medium of RPMI Medium (Solarbio company), oleic acid (OA, O7501), palm fibre Palmitic acid acid (PA, P9767) is purchased from SIGMA company, biochemistry detection kit (Co., Ltd, Bioengineering Research Institute is built up in Nanjing), Pancreas enzyme -EDTA digestive juice (Solarbio company), glutamate-pyruvate transaminase determination reagent kit (R1, R2) (Japan and Wako Pure Chemical Industries strain Formula commercial firm), glutamic-oxalacetic transaminease assay kit (R1, R2) (Japanese Wako Pure Chemical Industries, Ltd.).
2. laboratory apparatus
Inverted microscope (Olympus-ckx41), Biohazard Safety Equipment (Heal Force), AL204 type electronic analytical balance (Mettler Toledo instrument (Shanghai) Co., Ltd.), (it is limited that instrument is contained to 100 type multitube whirlpool mixed instrument of MTV-by Hangzhou Austria Company), 7180 type automatic clinical chemistry analyzer (Hitachi, Ltd) of Hitachi.
Two, experimental method
Influence of the 1.QFTA to LO2 lipid within endothelial cells level
1.1 cell culture
1640 culture medium of the L-02 cell containing 5% fetal calf serum, in 37 DEG C, containing 5%CO2Incubator in cultivate 48h, when cell 70%~80% merges, for testing.Oleic acid or palmitinic acid are dissolved in isopropanol alcohol, 500mM is prepared as Storing liquid.By cell kind in 96 orifice plates, about 10000, every hole cell, culture for 24 hours, sucks old culture medium, then will be thin Born of the same parents are randomly divided into 5 groups: blank group, (200mM FFAs, oleic acid: palmitinic acid=2: 1), (senior middle school's low dosage divides administration group model group Not Wei 2,4,8 μ g/ml QFTA culture solution), every group of 6 multiple holes, the culture solution that blank group adds 100 μ l new, model group and administration The culture solution that 100 μ l contain 200mM FFAs is added in group, continues culture for 24 hours, sucks culture solution, blank group and model group add 100 μ L new culture solution is administered high, normal, basic dosage group and is separately added into the QFTA culture solution that 100 μ l contain 2,4,8 μ g/ml, continues to cultivate 24h。
The detection of 1.2 fat drips oil red O stains
LO2 cell is washed twice with phosphate buffered saline (PBS) into the cell, fixes 30 minutes with 4% paraformaldehyde, then It is dyed at room temperature 1 hour with oil red O solution.Dyeing liquor is sucked, twice with pure water rinsing, it is sub- that 150 μ L dimethyl are added in every hole Sulfone, shaking measure absorbance with microplate reader under 510nm wavelength.
The measurement of 1.3 triglycerides (TG) content
Collect each processing group cell, histocyte enzymatic assays liver cell content of triglyceride.Concrete operation step is by examination Agent box specification carries out.
2. zoopery and serum analysis
The ICR mouse of 5 week old is placed in the room of temperature (22 ± 2 DEG C) and humidity-controlled (50% ± 5%).Conventional drink Eat (RD;10%kcal% fat) and HFD (60%kcal% fat;) (U.S. is new purchased from Research Diets for experimental diet The state Ze Xi), give overfeeding and drinking water.After adapting to 1 week, mouse is randomly divided into the following group: RD nursing group (n=7) is Blank control group, HFD nursing group (n=7) are that (n=7, HFD add QFTA 250mg/kg for model group and three treatment groups (QFTA250) group, HFD add QFTA 500mg/kg (QFTA500) group and HFD to add fenofibrate (FEN) 30mg/kg group as sun Property control group).Medium or corresponding drug are given to Mouse oral, dosage is once a day, to continue 12 weeks, measure body daily Weight.After handling 12 weeks, by mouse overnight fasting and blood is taken.After collecting blood sample, solidify blood at room temperature, then 4 DEG C serum is prepared in 10 minutes with 2,000r/min centrifugation.Serum is stored in -75 DEG C for future use.Use kit (Stanbio Laboratory, Boerne, USA) and automatic clinical chemistry analyzer measurement serum High Density Lipoprotein Cholesterol (HDL-C), it is low Density lipoprotein-cholesterol (LDL-C), the level of alanine aminotransferase (ALT) and aspartate transaminase (AST).
Three, experimental result
Influence of the 1.QFTA to LO2 lipid within endothelial cells level
Oil red O stain testing result is as shown in Figure 1, ordinate is meant that the lipid of model group Yu each administration group in Fig. 1 The percentage (unit: %) of content and blank group lipid content;The testing result of content of triglyceride in Fig. 2 as shown in Fig. 2, indulge Coordinate is the content of triglycerides, compared to the blank group compared with after free fatty acid acts on LO2 cell for 24 hours, intracellular fat drips contain Amount, which dramatically increases, illustrates that model foundation is obvious.Compared with model group, the intracellular fat drips content of administration group significant decrease (P < 0.05).Content of triglyceride in liver cell, administration group significantly reduce (P < 0.05) compared with model group.
Note: * represents the significant difference (P < 0.05 *) compared with model group in figure.
2. results of animal
Experimental result shows that the significant raising HDLC of QFTA is horizontal, while preventing HFD from feeding caused LDL-C level and increasing. Compared with HFD group, the significant reduction of ratio of QFTA group LDL-C and HDL-C.QFTA250, QFTA500 group are small compared with HFD group Mouse Serum ALT, AST level significantly reduce.Specific experiment the results are shown in Table 1.
The influence for the variation that table 1:QFTA induces ICR mouse high fat diet (HFD).(mean ± SD, n=7)
Note:*It represents compared with model group, significant difference (*P < 0.05),**It represents compared with model group, difference is extremely aobvious Write (**P<0.01)。
The experimental results showed that, compound provided by the invention can significantly reduce fat drips in liver cell caused by fatty acid above Content and content of triglyceride increase, and LDL-C/HDL-C, ALT, the AST for reducing mouse high fat diet (HFD) induction are increased, Effect is substantially suitable with positive drug, it is contemplated that this compound derives from Chinese medicine Sabia parviflora Wall.ex Roxb, clinical application for many years, is had no Serious toxic side effect report, therefore be expected to develop into the new safety with treatment fatty liver effect, it is less toxic, effective drug or Health care product.

Claims (11)

1. a kind of Sabia parviflora Wall.ex Roxb alkaloid compound or its pharmaceutical salt, chemical structure are as follows:
2. a kind of Sabia parviflora Wall.ex Roxb alkaloid compound according to claim 1 or its pharmaceutical salt, it is described can medicine Salt is hydrochloride, sulfate, phosphate, hydrobromate, nitrate, acetate, maleate, fumarate or succinic acid Salt.
3. the preparation method of Sabia parviflora Wall.ex Roxb alkaloid compound described in claim 1, comprising the following steps:
(1) it takes dry Sabia parviflora Wall.ex Roxb medicinal material as raw material, 10~14 times of quality of medicinal material of ethanol solution is added and carries out repeatedly It extracts, filtering, combined extract is concentrated under reduced pressure into no alcohol taste, obtains extract;
(2) taking the extract of step (1) that ethyl alcohol solubilising to concentration of alcohol is added is 15%~25%, and filtering removes insoluble matter, obtains To supernatant;
(3) macroporous resin column on the supernatant for taking step (2) to obtain successively uses water, 25%~35% ethyl alcohol, 45%~55% second Alcohol, 65%~75% ethyl alcohol, 95% or more ethanol elution, 4~6 column volumes of each gradient elution;Take 25%~35% second Alcohol elutes position through LH-20 gel filtration chromatography, affords 20 fractions with 15%~25% methanol, takes fraction 20 through preparing High performance liquid chromatography is finally separating to obtain the compound.
4. the preparation method of Sabia parviflora Wall.ex Roxb alkaloid compound according to claim 3, which is characterized in that the step (1) method of the extraction includes cold-maceration, percolation, microwave loss mechanisms, ultrasonic extraction, reflux extraction and continuous backflow Extraction method.
5. the preparation method of Sabia parviflora Wall.ex Roxb alkaloid compound according to claim 3, which is characterized in that step (1) Described in extracting method be reflux extraction, the number of the extraction is 3 times, and extraction time is respectively 2.5~3.5 hours, 1.5 ~2.5 hours and 1.5~3.5 hours.
6. the preparation method of Sabia parviflora Wall.ex Roxb alkaloid compound according to claim 3, which is characterized in that step (1) The concentration of alcohol is 50%~80%;And/or step (2) concentration of alcohol is 50%~95%.
7. the preparation method of Sabia parviflora Wall.ex Roxb alkaloid compound according to claim 3, which is characterized in that step (3) The macroporous resin column use following models one of resin column: HP-20, D101, AB-8,732 cation exchange resins, HPD400、HPD100。
8. the preparation method of Sabia parviflora Wall.ex Roxb alkaloid compound according to claim 3, which is characterized in that step (3) The efficient liquid-phase chromatography method, the column model are C18Chromatographic column, the mobile phase are 10%~80% methanol Aqueous solution or 10%~40% acetonitrile solution.
9. the preparation method of Sabia parviflora Wall.ex Roxb alkaloid compound according to claim 8, which is characterized in that the flowing It is mutually the aqueous solution of 25%~35% methanol.
10. Sabia parviflora Wall.ex Roxb alkaloid compound described in claim 1 or its pharmaceutical salt prevent and treat rouge in preparation Application in fat liver injury medicament health food and drug.
11. a kind of pharmaceutical composition, the Sabia parviflora Wall.ex Roxb alkaloids chemical combination described in claim 1 containing therapeutically effective amount Object and pharmaceutically acceptable carrier.
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