CN108059592A - Deoxygenate aromatic A of rhizoma nardostachyos and preparation method and application - Google Patents
Deoxygenate aromatic A of rhizoma nardostachyos and preparation method and application Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/79—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
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- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/703—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups
- C07C49/723—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups polycyclic
- C07C49/727—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups polycyclic a keto group being part of a condensed ring system
- C07C49/733—Unsaturated compounds containing a keto groups being part of a ring containing hydroxy groups polycyclic a keto group being part of a condensed ring system having two rings
Abstract
The present invention relates to deoxidation aromatic A of rhizoma nardostachyos and preparation method and application, the deoxidation aromatic A of rhizoma nardostachyos is isolated and purified from the rhizome of Valerianaceae rhizoma nardostachyos platymiscium rhizoma nardostachyos and obtained, promote activity with 5 hydroxytryptamine transporters (SERT), it can be applied in terms of the drug for treating the digestive system functions disorders such as the neuropsychiatric diseases such as depression, anxiety disorder, schizophrenia, obsession, nerve degenerative diseases, drug addiction and slow Constipation, irritable bowel syndrome and functional distension is prepared, there is important drug development to be worth.
Description
Technical field
The present invention relates to Plant Extracts and preparation method and application, especially deoxygenate the aromatic A of rhizoma nardostachyos and its system
Preparation Method and application.
Background technology
Serotonin transporter (SERT) is a kind of transmembrane transporter for having high affinity to 5-HT, containing about 630
Amino acid residue, encoding gene (SLC6A4) are located on No. 7 and No. 11 chromosomes respectively, are about outside 14 of 35kb by span
Aobvious son composition.SERT albumen includes 12-13 transmembrane region, and N-terminal and C-terminal are located in kytoplasm, has cAMP dependence eggs at N-terminal
White kinases binding site has one to be located at extracellular annulus between the 3rd and the 4th transmembrane region, is the glycosyl of N- connections
Change site.
SERT belongs to Na+/Cl-Dependent form transport protein is predominantly located at 5-HT serotonergic neurons.SERT is from nerve synapse gap
In reuptake 5-HT and enter presynaptic neuron, directly affect synaptic cleft 5-HT concentration, change postsynaptic receptor mediation letter
Number amount and acting duration.It moreover has been found that SERT is by placenta tissue, marrow, kidney, lung, the heart, adrenal gland, liver, first shape
The organs such as gland, thyroid gland, pancreas and small intestine are also distributed, and SERT is prompted to participate in different physiological roles.
SERT is the important molecule for transporting 5-HT, with many Physiological Psychology functions such as mood, appetite, sleep, memory, study
Correlation, SERT and 5-HT expression, which change, can cause anxiety, depression, obsession, neurosis or even schizophrenia, and and drug
It is additive closely related；It moreover has been found that SERT plays key player in gastrointestinal function disease, such as clinically slow transmission
The functional gastrointestinal diseases such as property constipation, irritable bowel syndrome, functional distension, using antidepressants, the anti-coke for SERT
Consider drug and achieve curative effect.
SERT is the important target spot of clinical medicine research and development.Classical antidepressants based on SERT target spots belong to selectivity more
SERT inhibitor (SSRI), such as Prozac (Fluoxetine)；Serotonin reuptake transporter accelerating agent (SSRE) then rare report,
So far reported that SSRE has Tianeptine (tianeptine), alias Tatinol (stablon), chemical constitution category tricyclic antidepressants resist
Depressant drug, clinic are mainly used for antidepression and antianxiety.Experimental studies have found that Tianeptine can promote 5-HT reuptakes, in nerve
In terms of structure plasticity, Tianeptine to stress/the hippocampal neuron dendron atrophy of cortisone induction has prevention effect, can
Hippocampus precursor multiplication, the decline of hippocampus volume and the N- acetyl aspartates concentration for resisting stress induction decline, and prevent apricot
Benevolence core dendron hyperplasia.In terms of nerve excitability, Tianeptine, which can overcome, stress block hippocampal long-term humidification,
Reverse stress be to inhibitory action of hippocampus-preceding cortex cynapse etc..In terms of neuroprotection, Tianeptine can reduce hippocampus and temporo
The Apoptosis of leaves layer.In terms of memory function, Tianeptine to stress reduced space memory impairment have blocking effect, increase
Memory is added to retain, attention is contributed to concentrate (the McEwen BS, Olie such as behavior, the illeffects of antagonism alcohol
JP.2005.Neurobiology of mood,anxiety,and emotions as revealed by studies of a
unique antidepressant:tianeptine.Molecular Psychiatry 10,525–537).In addition, how general thiophene is
Spit of fland can raise maincenter 5-HT metabolins 5-hydroxyindoleacetic acid, after deduction may be due to presynaptic membrane reuptake -5-HT increases, god
Accordingly increase through interior 5-HT catabolism related；Tianeptine may act on hypothalamus-pituitary-adrenal axis, make hypothalamus skin
Matter releasing factor and anterior pituitary adrenal cortical hormone concentration decline.
Tianeptine is effective to major depressive disorder, is better than Prozac to depression long-term efficacy, and safe, bad anti-
Should lack, be suitable for depression in old age, anxiolytic effect better than Prozac (sprout recklessly, Li Zhen .2007. Tianeptines pharmacological researches and
Clinical advances Guangdong medicine 28 (7)：1192-1193.) Tianeptine includes the action character of human body：It is disorderly to mental state
There is certain effect, between sedating antidepressants and excitability antidepressants；To Somatic discomfort, especially for anxiety and
The disorderly related upset,gastro-intestinal of mental state has obvious effect；The personality and conduct disorder occur to alcoholism patient during abstinence from alcohol
There is certain effect；Moreover, Tianeptine to following aspect without ill-effect：Sleep and vigilance；Cardiovascular system；Cholinergic system
(nonreactive cholinergic symptoms)；Drug habit.Above research has prompted serotonin reuptake transporter accelerating agent (SSRE) in clinical practice
The characteristics of middle and advantage.
Rhizoma nardostachyos (Nardostachys chinensis Batal.) is Valerianaceae rhizoma nardostachyos platymiscium, has regulating qi-flowing for relieving pain, opens
It is strongly fragrant to be amusing；The effect of external application clearing damp is subsided a swelling, rhizoma nardostachyos it has been reported that bioactivity act on nervous system including (1), such as anti-suppression
Strongly fragrant, calm and anticonvulsion, anti-Parkinson and reminiscence；(2) cardiovascular system is acted on, such as blood pressure lowering, anti-arrhythmia, is resisted
Myocardial ischemia, anti-cardiovascular injury；(3) respiratory system is acted on, such as enhances hypoxia-bearing capability；(4) it is antibacterial；(5) anti-liver injury
Deng.The chemical composition of rhizoma nardostachyos includes sequiterpene, triterpene, iridoid, cumarin, phenolic acid, flavones etc..
The content of the invention
The technical problems to be solved by the invention are to provide a kind of deoxidation rhizoma nardostachyos aromatic A.
Another technical problem to be solved by this invention is the preparation method for providing the above-mentioned aromatic A of deoxidation rhizoma nardostachyos.
Another technical problem to be solved by this invention is the application for providing the above-mentioned aromatic A of deoxidation rhizoma nardostachyos.
In order to solve the above technical problems, the technical scheme is that：
A kind of deoxidation aromatic A of rhizoma nardostachyos (desoxo-narchinol A), has structural formula shown in (I),
The above-mentioned aromatic A of deoxidation rhizoma nardostachyos, physical chemistry and Spectroscopic Properties：Yellow oily substance (methanol), C12H16O2。
There is blackening under 254nm ultraviolet lamps, unstressed configuration under 365nm ultraviolet lamps, 10% sulfuric acid ethyl alcohol shows red.V(MeOH)λmax:333、
228、204nm；CD(c 0.38,MeOH)λ(Δε):257(-4.53)、219(+6.73)nm.1H NMR(400MHz,DMSO-d6)
δH：7.04 (1H, dd, J=10.0,6.0Hz, H-7), 6.77 (1H, t, J=4.0Hz, H-1), 6.00 (1H, d, J=10.0Hz,
), H-8 2.28 (1H, m, H-4), 2.20 (2H, m, H-3), 1.44 (2H, m, H-2), 0.87 (3H, d, J=6.8Hz, H-12),
0.84 (3H, s, H-11), 5.19 (1H, d, J=5.3Hz ,-OH), 3.93 (1H, br s, H-6).13C NMR(100MHz,DMSO-
d6)δC：186.6(C-9),148.4(C-8),139.5(C-10),137.5(C-7),128.7(C-1),66.7(C-6),41.5
(C-5),30.2(C-4),25.6(C-2),25.3(C-3),19.5(C-11),14.9(C-12)。
The above-mentioned aromatic A of deoxidation rhizoma nardostachyos, chemical constitution feature are：Belong to nardosinone 6- catabolites of type sequiterpene, parent nucleus
Upper 6- hydroxyl can be substituted base acylation, phenolic ether, amide chemical conversion ester, phenolic ether or nitrogenous compound.
The preparation method of the above-mentioned aromatic A of deoxidation rhizoma nardostachyos, is as follows：
(1) rhizoma nardostachyos rhizome 70% (v/v) alcohol steep 3 times, every time 48 it is small when, merge extracting solution, be concentrated under reduced pressure, obtain slightly
Extract medicinal extract；Then put on 70% ethyl alcohol heat and state the dregs of a decoction 3 times, every time 2 it is small when, merge extracting solution, be concentrated under reduced pressure, again slightly
Extract medicinal extract；Merge crude extract medicinal extract twice and obtain the total medicinal extract of crude extract；
(2) gained the total medicinal extract of crude extract after moisture dissipates, respectively with isometric petroleum ether, ethyl acetate and n-butanol according to
Secondary extraction obtains petroleum ether part, ethyl acetate extract, n-butanol portion and water layer；Water layer is through 70% ethyl alcohol alcohol precipitation, on gained
Clear liquid concentration and recovery merges into medicinal extract and with n-butyl alcohol extract, then passes through D101 large pore resin absorption column alcohol-water (water
30%th, 50%, 70% and 95%) gradient elution, 95% alcohol elution are merged into acetic acid ethyl ester extract and obtain ethyl acetate
Position；
(3) by ethyl acetate extract through silica gel column chromatography, methylene chloride-methanol=100:0-0:100 solvent system gradients
Elution (described 100：0 100% dichloromethane eluent situation of finger, 0：100 refer to 100% methanol elution profile), obtain 15 fractions
Fr.1-15；
(4) methylene chloride-methanol=100:5-100:7 solvents elute fraction-fraction Fr.9 through silica gel column chromatography repeatedly,
100% ethyl acetate elutes, the aromatic A of isolated deoxidation rhizoma nardostachyos.
Applications of the above-mentioned aromatic A of deoxidation rhizoma nardostachyos in terms of the drug for promoting serotonin transporter (SERT) activity is prepared.
The above-mentioned aromatic A of deoxidation rhizoma nardostachyos is in terms of the drug for treating neuropsychiatric disease and/or drug addiction is prepared
Application.
Preferably, the application of the above-mentioned aromatic A of deoxidation rhizoma nardostachyos, the neuropsychiatric disease is depression, anxiety disorder, spirit point
Split disease, obsession or nerve degenerative diseases.
Applications of the above-mentioned aromatic A of deoxidation rhizoma nardostachyos in terms of the drug for treating digestive system function disorders is prepared.
Preferably, the application of the above-mentioned aromatic A of deoxidation rhizoma nardostachyos, the digestive system function disorders include slow transporting just
Secret, irritable bowel syndrome or functional distension.
Pharmaceutical composition with the above-mentioned aromatic A of deoxidation rhizoma nardostachyos, the compound comprising treatment and/or prevention effective dose
Deoxygenate the aromatic A of rhizoma nardostachyos and optional pharmaceutically acceptable excipient.
Above-mentioned pharmaceutically acceptable excipient can be any conventional excipient, particular excipient in field of pharmaceutical preparations
Selection by depending on being used to treat the administering mode of particular patient or disease type and state, for the conjunction of specific administration pattern
The preparation method of suitable pharmaceutical composition is completely in the knowledge of drug field technical staff.For example, can as pharmacy
Diluent of the excipient of receiving including pharmaceutical field routine, carrier, filler, adhesive, wetting agent, disintegrant, absorption promote
Into agent, surfactant, absorption carrier and lubricant etc., if necessary, flavouring agent, anti-corrosion can also be added in pharmaceutical composition
Agent and sweetener etc..
Tablet, pulvis, granule, capsule, oral liquid, paste, creme, injection breast can be made in aforementioned pharmaceutical compositions
The diversified forms such as agent, aseptic powder needle for injection, the drug of various dosage forms can be prepared according to the conventional method of pharmaceutical field.
The beneficial effects of the invention are as follows：
The above-mentioned aromatic A of deoxidation rhizoma nardostachyos is from Valerianaceae rhizoma nardostachyos platymiscium rhizoma nardostachyos (Nardostachys chinensis
Batal. isolate and purify and obtain in rhizome), have and promote serotonin transporter (SERT) activity, treatment can be used as depressed
The nervous system diseases such as disease, anxiety disorder, schizophrenia, obsession, nerve degenerative diseases, drug addiction and slow transmission
Property the digestive system functions disorders such as constipation, irritable bowel syndrome and functional distension medicine, have important
Drug development is worth.
Description of the drawings
Fig. 1 is to deoxygenate facilitations of the aromatic A of rhizoma nardostachyos to SERT activity, wherein, positive control drug is respectively 2.0 μM
Fluoxetine and 1.0 μM of Tianeptine, * * * p<0.001.
Specific embodiment
In order to which those skilled in the art is made to be better understood from technical scheme, With reference to embodiment
Technical solution of the present invention is described in further detail.
Laboratory apparatus and reagent：Fourier transform nuclear magnetic resonance spectrometer (Bruker companies of Switzerland, AVIII types 400MHz
And 600MHz)；Color developing agent：10% sulfuric acid ethyl alcohol.
Embodiment 1
Active ingredient deoxygenates the preparation (extraction separation process) of the aromatic A compounds of rhizoma nardostachyos：
Rhizoma nardostachyos pharmaceutical decocting piece is purchased from Anhui Jiren Pharmacy Co., Ltd.'s (lot number：110709, specification：1kg/ bags, the place of production：Four
River), about 20kg.Rhizoma nardostachyos rhizome 20kg 70% (v/v) alcohol steeps 3 times, every time 48 it is small when, merge extracting solution, be concentrated under reduced pressure,
Obtain crude extract medicinal extract 3kg；Then put on 70% ethyl alcohol heat and state the dregs of a decoction 3 times, every time 2 it is small when, merge extracting solution, be concentrated under reduced pressure,
Obtain crude extract medicinal extract 400g；Merge crude extract twice and obtain total medicinal extract 3.4kg；The total medicinal extract of gained crude extract, after moisture dissipates, successively
It is extracted with isometric petroleum ether, ethyl acetate, n-butanol, water layer is returned through 70% ethyl alcohol alcohol precipitation, gained supernatant concentration
Harvest medicinal extract simultaneously merges with n-butyl alcohol extract, then by D101 large pore resin absorption columns alcohol-water (water, 30%, 50%,
70% and 95%) gradient elution.95% alcohol elution is merged into acetic acid ethyl ester extract and obtains ethyl acetate extract.By acetic acid
Ethyl ester position (1.2kg) is through silica gel column chromatography, methylene chloride-methanol=100:0-0:100 solvent system gradient elutions, wherein,
Described 100：0 100% dichloromethane eluent situation of finger, 0：100 refer to 100% methanol elution profile, obtain 15 fraction Fr.1-15；
Methylene chloride-methanol=100:5-100:7 solvents elute fraction-fraction Fr.9 (40g) through silica gel column chromatography repeatedly, 100% second
Acetoacetic ester elutes, the aromatic A of isolated deoxidation rhizoma nardostachyos.
After measured, the aromatic A of rhizoma nardostachyos (desoxo-narchinol A), yellow oily substance (methanol), C are deoxygenated12H16O2。
There is blackening under 254nm ultraviolet lamps, unstressed configuration under 365nm ultraviolet lamps, 10% sulfuric acid ethyl alcohol shows red.V(MeOH)λmax:333、
228、204nm；CD(c 0.38,MeOH)λ(Δε):257(-4.53)、219(+6.73)nm.1H NMR(400MHz,DMSO-d6)
δH：7.04 (1H, dd, J=10.0,6.0Hz, H-7), 6.77 (1H, t, J=4.0Hz, H-1), 6.00 (1H, d, J=10.0Hz,
), H-8 2.28 (1H, m, H-4), 2.20 (2H, m, H-3), 1.44 (2H, m, H-2), 0.87 (3H, d, J=6.8Hz, H-12),
0.84 (3H, s, H-11), 5.19 (1H, d, J=5.3Hz ,-OH), 3.93 (1H, br s, H-6).13C NMR(100MHz,DMSO-
d6)δC：186.6(C-9),148.4(C-8),139.5(C-10),137.5(C-7),128.7(C-1),66.7(C-6),41.5
(C-5),30.2(C-4),25.6(C-2),25.3(C-3),19.5(C-11),14.9(C-12).The aromatic A of the deoxidation rhizoma nardostachyos belongs to
6- catabolites of nardosinone type sequiterpene, on parent nucleus 6- hydroxyls can be substituted base acylation, phenolic ether, amide chemical conversion ester,
Phenolic ether or nitrogenous compound.Structural formula is as follows：
Embodiment 2
Influence of the compound of the present invention to serotonin transporter (SERT)
Using the hSERT-HEK293 cell lines of stable transfection, with 4- (4- (dimethylamino) phenyl) -1-
methylpyridinium(APP+) it is fluorogenic substrate, detection compound deoxygenates the aromatic A of rhizoma nardostachyos to SERT in high intension system
The influence of activity.
1) laboratory apparatus and reagent
Laboratory apparatus：
High intension Operetta systems and Columbus data managements and analysis system (PerkinElmer), super-clean bench move
Liquid rifle (1000 μ L, 200 μ L, 20 μ L, 10 μ L, 2.5 μ L, Eppendorf companies of the U.S.)
Reagent and material：
Human embryonic kidney cell line HEK293 (the American Type Culture Collection committee of Chinese Academy of Sciences cell bank), hSERT pcDNA3
Plasmid (Addgene, plasmid 15483), MEM culture mediums (Gibco), APP+(Sigma), 33342 (Cell of Hoechst
Signaling Technology), 96 orifice plates (Costar 3605)
2) experimental implementation process
It initially sets up and identifies and stablize expression hSERT-HEK293 cell lines.With APP+For fluorogenic substrate, based in height
{ Liu Yanting, Ying Shusong, skill in martial arts is quiet, Dong Pengzhi, Wu Honghua, and Xu Yan leads to a kind of 5- hydroxyls of improvement of for the function of culvert system detectio SERT
Tryptamines transporter reactive compound High content screening method [J] Tianjin University Of Traditional Chinese Medicine journal, 2016,35 (03):180-
186.}
Specific steps：
(1) precision weighs the 1 gained deoxidation aromatic A of rhizoma nardostachyos of embodiment, the mother liquor of 20mM is configured to DMSO, with without phenol red
Training base in MEM bases dilutes drug to 10.0 μM, 1.0 μM, 0.1 μM.
(2) 1.0 × 10 are pressed4The density of cells/well is inoculated with the hSERT-HEK293 cells of stable transfection into 96 orifice plates,
37 DEG C, 5%CO2Under the conditions of cultivate for 24 hours.
(3) blank control group, 2.0 μM of Prozac groups of positive control and 1.0 μM of Tianeptine groups, testing drug are set up in experiment
Set up 10.0 μM respectively, 1.0 μM, 0.1 μM of group.Cell discards culture medium, is washed 2 times with PBS buffer solution, according to 80 μ L/ pore volumes
Add in each sample to be tested, each 3 multiple holes of concentration, at 37 DEG C, 5%CO2Under the conditions of be protected from light be incubated 2-3h.
(4) after the completion of being incubated, 20 μ L APP are added in per hole+, it is incubated 10 minutes.
(5) liquid in hole is discarded, is washed 2 times with PBS buffer solution, 1.0 μ g/mL Hoechst50 μ L are added in per hole, are protected from light
It is incubated 20min.
(6) liquid in orifice plate is discarded, PBS is washed 2-3 times, using the intracellular fluorescence intensity of high intension system detectio
Hoechst 33342Excitation：360-400nm, Emission：410-480nm
APP+Excitation：460-490nm, Emission：505-550nm
3) data analysis：
Graphical analysis is carried out using Columbus data managements and analysis system, according to 33342 fluorescence identifyings of Hoechst
Nuclear pattern determines cell, according to intracellular APP+Fluorescence intensity determines SERT transport activities, calculates relative intensity of fluorescence
=(the intracellular APP of medicine group+The intracellular APP of fluorescence intensity/control group+Fluorescence intensity) carry out one-way analysis of variance (one
way ANOVA)。
4) experimental result
As shown in Figure 1, one-way analysis of variance the results show deoxidation the aromatic A of rhizoma nardostachyos remarkably promote SERT transport activities F (5,
31)=498.3, p<0.0001).Dunnett Multiple range tests post-hoc tests (Dunnett's multiple comparison
Post hoc test) confirm that 3 proof load deoxidation aromatic A of rhizoma nardostachyos more significantly promote SERT work with blank control group
Property, 10.0 μM of (q=11.51, p<0.001), 1.0 μM of (q=8.724, p<And 0.1 μM of (q=8.673, p 0.001)<0.001),
2.0 μM of Prozacs of positive controls significantly suppress SERT activity (q=31.73, p compared with blank control group<0.001) it is, positive
Property control group Tianeptine can significantly increase SERT activity (q=4.279, p at 1.0 μM<0.001).
In summary, the serotonin transporter (SERT) is a kind of Na for having high affinity to 5-HT+/Cl-It relies on
Type turns transmembrane transporter, and 5-HT serotonergic neurons are predominantly located in central nervous system, by from nerve synapse gap again
Intake 5-HT enters presynaptic neuron, directly affects synaptic cleft 5-HT concentration, changes the amount of postsynaptic receptor mediation signal
And acting duration, so as to participate in a variety of Physiological Psychology functions (such as mood, appetite, sleep, memory, study)；It is digesting
System SERT is predominantly located at intestinal epithelial cell, reuptakes the 5-HT of intestinal mucosa layer chromaffin cell release to adjust stomach and intestine
Function, in addition, in devices such as placenta tissue, genital tract, marrow, kidney, lung, the heart, adrenal gland, liver, parathyroid gland, thyroid gland and pancreas
Official is distributed, and SERT is prompted to participate in different physiological roles.
SERT is the important target spot of clinical medicine research and development, and the serotonin reuptake transporter accelerating agent (SSRE) reported so far has thiophene
Nai Puting, clinic are mainly used for antidepression and antianxiety.Tianeptine includes the action character of human body：Have one to mental state disorder
It is set for using, between sedating antidepressants and excitability antidepressants；To Somatic discomfort, especially for anxiety and mental state
Disorderly related upset,gastro-intestinal has obvious effect；The personality and conduct disorder occur to alcoholism patient during abstinence from alcohol has one
It is set for using；Moreover, Tianeptine to following aspect without ill-effect：Sleep and vigilance；Cardiovascular system；Cholinergic system (nothing
Anticholinergic symptom)；Drug habit.Tianeptine belongs to a kind of SSRE, and action character has prompted serotonin reuptake transporter rush
Into agent (SSRE) in clinical practice the characteristics of and advantage.
The present invention is turned by carrying out the external serotonin that influences on the aromatic A of isolated deoxidation rhizoma nardostachyos from rhizoma nardostachyos rhizome
The research of body (SERT) activity is transported, it is found that the deoxidation aromatic A of rhizoma nardostachyos can remarkably promote SERT transport activities, it is sweet so as to confirm deoxidation
Abienol A is the unbalance caused relevant physiological mental diseases of adjusting SERT and digestive system function disorders active ingredient.Cause
This, the aromatic A of deoxidation rhizoma nardostachyos can be used for preparing the treatment neuropsychiatric diseases such as depression and anxiety disorder and irritable bowel syndrome
Wait the drug of functional disturbances of gastrointestinal tract disease.
Embodiment 3
Preparation method：The aromatic A of rhizoma nardostachyos will be deoxygenated according to the above ratio, newborn sugar and starch uniformly mixes, cross 200 mesh sieves, use water
Mixture after wetting is dried re-sieving, magnesium stearate is added in, then by mixture tabletting, every weight by uniform wet
250mg, active component content 10mg.
Embodiment 4
Capsule：Deoxygenate the aromatic A 20mg of rhizoma nardostachyos
Galactolipin 188mg
Magnesium stearate 2mg
Preparation method：The aromatic A of rhizoma nardostachyos will be deoxygenated according to the above ratio uniformly to mix with galactolipin, 200 mesh sieves be crossed, what is obtained
Mixture, add in magnesium stearate, be packed into No. 2 capsules to get.
It is above-mentioned to be retouched in detail to what aromatic A of the deoxidation rhizoma nardostachyos and preparation method and application was carried out with reference to specific embodiment
It states, is illustrative rather than limited, several embodiments can be included according to limited scope, therefore are not departing from this
Change and modification under invention general plotting should belong within protection scope of the present invention.
Claims (8)
1. a kind of aromatic A of deoxidation rhizoma nardostachyos, it is characterised in that：With structural formula shown in (I),
2. the preparation method of the aromatic A of rhizoma nardostachyos is deoxygenated described in claim 1, it is characterised in that：It is as follows：
(1) rhizoma nardostachyos rhizome 70% (v/v) alcohol steep 3 times, every time 48 it is small when, merge extracting solution, be concentrated under reduced pressure, obtain crude extract
Medicinal extract；Then put on 70% ethyl alcohol heat and state the dregs of a decoction 3 times, every time 2 it is small when, merge extracting solution, be concentrated under reduced pressure, again crude extract
Medicinal extract；Merge crude extract medicinal extract twice and obtain the total medicinal extract of crude extract；
(2) the gained total medicinal extract of crude extract is extracted successively with isometric petroleum ether, ethyl acetate and n-butanol respectively after moisture dissipates
It takes, obtains petroleum ether part, ethyl acetate extract, n-butanol portion and water layer；Water layer is through 70% ethyl alcohol alcohol precipitation, gained supernatant
Concentration and recovery merges into medicinal extract and with n-butyl alcohol extract, then by D101 large pore resin absorption columns alcohol-water according to water 30%,
50%th, 70% and 95% gradient elution, 95% alcohol elution are merged into acetic acid ethyl ester extract and obtain ethyl acetate extract；
(3) by ethyl acetate extract through silica gel column chromatography, methylene chloride-methanol=100:0-0:100 solvent system gradient elutions
(described 100：0 100% dichloromethane eluent situation of finger, 0：100 refer to 100% methanol elution profile), obtain 15 fraction Fr.1-
15；
(4) methylene chloride-methanol=100:5-100:7 solvents elute fraction-fraction Fr.9 through silica gel column chromatography repeatedly, and 100%
Ethyl acetate elutes, the aromatic A of isolated deoxidation rhizoma nardostachyos.
3. applications of the aromatic A of rhizoma nardostachyos in terms of the drug for promoting serotonin transporter activity is prepared is deoxygenated described in claim 1.
4. it deoxygenates the aromatic A of rhizoma nardostachyos described in claim 1 preparing to treat the medicine of neuropsychiatric disease and/or drug addiction
The application in object space face.
5. the application of the aromatic A of deoxidation rhizoma nardostachyos according to claim 4, it is characterised in that：The neuropsychiatric disease is suppression
Strongly fragrant disease, anxiety disorder, schizophrenia, obsession or nerve degenerative diseases.
6. the aromatic A of rhizoma nardostachyos is deoxygenated described in claim 1 in terms of the drug for treating digestive system function disorders is prepared
Application.
7. the application of the aromatic A of deoxidation rhizoma nardostachyos according to claim 6, it is characterised in that：The digestive system function is disorderly
Disease includes slow Constipation, irritable bowel syndrome or functional distension.
8. with the pharmaceutical composition that the aromatic A of rhizoma nardostachyos is deoxygenated described in claim 1, it is characterised in that：Include treatment and/or prevention
A effective amount of aromatic A of compound deoxidation rhizoma nardostachyos and optional pharmaceutically acceptable excipient.
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| CN108303480A (en) * | 2017-11-09 | 2018-07-20 | 天津中医药大学 | The quantitative detecting method and rhizoma nardostachyos active constituent of a kind of rhizoma nardostachyos active constituent and application |
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