CN109748941A - Gomuti sugarpalm fruit analgesic compounds and its preparation method and application - Google Patents
Gomuti sugarpalm fruit analgesic compounds and its preparation method and application Download PDFInfo
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Abstract
Gomuti sugarpalm fruit analgesic compounds and its preparation method and application, are related to analgesic compounds and its preparation method and application.Analgesic compounds of the invention are extracted from natural plants, and gomuti sugarpalm fruit analgesic compounds I, II, III, IV and V of the present invention all have analgesia, anti-inflammatory effect and effect.
Description
Technical field
The present invention relates to analgesic compounds and its preparation method and application.
Background technique
Pain is that body comes to harm a kind of aversion response generated after sexual stimulus, is often accompanied by fear, anxiety, uneasiness etc.
Emotional activity.Pain is a kind of symptom of certain diseases again, can make one to agonize.Severe pain removes and is reflected in sensorial pain
Not Anwai in bitter and mood, and can lead to physiological dysfunction, cause insomnia, or even induce and suffer a shock and threat to life.Therefore,
It is clinically appropriate to be necessary using antalgesic with alleviating severe pain and preventing shock, have in treatment disease and trauma nursing important
Meaning.
Summary of the invention
Analgesic compounds of the invention are extracted from natural plants, are used as the active constituent of analgesic.
The molecular formula of gomuti sugarpalm fruit analgesic compounds I is C10H18O7, molecular weight 250, molecular structural formula are as follows:
The molecular formula of gomuti sugarpalm fruit analgesic compounds II is C8H14O4, molecular weight 174, molecular structural formula are as follows:
The molecular formula of gomuti sugarpalm fruit analgesic compounds III is C14H22O5, molecular weight 270, molecular structural formula are as follows:
The molecular formula of gomuti sugarpalm fruit analgesic compounds IV is C23H18O7, molecular weight 406, molecular structural formula are as follows:
The molecular formula of gomuti sugarpalm fruit analgesic compounds V is C12H22O8, molecular weight 294, molecular structural formula are as follows:
Gomuti sugarpalm fruit analgesic compounds I are prepared according to the following steps:
One, the fresh fruit of gomuti sugarpalm fruit, extracting solution vacuum concentration are extracted with 70% EtOH；
Two, by step 1 concentrate H2O dissolution, then successively with petroleum ether, chloroform, ethyl acetate and n-butanol extraction
It takes, butanol extraction liquid vacuum concentration obtains n-butyl alcohol extract；
Three, silica gel column chromatography separation chromatography n-butyl alcohol extract, is 20:1 and the CH of 10:1 with volume ratio2Cl2/ MeOH according to
The CH of 10:1 is collected in secondary elution2Cl2/ MeOH eluent, every 1 times of column volume eluent is a, successively marks, and selects the 9th part and the
10 parts of eluents merge to obtain B5；
Four, chromatography B5, the MeOH/H for being 2:8 with volume ratio are separated with octadecylsilane chemically bonded silica chromatographic column2O is washed
It is de-, eluent is collected, B5-1 is obtained；
Five, preparative RP-HPLC is added in B5-1, and mobile phase is the MeOH/H of volume ratio 2:82O, flow velocity 5mL/min, tR
=30min collects eluent and obtains gomuti sugarpalm fruit analgesic compounds I.
Gomuti sugarpalm fruit analgesic compounds II are prepared according to the following steps:
One, the fresh fruit of gomuti sugarpalm fruit, extracting solution vacuum concentration are extracted with 70% EtOH；
Two, by step 1 concentrate H2O dissolution, then successively with petroleum ether, chloroform, ethyl acetate and n-butanol extraction
It takes, butanol extraction liquid vacuum concentration obtains n-butyl alcohol extract；
Three, silica gel column chromatography separation chromatography n-butyl alcohol extract, the CH for being 20:1 with volume ratio2Cl2/ MeOH elution, is collected
Eluent, every 1 times of column volume eluent is a, successively marks, selects the 2nd part of eluent, obtain A2；
Four, chromatography A2 is separated with octadecylsilane chemically bonded silica chromatographic column, is 2:8 and the MeOH/ of 3:7 with volume ratio
H2O is successively eluted, and collects the MeOH/H of 3:72O eluent obtains A2-2；
Five, preparative RP-HPLC is added in A2-2, and mobile phase is the MeOH/H of volume ratio 3:72O, flow velocity 5mL/min, tR
=23min collects eluent and obtains gomuti sugarpalm fruit analgesic compounds II.
Gomuti sugarpalm fruit analgesic compounds III are prepared according to the following steps:
One, the fresh fruit of gomuti sugarpalm fruit, extracting solution vacuum concentration are extracted with 70% EtOH；
Two, by step 1 concentrate H2O dissolution, then successively with petroleum ether, chloroform, ethyl acetate and n-butanol extraction
It takes, butanol extraction liquid vacuum concentration obtains n-butyl alcohol extract；
Three, silica gel column chromatography separation chromatography n-butyl alcohol extract, the CH for being 20:1 with volume ratio2Cl2/ MeOH elution, is collected
Eluent, every 1 times of column volume eluent is a, successively marks, selects the 2nd part of eluent, obtain A2；
Four, chromatography A2 is separated with octadecylsilane chemically bonded silica chromatographic column, is 2:8,3:7,4:6,5:5 with volume ratio
With the MeOH/H of 6:42O is successively eluted, and collects the MeOH/H of 6:42O eluent obtains A2-5；
Five, preparative RP-HPLC is added in A2-5, and mobile phase is the MeOH/H of volume ratio 6:42O, flow velocity 5mL/min, tR
=45min collects eluent and obtains gomuti sugarpalm fruit analgesic compounds III.
Gomuti sugarpalm fruit analgesic compounds IV is prepared according to the following steps:
One, the fresh fruit of gomuti sugarpalm fruit, extracting solution vacuum concentration are extracted with 70% EtOH；
Two, by step 1 concentrate H2O dissolution, then successively with petroleum ether, chloroform, ethyl acetate and n-butanol extraction
It takes, butanol extraction liquid vacuum concentration obtains n-butyl alcohol extract；
Three, silica gel column chromatography separation chromatography n-butyl alcohol extract, the CH for being 20:1 with volume ratio2Cl2/ MeOH elution, is collected
Eluent, every 1 times of column volume eluent is a, successively marks, selects the 2nd part of eluent, obtain A2；
Four, chromatography A2, the MeOH/H for being 2:8 with volume ratio are separated with octadecylsilane chemically bonded silica chromatographic column2O is washed
It is de-, eluent is collected, A2-1 is obtained；
Five, preparative RP-HPLC is added in A2-1, and mobile phase is the MeOH/H of volume ratio 2:82O, flow velocity 5mL/min, tR
=28min collects eluent and obtains gomuti sugarpalm fruit analgesic compounds IV.
Gomuti sugarpalm fruit analgesic compounds V are prepared according to the following steps:
One, the fresh fruit of gomuti sugarpalm fruit, extracting solution vacuum concentration are extracted with 70% EtOH；
Two, by step 1 concentrate H2O dissolution, then successively with petroleum ether, chloroform, ethyl acetate and n-butanol extraction
It takes, butanol extraction liquid vacuum concentration obtains n-butyl alcohol extract；
Three, silica gel column chromatography separation chromatography n-butyl alcohol extract, is 20:1 and the CH of 10:1 with volume ratio2Cl2/ MeOH according to
The CH of 10:1 is collected in secondary elution2Cl2/ MeOH eluent, every 1 times of column volume eluent is a, successively marks, and selects the 9th part and the
10 parts of eluents merge to obtain B5；
Four, chromatography B5 is separated with octadecylsilane chemically bonded silica chromatographic column, is 2:8 and the MeOH/ of 3:7 with volume ratio
H2O is successively eluted, and collects the MeOH/H of 3:72O eluent obtains B5-2；
Five, preparative RP-HPLC is added in B5-2, and mobile phase is the MeOH/H of volume ratio 2:82O, flow velocity 5mL/min, tR
=35min collects eluent and obtains gomuti sugarpalm fruit analgesic compounds V.
Gomuti sugarpalm fruit analgesic compounds I, II, III, application of the IV and V as analgesic active constituent.
Gomuti sugarpalm fruit analgesic compounds of the present invention I, II, III, IV and V have the function of analgesia, anti-inflammatory and effect.
Gomuti sugarpalm fruit analgesic compounds I of the present invention are white amorphous powder, are soluble in methanol, UV spectrum (MeOH) exists
Occur maximum absorption band, C at 203nm10H18O7, molecular weight 250, process1H-NMR spectrum,13C-NMR spectrum, HSQC and HMBC spectrum
Comprehensive analysis, determine that molecular structure is
Gomuti sugarpalm fruit analgesic compounds II of the present invention are faint yellow unformed powder, are soluble in methanol, UV spectrum (MeOH) exists
Occur maximum absorption band, C at 203nm8H14O4, molecular weight 174, process1H-NMR spectrum,13C-NMR spectrum, HSQC and HMBC spectrum
Comprehensive analysis, determine that molecular structure is
Gomuti sugarpalm fruit analgesic compounds III of the present invention are white amorphous powder, are soluble in methanol, UV spectrum (MeOH) exists
Occur maximum absorption band, C at 281nm14H22O5, molecular weight 270, process1H-NMR spectrum,13C-NMR spectrum, HSQC and HMBC spectrum
Comprehensive analysis, determine that molecular structure is
Gomuti sugarpalm fruit analgesic compounds IV of the present invention is white amorphous powder, is soluble in methanol, UV spectrum (MeOH) exists
Occur maximum absorption band, C at 266nm23H18O7, molecular weight 406, process1H-NMR spectrum, 13C-NMR spectrum, HSQC and HMBC spectrum
Comprehensive analysis, determine that molecular structure is
Gomuti sugarpalm fruit analgesic compounds V of the present invention are faint yellow unformed powder, are soluble in methanol, UV spectrum (MeOH) exists
Occur maximum absorption band, C at 203nm12H22O8, molecular weight 294, process1H-NMR spectrum,13C-NMR spectrum, HSQC and HMBC spectrum
Comprehensive analysis, determine that molecular structure is
I purity is high of gomuti sugarpalm fruit analgesic compounds that the method for the present invention obtains, up to 98.8% or more.
II purity is high of gomuti sugarpalm fruit analgesic compounds that the method for the present invention obtains, up to 98.4% or more.
III purity is high of gomuti sugarpalm fruit analgesic compounds that the method for the present invention obtains, up to 99.2% or more.
The gomuti sugarpalm fruit analgesic compounds IV purity is high that the method for the present invention obtains, up to 99.0% or more.
V purity is high of gomuti sugarpalm fruit analgesic compounds that the method for the present invention obtains, up to 98.1% or more.
Gomuti sugarpalm fruit analgesic compounds of the invention I, II, III, IV and V are separated from palmaceous gomuti sugarpalm fruit.
Carry out body analgesic experiment using acetic acid writhing test, the results show gomuti sugarpalm fruit analgesic compounds of the present invention I, II,
III, IV and V can conspicuousness inhibition mouse writhing reaction (P < 0.01).
Anti-inflammatory experiment, the results show gomuti sugarpalm fruit analgesia chemical combination of the present invention are carried out using xylene-induced ear swelling in mice method
Object I, II, III, IV and V can significantly reduce left ear weight (P < 0.01), significantly inhibit ear swelling (P < 0.01).
Gomuti sugarpalm fruit analgesic compounds of the invention I, II, III, IV and V can obviously relieve pain and inflammation.
Specific embodiment
The technical solution of the present invention is not limited to the following list, further includes between each specific embodiment
Any combination.
Specific embodiment 1: gomuti sugarpalm fruit analgesic compounds I are prepared according to the following steps:
One, the fresh fruit of gomuti sugarpalm fruit, extracting solution vacuum concentration are extracted with 70% EtOH；
Two, by step 1 concentrate H2O dissolution, then successively with petroleum ether, chloroform, ethyl acetate and n-butanol extraction
It takes, butanol extraction liquid vacuum concentration obtains n-butyl alcohol extract；
Three, silica gel column chromatography separation chromatography n-butyl alcohol extract, is 20:1 and the CH of 10:1 with volume ratio2Cl2/ MeOH according to
The CH of 10:1 is collected in secondary elution2Cl2/ MeOH eluent, every 1 times of column volume eluent is a, successively marks, and selects the 9th part and the
10 parts of eluents merge to obtain B5；
Four, chromatography B5, the MeOH/H for being 2:8 with volume ratio are separated with octadecylsilane chemically bonded silica chromatographic column2O is washed
It is de-, eluent is collected, B5-1 is obtained；
Five, preparative RP-HPLC is added in B5-1, and mobile phase is the MeOH/H of volume ratio 2:82O, flow velocity 5mL/min, tR=
30min collects eluent and obtains gomuti sugarpalm fruit analgesic compounds I.
The molecular formula of gomuti sugarpalm fruit analgesic compounds I is C10H18O7, molecular weight 250, molecular structural formula are as follows:
Specific embodiment 2: gomuti sugarpalm fruit analgesic compounds II are prepared according to the following steps:
One, the fresh fruit of gomuti sugarpalm fruit, extracting solution vacuum concentration are extracted with 70% EtOH；
Two, by step 1 concentrate H2O dissolution, then successively with petroleum ether, chloroform, ethyl acetate and n-butanol extraction
It takes, butanol extraction liquid vacuum concentration obtains n-butyl alcohol extract；
Three, silica gel column chromatography separation chromatography n-butyl alcohol extract, the CH for being 20:1 with volume ratio2Cl2/ MeOH elution, is collected
Eluent, every 1 times of column volume eluent is a, successively marks, selects the 2nd part of eluent, obtain A2；
Four, chromatography A2 is separated with octadecylsilane chemically bonded silica chromatographic column, is 2:8 and the MeOH/ of 3:7 with volume ratio
H2O is successively eluted, and collects the MeOH/H of 3:72O eluent obtains A2-2；
Five, preparative RP-HPLC is added in A2-2, and mobile phase is the MeOH/H of volume ratio 3:72O, flow velocity 5mL/min, tR
=23min collects eluent and obtains gomuti sugarpalm fruit analgesic compounds II.
The molecular formula of gomuti sugarpalm fruit analgesic compounds II is C8H14O4, molecular weight 174, molecular structural formula are as follows:
Specific embodiment 3: gomuti sugarpalm fruit analgesic compounds III are prepared according to the following steps:
One, the fresh fruit of gomuti sugarpalm fruit, extracting solution vacuum concentration are extracted with 70% EtOH；
Two, by step 1 concentrate H2O dissolution, then successively with petroleum ether, chloroform, ethyl acetate and n-butanol extraction
It takes, butanol extraction liquid vacuum concentration obtains n-butyl alcohol extract；
Three, silica gel column chromatography separation chromatography n-butyl alcohol extract, the CH for being 20:1 with volume ratio2Cl2/ MeOH elution, is collected
Eluent, every 1 times of column volume eluent is a, successively marks, selects the 2nd part of eluent, obtain A2；
Four, chromatography A2 is separated with octadecylsilane chemically bonded silica chromatographic column, is 2:8,3:7,4:6,5:5 with volume ratio
With the MeOH/H of 6:42O is successively eluted, and collects the MeOH/H of 6:42O eluent obtains A2-5；
Five, preparative RP-HPLC is added in A2-5, and mobile phase is the MeOH/H of volume ratio 6:42O, flow velocity 5mL/min, tR
=45min collects eluent and obtains gomuti sugarpalm fruit analgesic compounds III.
The molecular formula of gomuti sugarpalm fruit analgesic compounds III is C14H22O5, molecular weight 270, molecular structural formula are as follows:
Specific embodiment 4: gomuti sugarpalm fruit analgesic compounds IV is prepared according to the following steps:
One, the fresh fruit of gomuti sugarpalm fruit, extracting solution vacuum concentration are extracted with 70% EtOH；
Two, by step 1 concentrate H2O dissolution, then successively with petroleum ether, chloroform, ethyl acetate and n-butanol extraction
It takes, butanol extraction liquid vacuum concentration obtains n-butyl alcohol extract；
Three, silica gel column chromatography separation chromatography n-butyl alcohol extract, the CH for being 20:1 with volume ratio2Cl2/ MeOH elution, is collected
Eluent, every 1 times of column volume eluent is a, successively marks, selects the 2nd part of eluent, obtain A2；
Four, chromatography A2, the MeOH/H for being 2:8 with volume ratio are separated with octadecylsilane chemically bonded silica chromatographic column2O is washed
It is de-, eluent is collected, A2-1 is obtained；
Five, preparative RP-HPLC is added in A2-1, and mobile phase is the MeOH/H of volume ratio 2:82O, flow velocity 5mL/min, tR
=28min collects eluent and obtains gomuti sugarpalm fruit analgesic compounds IV.
The molecular formula of gomuti sugarpalm fruit analgesic compounds IV is C23H18O7, molecular weight 406, molecular structural formula are as follows:
Specific embodiment 5: gomuti sugarpalm fruit analgesic compounds V are prepared according to the following steps:
One, the fresh fruit of gomuti sugarpalm fruit, extracting solution vacuum concentration are extracted with 70% EtOH；
Two, by step 1 concentrate H2O dissolution, then successively with petroleum ether, chloroform, ethyl acetate and n-butanol extraction
It takes, butanol extraction liquid vacuum concentration obtains n-butyl alcohol extract 1；
Three, silica gel column chromatography separation chromatography n-butyl alcohol extract, is 20:1 and the CH of 10:1 with volume ratio2Cl2/ MeOH according to
The CH of 10:1 is collected in secondary elution2Cl2/ MeOH eluent, every 1 times of column volume eluent is a, successively marks, and selects the 9th part and the
10 parts of eluents merge to obtain B5；
Four, chromatography B5 is separated with octadecylsilane chemically bonded silica chromatographic column, is 2:8 and the MeOH/ of 3:7 with volume ratio
H2O is successively eluted, and collects the MeOH/H of 3:72O eluent obtains B5-2；
Five, preparative RP-HPLC is added in B5-2, and mobile phase is the MeOH/H of volume ratio 2:82O, flow velocity 5mL/min, tR
=35min collects eluent and obtains gomuti sugarpalm fruit analgesic compounds V.
The molecular formula of gomuti sugarpalm fruit analgesic compounds V is C12H22O8, molecular weight 294, molecular structural formula are as follows:
Gomuti sugarpalm fruit analgesic compounds I of the present invention are white amorphous powder, are passed through1H-NMR spectrum,13C-NMR spectrum, HSQC and
The comprehensive analysis of HMBC spectrum determines that the substance is 1'- [O- β-D- glucopyranoside]-4- butene-1-methyl.
Gomuti sugarpalm fruit analgesic compounds II of the present invention are faint yellow unformed powder, are passed through1H-NMR spectrum,13C-NMR spectrum,
The comprehensive analysis of HSQC and HMBC spectrum determines that the substance is 4- propoxyl group -5- hydroxymethylfurans -2- ketone.
1 gomuti sugarpalm fruit analgesic compounds I and II of table1H and13NMR data (MeOH)
aRecorded at 100MHz,bRecorded at 400MHz。
Gomuti sugarpalm fruit analgesic compounds III of the present invention are white amorphous powder, by 1H-NMR spectrum, 13C-NMR spectrum, HSQC
With the comprehensive analysis of HMBC spectrum, determine that the substance is that (+)-red -7-O- butyl is cured acylglycerol.
Gomuti sugarpalm fruit analgesic compounds V of the present invention are faint yellow unformed powder, are passed through1H-NMR spectrum,13C-NMR spectrum,
The comprehensive analysis of HSQC and HMBC spectrum determines that the substance is 1 '-[O- β-D- glucopyranoside] hydroxyl-1-3- acetone-2-,
2,3- methyl.
2 gomuti sugarpalm fruit analgesic compounds III and V of table1H and13NMR data (MeOH)
aRecorded at 100MHz,bRecorded at 400MHz。
Gomuti sugarpalm fruit analgesic compounds IV of the present invention is white amorphous powder, is passed through1H-NMR spectrum,13C-NMR spectrum, HSQC
With the comprehensive analysis of HMBC spectrum, determine that the substance is 4', 5,7- tri hydroxy isoflavone -8- [1 "-(3 ", 4 "-dihydroxy phenyl) second
Base].
3 gomuti sugarpalm fruit analgesic compounds IV's of table1H and13NMR data (MeOH)
ARecorded at 100MHz, bRecorded at 400MHz.
Experiment:
Test 1 analgesic experiment
Analgesic experiment uses acetic acid writhing test:
Mouse 204, male；It is deprived of food but not water overnight；It is using RANDOMIZED BLOCK DESIGN method that animal is random by weight size
It is divided into 17 groups, every group 12；Gomuti sugarpalm fruit analgesic compounds I, II, III, IV and V high dose group (0.030g/kg, ig), middle dosage
Group (0.015g/kg, ig), low dose group (0.008g/kg, ig), loxoprofen sodium group (0.023g/kg, ig, according to body surface face
Product scaling method is 2 times of people's clinical equivalent dosage) and model control group (isometric distilled water).It is administered once daily, continuously gives
Medicine 1d；After 30min is administered, after 0.8% acetic acid normal saline solution is slowly injected into along peritoneal wall, records mouse in 20min and turn round
Body number calculates inhibitory rate.
Inhibiting rate (%)=(model control group number-administration group number)/model group number × 100%
The results are shown in Table 1 for analgesic experiment, compared with model control group, gomuti sugarpalm fruit analgesic compounds I, II, III, IV and V
Each dosage and loxoprofen sodium can conspicuousness inhibition mouse writhing reactions (P < 0.01).Wherein, gomuti sugarpalm fruit analgesic compounds I,
II, III, the high dose group inhibitory rate of IV and V reaches 82.00% or more.
Table 4
Test 2 anti-inflammatory experiments
Anti-inflammatory experiment uses xylene-induced ear swelling in mice method:
Mouse 170, male；It is deprived of food but not water overnight.It is using RANDOMIZED BLOCK DESIGN method that animal is random by weight size
It is divided into 17 groups, every group 10: gomuti sugarpalm fruit analgesic compounds I, II, III, IV and V high dose group (0.030g/kg, ig), middle dosage
Group (0.015g/kg, ig), low dose group (0.008g/kg, ig), loxoprofen sodium group (0.023g/kg, ig) and blank control
Group (isometric solvent).It is administered once daily, successive administration 3 days, after last dose 30min, is smeared in mouse right ear front and back sides
20 μ L of dimethylbenzene.After 2.5h, mouse is put to death, 8mm punch lays mouse or so ear, and assay balance weighs weight.Calculate left and right
Ear weight difference, i.e. ear swelling.
Ear swelling (mg)=model control group ear weight (mg) ﹣ administration group ear weight (mg)
Anti-inflammatory experimental result is as shown in table 2, compared with blank control group, each dosage of gomuti sugarpalm fruit alcohol extract and loxoprofen sodium
Left ear weight (P < 0.01) can be significantly reduced, ear swelling (P < 0.01) is significantly inhibited.Wherein, gomuti sugarpalm fruit analgesic compounds I,
II, III, the high dose group inhibiting rate of IV and V is reached for 37.84% or more.
Table 5
Test 3 acute toxicity testings
3.1 use integral dose design method
It tests and is divided into control group and gomuti sugarpalm fruit analgesic compounds administration group, every group of 4 animals, male and female each 2.Using 1,3,
10,30,100,300,1000,3000mg/kg a total of eight dosage.The usually next day, gives next high dose, and dosage gradually adds
Greatly, when there is animal dead or when reaching upper dosage limit until.When there is no animal dead, MLD (minimal lethal dose)
It is greater than maximum dose level or limited amount of formulation with LD50.When all animals of certain dose occur dead, MLD and LD50 are answered
Between most latter two dosage.Dead when occurring in a certain dose fraction animal, Mortality appears in subsequent next high
Dosage first appears between dead dosage and previous low dosage at this point, MLD is located at, and LD50 then should be to first appear animal dead
Between the dosage died and all animals dosage of death.It were it not for animal dead, usually given with maximum dose level dynamic
Object 5-7 days, with the selection of high dose in the subsequent repeat administration test of determination.
Gomuti sugarpalm fruit analgesic compounds I and II do not occur death condition, LD under 3000mg/kg dosage50>3000mg/
kg.III, IV, V do not occur death condition under 1000mg/kg dosage, and animal is all dead under 3000mg/kg dosage,
1000mg/kg<LD50<3000mg/kg。
3.2 use horn method
200 ICR mouse, gomuti sugarpalm fruit analgesic compounds (5 kinds) dosage are respectively 1,2.15,4.64,10gkg-1,
Every group 10, half male and half female；Administered volume is 4mlkg-1, it is administered once altogether.Observe and record animal dead situation after being administered.
Gomuti sugarpalm fruit analgesic compounds I, II, III, IV, V are in 1gkg-1Do not occur death condition under dosage.
Gomuti sugarpalm fruit analgesic compounds I are in 4.64gkg-1、10g·kg-1The dosage group hero mouse death rate is respectively 80%,
100%, the female mice death rate is respectively 60%, 100%.LD50Value is male mouse 3.69gkg-1, 95% credibility interval is 2.71-
5.01g·kg-1；Female mice 4.30gkg-1, 95% credibility interval is 2.95-6.26gkg-1。
Gomuti sugarpalm fruit analgesic compounds II are in 4.64gkg-1、10g·kg-1The dosage group hero mouse death rate is respectively 80%,
80%, the female mice death rate is respectively 80%, 100%.LD50Value is male mouse 4.22gkg-1, 95% credibility interval is 2.53-
7.02g·kg-1；Female mice 3.69gkg-1, 95% credibility interval is 2.71-5.01gkg-1。
Gomuti sugarpalm fruit analgesic compounds III are in 2.15gkg-1、4.64g·kg-1、10g·kg-1The dosage group hero mouse death rate point
Not Wei 20%, 60%, 100%, the female mice death rate is respectively 40%, 40%, 100%.LD50Value is male mouse 3.69gkg-1,
95% credibility interval is 2.27-5.99gkg-1；Female mice 3.69gkg-1, 95% credibility interval is 2.17-6.28gkg-1。
Gomuti sugarpalm fruit analgesic compounds IV is in 2.15gkg-1、4.64g·kg-1、10g·kg-1The dosage group hero mouse death rate point
Not Wei 20%, 60%, 100%, the female mice death rate is respectively 40%, 40%, 100%.LD50Value is male mouse 3.69gkg-1,
95% credibility interval is 2.27-5.99gkg-1；Female mice 3.69gkg-1, 95% credibility interval is 2.17-6.28gkg-1。
Gomuti sugarpalm fruit analgesic compounds V are in 2.15gkg-1、4.64g·kg-1、10g·kg-1The dosage group hero mouse death rate point
Not Wei 40%, 80%, 100%, the female mice death rate is respectively 20%, 40%, 100%.LD50Value is male mouse 4.30gkg-1,
95% credibility interval is 2.65-6.98gkg-1；Female mice 3.69gkg-1, 95% credibility interval is 2.71-5.01gkg-1。
Experiments have shown that gomuti sugarpalm fruit analgesic compounds of the present invention I, II, III, IV, V there are excellent analgesia and antiphlogistic effects,
Toxicity is low, takes highly-safe.
Claims (11)
1. gomuti sugarpalm fruit analgesic compounds I, it is characterised in that the molecular formula of gomuti sugarpalm fruit analgesic compounds I is C10H18O7, molecular weight is
250, molecular structural formula are as follows:
2. gomuti sugarpalm fruit analgesic compounds II, it is characterised in that the molecular formula of gomuti sugarpalm fruit analgesic compounds II is C8H14O4, molecular weight is
174, molecular structural formula are as follows:
3. gomuti sugarpalm fruit analgesic compounds III, it is characterised in that the molecular formula of gomuti sugarpalm fruit analgesic compounds III is C14H22O5, molecular weight
It is 270, molecular structural formula are as follows:
4. gomuti sugarpalm fruit analgesic compounds IV, it is characterised in that the molecular formula of gomuti sugarpalm fruit analgesic compounds IV is C23H18O7, molecular weight
It is 406, molecular structural formula are as follows:
5. gomuti sugarpalm fruit analgesic compounds V, it is characterised in that the molecular formula of gomuti sugarpalm fruit analgesic compounds V is C12H22O8, molecular weight
It is 294, molecular structural formula are as follows:
6. the preparation method of gomuti sugarpalm fruit analgesic compounds I, it is characterised in that gomuti sugarpalm fruit analgesic compounds I are prepared according to the following steps:
One, the fresh fruit of gomuti sugarpalm fruit, extracting solution vacuum concentration are extracted with 70% EtOH；
Two, by step 1 concentrate H2O dissolution, then successively uses petroleum ether, chloroform, ethyl acetate and extracting n-butyl alcohol, positive fourth
Alcohol extract liquor vacuum concentration, obtains n-butyl alcohol extract；
Three, silica gel column chromatography separation chromatography n-butyl alcohol extract, is 20:1 and the CH of 10:1 with volume ratio2Cl2/ MeOH is successively washed
It is de-, collect the CH of 10:12Cl2/ MeOH eluent, every 1 times of column volume eluent is a, successively marks, selects the 9th part and the 10th part
Eluent merges to obtain B5；
Four, chromatography B5, the MeOH/H for being 2:8 with volume ratio are separated with octadecylsilane chemically bonded silica chromatographic column2O elution, is collected
Eluent obtains B5-1；
Five, preparative RP-HPLC is added in B5-1, and mobile phase is the MeOH/H of volume ratio 2:82O, flow velocity 5mL/min, tR=30min
It collects eluent and obtains gomuti sugarpalm fruit analgesic compounds I.
7. the preparation method of gomuti sugarpalm fruit analgesic compounds II, it is characterised in that gomuti sugarpalm fruit analgesic compounds II are made according to the following steps
It is standby:
One, the fresh fruit of gomuti sugarpalm fruit, extracting solution vacuum concentration are extracted with 70% EtOH；
Two, by step 1 concentrate H2O dissolution, then successively uses petroleum ether, chloroform, ethyl acetate and extracting n-butyl alcohol, positive fourth
Alcohol extract liquor vacuum concentration, obtains n-butyl alcohol extract；
Three, silica gel column chromatography separation chromatography n-butyl alcohol extract, the CH for being 20:1 with volume ratio2Cl2/ MeOH elution, collects elution
Liquid, every 1 times of column volume eluent is a, successively marks, selects the 2nd part of eluent, obtain A2；
Four, chromatography A2 is separated with octadecylsilane chemically bonded silica chromatographic column, is 2:8 and the MeOH/H of 3:7 with volume ratio2O is successively
Elution, collects the MeOH/H of 3:72O eluent obtains A2-2；
Five, preparative RP-HPLC is added in A2-2, and mobile phase is the MeOH/H of volume ratio 3:72O, flow velocity 5mL/min, tR=23min
It collects eluent and obtains gomuti sugarpalm fruit analgesic compounds II.
8. the preparation method of gomuti sugarpalm fruit analgesic compounds III, it is characterised in that gomuti sugarpalm fruit analgesic compounds III are made according to the following steps
It is standby:
One, the fresh fruit of gomuti sugarpalm fruit, extracting solution vacuum concentration are extracted with 70% EtOH；
Two, by step 1 concentrate H2O dissolution, then successively uses petroleum ether, chloroform, ethyl acetate and extracting n-butyl alcohol, positive fourth
Alcohol extract liquor vacuum concentration, obtains n-butyl alcohol extract；
Three, silica gel column chromatography separation chromatography n-butyl alcohol extract, the CH for being 20:1 with volume ratio2Cl2/ MeOH elution, collects elution
Liquid, every 1 times of column volume eluent is a, successively marks, selects the 2nd part of eluent, obtain A2；
Four, chromatography A2 is separated with octadecylsilane chemically bonded silica chromatographic column, is 2:8,3:7,4:6,5:5 and 6:4 with volume ratio
MeOH/H2O is successively eluted, and collects the MeOH/H of 6:42O eluent obtains A2-5；
Five, preparative RP-HPLC is added in A2-5, and mobile phase is the MeOH/H of volume ratio 6:42O, flow velocity 5mL/min, tR=45min
It collects eluent and obtains gomuti sugarpalm fruit analgesic compounds III.
9. the preparation method of gomuti sugarpalm fruit analgesic compounds IV, it is characterised in that gomuti sugarpalm fruit analgesic compounds IV are made according to the following steps
It is standby:
One, the fresh fruit of gomuti sugarpalm fruit, extracting solution vacuum concentration are extracted with 70% EtOH；
Two, by step 1 concentrate H2O dissolution, then successively uses petroleum ether, chloroform, ethyl acetate and extracting n-butyl alcohol, positive fourth
Alcohol extract liquor vacuum concentration, obtains n-butyl alcohol extract；
Three, silica gel column chromatography separation chromatography n-butyl alcohol extract, the CH for being 20:1 with volume ratio2Cl2/ MeOH elution, collects elution
Liquid, every 1 times of column volume eluent is a, successively marks, selects the 2nd part of eluent, obtain A2；
Four, chromatography A2, the MeOH/H for being 2:8 with volume ratio are separated with octadecylsilane chemically bonded silica chromatographic column2O elution, is collected
Eluent obtains A2-1；
Five, preparative RP-HPLC is added in A2-1, and mobile phase is the MeOH/H of volume ratio 2:82O, flow velocity 5mL/min, tR=28min
It collects eluent and obtains gomuti sugarpalm fruit analgesic compounds IV.
10. the preparation method of gomuti sugarpalm fruit analgesic compounds V, it is characterised in that gomuti sugarpalm fruit analgesic compounds V are made according to the following steps
It is standby:
One, the fresh fruit of gomuti sugarpalm fruit, extracting solution vacuum concentration are extracted with 70% EtOH；
Two, by step 1 concentrate H2O dissolution, then successively uses petroleum ether, chloroform, ethyl acetate and extracting n-butyl alcohol, positive fourth
Alcohol extract liquor vacuum concentration, obtains n-butyl alcohol extract；
Three, silica gel column chromatography separation chromatography n-butyl alcohol extract, is 20:1 and the CH of 10:1 with volume ratio2Cl2/ MeOH is successively washed
It is de-, collect the CH of 10:12Cl2/ MeOH eluent, every 1 times of column volume eluent is a, successively marks, selects the 9th part and the 10th part
Eluent merges to obtain B5；
Four, chromatography B5 is separated with octadecylsilane chemically bonded silica chromatographic column, is 2:8 and the MeOH/H of 3:7 with volume ratio2O is successively
Elution, collects the MeOH/H of 3:72O eluent obtains B5-2；
Five, preparative RP-HPLC is added in B5-2, and mobile phase is the MeOH/H of volume ratio 2:82O, flow velocity 5mL/min, tR=35min
It collects eluent and obtains gomuti sugarpalm fruit analgesic compounds V.
11. the application of gomuti sugarpalm fruit analgesic compounds I, II, III, IV and V, it is characterised in that gomuti sugarpalm fruit analgesic compounds I, II,
III, IV and V application as analgesic active constituent.
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| CN115093388A (en) * | 2022-07-27 | 2022-09-23 | 湖南正清制药集团股份有限公司 | Flavonoid compound and preparation method and application thereof |
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|---|---|---|---|---|
| CN106008432A (en) * | 2016-06-12 | 2016-10-12 | 王伟明 | Method for preparing celandine acid salt from arenga pinnata fruits |
| CN108465028A (en) * | 2018-05-18 | 2018-08-31 | 王伟明 | Gomuti palm relieves pain extract and preparation method thereof and purposes |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106008432A (en) * | 2016-06-12 | 2016-10-12 | 王伟明 | Method for preparing celandine acid salt from arenga pinnata fruits |
| CN108465028A (en) * | 2018-05-18 | 2018-08-31 | 王伟明 | Gomuti palm relieves pain extract and preparation method thereof and purposes |
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| Title |
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| 刘吉飞 等: "桄榔子的化学成分研究", 《中药材》 * |
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| CN115093388A (en) * | 2022-07-27 | 2022-09-23 | 湖南正清制药集团股份有限公司 | Flavonoid compound and preparation method and application thereof |
| CN115093388B (en) * | 2022-07-27 | 2023-12-05 | 湖南正清制药集团股份有限公司 | Flavonoid compound and preparation method and application thereof |
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