CN105713009B - Calamus alcoholic lactone compound and preparation method and application - Google Patents
Calamus alcoholic lactone compound and preparation method and application Download PDFInfo
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Abstract
The invention provides calamus alcoholic lactone compound and preparation method and application, the compound is { 6, 7, the α isobutyl groups 4 of 8 trihydroxy 4, 7 dimethyl hexahydros 6, 8 α epoxies chromene 2 (3H) ketone }, isolate and purify and obtain from grass-leaved sweetflag rhizome, with 5 hydroxytryptamine transporter (SERT) inhibitory activity, depression can be used for preparing, anxiety disorder, schizophrenia, obsession, applied in terms of the medicine of the diseases such as nervus retrogression, and applied in terms of the medicine preparation of the disease such as drug addiction and digestive system function disorder, it is worth with important drug development.
Description
Technical field
The present invention relates to traditional Chinese medicine research field, especially calamus alcoholic lactone compound and 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, its encoding gene (SLC6A4) are about respectively outside 14 of 35kb by span in No. 7 and No. 11 chromosomes
Aobvious son composition.SERT albumen includes 12~13 transmembrane regions, and N-terminal and C-terminal are located in kytoplasm, has cAMP dependences at N-terminal
Protein kinase binding site, there is one to be located at extracellular annulus between the 3rd and the 4th transmembrane region, be the sugar of N- connections
Base site.
SERT belongs to Na+/Cl-Dependent form transport protein, it 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 prompt SERT 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 changes can cause anxiety, depression, obsession, neurosis, or even schizophrenia, and and medicine
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 the antidepressants for SERT, anti-Jiao
Consider medicine and achieve curative effect.
SERT is the important target spot of clinical medicine research and development, and selective serotonin reuptake depressant (SSRI) includes fluorine west
Spit of fland, Paxil, Sertraline, Fluvoxamine, Citalopram etc., clinic are usually used in treating depression, anxiety disorder and obsession etc.,
Such medicine sedation is small, does not also damage Psychomotor ability, influences very little to cardiovascular and autonomic nervous system function.
Grass-leaved sweetflag Acorus tatarinowii are Acorus of Araceae plants, have removing dampness to restore normal functioning of the stomach, slit phlegm of having one's ideas straightened out, wake up
Refreshing effect of benefiting intelligence, grass-leaved sweetflag it has been reported that bioactivity act on nervous system including (1), such as antidepression, calmness and anti-frightened
Faint, brain protection and intelligence development, (2) act on cardiovascular system, such as lipid-loweringing and decreasing heart rate, (3) act on respiratory system, such as treat
Chronic bronchitis, bronchial astehma, (4) are antibacterial, (5) anticancer etc.；The chemical composition of grass-leaved sweetflag include volatile oil, lignanoid,
Phenolic acid, alkaloid, flavones etc., research shows, grass-leaved sweetflag volatile ingredient and involatile constituent have preferable antidepression to live
Property, and in terms of the material base of activity, volatile ingredient report is more, and involatile constituent is rarely reported.
The content of the invention
The technical problems to be solved by the invention are to provide calamus alcoholic lactone compound.
Another technical problem to be solved by this invention is the preparation method for providing above-mentioned calamus alcoholic lactone compound.
Another technical problem to be solved by this invention is the application for providing above-mentioned calamus alcoholic lactone compound.
In order to solve the above technical problems, the technical scheme is that：
A kind of calamus alcoholic lactone (tatarinolactone, TATe) compound, 6,7,8- -4 α of trihydroxy-isobutyl group -4,
7- dimethyl hexahydro -6,8 α-epoxy chromene -2 (3H) -one }, there is following structural formula (I) formula：
Preferably, above-mentioned calamus alcoholic lactone compound, its physical chemistry and Spectroscopic Properties are：White, needle-shaped crystals (first
Alcohol), it is single spot in various development systems, 10% sulfuric acid ethanol shows brown color spot；UV(MeOH)λmax:197nm；
CD (MeOH, c=3.0 × 10-3)λ(Δε):215(+0.51)、195(-0.72)nm；Nuclear magnetic data is：1H-NMR(CD3OD,
600MHz):δ 2.09 (1H, dd, J=10.8,16.8Hz, α-H-3), 2.55 (1H, dd, J=2.4,15.6Hz, β-H-3),
2.56 (1H, m, H-4), 1.58 (1H, dd, J=2.4,10.2Hz, α-H-5), 2.19 (1H, d, J=10.8Hz, β-H-5),
3.91 (1H, d, J=4.2Hz, H-8), 2.10 (1H, d, J=10.8Hz, α-H-9), 1.66 (1H, ddd, J=3.0,3.6,
3.8Hz, β-H-9), 2.21 (1H, m, H-10), 1.05 (3H, d, J=6.6Hz, H-11), 1.09 (3H, d, J=6.6Hz, H-
12), 1.37 (3H, s, H-13), 1.04 (3H, d, J=6.6Hz, H-14)；13C-NMR data are shown in specific embodiment part table 1.
Preferably, above-mentioned calamus alcoholic lactone compound, its chemical constitution include：
(1) 1,2- ester bond can fragment into 2 carboxylic acids and 8 α positions hydroxyl ketal groups, hydroxy-acid group can further by alcohols,
Phenols, acid amides or alkaloid substituent etherificate or amination, 6,7,8,8 α positions hydroxyls can be further by carboxylic acid, phenolic acid or amide-containings
The substituent esterification or amidatioon of group；
(2) 6,8 α-oxygen bridge can fragment into 6 dihydroxy ketals and 8 α positions hydroxyl ketal groups, and 6,7,8,8 α positions hydroxyls can
Further by the substituent esterification or amidatioon of carboxylic acid, phenolic acid or phosphinylidyne-containing amine group；
(3) 8 tertiary carbon hydroxyls can be substituted base acylation, phenolic ether, acid amides chemical conversion ester, phenolic ether or nitrogen-containing compound；
(4) 6,7 quaternary carbon hydroxyls can be substituted base acylation, phenolic ether in the case where organic acid and lewis acid are as catalysts conditions
Change, acid amides is melted into ester, phenolic ether or nitrogen-containing compound；Concrete condition is as shown in Figure 10.
The preparation method of above-mentioned calamus alcoholic lactone compound, is comprised the following steps that：
(1) per 20Kg grass-leaved sweetflags rhizome (Acorus of Araceae plant grass-leaved sweetflag Acorus tatarinowii rhizome)
Boiled 3 times with the decocting of 8,6,6 times of weight respectively, 1.5 hours every time, merge extract solution, be concentrated under reduced pressure into the 1/ of extracting liquid volume
5-1/10, obtain crude extract concentrate；
(2) gained crude extract concentrate, through D101 macroporous resin column chromatographies, alcohol-water (v/v) gradient elution, is obtained
30%th, 50%, 70%, 95%4 ethanol elution thing, solvent is recovered under reduced pressure respectively to without alcohol taste；
(3) pH=3~4 are adjusted with formic acid after 30% ethanol elution thing moisture is dissipated, isometric extracting n-butyl alcohol 3 times, are returned
Receive solvent and obtain n-butanol layer medicinal extract；
(4) n-butanol layer medicinal extract methanol-water (v/v) gradient elution, collects 50% methanol water elution stream through ODS column chromatographies
Part, obtained component separates through the methanol-water (v/v) of Sephadex LH-20 gel columns 50%, silica G column chromatography, and silicagel column is with dichloro
Methane-methanol (v/v) gradient elution, dichloromethane：Methanol=15:In 1 fraction eluted in the isolated calamus alcohol
Ester compounds.
Application of the above-mentioned calamus alcoholic lactone compound in terms of suppression serotonin transporter (SERT) active medicine is prepared.
Preferably, above-mentioned calamus alcoholic lactone class compound prepare depression, anxiety disorder, schizophrenia, obsession,
Application in terms of the medicines of disease such as nerve degenerative diseases, drug addiction and digestive system function disorder.
Pharmaceutical composition with above-mentioned calamus alcoholic lactone class compound, the calamus comprising treatment and/or prevention effective dose
Alcoholic lactone compound 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 the administering mode or disease type and state for treating particular patient, the conjunction for 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
The excipient of receiving includes the conventional diluent of pharmaceutical field, carrier, filler, adhesive, wetting agent, disintegrant, absorption rush
Enter 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 medicine of various formulations can be prepared according to the conventional method of pharmaceutical field.
The beneficial effects of the invention are as follows：
Calamus alcoholic lactone compound of the present invention, from Acorus of Araceae plant grass-leaved sweetflag Acorus
Isolate and purify and obtain in tatarinowii rhizome, have the function that to suppress serotonin transporter (SERT) activity, can conduct
Depression, anxiety disorder, schizophrenia, obsession, nerve degenerative diseases, drug addiction and digestive system function disorder etc.
The medicine of disease, there is important drug development to be worth.
Brief description of the drawings
Fig. 1 is the related figures of crucial NOESY of compound calamus alcoholic lactone；
Fig. 2 is inhibitory action of the compound calamus alcoholic lactone to SERT activity, wherein, 2 μM of positive control drug
Fluoxetine, * * p<0.01, * * * P<0.001；
Fig. 3 is compound calamus alcoholic lactone1H-NMR spectrum；
Fig. 4 is compound calamus alcoholic lactone13C-NMR spectrograms；
Fig. 5 is the HSQC correlation spectrograms of compound calamus alcoholic lactone；
Fig. 6 is the HMBC correlation spectrograms of compound calamus alcoholic lactone；
Fig. 7 is the NOESY spectrograms of compound calamus alcoholic lactone；
Fig. 8 is the low resolution ESI-MS mass spectrograms of compound calamus alcoholic lactone；
Fig. 9 is CD and the UV figure of compound calamus alcoholic lactone；
Figure 10 is the chemical constitution schematic diagram of compound calamus alcoholic lactone, wherein R1Substitute for carboxylic acid, phenolic acid or amide-type
Base, R2For carboxylic acid, phenolic acid or amide-type substituent, R3For carboxylic acid, phenolic acid or amide-type substituent；
Figure 11 is the fragmentation pattern of compound calamus alcoholic lactone structure elucidation.
Embodiment
In order that those skilled in the art is better understood from technical scheme, it is below in conjunction with the accompanying drawings and specific real
Mode is applied to be described in further detail technical scheme of the present invention.
Laboratory apparatus and reagent：Fourier transform nuclear magnetic resonance spectrometer (Bruker companies of Switzerland, AVIII types 400MHz
And 600MHz)；Developer：10% sulfuric acid ethanol.
Embodiment 1
The preparation (extraction separation process) of active component calamus alcoholic lactone
Grass-leaved sweetflag pharmaceutical decocting piece is purchased from Anhui Jiren Pharmacy Co., Ltd.'s (lot number：120519, specification：1Kg/ bags, the place of production：
Anhui), about 20Kg, decocted 3 times, each 1.5h with 8,6,6 times of waters respectively, merge extract solution, be recovered under reduced pressure to small size
(80L), through D101 macroporous resin column chromatographies after filtering, alcohol-water (v/v) gradient elution, solvent is recovered under reduced pressure, obtain 30%,
50%th, 70%, 95%4 ethanol elution thing.
30% ethanol elution thing moisture with formic acid adjusts pH=3~4 after dissipating, and isometric extracting n-butyl alcohol 3 times, takes n-butanol
Extract is recovered under reduced pressure solvent and obtains dry extract, and water is dissolved by ODS column chromatographies (methanol-water gradient elution), obtains 6 components,
Wherein 50% methanol-water eluate separates through the methanol-water (v/v) of Sephadex LH-20 gel columns 50%, silica G column chromatography, silicon
Glue post is with methylene chloride-methanol (v/v) gradient elution, dichloromethane：Methanol=15:Obtained in 1 elution fraction in the calamus alcohol
Ester compounds about 10.0mg, i.e. { 6,7,8- -4 α of trihydroxy-isobutyl group -4,7- dimethyl hexahydro -6,8 α-epoxy chromene -2
(3H) -one }.
Above-mentioned calamus alcoholic lactone compound (Fig. 1), white, needle-shaped crystals (methanol), in various solvent development systems,
For single spot, 10% sulfuric acid ethanol shows brown color spot；UV(MeOH)λmax:197nm；CD (MeOH, c=3.0 × 10-3)λ
(Δε):215(+0.51)、195(-0.72)nm；There is quasi-molecular ion peak m/z in low resolution ESI-MS mass spectrums (Fig. 8)：
323.33[M+Na]+With 299.16 [M-H]-, thus it is speculated that its molecular weight is 300, with reference to nuclear-magnetism hydrogen carbon modal data (Fig. 3~6), such as table 1
It is shown, thus it is speculated that its molecular formula is C15H24O6。
1H-NMR(CD3OD, 600MHz, Fig. 3) compose existing 3 tertiary carbon methyl hydrogen signal δH1.05 (3H, d, J=6.6Hz),
1.09 (3H, d, J=6.6Hz), 1.04 (3H, d, J=6.6Hz)；1 quaternary carbon methyl hydrogen signal δH1.37(3H,s)；3 Asias
Methyl hydrogen signal δH2.09 (1H, dd, J=10.8,16.8Hz), 2.55 (1H, dd, J=2.4,15.6Hz), 1.58 (1H, dd,
J=2.4,10.2Hz), 2.19 (1H, d, J=10.8Hz), 2.10 (1H, d, J=10.8Hz), 1.66 (1H, ddd, J=3.0,
3.6,3.8Hz)；2 methine hydrogen signal δH2.56(1H,m)、2.21(1H,m)。
13C-NMR(CD3OD, 150MHz, Fig. 4) spectrum in, give 15 carbon signals, with reference to hydrogen compose, thus it is speculated that be half as much again terpene
Class compound；δC175.3 be an ester carbonyl group carbon signal, δC113.1st, 103.1 be 2 ketal quaternary carbon signals, δC 70.0、
80.8 be 2 company's oxygen carbon signals.
According to HSQC, HMBC spectrogram (Fig. 5~6) can pushing-out structure fragment it is as shown in figure 11, the hydrogen atom (δ on 3 carbonH
2.55th, 2.09) with 2,4 α, 4,14 carbon atom (δC175.3rd, 57.4,32.1, correlation 16.9) be present, obtain fragment 1；8
Hydrogen atom (δ on carbonH3.91) with 8 α, 4 α, 6 carbon atom (δC113.1st, 57.4 correlation, 103.1) be present, on 13 carbon
Hydrogen atom (δH1.37) with 8,7,6 carbon atom (δC80.8th, 70.0, correlation 103.1) be present, obtain fragment 2；On 5 carbon
Hydrogen atom (δH2.19th, 1.58) with 4,4 α, 9,6,7 carbon atom (δC32.1st, 57.4,38.3,103.1, phase 70.0) be present
Close, obtain fragment 3.
The nuclear magnetic data of the calamus alcoholic lactone compound of table 1.
(CD3OD,1H-NMR in 600MHz,13C-NMR in 150MHz)
In summary information obtained by nuclear magnetic data, the planar structure of this calamus alcoholic lactone can be released with reference to ESI-MS, by two
Dimension NOESY spectrums (Fig. 7) can release the relative configuration of this calamus alcoholic lactone compound as shown in figure 1, itself CD and UV feature such as Fig. 9 institutes
Show.
Physicochemical property and Spectral Characteristic further according to calamus alcoholic lactone compound judge that its structure is as follows：
Embodiment 2
Compound calamus alcoholic lactone (tatarinolactone, TATe) compound of the present invention is transported to serotonin
The influence of body (SERT)
Using the hSERT-HEK293 cell lines of stable transfection, with 4- (4- (dimethylamino) phenyl) -1-
Methylpyridinium (APP+) is fluorogenic substrate, and calamus alcoholic lactone compound is detected in high intension system to SERT activity
Influence.
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), (Cell of Hoechst 33342
Signaling Technology), 96 orifice plates (Costar 3605)
2) experimental implementation process
Initially set up and identify stable expression hSERT-HEK293 cell lines and { pacify the people source 5- such as of heap of stone, Li Jing, golden blast
The foundation of hydroxytryptamine transporter stable expression cell line and its function investigation [J] military medicines 2011,35 (9):681-684}.
Using APP+ as fluorogenic substrate, function { Fowler A, Seifert N, the Acker V.et based on high intension system detectio SERT
al.A nonradioactive high-throughput/high-content assay for measurement of the
human serotonin reuptake transporter function in vitro[J].Journal of
Biomolecular Screening,2006,11(8):1027-1034}。
Specific steps：
(1) precision weighs calamus alcoholic lactone compound, and 20mM mother liquor is configured to DMSO, is trained with without phenol red MEM bases
Base dilutes medicine to 10 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 24h.
(3) test and set up blank control group, 2 μM of Fluoxetine groups of positive control, 10 μM of calamus alcoholic lactone, 1.0 μM,
0.1 μM of group.Cell discards culture medium, is washed 2 times with PBS, and each testing sample, Mei Genong are added according to 80 μ L/ pore volumes
Spend 3 multiple holes, at 37 DEG C, 5%CO2Under the conditions of lucifuge be incubated 2-3h.
(4) after the completion of being incubated, 20 μ L APP+ are added per hole, are incubated 10 minutes.
(5) liquid in hole is discarded, is washed 2 times with PBS, 1.0 μ g/mL Hoechst50 μ L, lucifuge are added per hole
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 33342 Excitation：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 the fluorescence identifyings of Hoechst 33342
Nuclear pattern determines cell, determines SERT transport activities according to intracellular APP+ fluorescence intensities, calculates relative intensity of fluorescence
=(intracellular APP+ fluorescence intensities medicine group/intracellular APP+ fluorescence intensities control group) carries out ANOVA analyses.
4) experimental result
Experimental result is as shown in Fig. 2 1.0 μM of display, 0.1 μM of calamus alcoholic lactone compound can significantly inhibit SERT transhipments
Activity.
In summary, the serotonin transporter (SERT) is a kind of transmembrane transport egg for having high affinity to 5-HT
In vain, have point in organs such as placenta tissue, marrow, kidney, lung, the heart, adrenal gland, liver, parathyroid gland, thyroid gland, pancreas and small intestines
Cloth, belong to Na+/Cl-Dependent form transport protein, 5-HT serotonergic neurons are predominantly located at, 5-HT is reuptaked from nerve synapse gap
Into presynaptic neuron, synaptic cleft 5-HT concentration is directly affected, the amount and effect for changing postsynaptic receptor mediation signal are held
The continuous time, so as to participate in a variety of Physiological Psychology functions (such as mood, appetite, sleep, memory, study).
SERT inhibitor is the psychological disease such as clinical treatment depression, anxiety disorder, obsession, neurosis, schizophrenia
Disease, and a kind of medicine of the functional gastrointestinal disease such as slow Constipation, irritable bowel syndrome, functional distension.Fluorine west
The clinical common medicine such as spit of fland, Paxil, Sertraline, Fluvoxamine, Citalopram, belongs to such.Such medicine sedation is small,
Also Psychomotor ability is not damaged, very little is influenceed on cardiovascular and autonomic nervous system function.
The present invention is turned by carrying out the external serotonin that suppresses to isolated calamus alcoholic lactone from grass-leaved sweetflag rhizome
The research of body (SERT) activity is transported, it is found that calamus alcoholic lactone can significantly inhibit SERT transport activities, so as to confirm in calamus alcohol
Ester is one of active ingredient of the unbalance caused relevant physiological mental diseases of suppression SERT.Therefore, calamus alcoholic lactone can be used
To prepare the medicine of the Physiological Psychology diseases such as treatment depression.
Embodiment 3
Preparation method：Calamus alcoholic lactone, newborn sugar and starch are uniformly mixed according to the above ratio, cross 200 mesh sieves, it is uniform with water
Wetting, the mixture after wetting is dried re-sieving, adds magnesium stearate, then by mixture tabletting, every weight 250mg, lived
Property component content is 10mg.
Embodiment 4
Capsule：Calamus alcoholic lactone 20mg
Galactolipin 188mg
Magnesium stearate 2mg
Preparation method：Calamus alcoholic lactone is uniformly mixed with galactolipin according to the above ratio, crosses 200 mesh sieves, it is mixed what is obtained
Compound, magnesium stearate is added, load No. 2 capsules, produce.
Above-mentioned reference embodiment carries out detailed to the calamus alcoholic lactone compound and preparation method and application
Description, is illustrative rather than limited, several embodiments can be included according to limited scope, therefore do not departing from
Changing and modifications under present general inventive concept, it should belong within protection scope of the present invention.
Claims (5)
- A kind of 1. calamus alcoholic lactone compound, it is characterised in that：For { -4 α of 6,7,8- trihydroxies-isobutyl group -4,7- dimethyl six Hydrogen -6,8 α-epoxy chromene -2 (3H) -one }, there is structure shown in formula (I)：
- 2. the preparation method of the calamus alcoholic lactone compound described in claim 1, it is characterised in that：Comprise the following steps that：(1) boiled 3 times with the decocting of 8,6,6 times of weight respectively per 20Kg grass-leaved sweetflags rhizome, 1.5 hours every time, merge extract solution, subtract Pressure is concentrated into the 1/5-1/10 of extracting liquid volume, obtains crude extract concentrate；(2) gained crude extract concentrate, through D101 macroporous resin column chromatographies, alcohol-water (v/v) gradient elution, obtain 30%, 50%th, 70%, 95%4 ethanol elution thing, solvent is recovered under reduced pressure respectively to without alcohol taste；(3) pH=3~4 are adjusted with formic acid after 30% ethanol elution thing moisture is dissipated, isometric extracting n-butyl alcohol 3 times, recovery is molten Agent obtains n-butanol layer medicinal extract；(4) n-butanol layer medicinal extract methanol-water (v/v) gradient elution, collects 50% methanol water elution fraction, institute through ODS column chromatographies Component through the methanol-water (v/v) of Sephadex LH-20 gel columns 50% separation, silica G column chromatography, silicagel column with dichloromethane- Methanol (v/v) gradient elution, dichloromethane：Methanol=15:Isolated calamus alcoholic lactone chemical combination in 1 fraction eluted Thing.
- 3. calamus alcoholic lactone compound the answering in terms of suppression serotonin transporter active medicine is prepared described in claim 1 With.
- 4. calamus alcoholic lactone class compound described in claim 1 is preparing depression, anxiety disorder, schizophrenia, forced Disease, nerve degenerative diseases, drug addiction and digestive system function disorders medicine in terms of application.
- 5. the pharmaceutical composition with the calamus alcoholic lactone class compound described in claim 1, it is characterised in that：Include treatment And/or calamus alcoholic lactone compound and the optional pharmaceutically acceptable excipient of prevention effective dose.
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| JPH0386822A (en) * | 1989-08-30 | 1991-04-11 | Yoshinori Asakawa | Nervous cell alternation-repairing agent |
| KR100191901B1 (en) * | 1996-04-01 | 1999-06-15 | 박원훈 | Novel sesquiterpene ester compound |
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| Title |
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| 石菖蒲化学成分的分离与结构鉴定;吴春华，等;《中国药物化学杂志》;20140630;第24卷(第3期);第209-213页 * |
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