CN107648346A - Application of the safron based composition in preparing treatment or improving the medicine of depression - Google Patents
Application of the safron based composition in preparing treatment or improving the medicine of depression Download PDFInfo
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- CN107648346A CN107648346A CN201711020810.3A CN201711020810A CN107648346A CN 107648346 A CN107648346 A CN 107648346A CN 201711020810 A CN201711020810 A CN 201711020810A CN 107648346 A CN107648346 A CN 107648346A
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- Prior art keywords
- safron
- based composition
- depression
- application according
- gentibiosides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/74—Rubiaceae (Madder family)
- A61K36/744—Gardenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
Abstract
The invention provides a kind of application of safron based composition in preparing treatment or improving the medicine of depression, it is related to antidepressant agents field.Research finds that the mouse upper eyelid that safron based composition can be significantly caused by antagonism reserpine is sagging, significantly improves akinetic situation, significantly reducing the outstanding tail dead time and increase syrup preference coefficient, illustrate that safron based composition has preferable antidepressant effect, a variety of symptoms of depression can be improved, as antidepressants, research and treatment for depression provide new scheme.
Description
Technical field
The present invention relates to antidepressant agents field, is controlled in particular to a kind of safron based composition in preparation
Application in the medicine for the treatment of or improvement depression.
Background technology
Depression (Depression) is affective disorders (mooddisorders) main Types, with notable
Lasting depressed, speech is reduced, spirit and be slow in action etc. is characterized, and clinical manifestation is various somatizations, physiology work(
The clinical syndrome of energy obstacle, the patient of serious illness even have the attempt and behavior of suicide, and are shown as depression chronic more
Recurrent exerbation.Depression performance is various, and the cause of disease, pathogenesis is intricate, and drug therapy is treatment method main at present.
The quickening of rhythm of life, the pressure of people is increasing, and the trend risen year by year is presented in the incidence of disease of depression.According to
The World Health Organization counts, and depression turns into the fourth-largest illness in the world, it is contemplated that to the year two thousand twenty, is likely to become and is only second to coronary heart disease
Second largest disease.Depression seriously perplexs the live and work of patient, white elephant is brought to family and society, according to system
Meter, the patients with depression that there are about 15% die from suicide.The treatment of depression is mainly based on chemotherapy, but for a long time at present
Occur serious toxic side effect after taking, and there is chemicals antidepression spectrum it is narrow, easily recur the shortcomings of.Therefore, act on
Gently, the research and development of the small antidepressant of toxic side effect have very wide market prospects and far-reaching social effect.
The content of the invention
The first object of the present invention is that providing a kind of safron based composition is preparing treatment or improving depression
Medicine in application, safron based composition can be effectively improved a variety of symptoms of depression mouse, show that it can be with
As antidepressants, research and treatment for depression provide new scheme.
The second object of the present invention is to provide a kind of medicine for being used to treat depression, and the medicine is included from Chinese medicine cape jasmine
Middle to extract obtained safron based composition, it can improve or treat a variety of symptoms of depression.
In order to realize the above-mentioned purpose of the present invention, spy uses following technical scheme：
A kind of application of safron based composition in preparing treatment or improving the medicine of depression.
A kind of to be used to treat the medicine of depression, it includes safron based composition and pharmaceutically acceptable
Auxiliary material.
Compared with prior art, beneficial effects of the present invention for example including：
Inventor, which studies, to be found, the safron based composition that extraction obtains from plant (such as Chinese medicine cape jasmine) has
Antidepressant effect, a variety of symptoms of the depression of depression can be improved.Animal experiment shows, is seen by upper eyelid degree of sag
Examine, move can not observe, spacious field experiment, tail-suspention test and syrup preference experiment etc. Behavior test, find safron class
Composition can be significantly caused by antagonism reserpine mouse upper eyelid it is sagging, significantly improve akinetic situation, significantly reduce
Outstanding tail dead time and increase syrup preference coefficient, illustrate that safron based composition has preferable antidepressant effect.
Embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the present invention.It is unreceipted specific in embodiment
Condition person, the condition suggested according to normal condition or manufacturer are carried out.Agents useful for same or the unreceipted production firm person of instrument, it is
The conventional products that can be obtained by commercially available purchase.
Present embodiment provides a kind of safron based composition in preparing treatment or improving the medicine of depression
Using.
Safron based composition in present embodiment is using Chinese medicine cape jasmine as raw material, passes through large pore resin absorption column
Chromatographic isolation obtains.
Further, the safron based composition includes neocrocin B and the double-β-D- gentiobioses of crocetin
Glycosides.
Further, the safron based composition also includes crocetin list-β-D- O-gentibiosides.
Further, the safron based composition also includes crocetin-β-D- glucopyranosyl-β-D- rough gentian
Double-β-D- the glucopyranosides of bioside, crocetin, the double-β-D- O-gentibiosides of 13Z- crocetins and crocetin
Single-β-D- glucopyranosides.
Further, the safron based composition also include 13Z- crocetin -8-O- β-D- O-gentibiosides and
13Z- crocetin -8'-O- β-D- O-gentibiosides.
The structure of above-claimed cpd is as follows：
1. double-β-D- the O-gentibiosides of crocetin
2. crocetin-β-D- glucopyranosyl-β-D- O-gentibiosides
3. double-β-D- the glucopyranosides of crocetin
Double-β-D- the O-gentibiosides of 4.13Z- crocetins
5.neocrocin B
6. crocetin list-β-D- O-gentibiosides
7.13Z- crocetin -8-O- β-D- O-gentibiosides
8.13Z- crocetin -8'-O- β-D- O-gentibiosides
9. crocetin list-β-D- glucopyranosides
Further, the preparation method of this kind of safron based composition includes：
Step S1:Cape jasmine fruit is extracted using solvent extraction method, obtains cape jasmine total extract；
Wherein, solvent extraction method includes：Decocting method, heating and refluxing extraction method, ultrasonic vibration extraction method, percolation and dipping
Any one or more in method.The Extraction solvent that solvent extraction method uses optionally, is for 55~65Vol% alcoholic solution
Elect 55~65Vol% ethanol or methanol solution as；The volume fraction of alcohol is 55~65Vol% in alcoholic solution, or for 58~
62Vol%, or be 60Vol%.
When being extracted using heating and refluxing extraction method, solid-liquid ratio (i.e. the mass ratio of raw material and Extraction solvent) is 1：3
~5, or be 1：4.More preferable mode is：With the 60Vol% ethanol solutions heating and refluxing extraction 3 times of 4 times of amounts, every time 2
Hour.After extraction, extract solution is filtered, removes solvent, you can obtain cape jasmine total extract.
Step S2:The cape jasmine total extract is separated with macroporous adsorbent resin chromatography, eluant, eluent is water and 30~95Vol%
Ethanol, collect 65~75Vol% ethanol elution part, concentration.
Further, in separation process, successively with the water of 4 times of bed volumes, 25~35Vol%, 45~55Vol%,
65~75Vol%, 90~100Vol% ethanol carry out gradient elution.It is more highly preferred to, elution program is：Successively with 4 times of posts
Water, 28~32Vol%, 48~52Vol%, 68~72Vol%, the 93~97Vol% ethanol of bed volume carry out gradient elution.
Present embodiment also provide it is a kind of be used to treat the medicine of depression, it include safron based composition, with
And pharmaceutically acceptable auxiliary material.
Wherein, component of safron based composition and preparation method thereof is as described above.In order that the medicine is quick, connects
The continuous and discharge active component in a very long time, medicine of the invention can be according to being disclosed in those in the art
Conventional method manufactures.The method of administration of the medicine of the present invention is oral, nasal inhalation or parenteral.The preparation of the medicine can
To be powder, particle, tablet, emulsion, syrup, aerosol, soft capsule, hard shell capsules, sterile injectable preparation and sterilized powder etc..
Herein, it is physiologically acceptable that term " pharmaceutically acceptable ", which refers to the compound when compound is to human administration,
, and the allergic reactions such as gastrointestinal disturbance, dizziness or these similar anaphylactoid systemic anaphylaxis will not occur.
In the present invention, " pharmaceutically acceptable auxiliary material " includes but is not limited to：Adhesive (such as microcrystalline cellulose, alginic acid
Salt, gelatin and polyvinylpyrrolidone), filler (such as starch, sucrose, glucose and anhydrous lactic acid), disintegrant (as be crosslinked
PVP, crosslinked carboxymethyl fecula sodium, Ac-Di-Sol and low-substituted hydroxypropyl cellulose), lubricant (stearic acid
Magnesium, aluminum stearate, talcum, polyethylene glycol, sodium benzoate), wetting agent (such as glycerine), surfactant (such as hexadecanol) and
Sorbefacient, flavouring, sweetener, diluent, coating agent etc..
The feature and performance of the present invention are described in further detail with reference to embodiments：
Embodiment 1
Cape jasmine dry mature fruit 40.0kg is taken, after appropriate crush, is heated to reflux carrying with the 60Vol% ethanol of 4 times of amounts
Take 3 times, every time 2 hours.Merge extract solution, decompression boils off solvent, obtains cape jasmine total extract 6.2kg；Dissolved and extracted with suitable quantity of water
Thing, centrifugation, carry out macroreticular resin open column chromatography (20.0 × 90cm), successively with the water of 4 times of bed volumes, 30Vol%,
50Vol%, 70Vol%, 95Vol% ethanol carry out gradient elution, collect each several part eluent, solvent is recovered under reduced pressure respectively,
Obtain water elution, 30Vol% ethanol elutions built-up section about 4.5kg, 50Vol% ethanol elutions part 710.0g, 70Vol% second
Alcohol elution fraction 150.0g, 95Vol% ethanol elution part 112.0g, wherein, 70Vol% ethanol elution part is cape jasmine
Safron based composition (GJ-4).
Embodiment 2
The test of pesticide effectiveness of the cape jasmine safron based composition in terms of reserpine induced mice symptoms of depression is improved：
First, experimental program：
ICR mouse, male, 22~25g of body weight, 175, divide 7 groups, every group 25, each group is control group, model respectively
Group, Prozac (20mg/kg) group, GJ-4 (12.5mg/kg) group, GJ-4 (25mg/kg) group, GJ-4 (50mg/kg) group, GJ-4
(100mg/kg) group.(blank control group and model group gavage give same dosage for GJ-4 and positive drug (Prozac) gastric infusion
CMC-Na), (same dose of physiology salt is injected intraperitoneally in blank control group to 30min pneumoretroperitoneums injection reserpine (0.2mg/kg)
Water), continuous 14 days, body weight and appetite monitoring were carried out daily.
2nd, ptosis degree is observed
Mouse carries out ptosis degree observation after last gives reserpine 1h.Mouse is put and observed on the top of the shelf
Whether 15s, observation animal there is ptosis and ptosis degree and are scored.0 point, eyelid is not turned off；1 point, eyelid
Close 1/4；2 points, eyelid closes 1/2；3 points, eyelid closes 3/4；4 points, eyelid Close All, it the results are shown in Table 1.
Influences of the table 1.GJ-4 to mouse ptosis degree
Note：**P<0.01vs. blank control group mouse,#P<0.05,##P<0.01vs. model mices
Test result indicates that mouse it is continuous give reserpine 14 days after there is ptosis, open eyes can not situation.With
Model group compared to each dosage groups of GJ-4 can dose dependent improvement mouse ptosis.
3rd, motion can not be observed
After the observation of ptosis degree, carrying out motion can not observe each group mouse.Animal is placed on to diameter 7.5cm circle
Shape blank sheet of paper center, compares the number of elements that each group mouse is gone too far, and observes 15s, and calculating the rate that goes too far, (number of elements for the rate that goes too far=go too far/total is only
Number * 100%), it the results are shown in Table 2.
Table 2.GJ-4 is unable to the influence of degree to mouse movement
Note：**P<0.01vs. blank control group mouse,#P<0.05,##P<0.01vs. model mices
Test result indicates that the observation by being unable to degree to motion finds that model mice goes too far rate compared with normal mouse
Significantly reduce, the GJ-4 100mg/kg and 50mg/kg groups rate that goes too far substantially increases.
4th, spacious field is tested
Spacious field experiment is to evaluate the classical way of laboratory rodent motor function and state anxiety, is widely used in essence
The basic research of refreshing Neuropharmacology.Each group mouse carries out spacious field experiment after motion can not be observed, and spacious field is 50cm × 50cm
× 50cm square open top container, ground are divided into 25 10cm × 10cm lattice with black paint pen, clean square chest
Inwall and bottom surface, in order to avoid odor impact test result next time that last time animal is remaining.Mouse is put into center according to same direction
Between grid, observation mouse goes out the time (i.e. incubation period) of grid first and the interior grid numbers passed by of 5min (are gone out with hind leg
Grid is defined), it the results are shown in Table 3.
Table 3.GJ-4 tests the influence of incubation period and lattice number of passing by mouse spacious field
Note：**P<0.01vs. blank control group mouse,#P<0.05,##P<0.01vs. model mices
After being tested by spacious field as can be seen that giving reserpine, model group mouse movement function is substantially suppressed, and is given
After GJ-4 100mg/kg and 50mg/kg, mouse incubation period substantially shortens, and lattice number of passing by substantially increases, and motor function obtains significantly
Improve；25mg/kg and 12.5mg/kg has improved trend to locomitivity, but there was no significant difference.GJ-4 100mg/kg and
50mg/kg reduces the preclinical effect of spacious field experiment and is substantially better than positive drug Prozac, and GJ-4100mg/kg is real to improving spacious field
Test and walk out grid number and be better than Prozac.
5th, tail-suspention test
Tail suspension test is a kind of experimental method of quick and easy effectively evaluating mouse Degree of Depression again, extensive use
Screened in depression Mechanism Study and antidepressant.Away from an adhesive plaster is glued at sharp 2cm on mousetail, hang on away from ground
On the shelf of 30cm eminences, the video record mouse time motionless in 6min, 4 are the results are shown in Table.
Influences of the table 4.GJ-4 to the mouse tail suspension dead time
Note：***P<0.001vs. blank control group mouse,###P<0.001vs. model mices
By tail-suspention test as can be seen that continuously giving reserpine 14 days, the motionless time in model group mouse tail suspension 6min
Dramatically increased compared with blank control group, show as behavioral despair.It is motionless that each dosage of GJ-4 can substantially reduce mouse tail suspension
Time (P<0.001), desperate degree significantly mitigates.
6th, syrup preference is tested
Americanism medical diagnosis on disease thinks that the key character of depression hypotype is pair with the statistic handbook third edition (DSM- III)
Award the decline of reactivity, i.e. anhedonia.And the experiment of syrup preference is to detect rodent to the reactive best of award
Mode, therefore one of index that syrup preference can be as evaluation depression model animal.1% sucrose water, specific method are chosen in this experiment
It is as follows：1st day：2 bottles fill 1% sucrose water 200ml；2nd day：1 bottle of 1% sucrose water and 1 bottle of pure water, each 200ml；3rd day：
It is fasting for solids and liquids；4th day：1 bottle of 1% sucrose water and 1 bottle of pure water, each 200ml；5th day：Measure syrup and pure water consumption
Amount.Syrup preference coefficient=syrup consumption/(syrup+pure water consumption) × 100%.By the syrup for determining consumption in the 5th day
And the amount of pure water calculates the syrup preference coefficient of mouse, so as to compare the difference between normal group and model group, as a result sees
Table 5.
Influences of the table 5.GJ-4 to mouse syrup preference
By syrup experiment as can be seen that model group mouse significantly reduces with respect to blank control group to the preference of syrup, GJ-
The consumption of 4 100mg/kg, 50mg/kg and 25mg/kg mouse sucrose waters dramatically increases, and effect is better than positive drug Prozac, table
The bright preference increase to syrup, the reactivity of award is made moderate progress, GJ-4 12.5mg/kg group sugar consumption amounts have it is increased become
Gesture.
In summary, the safron based composition in the present invention is extracted from cape jasmine, through a macroporous resin column
Isolated, GJ-4 process of enriching is simple, economical quick.Depressed mouse model is caused to GJ-4's using the reserpine of classics
Antidepressant effect is evaluated, and is observed by upper eyelid degree of sag, motion can not be observed, spacious field is tested, tail-suspention test and sugar
The Behavior tests such as water preference experiment, find the mouse that GJ-4 100mg/kg and 50mg/kg can significantly caused by antagonism reserpine
Upper eyelid is sagging, significantly improves akinetic situation, significantly reduces outstanding tail dead time, and increase syrup preference coefficient,
Prompting GJ-4 has preferable antidepressant effect.Prozac is a line clinical application of current treating depression, and inventor studies
It was found that the drug effect of GJ-4 high dose groups is suitable with Prozac, to prompt, safron based composition can be used as antidepressants,
Research and treatment for depression provide new scheme.
Although illustrate and describing the present invention with specific embodiment, but will be appreciated that without departing substantially from the present invention's
Many other change and modification can be made in the case of spirit and scope.It is, therefore, intended that in the following claims
Including belonging to all such changes and modifications in the scope of the invention.
Claims (10)
- A kind of 1. application of safron based composition in preparing treatment or improving the medicine of depression.
- 2. application according to claim 1, it is characterised in that the safron based composition is extracted from cape jasmine Obtain.
- 3. application according to claim 1, it is characterised in that the safron based composition includes neocrocin B and the double-β-D- O-gentibiosides of crocetin.
- 4. application according to claim 3, it is characterised in that the safron based composition also includes crocetin Single-β-D- O-gentibiosides.
- 5. application according to claim 3, it is characterised in that the safron based composition also includes safflower Double-β-D- the glucopyranosides of acid-β-D- glucopyranosyl-β-D- O-gentibiosides, crocetin, 13Z- crocetins Double-β-D- O-gentibiosides and crocetin list-β-D- glucopyranosides.
- 6. application according to claim 3, it is characterised in that the safron based composition also includes 13Z- safranine Spend acid -8-O- β-D- O-gentibiosides and 13Z- crocetin -8'-O- β-D- O-gentibiosides.
- 7. application according to claim 3, it is characterised in that the preparation method bag of the safron based composition Include：Cape jasmine fruit is extracted using solvent extraction method, obtains cape jasmine total extract；The Cape jasmine is separated with macroporous adsorbent resin chromatography Sub- total extract, eluant, eluent are water and 30~95Vol% ethanol, collect 65~75Vol% ethanol elution part, concentration.
- 8. application according to claim 7, it is characterised in that it is total to separate the cape jasmine with the macroporous adsorbent resin chromatography During extract, successively with the water of 4 times of bed volumes, 25~35Vol%, 45~55Vol%, 65~75Vol%, 90~ 100Vol% ethanol carries out gradient elution.
- 9. application according to claim 7, it is characterised in that the solvent extraction method includes heating and refluxing extraction method, institute Stating heating and refluxing extraction method includes：Extracted 1~3 time with 55~65Vol% alcoholic solution, solid-liquid ratio 1：3~5.
- 10. a kind of medicine for being used to treat depression, it is characterised in that it includes safron based composition and pharmacy Upper acceptable auxiliary material.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109170060A (en) * | 2018-10-25 | 2019-01-11 | 高蕊 | A kind of beverage and preparation method thereof for improving mood |
| CN115105471A (en) * | 2022-06-06 | 2022-09-27 | 中国药科大学 | Crocin suspension and application thereof in preparation of rapid antidepressant drug |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109170060A (en) * | 2018-10-25 | 2019-01-11 | 高蕊 | A kind of beverage and preparation method thereof for improving mood |
| CN115105471A (en) * | 2022-06-06 | 2022-09-27 | 中国药科大学 | Crocin suspension and application thereof in preparation of rapid antidepressant drug |
| CN115105471B (en) * | 2022-06-06 | 2023-01-20 | 中国药科大学 | Crocin suspension and application thereof in preparation of rapid antidepressant drug |
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Application publication date: 20180202 |