CN106138072A - Treatment depression combination drug based on asiaticoside - Google Patents
Treatment depression combination drug based on asiaticoside Download PDFInfo
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Abstract
A kind for the treatment of depression combination drug based on asiaticoside, comprises asiaticoside and Borneolum Syntheticum, belongs to field of medical technology.The present invention compares that to be used alone the asiaticoside curative effect of Isodose higher, and has rapid-action, the obvious feature of effect.It is big to there is side effect in the shortcoming used existing antidepressant drug clinically, particularly long-term taking, and the defect that treatment cost is high, it is provided that rapid-action is cheap, a kind of drug regimen that side effect is less.Asiaticoside and Chinese medicine Borneolum Syntheticum combination application can obtain has more preferable therapeutic effect than being used alone asiaticoside.It is demonstrated experimentally that this pharmaceutical composition is possible not only to strengthen the therapeutic effect of medicine, and the actually used dosage of asiaticoside can be reduced, thus treatment cost is greatly reduced.
Description
Technical field
The present invention relates to the technology of a kind of pharmaceutical field, a kind for the treatment of depression based on asiaticoside is multiple
Composite medicine.
Background technology
Depressive disorder has become as common disease.Epidemiological study shows, whole world depression rate is about
3.1%, it is number four in world's disabling disease at present, it is contemplated that the year two thousand twenty will be number two, and be only second to ischemic heart desease.
China's depression rate is about 3%～5%, has had more than 26,000,000 patients.2004 one open in 14 countries
15 survey results of relevant depression of exhibition show, the annual loading of depression is 0.8% 9.6%, and wherein the U.S. is the highest,
Nigeria is minimum；BeiJing, China, Shanghai are respectively 2.5% and 1.7%." WHO Report in 2002 " is mentioned,
By the growth rate of nowadays sickness rate, it is likely to become to the year two thousand twenty depression and is only second to cardiopathic second largest disease.More worth
Being concerned with, the number that children and adolescents suffers from depression is being continuously increased, pre-school age prevalence about 0.3%, school age is about
2%, juvenile era prevalence is substantially increased to 5% 10%.Before 10 years old, men and women is ill is in similar proportion, later with the age
Increase women prevalence to be gradually increased, men and women than about 1:2, wherein postpartum depression modal class in being women mental disorder
Type.In the investigation of China, the incidence rate of postpartum depression is 10% 38%.Meanwhile, its children suffer from the wind of mental sickness
Danger is 4 times of the children of normal mother.
At present, in the medicine for the treatment of depression, chemicals curative effect is the most rapid-action, universally recognized is two class medicines: the
Generation classics antidepressants: monoamines oxidase inhibitor (MAOI) and tricyclic antidepressant (TCA), and the second filial generation is novel anti-
Depressant drug.Wherein in second filial generation newly-developed antidepressant currently used most common be 5 hydroxytryptamine reuptake inhibitors (SSRI)
Class medicine, including fluoxetine, paroxetine, Sertraline, fluvoxamine, citalopram, escitalopram.Although said medicine
Clinical effective, but drug side effect is relatively big, and such as, the untoward reaction that SSRI class drug main is wanted is gastrointestinal reaction, additionally also has
Headache, insomnia, erythra and sexual dysfunction etc..
Herba Centellae is the herb of samphire Herba Centellae Centella asiatica (L.) Urh.Herba Centellae has heat clearing away
Dampness removing, effect of removing toxic substances and promoting subsidence of swelling, main chemical compositions is triterpene saponin componds.Research shows that Herba Centellae preparation is to improving Jiao
Consider symptom and also have certain effect.Zhang Zhongqi etc. find, 3 kinds of extracts of Herba Centellae the most all can suppress the outer monoamine oxidase, MAO of Mice Body
The activity of A, wherein optimal with 50% ethanol extract inhibition, when dosage 50 μ g/mL, suppression degree and antidepressant chlorine shellfish
Amine 5 μ g/mL is suitable, and suppression ratio reaches 80%.In Herba Centellae, contained monomer component asiaticoside is to Depression trend caused by forced swimming
There is antagonism.And having result of study to show, asiaticoside has on the hypothalamo pituitary kidney improving depression rat disorder
Gland cortex and the effect of hypothalaamus-pituitary-adrenal axis, improve the body resistance to various nonspecific stimulations, it is to avoid mistake
Degree stress the caused dysfunction such as body hypothalamo pituitary adrenal cortex and hypothalaamus-pituitary-adrenal axis, thus have
Certain antidepressant effect.
Current antidepressant Chinese medicine research problems faced is, the chemical composition of many Chinese medicines can not or cannot easily penetrate
Blood brain barrier, so that the cerebral tissue Chinese medicine component content of target site is low, druggability is bad, affects the exploitation of medicine.Accumulated snow
Grass glycosides also faces same problem, although has been reported that have certain antidepressant effect, but fails to develop new drug always.With Borneolum Syntheticum it is
The causing resuscitation with aromatic drugs Effective Component of Chinese Medicine represented is fat-soluble by force, relative molecular mass is little, and not only self is the most efficiently and effectively through blood brain
Barrier enters cerebral tissue, and other maincenter curative drugs can be assisted through blood brain barrier, the infringement to cerebral tissue of this medicine
Can property be little, and has the effect of two-ways regulation blood-brain barrier permeability, but promote that asiaticoside passes through blood brain barrier, at present
Have no report.
Borneolum Syntheticum (1,7,7 trimethyl two cycloheptyl～2 alcohol) is the processed goods of Spore density Borneolum Syntheticum resin or Compositae is planted
The crystallization that thing Herba Blumeae Balsamiferae leaf extracts, or the highly finished product with Camphora, Oleum Terebinthinae etc. as raw material, through being chemically synthesized.Borneolum Syntheticum is relative
Molecular mass is 154.24, is the fat-soluble Monoterpenes of little molecule.The traditional Chinese medical science is thought, Borneolum Syntheticum have sensible, dissipate fire, removing nebula improving eyesight,
The effect of reducing swelling and alleviating pain.Modern study result all shows: can absorb rapidly through gastrointestinal tract after Borneolum Syntheticum is for oral administration, be distributed widely in the heart
Flesh, lung, spleen, and easily enter cerebral tissue through blood brain barrier.Borneolum Syntheticum mainly with original shape from excrement, urine ejection, at liver, kidney, lung
The most rapidly, Borneolum Syntheticum is drained not only by Liver and kidney in middle decline, it is also possible to by lungs from breathing or the discharge of other approach, point out ice
Sheet can repeated multiple times be administered in clinic.
Depression is the mental sickness that a kind of sickness rate is high, relapse rate is high, homicide rate is high.Clinical research finds, treatment is thought
Laughing at the fastest patient, cure rate is the highest.The cure rate of the patient of onset in 1 week and onset in 46 weeks is respectively 60% 70% and 20%
Left and right.But when patients with depression is treated, there is the difficult problem that onset is delayed in Chinese medicine and natural drug.Most patients wishes treatment
After, symptom can be alleviated immediately, but generally Chinese medicine or crude drug onset averagely need 24 weeks, causes some patients at the beginning for the treatment of
Phase is easy for abandoning.Shorten the important leverage that the drug effect time is raising depressive patient curative compliance, improve whole treatment
Effect, shortens treatment cycle, alleviates patient mental's misery and financial burden.Therefore, in the urgent need to exploitation rapid-action, curative effect is steady
The anti-depression Chinese medicament fixed, side effect is little or natural drug, treat lag time to shorten, improve patient compliance, reduce medicine
Side effect.
So it is little to develop side effect, rapid-action Chinese medicine or natural drug is significant and application prospect.
Summary of the invention
The present invention is directed to deficiencies of the prior art, propose a kind of depression composite medicine based on asiaticoside
Thing, compares that to be used alone the asiaticoside curative effect of Isodose higher, and has rapid-action, the obvious feature of effect.To existing
The shortcoming used clinically of antidepressant drug, particularly to there is side effect big for long-term taking, and the defect that treatment cost is high carries
For rapid-action, cheap, that side effect is less a kind of drug regimen.Asiaticoside is permissible with Chinese medicine Borneolum Syntheticum combination application
Acquirement ratio is used alone asiaticoside and has more preferable therapeutic effect.It is demonstrated experimentally that this pharmaceutical composition is possible not only to strengthen medicine
The therapeutic effect of thing, and the actually used dosage of asiaticoside can be reduced, thus treatment cost is greatly reduced.
The present invention is achieved by the following technical solutions:
The present invention relates to a kind for the treatment of depression combination drug based on asiaticoside, containing asiaticoside and Borneolum Syntheticum, its
Weight ratio is 1:(1～100).
Preferably, in aforementioned pharmaceutical compositions, the weight ratio of asiaticoside and Borneolum Syntheticum is 1:3.
Described combination drug, uses but is not limited to tablet, granule, capsule, soft capsule, injection or transdermal patch
Form, wherein: tablet, granule contain the above adjuvant of the following two kinds: amylum pregelatinisatum, lactose, low substituted hydroxy-propyl fiber, hard
Fatty acid magnesium, microcrystalline Cellulose, hydroxypropyl cellulose, starch slurry lactose, mannitol, propylene glycol, micropowder silica gel, cross-linked carboxymethyl fibre
Dimension element is received；Described capsule contains the above adjuvant of the following two kinds: amylum pregelatinisatum, lactose, low substituted hydroxy-propyl fiber, crystallite are fine
Dimension element and micropowder silica gel；Described injection contains more than one adjuvants following: benzyl alcohol, soybean oil, propylene glycol, Polyethylene Glycol,
Lecithin, normal saline, glucose；Described transdermal patch contains the above adjuvant of the following two kinds: medical porous macromolecule membrane, third
Glycol, nonoxynolum, azone, polyvinyl alcohol, sodium carboxymethyl cellulose.In the above-mentioned pharmaceutical preparation containing asiaticoside, each
The effective dose that part preparation unit contains asiaticoside is 0.1mg～30mg.
The present invention relates to the process for producing granula of a kind of depression combination drug based on asiaticoside, by by accumulated snow
Grass glycosides and Borneolum Syntheticum mix homogeneously, add propylene glycol and ethanol be stirring solvent uniformly after make soft material, through pelletizing, being dried, whole
Obtain with magnesium stearate mixing granulation after Li.
Described mix homogeneously, preferably further adds starch, dextrin and low-substituted hydroxypropyl cellulose.
Described ethanol, concentration is 60% (v/v).
The weight ratio of described asiaticoside, Borneolum Syntheticum, starch, dextrin and low-substituted hydroxypropyl cellulose is: (0.6～
1.2):3:40:30:5。
The present invention relates to the capsule preparation method thereof of a kind of depression combination drug based on asiaticoside, by asiaticoside
With Borneolum Syntheticum mix homogeneously, add propylene glycol and ethanol be stirring solvent uniformly after make soft material, with magnesium stearate after the powder that sieves
Mixing granulation obtains.
Described mix homogeneously, preferably further adds lactose, mannitol, micropowder silica gel, microcrystalline Cellulose or crosslinking carboxylic
Sodium carboxymethylcellulose pyce.
Described ethanol, concentration is 60% (v/v).
Described asiaticoside, Borneolum Syntheticum, lactose, mannitol, micropowder silica gel, microcrystalline Cellulose, cross-linked carboxymethyl cellulose
The weight ratio of sodium is: 1:(1～100): (10～100): (0.2～0.8): (0.05～0.1): (0.05～0.3): (0.05～
0.3)。
Described magnesium stearate with the weight ratio of sieve powder is: 0.5% 2%.
The present invention relates to the oral liquor of a kind of depression combination drug based on asiaticoside, by by Borneolum Syntheticum
Add Polyethylene Glycol, tween and asiaticoside after being dissolved in propylene glycol, add distilled water diluting after being sufficiently mixed and get final product.
The usage ratio of described Borneolum Syntheticum, Polyethylene Glycol, tween and asiaticoside is:
(1～100): (0.01～0.2): (0.01～0.2): 1.
Technique effect
Compared with prior art, when the present invention contains the compositions treatment depression of asiaticoside Borneolum Syntheticum, achieve good
Therapeutic effect.Said composition can significantly improve the state of an illness of patients with depression, and it has following prominent compared with prior art
Go out advantage:
1), during asiaticoside Borneolum Syntheticum complex therapies depression, asiaticoside has certain antidepressant effect, but individually fills
Stomach gives asiaticoside (30mg/kg), and in the noisy tissue of rat, inspection does not measures Herba Centellae；The complex of Isodose asiaticoside fills
After stomach is administered, in cerebral tissue, between 15 minutes to 180 minutes, all detect asiaticoside, illustrate that Borneolum Syntheticum may be long-pending by improving
Asiaticoside absorbs and target site is distributed so that effect is lasting, rapid-action, is expected to add the compliance of patients with depression,
And the dosage of asiaticoside can be reduced, thus further consolidated the therapeutic effect of pharmaceutical composition.
2) it is all the monomer extracted in Chinese medicine due to asiaticoside, Borneolum Syntheticum, safe nothing in terms of embodiment situation
Poison, side effect is little, and animal does not has obvious gastrointestinal side effect.
3) asiaticoside is the Chinese medicine monomer extracted from Chinese medicine Herba Centellae, Borneolum Syntheticum be from Compositae Herba Blumeae Balsamiferae stem and leaf or
Canella Borneolum Syntheticum Camphor tree branch and leaf obtain through steam distillation recrystallization, disclose more preparation method in existing technology,
Its preparation is simple, and aboundresources, cheap, toxic and side effects is low.It, compared with existing treating depression medicine, can alleviate
The financial burden of patient.After adding Borneolum Syntheticum, asiaticoside consumption halves, and Borneolum Syntheticum price is only the 1/8000 of asiaticoside.
Detailed description of the invention
Embodiment 1
Prepared by medicament composition granule agent
The constituent content that the present embodiment uses is: asiaticoside 1.2g, Borneolum Syntheticum 3g, starch 40g, dextrin 30g, low replacement hydroxyl
Propyl cellulose 5g, 60% ethanol, propylene glycol, magnesium stearate 1g.
The preparation technology of the present embodiment is: by the asiaticoside of above-mentioned raw materials proportioning, Borneolum Syntheticum, starch, dextrin, low replacement hydroxyl
Propyl cellulose mix homogeneously, separately takes appropriate propylene glycol, 60% ethanol, adds in mixed-powder, soft material processed after mix homogeneously,
Being pelletized by 16 mesh sieves, less than 45 DEG C are dried.After being dried, carry out granulate with 18 mesh sieves, sift out the fine powder in dry granular, with mistake
The magnesium stearate mixing of sieve, mixs homogeneously with dry granule the most again, and subpackage 400 wraps and get final product, specification.
Embodiment 2
Prepared by medicament composition granule agent
The constituent content that the present embodiment uses is: asiaticoside 0.6g, Borneolum Syntheticum 3g, starch 40g, dextrin 30g, low replacement hydroxyl
Propyl cellulose 5g, 60% ethanol, propylene glycol, magnesium stearate 1g.
The preparation technology of the present embodiment is: by the asiaticoside of above-mentioned raw materials proportioning, Borneolum Syntheticum, starch, dextrin, low replacement hydroxyl
Propyl cellulose mix homogeneously, separately takes appropriate propylene glycol, 60% ethanol, adds in mixed-powder, soft material processed after mix homogeneously,
Being pelletized by 16 mesh sieves, less than 45 DEG C are dried.After being dried, carry out granulate with 18 mesh sieves, sift out the fine powder in dry granular, with mistake
The magnesium stearate mixing of sieve, mixs homogeneously with dry granule the most again, and subpackage 400 wraps and get final product.
Embodiment 3
Prepared by asiaticoside granule
The constituent content that the present embodiment uses is: asiaticoside 1.2g, starch 40g, dextrin 30g, low substituted hydroxy-propyl are fine
Dimension element 5g, 60% ethanol, propylene glycol, magnesium stearate 1g.
The preparation technology of the present embodiment is: by the asiaticoside of above-mentioned raw materials proportioning, starch, dextrin, low substituted hydroxy-propyl
Cellulose mix homogeneously, separately takes appropriate propylene glycol, 60% ethanol, adds in mixed-powder, and after mix homogeneously, soft material processed, passes through
16 mesh sieves are pelletized, and less than 45 DEG C are dried.After being dried, carry out granulate with 18 mesh sieves, sift out the fine powder in dry granular, and sieve
Magnesium stearate mixes, and mixs homogeneously with dry granule the most again, and subpackage 400 wraps and get final product.
Embodiment 4
Prepared by asiaticoside granule
The constituent content that the present embodiment uses is: asiaticoside 0.6g, starch 40g, dextrin 30g, low substituted hydroxy-propyl are fine
Dimension element 5g, 60% ethanol, propylene glycol, magnesium stearate 1g.
The preparation technology of the present embodiment is: by the asiaticoside of above-mentioned raw materials proportioning, starch, dextrin, low substituted hydroxy-propyl
Cellulose mix homogeneously, separately takes appropriate propylene glycol, 60% ethanol, adds in mixed-powder, and after mix homogeneously, soft material processed, passes through
16 mesh sieves are pelletized, and less than 45 DEG C are dried.After being dried, carry out granulate with 18 mesh sieves, sift out the fine powder in dry granular, and sieve
Magnesium stearate mixes, and mixs homogeneously with dry granule the most again, and subpackage 400 wraps and get final product.
Embodiment 5
Prepared by Borneolum Syntheticum granule
The present embodiment use constituent content be: Borneolum Syntheticum 3g, starch 40g, dextrin 30g, low-substituted hydroxypropyl cellulose 5g,
60% ethanol, propylene glycol, magnesium stearate 1g.
The preparation technology of the present embodiment is: by the Borneolum Syntheticum of above-mentioned raw materials proportioning, starch, dextrin, low substituted hydroxy-propyl fiber
Element mix homogeneously, separately takes appropriate propylene glycol, 60% ethanol, adds in mixed-powder, and soft material processed after mix homogeneously, by 16 mesh
Sieve series grain, less than 45 DEG C are dried.After being dried, carry out granulate with 18 mesh sieves, sift out the fine powder in dry granular, with the tristearin sieved
Acid magnesium mixing, mixs homogeneously with dry granule the most again, tabletting and get final product.
Embodiment 6
Prepared by medicament composition capsule agent
The constituent content that the present embodiment uses is: asiaticoside 1.2g, Borneolum Syntheticum 6g, lactose 30g, mannitol 50g, micropowder silicon
Glue 15g, microcrystalline Cellulose 50g, cross-linking sodium carboxymethyl cellulose 20g, 60% ethanol, propylene glycol.
The preparation technology of the present embodiment is: by the micropowder silica gel in said components proportioning, microcrystalline Cellulose and crosslinking carboxylic first
Base sodium cellulosate crosses 100 mesh sieves, after weighing asiaticoside, Borneolum Syntheticum, lactose, mannitol mix homogeneously, adds said components and joins
The micropowder silica gel of ratio, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose.Mix homogeneously, adds 60% ethanol solution, propylene glycol system
Becoming soft material, 18 mesh sieve granules, wet granular is lower dry in 45 degree, and 16 mesh sieve granulate load capsule, to obtain final product.
Embodiment 7
Prepared by drug composition oral liquid
The constituent content that the present embodiment uses is: asiaticoside 12g, Borneolum Syntheticum 30g, propylene glycol, Polyethylene Glycol, Tween 80
20mL, distilled water 8000mL.
The preparation technology of the present embodiment is: according to the Borneolum Syntheticum of said components proportioning, adds appropriate propylene glycol and dissolves, then adds
Entering Polyethylene Glycol 9 10mL and drip vibration mixing, add Tween 80 20mL vibration mixing, add asiaticoside, vibration is dissolved
After, add distilled water 8000mL and get final product, sterilizing, canned one-tenth 10mL/ props up.
Embodiment 8
Prepared by drug composition oral liquid
The constituent content that the present embodiment uses is: asiaticoside 6g, Borneolum Syntheticum 30g, propylene glycol, Polyethylene Glycol, Tween 80
20mL, distilled water 8000mL.
The preparation technology of the present embodiment is: according to the Borneolum Syntheticum of said components proportioning, adds appropriate propylene glycol and dissolves, then adds
Entering Polyethylene Glycol 9 10mL and drip vibration mixing, add Tween 80 20mL vibration mixing, add asiaticoside, vibration is dissolved
After, add distilled water 8000mL and get final product, sterilizing, canned one-tenth 10mL/ props up.
Embodiment 9
Prepared by drug composition oral liquid
The constituent content that the present embodiment uses is: asiaticoside 12g, Borneolum Syntheticum 15g, propylene glycol, Polyethylene Glycol, Tween 80
20mL, distilled water 8000mL.
The preparation technology of the present embodiment is: according to the Borneolum Syntheticum of said components proportioning, adds appropriate propylene glycol and dissolves, then adds
Entering Polyethylene Glycol 9 10mL and drip vibration mixing, add Tween 80 20mL vibration mixing, add asiaticoside, vibration is dissolved
After, add distilled water 8000mL and get final product, sterilizing, canned one-tenth 10mL/ props up.
Embodiment 10
Prepared by drug composition oral liquid
The constituent content that the present embodiment uses is: asiaticoside 6g, Borneolum Syntheticum 15g, propylene glycol, Polyethylene Glycol, Tween 80
20mL, distilled water 8000mL.
The preparation technology of the present embodiment is: according to the Borneolum Syntheticum of said components proportioning, adds appropriate propylene glycol and dissolves, then adds
Entering Polyethylene Glycol 9 10mL and drip vibration mixing, add Tween 80 20mL vibration mixing, add asiaticoside, vibration is dissolved
After, add distilled water 8000mL and get final product, sterilizing, canned one-tenth 10mL/ props up.
Embodiment 11
Prepared by Borneolum Syntheticum oral liquid
The constituent content that the present embodiment uses is: Borneolum Syntheticum 30g, propylene glycol, Polyethylene Glycol, Tween 80 20mL, distilled water
8000mL。
The preparation technology of the present embodiment is: according to the Borneolum Syntheticum of said components proportioning, adds appropriate propylene glycol and dissolves, then adds
Enter Polyethylene Glycol 9 10mL and drip vibration mixing, add Tween 80 20mL vibration mixing, add distilled water 8000mL and get final product, going out
Bacterium, canned one-tenth 10mL/ props up.
Embodiment 12
Prepared by Borneolum Syntheticum oral liquid
The constituent content that the present embodiment uses is: Borneolum Syntheticum 15g, propylene glycol, Polyethylene Glycol, Tween 80 20mL, distilled water
8000mL。
The preparation technology of the present embodiment is: according to the Borneolum Syntheticum of said components proportioning, adds appropriate propylene glycol and dissolves, then adds
Enter Polyethylene Glycol 9 10mL and drip vibration mixing, add Tween 80 20mL vibration mixing, add distilled water 8000mL and get final product, going out
Bacterium, canned one-tenth 10mL/ props up.
Embodiment 13
Prepared by asiaticoside oral liquid
The constituent content that the present embodiment uses is: asiaticoside 12g, propylene glycol, Polyethylene Glycol, Tween 80 20mL, steaming
Distilled water 8000mL.
The preparation technology of the present embodiment is: takes propylene glycol and dissolves, and adds Polyethylene Glycol 9 10mL and drips vibration mixing, then adds
Enter Tween 80 20mL vibration mixing, add asiaticoside, after vibration is dissolved, add distilled water 8000mL and get final product, sterilizing, canned
10mL/ is become to prop up.
Embodiment 14
Prepared by asiaticoside oral liquid
The constituent content that the present embodiment uses is: asiaticoside 6g, propylene glycol, Polyethylene Glycol, Tween 80 20mL, distillation
Water 8000mL.
The preparation technology of the present embodiment is: the preparation technology of the present embodiment is: takes propylene glycol and dissolves, adds Polyethylene Glycol
9 10mL drip vibration mixing, add Tween 80 20mL vibration mixing, add asiaticoside, after vibration is dissolved, add distillation
Water 8000mL and get final product, sterilizing, canned one-tenth 10mL/ props up.
The pharmacodynamics of the rat depression model caused by chronic unpredictable stimulation model (CUS) is tested by said medicine
Laboratory animal is SD male rat 180 220g, Shanghai Communications University's Experimental Animal Center be responsible for tieing up from Beijing
Laboratory animal Technology Co., Ltd. of tonneau China buys.
The making of animal model: after rat adapts to one week, the sucrose water consumption through 72h is trained, and carries out sucrose diseases caused by retention of fluid water
Horizontal checkout.Sucrose water consumption is trained: experiment starts to place two bottles of identical sucrose water on cage, wherein after 24h
One bottle of sucrose water changes same water into, places 24h, then water 14h is prohibited in fasting.Then single Mus list cage is raised, and cage places one bottle
75mL water and one bottle of 75mL sucrose water carry out sucrose diseases caused by retention of fluid water horizontal 1h test, reject underproof rat.Other rats are random
The blank group of distribution, model group, positive controls (fluoxetine group 10mg/kg/d), Borneolum Syntheticum matched group (30mg/kg/d), combination medicine
Thing low dose group (15mg/kg/d), composition of medicine high dose group (15mg/kg/d), asiaticoside low dose group (15mg/kg/
D), asiaticoside high dose group (30mg/kg/d), eight groups altogether, often group 8.Blank 4, every cage of group, with other group rats
Raising in the environment of mutually isolated, bio-occlusion and feedstuff and drinking-water, do not accept any stimulation as required.The single Mus of remaining group is single
Cage is raised.Gastric infusion before stress stimulation 1h.In addition to blank group does not gives any stimulation, other groups accept nine kinds of stimulations.Often
Planting stimulation to be used 23 times, homologous stimulus discontinuously occurs, makes rat can not expect the stimulation that will occur.
Particularly as follows: 20 20KHZ white noise 1 2h stroboscopic illumination (120flashes/min) overnight 12h, fasting 24h, taboo water
24h, restraint 1 2h and all night illumination 12h, folder tail 1min, wet environment 24h, 10 DEG C of 5min of forced swimming, 45 ° of inclinations are raised
Support, group support overnight 12h.Every kind stimulates random, and every day, one stimulated, and continued 21 days.During stress stimulation, except water is prohibited in fasting
Outside with sucrose water horizontal checkout, free diet is drunk water.
Evaluation method 1: swimming test: rat proceeds by forced swim test on the 3rd day in modeling, experiment is big before starting
Mus puts into diameter 20cm, high 40 centimetres, adapts to 15min in the garden type resin transparent glass tank of depth of water 15cm, and after 24h, last is given
After medicine 1h, being put into by rat in said apparatus, shooting records the non-swimming time in each rat 5min.
Evaluation method 2: sucrose preference is tested: carry out 4 sucrose preference experiments, curfew water fasting before experiment during modeling
14h, starts experiment the next morning, the drinking water of rat changes the fresh sucrose solution of 150ml 1% one bottle and a bottle normal into
Drinking water, withdraws sucrose solution after 1h.Sucrose preference experiment index=sucrose diseases caused by retention of fluid consumption/(sucrose water+normal drinking water).Real
After testing end 1h, rat can free diet.
Evaluation method 3: Open field test: modeling carried out Open field test after 21 days.Rat is first put 100 decibels of white noise 1h
After, rat is put into spacious case (100cm × 100cm × 50cm 5*5 grid) middle, tests 6 minutes, 5min after record rat
Walk number of times between interior grid, lift limb number of times.The activity form of rat mainly has two kinds, and one is horizontal anomalous movement, can represent wherein
The irritability of pivot nervous system, in being co-located on a grid with extremity be 1 point；Two is Vertical movements, represents its curious journey
Degree, lift with forelimb, rear be once 1 point.
Evaluation method 4: animal model evaluation: by following table it can be seen that model group was the 3rd day of experiment, force trip
The swimming dead time is compared blank group and is just obviously prolonged (P < 0.05 or P < 0.01), when 14 days, and its sucrose preference function of model group
Just it is substantially less than blank group and positive drug group, shows that the rat depression model set up by the method is reliable, can be used for depression and control
Treat the medical judgement of medicine.Above-mentioned animal model, after 21 days, carries out sugar consumption experiment, Open field test, tests the spontaneous work of rat
Dynamic, learning capacity, appetite etc..Each group rat behavior measurement result is as shown in the table.
Evaluation method 5: statistical method: experimental data x ± s represents, carries out statistical analysis with SPSS 21 software kit,
Use ANOVA post hoc test to carry out statistical analysis, indicate significant difference with P < 0.05.
The impact on the rat forced swimming dead time of the table 1 each administration group
Compared with normal group, ##P < 0.01；* P < 0.05, * * P < 0.01 compared with model group.
The impact on the rat sucrose preference function caused by rat CUS of the table 2 each administration group
Compared with normal group, #P < 0.05, ##P < 0.01；* P < 0.05, * * P < 0.01 compared with model group.
Table 3 each administration group is on the rat amount of drinking water caused by rat CUS, the impact of appetite
Compared with normal group, #P < 0.05, ##P < 0.01；* P < 0.05, * * P < 0.01 compared with model group
The impact on the rat autonomic activities caused by rat CUS of the table 4 each administration group
Compared with normal group, #P < 0.05, ##P < 0.01；* P < 0.05, * * P < 0.01 compared with model group
As can be seen from Table 1: each group is administered and started the animal forced swimming dead time at the 3rd day, and model group is significantly higher than
Positive group and administration group, illustrate successive administration 3 days, represents that acute administration effectively shortens the dead time of rat, Ke Yigai
The desperate behavior in forced swimming process of kind rat, shows that asiaticoside composition of medicine group and non-combined medicine group are respectively provided with long-pending
The therapeutical effect of pole, and oral liquid effect is better than granule.It is embodied in:
1) the rat forced swimming dead time of asiaticoside treatment group has significant difference, just agent compared with model group
Amount can shorten the dead time of rat.
2) the composition of medicine treatment group rat forced swimming dead time has significant difference, high low dosage compared with model group
The dead time of rat can be shortened, and high dose group is less than the low dose group dead time, show acute administration, force
Swimming test there may be dose dependent.
As can be seen from Table 2: during modeling in 21 days, when the 14th day, its sucrose preference function model group and blank group, sun
Property medicine group, composition of medicine high dose group there is significant difference, show modeling success, the sucrose preference function model when the 21st day
Group and blank group, positive drug group, composition of medicine high dose, asiaticoside low dose group is compared has significant difference, shows group
Composite medicine is administered has positive therapeutical effect, has further DEVELOPMENT PROSPECT.
As can be seen from Table 3: rat is after experience chronic unpredictable stimulation in 21 days, and the appetite of model group rats compares sky
White group, positive drug group, administration group significantly reduce, and show that composition of medicine long term administration can improve chronic unpredictable stimulation and make
Becoming depressive symptom, composition of medicine high dose group effect and positive drug administration group effect are suitable.
As can be seen from Table 4: after modeling 21 days, carry out Open field test test, result display model group rat autonomic activities
Ability is want substantially to reduce than other groups.Cannot predict under stimulation chronic, composition of medicine administration group can increase the work of rat
Momentum, improves its spontaneous activity ability.Composition of medicine administering effect is better than positive drug.
Aforementioned pharmaceutical compositions is administered and is preferably oral administration.As shown in the embodiment of the invention, it will thus be seen that be respectively administered
Group, the 3rd day rat forced swimming dead time difference strengthens, wherein asiaticoside administration group and asiaticoside Borneolum Syntheticum compound recipe
Group is respectively provided with positive therapeutical effect.It is embodied in:
1) the forced swimming dead time of asiaticoside Borneolum Syntheticum compound treatment group significance compared with model group reduces, with sun
Property agents fluoxetine group, asiaticoside group, Borneolum Syntheticum matched group are compared, asiaticoside Borneolum Syntheticum compound recipe high dose group and asiaticoside ice
Sheet compound recipe low dose group significantly shortens the rat dead time, and wherein medicine composite for curing is after 21 days, its sucrose preference function
Close with positive drug fluoxetine group, Open field test score is less than positive drug fluoxetine group, illustrates that this drug regimen is evident in efficacy,
And than individually giving the asiaticoside better efficacy (table 1, table 2) of Isodose.
2) compare with the asiaticoside group of matched doses, asiaticoside and Borneolum Syntheticum combination compound treatment group rat forced swimming
Dead time substantially shortens, and sucrose preference function significantly improves, and amount of drinking water and food-intake substantially increase, and particularly autonomic activities is surveyed
Walking number of times and lifting the increase of limb number of times equal significance of test result display compound recipe group, points out asiaticoside and Borneolum Syntheticum combination compound recipe group
Property more evident in efficacy than Isodose asiaticoside group strengthen (table 4), this show asiaticoside of the present invention can and Borneolum Syntheticum
Comparison combination, there is synergism in compound treatment group, few side effects is rapid-action, improves the symptom of depressive patient.
3) though the forced swimming dead time relatively model group of Borneolum Syntheticum treatment group is compared significance and shortened, but still significance is big
Compare and normal group in positive drug fluoxetine group；Amount of drinking water and food-intake and self-service movable number of times significance are less than positive drug
Fluoxetine group, only sucrose preference result difference compared with positive drug fluoxetine group is the most notable；Illustrate that Borneolum Syntheticum itself pressed down without notable resisting
Yu Xiaoguo.
Above-mentioned be embodied as can by those skilled in the art on the premise of without departing substantially from the principle of the invention and objective with difference
Mode it is carried out local directed complete set, protection scope of the present invention is as the criterion with claims and is not embodied as institute by above-mentioned
Limit, each implementation in the range of it is all by the constraint of the present invention.
Claims (12)
1. a treatment depression combination drug based on asiaticoside, it is characterised in that containing asiaticoside and Borneolum Syntheticum, it is heavy
Amount ratio is 1:(1～100).
Treatment depression combination drug the most according to claim 1, is characterized in that, described asiaticoside and the weight of Borneolum Syntheticum
Amount ratio is 1:3.
Treatment depression combination drug the most according to claim 1 and 2, is characterized in that, described treatment depression is combined
Medicine, uses tablet, granule, capsule, soft capsule, injection or transdermal patch form, wherein: every a preparation unit contains
The effective dose having asiaticoside is 0.1mg～30mg；
Described tablet, granule contain the above adjuvant of the following two kinds: amylum pregelatinisatum, lactose, low substituted hydroxy-propyl fiber, hard
Fatty acid magnesium, microcrystalline Cellulose, hydroxypropyl cellulose, starch slurry lactose, mannitol, propylene glycol, micropowder silica gel, cross-linked carboxymethyl fibre
Dimension element is received；
Described capsule contains the above adjuvant of the following two kinds: amylum pregelatinisatum, lactose, low substituted hydroxy-propyl fiber, crystallite are fine
Dimension element and micropowder silica gel；
Described injection contains more than one adjuvants following: benzyl alcohol, soybean oil, propylene glycol, Polyethylene Glycol, lecithin, life
Reason saline, glucose；
Described transdermal patch contains the above adjuvant of the following two kinds: medical porous macromolecule membrane, propylene glycol, nonoxynolum, nitrogen
Ketone, polyvinyl alcohol, sodium carboxymethyl cellulose.
4. according to a process for producing granula for described treatment depression combination drug arbitrary in claims 1 to 3, its feature
Be, by by asiaticoside and Borneolum Syntheticum mix homogeneously, add propylene glycol and ethanol be stirring solvent uniformly after make soft material, warp
Cross granulation, be dried, obtain with magnesium stearate mixing granulation after granulate.
Preparation method the most according to claim 4, is characterized in that, described mix homogeneously, adds starch, dextrin further
And low-substituted hydroxypropyl cellulose.
Preparation method the most according to claim 5, is characterized in that, described asiaticoside, Borneolum Syntheticum, starch, dextrin and low
The weight ratio replacing hydroxypropyl cellulose is: (0.6～1.2): 3:40:30:5.
7. according to a capsule preparation method thereof for described treatment depression combination drug arbitrary in claims 1 to 3, its feature
Be, by asiaticoside and Borneolum Syntheticum mix homogeneously, add propylene glycol and ethanol be stirring solvent uniformly after make soft material, through sieving
Obtain with magnesium stearate mixing granulation after powder.
Preparation method the most according to claim 7, is characterized in that, described mix homogeneously, adds lactose, manna further
Alcohol, micropowder silica gel, microcrystalline Cellulose or cross-linking sodium carboxymethyl cellulose.
Preparation method the most according to claim 8, is characterized in that, described asiaticoside, Borneolum Syntheticum, lactose, mannitol, micro-
Powder silica gel, microcrystalline Cellulose, the weight ratio of cross-linking sodium carboxymethyl cellulose be: 1:(1～100): (10～100): (0.2～
0.8): (0.05～0.1): (0.05～0.3): (0.05～0.3).
Preparation method the most according to claim 7, is characterized in that, described magnesium stearate with the weight ratio of sieve powder is:
0.5% 2%.
11. 1 kinds of oral liquors according to described treatment depression combination drug arbitrary in claims 1 to 3, it is special
Levy and be, by adding Polyethylene Glycol, tween and asiaticoside after being dissolved in propylene glycol by Borneolum Syntheticum, add after being sufficiently mixed and steam
Distilled water dilutes and get final product.
12. preparation methoies according to claim 11, is characterized in that, described Borneolum Syntheticum, Polyethylene Glycol, tween and Herba Centellae
The usage ratio of glycosides is: (1～100): (0.01～0.2): (0.01～0.2): 1.
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| CN113908183A (en) * | 2021-08-10 | 2022-01-11 | 美益添生物医药(武汉)有限公司 | Application of asiaticoside in preparing lactobacillus proliferation promoter |
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| CN1879712A (en) * | 2006-05-02 | 2006-12-20 | 沈阳药科大学 | Novel use of asiaticoside in resisting anxiety and depression |
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| CN113908183A (en) * | 2021-08-10 | 2022-01-11 | 美益添生物医药(武汉)有限公司 | Application of asiaticoside in preparing lactobacillus proliferation promoter |
| CN113908183B (en) * | 2021-08-10 | 2023-08-08 | 美益添生物医药(武汉)有限公司 | Application of centella asiatica total glycosides in preparing lactobacillus proliferation promoter |
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Application publication date: 20161123 |