CN103980197B - Spina Date Seed alkaloid monomer composition acid Lee alkali and preparation method thereof and application - Google Patents
Spina Date Seed alkaloid monomer composition acid Lee alkali and preparation method thereof and application Download PDFInfo
- Publication number
- CN103980197B CN103980197B CN201410093588.XA CN201410093588A CN103980197B CN 103980197 B CN103980197 B CN 103980197B CN 201410093588 A CN201410093588 A CN 201410093588A CN 103980197 B CN103980197 B CN 103980197B
- Authority
- CN
- China
- Prior art keywords
- spina date
- date seed
- alkali
- lee
- preparation
- 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
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/18—Ring systems of four or more rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a kind of Spina Date Seed alkaloid monomer composition acid Lee alkali and preparation method thereof and application, acid Lee alkali adsorbs to obtain Spina Date Seed total alkaloids by Spina Date Seed medicinal material through macroporous adsorptive resins, by aluminum oxide column chromatography, extract is separated further again, finally be separated flow point with preparative high performance liquid chromatography to obtain, preparation method is stable can be repeated, yield is high, and the high-purity monomer composition obtained can be used as reference substance and uses.Pharmacodynamic experiment shows that Spina Date Seed alkaloid monomer acid Lee alkali is the effective constituent that Spina Date Seed plays " resolving stagnation for tranquilization " effect, has the effect of prevention and therapy insomnia, dysthymia disorders, may be used for the research and development application of thymoleptic.And have no side effect, without the excitement uneasiness of conventional thymoleptic, renal shutdown, constipation, dizzy, the shortcoming such as to tremble.
Description
Technical field
The present invention relates to a kind of Chinese medical extract and preparation method, specifically, relate to Spina Date Seed alkaloid monomer composition and preparation method thereof and application.
Background technology
Along with social competition's aggravation, rhythm of life are accelerated, the sickness rate of the Emotional disorder such as dysthymia disorders, insomnia just sharply rises, and patient normally cannot carry out study and work, and quality of life sharply declines.For the treatment of dysthymia disorders, since the 1950's, existing many thymoleptic come out.Can be divided into according to pharmacological action: serotonin reuptake inhibitor, oxidase inhibitor, Phenylpiperazine derivatives, serotonin-NRI, aminoketones thymoleptic, tricyclic antidepressant etc.But the shortcomings such as the offer limited effectiveness of Western medicine, easy generation resistance and side effect are obvious, make it apply and are extremely restricted.Chinese medicine has the feature of multicomponent, Mutiple Targets, works by too many levels, has synergistic effect.So Study and Development has dissimilar and Chinese medicine that is mechanism of action, has huge marketable value.
China's traditional Chinese medicine is thought, is insomnia and namely has a sleepless night; Dysthymia disorders belongs to " melancholia ", and being insomnia all belongs to Emotional disorder category with melancholia, is all because emotional stimulation causes yin-Yang disorder of vital energy and blood, and function is disorderly, so that the mind is lost and supported or caused by uneasiness, be the important factor of human body cause illness.Clinical study shows that patients with depression often shows and upsets, the features such as anxiety, there is the patient of 80% also to occur serious insomnia, therefore often adopt class treatment by Chinese herbs dysthymia disorders of having one's ideas straightened out of calming the nerves, the highest with the frequency of utilization of tranquilizer Spina Date Seed in all kinds of anti-depression Chinese medicament compound.
Spina Date Seed, as traditional resolving stagnation for tranquilization class Chinese medicine, has tonifying liver, Ning Xin, arrest sweating, the effect of promoting the production of body fluid, cures mainly diseases such as " restlessness of asrhenia type and insomnia ", have antidepressant and sedative-hypnotic effect concurrently, evident in efficacy.For one of food and medicament dual-purpose Chinese medicine that the Ministry of Health of China specifies, free of toxic effects.This Chinese medicine also has hypoglycemic, reducing blood-fat, the anti-ageing effect of waiting for a long time simultaneously, and these can make up the deficiency of Western medicine preparation.But because in medicinal material, active constituent content is low, dose is larger; And containing a large amount of invalid components, easily cause side reaction.
Summary of the invention
The invention provides a kind of Spina Date Seed alkaloid monomer composition acid Lee alkali and its preparation method and application, in solution prior art, thymoleptic side reaction is many, the problem that Chinese medicine taking amount is large.
The present invention is achieved through the following technical solutions: a kind of Spina Date Seed alkaloid monomer composition acid Lee alkali, available following method obtains, and the method comprises the steps:
(1) by Spina Date Seed pulverizing medicinal materials, by 40 mesh sieves, respectively with 4-10 times amount (w/v) 0.2-2% salt acid dipping 2-3 time, each 12-24h, merging filtrate, centrifuging and taking supernatant liquor adsorbs through macroporous adsorptive resins, after distilled water wash-out, again with 60-80% ethanolic soln wash-out, ethanol is reclaimed in underpressure distillation, obtains Spina Date Seed total alkaloids;
(2) step (1) gained Spina Date Seed total alkaloids position is dissolved in distilled water, w/v=5:1, regulates pH10-12 with ammoniacal liquor; With butanol solution extraction, by organic layer underpressure distillation, recycling design obtains n-butanol layer extract; Be separated further extract with aluminum oxide column chromatography, gradient is followed successively by: 100% methyl alcohol, methanol-water (1:1), 100% water; Get 100% methanol-eluted fractions, vacuum distillation drying obtains flow point A;
(3) be separated flow point A with preparative high performance liquid chromatography, chromatographic condition is: preparative chromatography post YMC-PACKPolymerC
18(300 × 20mm, 10 μm); Moving phase is methyl alcohol: water, and ammoniacal liquor regulates pH; Flow velocity 1-2mL/min; Sample size 2mL; Determined wavelength 282nm.Collect No. 3 peak compositions, after vacuum distillation drying, obtain sour Lee's alkali monomer.
Obtained sour Lee's alkali structural formula is:
Structural Identification data: faint yellow needle, aobvious blue-fluorescence under ultraviolet lamp 254nm, the colour developing of improvement Dragendorff's reagent is in orange red.
1h-NMR(400MHzMeOD-d4): 3.72(6H, s, 2*OMe), 6.39(1H, d, 9-H), 6.41(1H, s, 3-H) and 6.61(1H, d, J=7.8Hz, 8-H); Its
13c-NMR(100MHzMeOD-d4) major chemical shift is as follows: 43.5,53.8(N-Me), 24.6(2*Me), 56.0,56.3(10,11-MeO), 150.8,151.7(2,10). contrast pertinent literature deterministic compound 3 is accredited as sour Lee's alkali (zizyphusine).
A preparation method for Spina Date Seed alkaloid monomer composition acid Lee alkali, comprises the steps:
(1) by Spina Date Seed pulverizing medicinal materials, by 40 mesh sieves, respectively with 4-10 times amount (w/v) 0.2-2% salt acid dipping 2-3 time, each 12-24h, merging filtrate, centrifuging and taking supernatant liquor adsorbs through macroporous adsorptive resins, after distilled water wash-out, again with 60-80% ethanolic soln wash-out, ethanol is reclaimed in underpressure distillation, obtains Spina Date Seed total alkaloids;
(2) step (1) gained Spina Date Seed total alkaloids position is dissolved in distilled water, w/v=5:1, regulates pH10-12 with ammoniacal liquor; With butanol solution extraction, by organic layer underpressure distillation, recycling design obtains n-butanol layer extract; Be separated further extract with aluminum oxide column chromatography, gradient is followed successively by: 100% methyl alcohol, methanol-water (1:1), 100% water; Get 100% methanol-eluted fractions, vacuum distillation drying obtains flow point A;
(3) be separated flow point A with preparative high performance liquid chromatography, chromatographic condition is: preparative chromatography post YMC-PACKPolymerC
18(300 × 20mm, 10 μm); Moving phase is methyl alcohol: water, and ammoniacal liquor regulates pH; Flow velocity 1-2mL/min; Sample size 2mL; Determined wavelength 282nm.Collect No. 3 peak compositions, after vacuum distillation drying, obtain sour Lee's alkali monomer.
In the preparation method of described Spina Date Seed alkaloid monomer composition acid Lee alkali, step (1) is preferably Spina Date Seed pulverizing medicinal materials, by 40 mesh sieves, respectively with 7 times, 4 times amount 0.5% salt acid dipping 2 times, each 24h, merging filtrate, centrifuging and taking supernatant liquor adsorbs through X-5 type macroporous adsorptive resins, after distilled water wash-out, again with 70% ethanolic soln wash-out, ethanol is reclaimed in underpressure distillation
Obtain Spina Date Seed total alkaloids.
Optional X-5, AB-8 or D-101 type of macroporous adsorptive resins in described step (1).
Methyl alcohol in described step (3): water=3:1, ammoniacal liquor regulates pH=8-10.
A kind of Spina Date Seed alkaloid monomer composition acid Lee alkali is preparing the application in prevention and therapy insomnia, antidepressant agents.
Comprise a preparation for Spina Date Seed alkaloid monomer composition acid Lee alkali, formulation is oral dosage form or inhalation.
Described oral dosage form is orally disintegrating tablet.
Beneficial effect of the present invention is: 1. pharmacodynamic experiment of the present invention discloses Spina Date Seed alkaloid monomer acid Lee alkali is the effective constituent that Spina Date Seed plays " resolving stagnation for tranquilization " effect, there is the effect of prevention and therapy insomnia, dysthymia disorders, may be used for the research and development application of thymoleptic.And have no side effect, without the excitement uneasiness of conventional thymoleptic, renal shutdown, constipation, dizzy, the shortcoming such as to tremble.
2. preparation method of the present invention is stable can repeat, and yield is high, and the high-purity monomer composition obtained can be used as reference substance and uses, and solves the technical problem of Spina Date Seed alkaloid monomer composition preparation research deficiency.
Accompanying drawing explanation
Fig. 1 is that preparative high-performance liquid chromatographic is separated flow point A figure;
Fig. 2 is the mass spectroscopy figure of sour Lee's alkali;
Fig. 3 is model group serum HPLC spectrogram;
Fig. 4 is Spina Date Seed total alkaloids administration group serum HPLC spectrogram;
Fig. 5 is model group serum T IC-MS spectrogram;
Fig. 6 is Spina Date Seed total alkaloids administration group serum T IC-MS spectrogram.
Embodiment
Below in conjunction with drawings and Examples, the present invention is described in detail.
Embodiment 1
Sour Lee's alkaline extraction separation method in Spina Date Seed, the method comprises the following steps:
By Spina Date Seed medicinal material 120g respectively with 7 times amount, 4 times amount (w/v) 0.5% salt acid dipping 2 times, each 24h, merging filtrate, centrifuging and taking supernatant liquor adsorbs through X-5 macroporous adsorptive resins, after distilled water wash-out, again with 70% ethanolic soln wash-out, ethanol is reclaimed in underpressure distillation, obtains Spina Date Seed total alkaloids (3.07g).
Spina Date Seed alkaloid position is dissolved in (w/v=5:1) in distilled water, regulates pH for 12 with ammoniacal liquor.With butanol solution extraction, by organic layer underpressure distillation, recycling design obtains n-butanol layer extract.Be separated further n-butanol layer extract with neutral aluminum oxide column chromatography, gradient is followed successively by: 100% methyl alcohol, methanol-water (1:1), 100% water.Get 100% methanol-eluted fractions, vacuum distillation drying obtains flow point A(0.309g).
Be separated flow point A with preparative high performance liquid chromatography, chromatographic condition is: preparative chromatography post YMC-PACKPolymerC
18(300 × 20mm, 10 μm); Moving phase is methyl alcohol: water=3:1, and ammoniacal liquor regulates pH=9; Working time 55min; Flow velocity 2mL/min; Sample size 2mL; Determined wavelength 282nm.As shown in Figure 1, No. 3 peak purities are higher, it is collected, after vacuum distillation drying monomer component acid Lee's alkali (21.3mg).Be 6.39 × 10 by crude drug productive rate
-3%.
Embodiment 2
Serum drug chemical process acid Lee alkali is that Spina Date Seed alkaloid enters blood effective constituent.
1. laboratory animal
Healthy male ICR mouse (SPF level, body weight 20 ± 2g); Be purchased from Institute of Radiation Medicine, Chinese Academy of Medical Sciences's Experimental Animal Center, conformity certification number: SCXK(capital) 2009-0004; Laboratory rearing 3 days before experiment, conform.Room temperature 22 ± 2 DEG C, relative humidity 65% ~ 70%.Day illumination 12h, free diet, takes the photograph water.
2. method and result
The preparation of 2.1 liquids and medication
Precision takes Spina Date Seed alkaloid extractive part, is dissolved in distilled water, makes 20mg/mL liquid.By 10 mouse random number, wherein 1 ~ No. 5 is model group, and 6 ~ No. 10 is administration group; Model group sooner or later each gavage gives 0.2mL distilled water, and administration group mouse sooner or later each gavage gives 200mg/kg dosage alkaloid extract, successive administration 7 days.
The preparation of 2.2 serum samples
After the 7th day the 2nd time administration 60min, by model group and the depressed stimulation of outstanding tail 1min simulation respectively of administration group mouse, immediately pluck eyeball and get blood; After gained blood sample leaves standstill 30min, with the centrifugation 10min of 5000r/min in supercentrifuge, get supernatant; Model group, supernatant liquor that the blood sample removing protein of each 5 mouse of administration group obtains are merged respectively, obtains model serum sample and Contained Serum sample.
2.3 experimental techniques and result
By model group serum test liquid and administration group serum test liquid respectively sample introduction scan, assist nucleo plasmic relation to carry out the determination of chromatographic peak with retention time.Model group and the contrast of administration group serum HPLC spectrogram will be respectively, a peak (t in administration group serum spectrogram shown in Fig. 3 and Fig. 4
r=25.5min), b peak (t
r=31.2min) and c peak (t
r=41.8min) be do not occur in model serum spectrogram.Wherein the retention time at a peak is corresponding with Lee's alkali sour in Spina Date Seed total alkaloids, has also occurred the molecular ion peak of sour Lee's alkali in TIC-MS spectrogram.By the intuitive analysis of the TIC-MS color atlas of Fig. 6, administration group serum test liquid have at 19min place a nucleo plasmic relation be 342.6 molecular ion peak, and Fig. 5 model group test liquid occurs without this peak at corresponding time point, known its is that Spina Date Seed alkaloid position oral administration absorbs the composition entering blood; Contrast with scanning result under Fig. 2 item and confirm, this composition is that sour Lee's alkali enters blood with prototype.
Embodiment 3
The pharmacodynamics test of Spina Date Seed alkaloid monomer acid Lee alkali
1. material
1.1 laboratory animal: laboratory animal: male ICR mouse 40 (SPF levels, body weight 20 ± 2g) be purchased from institute of lab animals of China Concord Medical Science University of the Chinese Academy of Medical Sciences of Beijing HFK Bio-Technology Co., Ltd., conformity certification number: SCXK(capital) 2009-0008.Laboratory rearing 3 days before experiment, conform.Room temperature 22 ± 2 DEG C, relative humidity 65% ~ 70%.Illumination 12h, free diet, takes the photograph water.
1.2 medicines and reagent: Spina Date Seed (Anguo City Qi Rui Chinese medicinal materials limited liability company, lot number: 100607, through the qualification of crude drug teaching and research room of Medical University Of Tianjin); Resolving stagnation for tranquilization particle (Jilin common people's hall pharmaceutcal corporation, Ltd, lot number: 20100103075), venlafaxine hydrochloride slow-release capsule (Efexor XR, Irish Wyeth, lot number: 0902052).
2. pharmacodynamic evaluation
Laboratory animal divides into groups and administration by table 1 by 2.1, in the morning every day 9:00 ~ 10:00 gavage once, continuous gavage 14 days.
2.2 with above threshold dose of sodium pentobarbitone cooperative experiment: respectively organizing mouse stomach administration 0.5h pneumoretroperitoneum injects above threshold dose of sodium pentobarbitone, and dosage is 40mg/kg.Timing is started, record Sleep latency and the length of one's sleep after injection.With during righting reflex loss for sleep initial time, righting reflex revert to sleep the end time.After abdominal injection to sleep initial is Sleep latency during this period of time, latent period more than 15min, by 15min record.
2.3 mouse forced swimming test: dosage regimen is the same, after last administration, 1h tests.Test after mouse training swimming 6min, 24h before experiment: the 5000ml beaker (high 20cm, diameter 14cm) mouse being put into depth of water 10cm, water temperature 25 ± 2 DEG C.Observe 6min, the dead time of mouse in the rear 4min of the relatively more each group of record.
2.4 mouse forced swimming test: mouse is put into separately a diameter 18cm, in the transparent glass cylinder of high 30cm.Glass jar is placed in quiet room, more than depth of water 10cm in cylinder, water temperature about 45 DEG C.6min is carried out in experiment.When experiment starts, mouse is attempted struggle and runs away, but feel hopeless after namely stop struggling, only by head above water, a kind of motionless state of the floating maintenance of limbs.Dead time of mouse in 4min after record, with floating dead time of mouse as the index judging depressed severity.Each experiment post-flush water vat, changes water, avoids affecting next animal testing.
3. statistical analysis
Data represent with the form of means standard deviation.One-way analysis of variance method is adopted to carry out statistical analysis.Data are by SPSS software processes, p<0.05 or p<0.01 has significant difference.
The grouping of table 1 laboratory animal and dosage regimen
| Group | Number of animals | Dosage |
| Model control group (distilled water) | 10 | 0.1ml/10g |
| Positive controls | 10 | VENLAFAXINE HCL 9.38mg/kg or resolving stagnation for tranquilization particle 1.25g/kg |
| Acid Lee alkali low dose group | 10 | 10mg/kg |
| Acid Lee alkali high dose group | 10 | 20mg/kg |
4. result
Statistical content comprises and the dead time in dead time in Sleep latency in above threshold dose of sodium pentobarbitone cooperative experiment and the length of one's sleep, mouse forced swimming test and Tail suspension test.
Alkaloid monomer acid Lee alkali of 4.1 embodiments is on the above threshold synergistic impact of dose of sodium pentobarbitone tranquilizing soporific
Each group of mice sleep latent period and the length of one's sleep the results are shown in Table 2.
Alkaloid monomer acid Lee alkali of table 2 embodiment is on mouse above threshold dose of sodium pentobarbitone tranquilizing soporific synergy impact
| Group | Sleep latency (s) | The length of one's sleep (min) |
| Model control group | 691.8±228.3 | 17.0±8.8 |
| Resolving stagnation for tranquilization groups of grains | 632.5±189.6 | 30.2±12.4 |
| Acid Lee alkali low dose group | 562.1±165.1 | 38.0±16.1* |
| Acid Lee alkali high dose group | 431.4±122.1** | 39.7±17.9** |
Note: * compares p<0.05 with model control group, * * compares p<0.01 with model control group
Shown by table 2 result: alkaloid monomer acid Lee alkali high dose group compares with model control group, and Sleep latency difference has height statistical significance (P<0.01), obviously shortening each administration group mice sleep latent period.The each dosage group of acid Lee's alkali compares with model control group, the length of one's sleep, difference had height statistical significance (P<0.05, P<0.01), all can significant prolongation each administration group mouse above threshold length of one's sleep caused by dose of sodium pentobarbitone.
Alkaloid monomer acid Lee alkali of 4.2 embodiments is on the impact of mouse forced swimming test dead time
Each group of mouse forced swimming test dead time the results are shown in Table 5.
The sour Lee's alkali of table 3 is on the impact of mouse forced swimming test dead time
| Group | The accumulative dead time (7 days) | The accumulative dead time (14 days) |
| Model control group | 60.8±16.5 | 78.6±24.3 |
| VENLAFAXINE HCL group | 46.8±14.0 | 28.2±30.2** |
| Acid Lee alkali low dose group | 43.5±13.9 | 32.9±26.2* |
| Acid Lee alkali high dose group | 36.2±13.5 | 26.3±20.4** |
Note: * compares p<0.05 with model control group, * * compares p<0.01 with model control group
The motionless state that mouse shows in forced swimming model reflects the desperate behavior of animal, can the depressive state of simulating human.From table 3, administration 7 days swimming test results are found out, each administration group FST adds up the dead time and compares with model control group, and numerical value has the trend of reduction, but difference does not all have statistical significance.Administration as shown in table 3 14 days swimming results, compared with model control group, alkaloid low dose group difference has statistical significance (P<0.05).Positive controls, alkaloid high dose group compare with model control group, there is remarkable statistical significance (P<0.01).
Alkaloid monomer acid Lee alkali of 4.3 embodiments is on the impact of mouse tail suspension dead time
Experimental result is in table 4.
Alkaloid monomer acid Lee alkali of table 4 embodiment is on the impact of Tail suspension test dead time
| Group | The accumulative dead time (7 days) | The accumulative dead time (14 days) |
| Model control group | 102.3±24.7 | 125.6±29.0 |
| VENLAFAXINE HCL group | 59.1±24.2** | 68.3±27.7** |
| Acid Lee alkali low dose group | 74.2±24.1* | 71.5±23.4** |
| Acid Lee alkali high dose group | 62.9±24.7** | 67.1±24.6** |
Note: * compares p<0.05 with model control group, * * compares p<0.01 with model control group
As can be seen from table 4, learnt by the outstanding caudal knot fruit of administration 7 days, compare with model control group, alkaloid low dose group has statistical significance (P<0.05).There is remarkable statistical significance (P<0.01) in positive controls, alkaloid high dose group difference compared with model control group.By table 4 mouse administration 14 Tian Xuan mantissa according to learning, administration is respectively organized TST and is added up the dead time and compare with model control group, and difference has remarkable statistical significance (P<0.01).
Although invention has been described by reference to the accompanying drawings above; but the present invention is not limited to above-mentioned embodiment; above-mentioned embodiment is only schematic; instead of it is restrictive; for the person of ordinary skill of the art; under the prerequisite not departing from inventive principle, can also make some improvements and modifications, these improvements and modifications all belong to protection scope of the present invention.
Claims (4)
1. a preparation method for Spina Date Seed alkaloid monomer composition acid Lee alkali, is characterized in that, comprise the steps:
(1) by Spina Date Seed pulverizing medicinal materials, by 40 mesh sieves, respectively with 4-10 times amount, the acid dipping of 0.2-2% salt 2-3 time, each 12-24h, merging filtrate, centrifuging and taking supernatant liquor adsorbs through macroporous adsorptive resins, after distilled water wash-out, again with 60-80% ethanolic soln wash-out, ethanol is reclaimed in underpressure distillation, obtains Spina Date Seed total alkaloids;
(2) step (1) gained Spina Date Seed total alkaloids position is dissolved in distilled water, mass concentration w/v=5:1, regulates pH10-12 with ammoniacal liquor; With butanol solution extraction, by organic layer underpressure distillation, recycling design obtains n-butanol layer extract; Be separated further extract with aluminum oxide column chromatography, gradient is followed successively by: 100% methyl alcohol, methanol-water 1:1,100% water; Get 100% methanol-eluted fractions, vacuum distillation drying obtains flow point A;
(3) be separated flow point A with preparative high performance liquid chromatography, chromatographic condition is: preparative chromatography post YMC-PACKPolymerC
18; Moving phase is methyl alcohol: water=3:1, and ammoniacal liquor regulates pH=9; Working time 55min; Flow velocity 2mL/min; Sample size 2mL; Determined wavelength 282nm; Collect No. 3 peak compositions, after vacuum distillation drying, obtain sour Lee's alkali monomer; Described preparative chromatography post is 300 × 20mm, 10 μm.
2. the preparation method of Spina Date Seed alkaloid monomer composition acid Lee alkali according to claim 1, it is characterized in that, in above-mentioned preparation method, step (1) is by Spina Date Seed pulverizing medicinal materials, by 40 mesh sieves, respectively with 7 times, 4 times amount, 0.5% salt acid dipping 2 times, each 24h, merging filtrate, centrifuging and taking supernatant liquor adsorbs through X-5 type macroporous adsorptive resins, after distilled water wash-out, again with 70% ethanolic soln wash-out, ethanol is reclaimed in underpressure distillation, obtains Spina Date Seed total alkaloids.
3. the preparation method of Spina Date Seed alkaloid monomer composition acid Lee alkali according to claim 1, is characterized in that, optional X-5, AB-8 or D-101 type of macroporous adsorptive resins in described step (1).
4. sour Lee's alkali is preparing the application in prevention and therapy antidepressant agents.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410093588.XA CN103980197B (en) | 2014-03-13 | 2014-03-13 | Spina Date Seed alkaloid monomer composition acid Lee alkali and preparation method thereof and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410093588.XA CN103980197B (en) | 2014-03-13 | 2014-03-13 | Spina Date Seed alkaloid monomer composition acid Lee alkali and preparation method thereof and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103980197A CN103980197A (en) | 2014-08-13 |
| CN103980197B true CN103980197B (en) | 2015-11-11 |
Family
ID=51272394
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410093588.XA Active CN103980197B (en) | 2014-03-13 | 2014-03-13 | Spina Date Seed alkaloid monomer composition acid Lee alkali and preparation method thereof and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103980197B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108635352A (en) * | 2018-05-16 | 2018-10-12 | 天津医科大学 | Magnoflorine is in the Use and preparation method for preparing prevention insomnia antidepressant agents |
| CN108478575B (en) * | 2018-05-16 | 2021-02-26 | 天津医科大学 | Magnoflorine preparation, preparation method and application thereof |
| CN109674859A (en) * | 2018-12-14 | 2019-04-26 | 天津医科大学 | Semen ziziphi spinosae alkaloid and flavones compatibility prevent and treat blahs aypnia disease |
| CN110974874A (en) * | 2019-08-05 | 2020-04-10 | 泰州医药城国科化物生物医药科技有限公司 | Method for preparing flavone and saponin components in spina date seed extract |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101926865A (en) * | 2010-09-11 | 2010-12-29 | 天津医科大学 | Spina date seed depression-resolving and nerve-soothing composition and preparation method thereof |
-
2014
- 2014-03-13 CN CN201410093588.XA patent/CN103980197B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101926865A (en) * | 2010-09-11 | 2010-12-29 | 天津医科大学 | Spina date seed depression-resolving and nerve-soothing composition and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| Sedative Activity and Its Active Components of Zizyphi fructus;Byung Hoon Han et al;《Archives of Pharmacal Research》;19871201;第10卷(第4期);208-211，第208页Fig.1、左栏第1段，第209页Table 1、右栏实验方法第2段 * |
| 酸枣仁抗氧化成分的分离及其相互作用研究;丁轲 等;《高校化学工程学报》;20131107;第27卷(第5期);842-853，第849页图10 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103980197A (en) | 2014-08-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103599148B (en) | Husky fluffy extractive of general flavone and its preparation method and application | |
| CN103980197B (en) | Spina Date Seed alkaloid monomer composition acid Lee alkali and preparation method thereof and application | |
| CN101721567B (en) | Grassleaf sweetflag rhizome extract, preparation method and application thereof | |
| CN102283910B (en) | Chinese medicinal composition with anti-depression effect and preparation and preparation method thereof | |
| CN102935100A (en) | Preparation method and applications of queen lagerstroemia folium apocyni veneti general flavones | |
| CN102895278A (en) | Application of arctinin and arctigenin in resisting parkinsonism | |
| CN1689596A (en) | Hypericum perforatum extract and its preparation process | |
| CN1969945A (en) | Chinese medicinal blood tonic and preparation process thereof | |
| CN102178721B (en) | Application of fiveleaf gynostemma herb suspension and extract to preparation of drug for treating and resisting depression | |
| CN105267274A (en) | Atractylenolide extract having antiparkinsonian effect, preparation method and application thereof | |
| CN1799564A (en) | Application of valeriana wallichii and its extract in preparation of medicine for treating anxiety neurosis | |
| CN102106890B (en) | Applications and preparation method of saussurea total sesquiterpene lactone | |
| CN105012356B (en) | Purposes of the ganoderic acid A in depression | |
| CN110507753A (en) | A kind of traditional Chinese medicine extract composition and its preparation method and application for treating cognitive disorder disease | |
| CN102670752A (en) | Application of tree peony bark extract to preparation of medicament for treating depression | |
| CN1188406C (en) | Cattail pollen extract and preparation process and use thereof | |
| CN102125573A (en) | Use of ginsenoside Rg1 in preparation of antidepressant | |
| CN101904894B (en) | Application of lamiophlomis rotate total glycosides in preparing medicines | |
| CN103251757B (en) | Borneol-containing compound preparation as well as preparation method and application thereof | |
| CN106074643B (en) | Application of acanthopanax giraldii harms leaf and extract thereof in preparing anti-fatigue medicine or health food | |
| CN106852973A (en) | A kind of traditional Chinese medicine extract composition, Its Preparation Method And Use | |
| CN102743373A (en) | Application of Casticin in medicine preparation for analgesia | |
| CN110279738A (en) | A kind of extracting method of antidepressant spermidine active component and the purposes of spermidine effective part extract | |
| CN103385929A (en) | A traditional Chinese medicine composition used for treating Alzheimer's dementia, preparation thereof and an application thereof | |
| CN104130232B (en) | The method of purification of a kind of EGCG and the EGCG of acquisition and pharmaceutical composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP02 | Change in the address of a patent holder | ||
| CP02 | Change in the address of a patent holder |
Address after: No. 1, Rongyuan Road, Huayuan Industrial Zone, High-tech Industrial Development Zone, Binhai New Area, Tianjin 300384 Patentee after: Tianjin Medical University Address before: 300070 No. 22 Meteorological Observatory Road, Heping District, Tianjin Patentee before: Tianjin Medical University |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20221027 Address after: No. 39, Xuzhuang Village, Heihu Temple Township, Liangshan County, Jining City, Shandong Province 272600 Patentee after: Zhang Xianyong Address before: Room 508, 5th Floor, Building 1, Yard 3, Jinguan North Second Street, Shunyi District, Beijing 101399 Patentee before: Beijing Building Ark Technology Co.,Ltd. Effective date of registration: 20221027 Address after: Room 508, 5th Floor, Building 1, Yard 3, Jinguan North Second Street, Shunyi District, Beijing 101399 Patentee after: Beijing Building Ark Technology Co.,Ltd. Address before: No. 1, Rongyuan Road, Huayuan Industrial Zone, High-tech Industrial Development Zone, Binhai New Area, Tianjin 300384 Patentee before: Tianjin Medical University |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20230426 Address after: 570100 East side of the 1st floor of Building 1, No. 16 Yaogu Yiheng Road, Yaogu Industrial Park, High tech Zone, Xiuying District, Haikou City, Hainan Province Patentee after: Kampo Extract Biotechnology (Hainan) Co.,Ltd. Address before: No. 39, Xuzhuang Village, Heihu Temple Township, Liangshan County, Jining City, Shandong Province 272600 Patentee before: Zhang Xianyong |