CN107176960B - A kind of alkaloid compound and its preparation and application - Google Patents
A kind of alkaloid compound and its preparation and application Download PDFInfo
- Publication number
- CN107176960B CN107176960B CN201610137352.0A CN201610137352A CN107176960B CN 107176960 B CN107176960 B CN 107176960B CN 201610137352 A CN201610137352 A CN 201610137352A CN 107176960 B CN107176960 B CN 107176960B
- Authority
- CN
- China
- Prior art keywords
- preparation
- compound
- formula
- component
- molecular weight
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
Abstract
The present invention provides compound shown in a kind of formula (I) and its preparation and application, the compound has stronger lipase inhibiting activity.
Description
Technical field
The present invention relates to pharmaceutical technology field more particularly to a kind of alkaloid compound and its preparations and application.
Background technique
Summer inaction Papaveraceae Corydalis Subgen. Capnites plant lies prostrate raw corydalis [Corydalis decumbens (Thunb)
Pers. stem tuber].Main product is saved in Jiangxi, Hunan, Fujian, Zhejiang, Anhui etc., is preferred with Jiangxi yield and quality.It records in middle traditional Chinese medicines
Allusion quotation 2010 version one, there is the effect of promoting blood circulation and removing obstruction in channels, promoting qi circulation and relieving pain.Clinically it is usually used in treating the protrasion of the lumbar intervertebral disci, sits
Osteoneuralgia, rheumatic arthritis etc..There are many decumbent corydalis tuber preparation developed at present, wherein corypalis tablet, Compound"Xia Tianwu"
Piece, decumbent corydalis tuber eye drop, Rhizoma corydalis decumbenti Injection have been put into Traditional Chinese medicine historical preparation protection kind.
Summary of the invention
In view of this, the technical problem to be solved in the present invention is that provide a kind of compound and its preparation and application, preparation
Compound have certain inhibiting effect for lipase.
The present invention provides a kind of alkaloid compounds, have structure shown in formula (I):
The present invention also provides a kind of preparation methods of compound shown in formula (I), comprising:
A summer useless alcohol steep) is obtained into medicinal extract；
B the obtained medicinal extract of step A) is mixed with water), is successively extracted with petroleum ether and ethyl acetate, respectively obtains petroleum
Ether extract and acetic acid ethyl ester extract；
C) acetic acid ethyl ester extract for obtaining step B) carries out pillar layer separation, is carried out with chloroform, methanol mixed solvent
Gradient elution, the chloroform, methanol volume ratio be (100:0)~(0:100), collect molecular weight be 263 component；
D standby chromatography, semi-preparative liquid chromatography or system) are suppressed in the group lease making that the molecular weight for collecting step C) is 263
Standby chromatographic isolation, obtains compound shown in formula (I)；
Preferably, the step C) in collect molecular weight be 263 component specifically:
C1) eluent that gradient elution obtains is merged into similar flow point after TLC is detected and be grouped；
C2) component after step C1) grouping is detected using LC-MS, by the compound for being 263 containing molecular weight
Component merges；
C3 polarity segments) are carried out to the component that step C2) is obtained using HPLC；
C4) component after step C3) segmentation is detected using LC-MS, collects the component that molecular weight is 263.
Preferably, the step C1) in, it is grouped into points 10 groups.
Preferably, the step C3) in, polarity segments are to be divided into 10 sections according to polarity difference.
Preferably, the step A) in ethyl alcohol be 60%~95% ethyl alcohol.
Preferably, the step A) specifically:
By summer useless alcohol steep, filtrate is concentrated to get medicinal extract after filtering.
The present invention also provides compounds shown in a kind of formula (I) to treat the application in high blood cholesterol drug in preparation,
The present invention also provides a kind of pharmaceutical composition, including compound shown in formula (I),
Preferably, described pharmaceutical composition is for treating hyperlipidemia or slimming medicine.
Compared with prior art, the present invention provides a kind of compounds with structure shown in formula (I), for lipase
There is certain inhibiting effect, can be used for preparing high blood cholesterol drug, slimming medicine.
Detailed description of the invention
Fig. 1 is the HR-ESI-Q-TOF-MS figure of compound shown in formula provided by the invention (I)；
Fig. 2 is the nucleus magnetic hydrogen spectrum figure of compound shown in formula provided by the invention (I)；
Fig. 3 is the nuclear-magnetism carbon spectrogram of compound shown in formula provided by the invention (I)；
Fig. 4 is the HSQC figure of compound shown in formula provided by the invention (I)；
Fig. 5 is the HMBC figure of compound shown in formula provided by the invention (I)；
Fig. 6 is compound shown in formula provided by the invention (I)1H-1H COSY figure.
Specific embodiment
The present invention provides a kind of alkaloid compounds, have structure shown in formula (I):
The present invention also provides a kind of preparation methods of compound shown in formula (I), comprising:
A summer useless alcohol steep) is obtained into medicinal extract；
B the obtained medicinal extract of step A) is mixed with water), is successively extracted with petroleum ether and ethyl acetate, respectively obtains petroleum
Ether extract and acetic acid ethyl ester extract；
C) acetic acid ethyl ester extract for obtaining step B) carries out pillar layer separation, is carried out with chloroform, methanol mixed solvent
Gradient elution, the chloroform, methanol volume ratio be (100:0)~(0:100), collect molecular weight be 263 component；
D standby chromatography, semi-preparative liquid chromatography or system) are suppressed in the group lease making that the molecular weight for collecting step C) is 263
Standby chromatographic isolation, obtains compound shown in formula (I)；
The present invention is using decumbent corydalis as medicine material as raw material, summer that the decumbent corydalis as medicine material can be known to the skilled person
Without medicinal material, the present invention has no its source specifically limited.
The present invention first extracts decumbent corydalis as medicine material with ethyl alcohol, and filtrate is concentrated to get medicinal extract after filtering.In the present invention,
The ethyl alcohol is preferably 60%~95% ethyl alcohol (volume fraction), more preferably 80%~95% ethyl alcohol；The decumbent corydalis as medicine material
The ratio of weight and ethyl alcohol volume is preferably 1:(6~10), more preferably 1:(7~9), in some embodiments of the invention
In, the ratio is 1:8.The extraction is preferred to be carried out 3~4 times.In aforementioned proportion, decumbent corydalis as medicine material unit of weight is g, ethyl alcohol
Volume unit is mL.
The present invention is to the method for above-mentioned concentration and is not particularly limited, and can be method for concentration well known in the art, the present invention
It is preferred that being concentrated using the method for decompression, removes solvent and obtain concentrate.
After obtaining medicinal extract, it is mixed with water, is dispersed in water medicinal extract, then successively extracted with petroleum ether and ethyl acetate
Take, be concentrated, dry after respectively obtain petroleum ether extract and acetic acid ethyl ester extract；It is special that the present invention has no the dosage of water
It limits, medicinal extract can be made to disperse；In the present invention, the weight ratio of the petroleum ether volume and medicinal extract is preferably (1~5): 1,
In some embodiments of the invention, the ratio is 1:1,2:1,3:1,5:1；The ethyl acetate volume and medicinal extract
Weight ratio is preferably (1~5): 1, in some embodiments of the invention, the ratio is 1:1,2:1,3:1,5:1；On
The unit for stating ratio is mL/g；In the present invention, the number of the extraction is preferably 3~6 times.
Then, obtained acetic acid ethyl ester extract is subjected to pillar layer separation, present invention preferably employs silicagel columns, with chlorine
Imitative, methanol mixed solvent carries out gradient elution, the chloroform, methanol volume ratio be (100:0)~(0:100), passed by polarity
Promote row gradient elution, collects the component that molecular weight is 263；Concentration gradient of the present invention to the chloroform, methanol mixed solvent
And be not particularly limited, it can choose according to actual needs.
In the present invention, above-mentioned collection molecular weight be 263 component specifically:
C1) eluent that gradient elution obtains is merged into similar flow point after TLC is detected and be grouped；
C2) component after step C1) grouping is detected using LC-MS, by the compound for being 263 containing molecular weight
Component merges；
C3 polarity segments) are carried out to the component that step C2) is obtained using HPLC；
C4) component after step C3) segmentation is detected using LC-MS, collects the component that molecular weight is 263.
The step C1) in, similar flow point refers to the similar component of polarity.It, will in some embodiments of the invention
The similar component of polarity is merged after TLC is detected, is divided into 10 groups by the eluent that gradient elution obtains.
Step C2) in, it is detected using LC-MS, the leading ion in the LC-MS detection of compound under cation mode
Segment are as follows: m/z 264.0869 [M+H]+, m/z 549.1484 [2M+Na]+。
Step C3) component that is obtained using HPLC to step C2) is when carrying out polarity segments, in certain specific realities of the invention
It applies in example, is divided into 10 sections.
Step C4) in, it is detected using LC-MS, the leading ion in the LC-MS detection of compound under cation mode
Segment are as follows: m/z 264.0869 [M+H]+, m/z 549.1484 [2M+Na]+。
It is middle to suppress standby chromatography, semi-preparative liquid chromatography or preparation chromatographic isolation after collecting component, formula (I) can be obtained
Shown compound；
The present invention has carried out Structural Identification to obtained compound, as a result referring to FIG. 1 to FIG. 6, wherein Fig. 1 is the present invention
The HR-ESI-Q-TOF-MS of compound shown in the formula (I) of offer schemes, and Fig. 2 is the core of compound shown in formula provided by the invention (I)
Magnetic hydrogen spectrogram, Fig. 3 are the nuclear-magnetism carbon spectrogram of compound shown in formula provided by the invention (I), and Fig. 4 is formula provided by the invention (I)
The HSQC of shown compound schemes, and Fig. 5 is the HMBC figure of compound shown in formula provided by the invention (I), and Fig. 6 is provided by the invention
Compound shown in formula (I)1H-1H COSY figure.
Specifically, can learn that m/z is 264.0869 [M+H] by the mass spectral analysis of Fig. 1+(calculated value is
264.0866), 549.1484 [2M+Na]+, and then determine that compound molecule formula is C13H13NO5, calculating degree of unsaturation is 8.
This compound13C NMR (being shown in Table 1) display has 13 carbon signals, has 5 Asias in conjunction with the supposition of hsqc spectrum diagram data
Methyl (wherein 1 is even oxygen carbon), 2 methines (being olefinic carbon) and 6 quaternary carbons [1 ester carbonyl group, 1 amidocarbonylation, 4
Olefinic carbon (two of them connect oxygen)].In addition, according to nuclear magnetic spectrogram1H NMR data (being shown in Table 1) is it is found that there are the methylenes of two company's oxygen
Base [δH6.09 (s, 2H) and 4.44 (s, 2H)], 3 methylene [δ being mutually coupledH3.60 (t, J=6.9Hz, 2H),
2.35 (t, J=6.8Hz, 2H), 2.02-1.90 (m, 2H)] and 2 fragrant Hydrogen Proton [δ being mutually coupledH7.01 (d, J=
7.8Hz, 1H) and 6.95 (d, J=7.9Hz, 1H)].In addition, in conjunction with1H,1H-COSY spectrogram (Fig. 6) is it is found that there are an Asias
Methylenedioxy group and-a CH2CH2CH2Structure fragment.6 olefinic carbon signals and 2 carbonyl carbon signals account for altogether 8 unsaturations
5 of the inside, thus it is speculated that there are three rings for this compound tool.The NMR nuclear magnetic spectrogram that the structure of compound 1 further passes through 2D is solved
Analysis, especially HMBC spectrogram.In the HMBC spectrogram of compound 1, H2-15(δH6.09, s, 2H) and C-10 (δC149.7) and
C-11(δC144.6) related description methylene-dioxy is connected on C-10 and C-11；H2-8(δH4.44, s, 2H) and C-6 (δC
177.0) related description ester carbonyl group is connected with C-8；H2-5(δH2.35, t, J=6.8Hz, 2H), H2-4(δH 2.02–1.90,m,
2H) with C-6 (δC177.0) related supposition-CH2CH2CH2It is connected with C-6；H2-3(δH3.60, t, J=6.9Hz, 2H) and C-2
Correlation speculates that amidocarbonylation is connected on C-3.3 ring structures of compound 1 need the nitrogen-atoms on amide groups to connect with C-14, this
Speculate and passes through C-14 (δC136.3) chemical shift is confirmed compared with low field.In conclusion the structure of compound 1 is accredited as such as formula
(I) shown in, and it is named as decumbensalkal.All hydrocarbon signals assignments are referring to table 1.Through SciFinder Scholar
Network retrieval finds that this compound has no document report, shows it for a new alkaloid compound.
The nuclear magnetic data of 1 compound of table
(deuterated CD3OD,1H-NMR 400MHz,13C-NMR 100MHz)
Crucial HMBC coherent signal (H → C) and 1H-1H COSY (H-C) signal
The present invention also provides a kind of application of the compound shown in formula (I) in preparation treatment high blood cholesterol drug.
Through the embodiment of the present invention it is found that compound on fatty enzyme of the present invention has good inhibiting effect.
The present invention also provides a kind of pharmaceutical compositions, including compound shown in formula (I).
In the present invention, it is also preferable to include auxiliary materials acceptable in drug in described pharmaceutical composition.
In the present invention, described pharmaceutical composition is for treating hyperlipidemia or slimming medicine.
Invention has obtained compound shown in formula (I), and by above-mentionedization by extracting research to decumbent corydalis as medicine material
It closes object and carries out cell experiment, it is found that it has obvious inhibiting effect to lipase, and then in preparation treatment high blood cholesterol drug or subtract
Fertile drug field has potential application.
In order to further illustrate the present invention, below with reference to embodiment to compound provided by the invention and its preparation and application
It is described in detail.
Embodiment 1
Decumbent corydalis as medicine material 1000g is taken, is extracted 3 times with 95% ethyl alcohol 8000mL, filtrate concentration and recovery ethyl alcohol obtains after filtering
Medicinal extract.
This medicinal extract is re-dissolved in water and suspension is made, and is successively extracted with petroleum ether and ethyl acetate, the liquid bulk extracted every time
Product ratio is 1:1, is extracted 3 times, petroleum ether extract and acetic acid ethyl ester extract is concentrated under reduced pressure to obtain in combining extraction liquid.
Acetic acid ethyl ester extract is separated using silica gel column chromatography, chloroform-methanol in varing proportions mixes solvent
(100:0~0:100) is incremented by by polarity carries out gradient elution, and presses volume collection flow point, mono- fraction of every 1000mL.Then,
Merge similar flow point after TLC is detected, is divided into 10 components, is denoted as Fr.l-Fr.10.
Using LC-MS test analysis 10 components of above-mentioned gained, the component for the compound for being 263 containing molecular weight is tracked,
It merges, obtained component carries out polarity segments through preparation HPLC after merging, is divided into 10 sections (being denoted as A-1 to A-10), then
Tracking molecular weight using LC-MS test analysis is that 263 compounds are present in A-9 set of segmentation, and A-9 set of segmentation is partly prepared
Liquid chromatogram separation, obtains compound 10.8mg shown in formula (I) of the present invention.
Through detecting, purity 98%.
Its HR-ESI-Q-TOF-MS figure is shown in Fig. 1, and as shown in Figure 1, molecular weight is 264.0869 [M+H]+。
Magnetic resonance detection is carried out to the compound of preparation and determines that its structure, testing result are shown in Fig. 2~Fig. 6, nuclear-magnetism number
According to see Table 1 for details.
As above-mentioned detection it is found that compound prepared by the present invention has structure shown in formula (I).
Embodiment 2
Decumbent corydalis as medicine material 1000g is taken, is extracted 3 times with 95% ethyl alcohol 6000mL, filtrate concentration and recovery ethyl alcohol obtains after filtering
Medicinal extract.
This medicinal extract is re-dissolved in water and suspension is made, and is successively extracted with petroleum ether and ethyl acetate, the liquid bulk extracted every time
Product ratio is 2:1, is extracted 3 times, petroleum ether extract and acetic acid ethyl ester extract is concentrated under reduced pressure to obtain in combining extraction liquid.
Acetic acid ethyl ester extract is separated using silica gel column chromatography, petroleum ether-acetone in varing proportions mixes solvent
(100:0~0:100) is incremented by by polarity carries out gradient elution, and presses volume collection flow point, mono- fraction of every 1000mL.Then,
Merge similar flow point after TLC is detected, is divided into 10 components, is denoted as Fr.l-Fr.10.
Using LC-MS test analysis 10 components of above-mentioned gained, the component for the compound for being 263 containing molecular weight is tracked,
It merges, obtained component carries out polarity segments through preparation HPLC after merging, is divided into 10 sections (being denoted as A-1 to A-10), then
Tracking molecular weight using LC-MS test analysis is that 263 compounds are present in A-8 set of segmentation, and A-8 set of segmentation is partly prepared
Liquid chromatogram separation, obtains compound 7.5mg shown in formula (I) of the present invention.
Through detecting, purity 98%.
The compound of preparation is detected through HR-ESI-Q-TOF-MS, and molecular weight is 264.0869 [M+H]+。
Magnetic resonance detection is carried out to the compound of preparation and determines its structure, it was demonstrated that compound prepared by the present invention has formula
(I) structure shown in.
Embodiment 3 inhibits lipase active experiment
1. drug, materials and methods
1.1 drug
Decumbent corydalis tuber noval chemical compound prepared by embodiment 1
1.2 material
Porcine pancreatic lipase, 4- nitrobenzene palmitate, gum arabic powder, orlistat, sigma company；
Tris, Amersco；
Isopropanol, Sinopharm Chemical Reagent Co., Ltd.；
NaTDC, Sinopharm Chemical Reagent Co., Ltd.；
DMSO, Sinopharm Chemical Reagent Co., Ltd.；
Hydrochloric acid, Nanjing Chemistry Reagent Co., Ltd..
Microplate reader, molecular devices spectraMax M2e；
Balance, Mettler Toledo AL104；
Centrifuge, Eppendorf 5424.
1.3 methods:
(1) preparation of reagents
Compounding medicine: it weighs sample (compound or orlistat shown in formula (I)) and is dissolved in DMSO and be configured to 200mg/mL
Mother liquor, -20 DEG C of preservations.
Buffer: 50mM Tris-HCl solution contains 0.1% gum arabic powder and 0.2% NaTDC, pH
Value is 10.0.
Enzyme solutions are prepared: buffer 1.2mg/mL enzyme used, is mixed, 5000rpm is centrifuged 5 minutes, takes supernatant, and it dispenses ,-
70 DEG C of preservations.
Substrate solution is prepared: weighing 0.302g pNPP (4-NPP), 32ml isopropanol, excusing from death cream is added
Change, as 25mMpNPP, packing, 4 DEG C of preservations.
(2) lipase inhibitor determination of activity
In 96 porocyte culture plates, 198 μ l buffers are added, add 9.6 μ l 50mg/mL sample mother liquors, mixes,
Make its initial concentration 2.4mg/ml.Again with buffer carry out doubling dilution make its concentration be followed successively by 1.2mg/ml, 0.6mg/ml,
0.3mg/ml,0.15mg/ml.Lipase solution buffer dilutes 120 times, and substrate dilutes 50 times with buffer.The above dilution
Reagent afterwards is stand-by.
96 porocyte culture plates are taken, are separately added into buffer, inhibitor and lipase according to grouping different in table 2,37
DEG C be incubated for 10 minutes.After ten minutes, 100 μ l substrates are added in every hole for lipase and inhibitor preincubate, and 37 DEG C are reacted 60 minutes.?
The light absorption value in each hole is measured at microplate reader OD405nm.
2 lipase inhibitor of table screens reaction system (200 μ l)
In table 2,
A: for unchecked dose of enzyme activity；A: for unchecked dose of blank control (not enzyme)；
B: for the enzyme activity of inhibiting；B: for the blank control (not enzyme) of inhibiting.
2. result treatment and analysis
The calculation formula of fatty enzyme inhibition rate: Inhibition rate%=[1- (B-b)/(A-a)] × 100.
Calculated result is shown in Table 3, and table 3 is that each dosage group of compound shown in formula (I) summarizes the inhibiting effect of lipase, by table
3 as it can be seen that the inhibition lipase active that each dosage group of compound can be different degrees of shown in formula prepared by the present invention (I).
Inhibiting effect of each dosage group of compound to lipase shown in 3 formula of table (I)
**P < 0.01, compared with the control group.
It is above-mentioned the experimental results showed that, compound on fatty enzyme shown in formula (I) prepared by the present invention have In-vitro Inhibitory Effect,
And dose-effect relationship is presented.
4 reducing blood lipid of embodiment measurement
1. drug, materials and methods
1.1 drug
Decumbent corydalis tuber noval chemical compound prepared by embodiment 1
1.2 material
Simvastatin, Sigma；
Balance, Mettler Toledo；
Centrifuge, Eppendorf 5424；
Microplate reader, molecular devices spectraMax M2e；
Total cholesterol (TC) assay kit, triglycerides (TG) assay kit, low-density lipoprotein (LDL-C) measurement
Kit and high-density lipoprotein (HDL-C) assay kit, Zhongsheng Beikong Biological Science & Technology Co., Ltd.；Alanine amino
Transferase (ALT) assay kit, aspartate amino transferase (AST) assay kit, Nanjing is built up bioengineering and is ground
Study carefully institute.
Animal: male SD rat, weight (50 ± 10) g are provided, credit number purchased from Zhejiang Province's Experimental Animal Center:
SCXK (Zhejiang) 2008-0033.
Feed: basal nutrient feed and nutrient fodder high in fat are (phonetic containing 3% cholesterol, 0.2% cholic acid, 0.5% rosickyite oxygen
Pyridine, 10% lard) it is provided by Jiangning Qinglongshan animal reproduction field.
1.3 methods:
(1) modeling
It SD rat 120, randomly selects 15 and is only used as blank control group.Blank control group gives basal nutrient feed,
Remaining and 105 be only given nutrient fodder high in fat, gives 15g/d nutrient fodder high in fat, free water daily within the 1st week.During modeling, weekly
Last gives the level for taking blood examination to survey TC or TG after nutrient fodder 16h high in fat.TC the or TG level of rat is more than normal group after 6 weeks
Rat (P < 0.05) is modeling success.
(2) grouping and administration
The successful rat of modeling is randomly divided into model group, positive control (Simvastatin) group, the high agent of decumbent corydalis tuber noval chemical compound
Amount group, decumbent corydalis tuber noval chemical compound middle dose group, decumbent corydalis tuber noval chemical compound low dose group, every group 15.Administration group and model group after
Continue and give food high lipid food, blank control group feeds basal feed.It is new that dosage is respectively as follows: Simvastatin 10mg/kg, decumbent corydalis tuber
Compound high dose group 50mg/kg, decumbent corydalis tuber noval chemical compound middle dose group 25mg/kg, decumbent corydalis tuber noval chemical compound low dose group
12.5mg/kg.Suspension is made into pure water, gastric infusion volume is 10mL/kg, continuous 6 weeks.Administration time is daily 16:
00.Isometric pure water is given in model group stomach-filling, and blank control group is with no treatment.
(3) detection method
Weight (being accurate to 0.1g) is surveyed once with electronic balance weekly, detects the horizontal big substantially to observe of TC or TG weekly
The modeling and treatment condition of mouse.Before being put to death to the animal of administration 6 weeks (12h empty stomach before putting to death), weigh, with 1% amobarbital
Sodium intraperitoneal injection of anesthesia rat, takes liver organization and weighs weight in wet base.
Thoracic cavity is opened, directly take a blood sample 4~6mL from heart, anticoagulant heparin separates serum, according to the measurement of kit requirement
Condition and program determination serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein
(HDL-C), alanine aminotransferase (ALT), aspartate amino transferase (AST) content.
2. result treatment and analysis
The influence of 2.1 pairs of rat fats
Experimental result is shown in Table 4, and table 4 is that rat fat measurement result summarizes, by table 4 as it can be seen that compared with blank control group, mould
The content apparent increase (P < 0.01) of the total cholesterol, triglycerides and low-density lipoprotein of type group rat, high-density lipoprotein
Content significantly reduce (P < 0.05)；Each dosage group of decumbent corydalis tuber noval chemical compound can be different degrees of reduction obese rat total gallbladder it is solid
Alcohol, triglycerides and low-density lipoprotein content；Decumbent corydalis tuber noval chemical compound high dose group can also increasing high density lipoprotein contain
It measures (P < 0.05).
4 rat fat of table measurement summarize (N=15)
*P < 0.05,**P < 0.01, compared with the control group；#P < 0.05,##P < 0.01, compared with model group；
The influence of 2.2 pairs of rat body weights and liver function
Table 5 is rat body weight, liver function test result, by table 5 as it can be seen that compared with blank control group, model group rats
Weight, liver weight, AST, ALT value dramatically increase (P < 0.01)；The high, medium and low dosage group of decumbent corydalis tuber noval chemical compound can be different degrees of
Mitigate the weight and liver weight of rat；Decumbent corydalis tuber noval chemical compound is high, middle dose group can obviously reduce rat AST and ALT (P <
0.01)。
5 rat body weight of table, liver function test result (N=15)
**P < 0.01, compared with the control group；#P < 0.05,##P < 0.01, compared with model group；
Above-mentioned experimental result shows that compound shown in the formula (I) of the application preparation, each dosage group can subtract in various degree
The compound of the weight of light hyperlipidemia rats and liver weight, high dose and middle dosage can reduction TC, TG, LDL- in various degree
C, the content of AST and ALT；High doses of compounds group can also increasing high density lipoprotein content.Show the application preparation
Compound shown in formula (I) has certain reducing blood lipid, antiobesity action, can be used for hyperlipidemia, and high with decumbent corydalis tuber noval chemical compound
Dosage group effect is more excellent.
Decumbent corydalis tuber noval chemical compound of the present invention is compound shown in the formula (I) of the application preparation.
The above description of the embodiment is only used to help understand the method for the present invention and its core ideas.It should be pointed out that pair
For those skilled in the art, without departing from the principle of the present invention, the present invention can also be carried out
Some improvements and modifications, these improvements and modifications also fall within the scope of protection of the claims of the present invention.
Claims (10)
1. a kind of alkaloid compound has structure shown in formula (I):
2. a kind of preparation method of compound shown in formula (I), comprising:
A summer useless alcohol steep) is obtained into medicinal extract；
B the obtained medicinal extract of step A) is mixed with water), is successively extracted with petroleum ether and ethyl acetate, petroleum ether extraction is respectively obtained
Take object and acetic acid ethyl ester extract；
C) acetic acid ethyl ester extract for obtaining step B) carries out pillar layer separation, carries out gradient with chloroform, methanol mixed solvent
Elution, the chloroform, methanol volume ratio be (100:0)~(0:100), collect molecular weight be 263 component；
D standby chromatography, semi-preparative liquid chromatography) are suppressed in the group lease making for being 263 by the molecular weight that step C) is collected or prepare color
Spectrum separation, obtains compound shown in formula (I)；
3. preparation method according to claim 2, which is characterized in that the step C) in collect molecular weight be 263 group
Point specifically:
C1) eluent that gradient elution obtains is merged into similar flow point after TLC is detected and be grouped；
C2) component after step C1) grouping is detected using LC-MS, by the component for the compound for being 263 containing molecular weight
Merge；
C3 polarity segments) are carried out to the component that step C2) is obtained using HPLC；
C4) component after step C3) segmentation is detected using LC-MS, collects the component that molecular weight is 263.
4. preparation method according to claim 3, which is characterized in that the step C1) in, it is grouped into points 10 groups.
5. preparation method according to claim 3, which is characterized in that the step C3) in, polarity segments are according to polarity
Difference is divided into 10 sections.
6. preparation method according to claim 2, which is characterized in that the step A) in ethyl alcohol be 60%~95% second
Alcohol.
7. preparation method according to claim 2, which is characterized in that the step A) specifically:
By summer useless alcohol steep, filtrate is concentrated to get medicinal extract after filtering.
8. a kind of application of the compound shown in formula (I) in preparation treatment high blood cholesterol drug,
9. a kind of pharmaceutical composition, including compound shown in formula (I),
10. application of the pharmaceutical composition as claimed in claim 9 in preparation treatment high blood cholesterol drug or slimming medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610137352.0A CN107176960B (en) | 2016-03-10 | 2016-03-10 | A kind of alkaloid compound and its preparation and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610137352.0A CN107176960B (en) | 2016-03-10 | 2016-03-10 | A kind of alkaloid compound and its preparation and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107176960A CN107176960A (en) | 2017-09-19 |
| CN107176960B true CN107176960B (en) | 2019-07-12 |
Family
ID=59830704
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610137352.0A Active CN107176960B (en) | 2016-03-10 | 2016-03-10 | A kind of alkaloid compound and its preparation and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107176960B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101289471A (en) * | 2007-04-18 | 2008-10-22 | 代龙 | Process for separating total alkaloids of corydalis rhizome form Chinese medicament extracting solution of corydalis rhizome |
| CN105311119A (en) * | 2014-08-04 | 2016-02-10 | 上海医药工业研究院 | Refined rhizoma corydalis decumbentis total alkaloid product, preparation method thereof, pharmaceutical composition and application of refined rhizoma corydalis decumbentis total alkaloid product and pharmaceutical composition |
| CN105367580A (en) * | 2014-08-29 | 2016-03-02 | 上海医药工业研究院 | Preparation method of corydalis amabilis alkaloid monomers |
-
2016
- 2016-03-10 CN CN201610137352.0A patent/CN107176960B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101289471A (en) * | 2007-04-18 | 2008-10-22 | 代龙 | Process for separating total alkaloids of corydalis rhizome form Chinese medicament extracting solution of corydalis rhizome |
| CN105311119A (en) * | 2014-08-04 | 2016-02-10 | 上海医药工业研究院 | Refined rhizoma corydalis decumbentis total alkaloid product, preparation method thereof, pharmaceutical composition and application of refined rhizoma corydalis decumbentis total alkaloid product and pharmaceutical composition |
| CN105367580A (en) * | 2014-08-29 | 2016-03-02 | 上海医药工业研究院 | Preparation method of corydalis amabilis alkaloid monomers |
Non-Patent Citations (2)
| Title |
|---|
| 夏天无生物碱的高速逆流色谱分离纯化;王岱杰 等;《分析化学》;20100630;第38卷(第6期);第783-788页 |
| 夏天无的化学成分研究;廖惠平 等;《中草药》;20141130;第45卷(第21期);第3067-3070页 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107176960A (en) | 2017-09-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Nie et al. | Assessment of in vitro cardiotoxicity of extract fractions and diterpene alkaloids from Aconitum leucostomum Worosch: a short communication | |
| CN106748666B (en) | Natural medicine for reducing blood sugar and its use in preparing medicine for diabetes or obesity | |
| US10093695B2 (en) | Sterol derivative, preparation method therefor and use thereof | |
| CN111166731A (en) | Application of kaurane diterpenoid compounds derived from potentilla anserine in inhibiting lipopexia | |
| CN107802626B (en) | Hypoglycemic composition and preparation method and application thereof | |
| CN105949156A (en) | Pharmaceutical composition of itraconazole and pharmaceutical application of pharmaceutical composition | |
| CN107176960B (en) | A kind of alkaloid compound and its preparation and application | |
| CN111153955A (en) | Gynostemma pentaphylla extract with lipid-lowering effect and preparation method and application thereof | |
| CN106619652A (en) | Preparation method of spermacoce latifolia triterpenoids and application of spermacoce latifolia triterpenoids in preparation of glycosidase inhibitor drug | |
| CN105198943B (en) | A kind of entitled tea hill how glycosides A acylated flavonoids glucosides and its preparation method and application | |
| CN111150740A (en) | Lipid-lowering active ingredient and lipid-lowering composition in panax japonicus and application of lipid-lowering active ingredient and lipid-lowering composition | |
| CN109810154B (en) | Sabia parviflora Wall.ex Roxb alkaloid compound, preparation method, using and combinations thereof | |
| CN106491670A (en) | A kind of Fructus Bruceae extract, extracting method and application | |
| CN114262294B (en) | Phenyl isoquinoline alkaloid compound and preparation method and application thereof | |
| CN107674108B (en) | Application of stigmastane steroid compound in preparing medicine for treating diabetes or obesity | |
| CN109206429A (en) | A kind of isoquinoline alkaloid compound and its preparation method and application | |
| CN107325069B (en) | Extraction method of sesquiterpenoids | |
| CN104161859B (en) | It is a kind of to be used to treat Chinese medicine composition of the spleen and stomach illness and preparation method thereof | |
| CN106748778B (en) | New bibenzyl natural medicine with hypoglycemic effect and its prepn and use | |
| CN106265681A (en) | Compound 2 α, 3 β dihydroxy 23 aldehyde radical olive 12 alkene 28 acid application in preparing glycosidase inhibitor | |
| CN104710395B (en) | A kind of compound and its preparation method and application | |
| CN101570485B (en) | Sugar alcohol ester of long-chain fatty acid, separation and extraction method thereof and application thereof in inhibiting the activity of aromatizing enzyme | |
| CN110585221A (en) | Albizzia julibrissin new lignan compound for improving steatosis and application thereof | |
| CN110638822A (en) | Albizzia julibrissin glycoside compound for promoting endothelial cell proliferation and application thereof | |
| CN104450818B (en) | A kind of method and its application that pyrroles's acid compound is prepared using hickory chick |
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 |