CN104083463B - Application of medicine composition for preparation of alcohol addiction or/and dependence drugs - Google Patents
Application of medicine composition for preparation of alcohol addiction or/and dependence drugs Download PDFInfo
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Abstract
The invention provides an application of a medicine prepared from the following active pharmaceutical ingredients in parts by weight to preparation of medicines for treating alcohol addiction or/and alcohol dependence: 3-10 parts of monkshood or aconite and 3-35 parts of ginseng. The medicine comprises two medicines including monkshood or aconite and ginseng, wherein monkshood or aconite serves as the monarch medicine, has the functions of tonifying yang of the spleen and the kidney and transforming cold to dispel dampness and is directly aimed at the primary symptom of alcohol addiction; ginseng serves as the ministerial medicine and has the functions of tonifying qi and the spleen and tonifying qi and blood of the spleen and the kidney; and the two medicines are jointly used and have the functions of warming yang and tonifying the spleen. The whole preparation is rigorous in components and definite in curative effects. A medicine composition can effectively eliminate the psychology of alcohol addiction and addiction memories of behaviors, has a good effect of abstaining from alcohol addiction and provides a new choice for clinical medication.
Description
Technical field
The present invention relates to a kind of new application of pharmaceutical composition.
Background technology
Alcohol addiction is a kind of runaway drinking behavior, is mainly shown as to obtaining strongly craving for of alcohol, mandatory
Drinking in ground, and develops into alcohol tolerance and alcohol dependence.As other addictive drug associated diseases, the core of alcohol addiction
Heart feature be give up after still long-standing again drink behavior.
For alcohol dependence patient, " Drug addiction " that how to eliminate alcohol is fundamentally to realize treatment and success
Key, because patient often exists to the strong serious hope of alcohol and the disguise of poisoning symptom, clinically completely real
Existing abstinence from alcohol is extremely difficult.Currently for alcohol addiction patient treatment mainly based on drug therapy, U.S. FDA approval on
The medicine for drinking habit in city mainly has disulfiram, naltrexone and Acamprosate.These three medicines may have one in Clinical practice
Determine effect, but the generation for the multiple drink behavior after eliminating the strong drug craving of alcohol addiction patient, giving up does not have work
With, and disulfiram clinical side effects are big, and there is related hepatic lesion, its definite curative effect and mechanism and still need to further in naltrexone
Research.Generally speaking, doctor trained in Western medicine does not obtain preferable progress for the treatment of alcohol addiction patient's abstinence from alcohol.
China's traditional Chinese medicine, is expressly recited the history at least more than one thousand years using Chinese medicine alcoholic disease, shape
Become itself complete and unique theoretical system a set of.Think that wine is external damp and hot heresy, after excessive consumption of alcohol, first
Undermine taste, and spleen liked dry and disliked wet, therefore endogenous damp formation is thus burnt in retardance, spleen soil stop up stagnant, near and liver network is not smooth, in vivo
The pathological products such as gas, blood, phlegm, the stasis of blood and damp and hot mutual stasis, the development with the state of an illness is finally involved kidney, is become " persistent ailment ".And
And traditional Chinese medicine just has the document of Chinese herbal medicine energy relieving alcoholism, drug rehabilitation to record from ancient times.As《Sheng Nong's herbal classic》In, just remember
Carry：" all poison of root of kudzu vine solution ", Tang's SUN Si miao《Prescriptions worth thousand gold》Also have " saying of root of kudzu vine principal solution wine poison ", Ming Dynasty's book on Chinese herbal medicine monumental work《Herbal guiding principle
Mesh》The content of middle antialcoholic drug is very abundant, has recorded antialcoholic drug and count roughly 100 kinds in book, be distributed widely in mineral drug, animal drugs,
Among autonomic drug, come out to the Qing Dynasty with a series of monographs about drug rehabilitation, detoxification by Chinese medicine arises at the historic moment and has more than 200 so far
The history in year, has gained most valuable experience, and has founded a series of traditional Chinese medical science drug rehabilitation methods, including the pure Chinese medicine side of giving up medicine,
Chinese medical discrimination adds opium and successively decreases drug rehabilitation side's medicine, datura flower drug rehabilitation etc., establishes strengthening vital QI to eliminate pathogenic factors, Yin-nourishing and Yang-supporting, help internal organs, dispels
Total principles of reatment such as cigarette poison, the smooth qi and blood of tune.In addition, efficient, the advantage such as low toxicity, inexpensive, Mutiple Targets of Chinese herbal medicine itself, because
This, Chinese medicine alcohol addiction has certain advantage.
Monkshood or rhizome of Chinese monkshood indication：Recuperating depleted yang, mends fire supporing yang, by wind-cold damp pathogen；The indication of ginseng：Tonifying Qi is solid
Table, diuretic and maintain drug, apocenosis, expelling pus and promoting granulation.The report two herbal medicines being applied in combination at present, such as application number：
200410013941.5；Denomination of invention：One kind treats bradycardic Chinese medicine, and one kind treats bradycardic Chinese medicine, by 40～
The oral formulations that 60% ginseng and monkshood or the rhizome of Chinese monkshood obtain for Raw material processing.The present invention is through rat amiodarone and two kinds of inderal
The pharmacodynamics test of chronic rhythm of the heart model proves, all can the bradycardic heart rate of significantly raised both models.And long-term taking
Safe and free of toxic and side effects.
Content of the invention
The technical scheme is that and provide a kind of new application of pharmaceutical composition.
The invention provides the medicine that the bulk drug containing following weight proportioning is prepared from is in preparation treatment alcohol addiction
Or/and the purposes in the medicine relying on：Monkshood or rhizome of Chinese monkshood 3-10 part, ginseng 3-35 part.
It is further preferred that described medicine is the preparation being prepared from by the bulk drug of following weight proportioning：
Monkshood or rhizome of Chinese monkshood 3-10 part, ginseng 3-35 part.
It is further preferred that described bulk drug weight proportion is：Monkshood or rhizome of Chinese monkshood 5-10 part, ginseng 10-35 part.
It is further preferred that described bulk drug weight proportion is：Monkshood or 10 parts of the rhizome of Chinese monkshood, 35 parts of ginseng.
Wherein, described monkshood is unprocessed Radix Aconiti Lateralis and/or RADIX ACONITI LATERALIS PREPARATA, and the rhizome of Chinese monkshood is monkshood and/or radix aconiti agrestis；Described ginseng is made a living
Ginseng and/or moxibustion ginseng.
Described preparation is oral formulations.
Wherein, described oral formulations are granule, powder, pill, capsule, soft capsule, tablet or oral liquid.
The preparation method of described medicine comprises the steps：
A, weigh bulk drug；
B, bulk drug is directly beaten powder, or add water to cook, add pharmaceutically acceptable auxiliary material or the preparation of complementary composition
Become the preparation pharmaceutically commonly used.
Described medicine is that treatment long-term alcohol leads to damp heat in the spleen and the stomach, with the passing of time conversion of dampness into old, damages yang-energy, the spleen kidney of formation
The medicine of the card of the deficiency of yang.
In order to eliminate the height drink rate again after alcohol addiction patient craves for and gives up for the strong spirit of alcohol, the present invention
The locomotor sensitivity animal two being relied on behavior using the Conditioned place preference of internationally recognized research Drug habituation psychological dependence
Kind of classical animal model, provide that a kind of drug effect is good, low toxicity, Mutiple Targets, the ideal medicament group of inexpensive treatment alcohol addiction
Compound, and its production and use.
Oneself generally acknowledges that " organic conception ", " diagnosis and treatment based on an overall analysis of the illness and the patient's condition ", " compound use ", " compound compatibility medication is such as used military forces " are the traditional Chinese medical science at present
Most scientific maximally effective several big advantages, wherein " compound compatibility medication is such as used military forces " are the original theories of traditional Chinese medicine of luxuriant and rich with fragrance Chang Kexue.In
Cure in prescription and medicine tight compatibility all linked with one another as arrayed troops for battle, be that it is better than the effectively treatment means of western medicine formula.
TCM prescription theory thinks, each prescription, not only needs to select the appropriate compatibility of suitable medicine according to etiology and pathogenesis, also should simultaneously
Meet the basic structure of prescription, i.e. the prescription compatibility of " monarch, minister, help, make ", the prescription compatibility of so-called " monarch, minister, help, make " it is simply that
It sets up the scientific matching on the comprehensive judgement basis to the disease interpretation of the cause, onset and process of an illness.Middle medical square passes through too many levels, Mutiple Targets are integrated
The biological mechanism adjusting, to alcohol addiction and rely on such mechanism complicated difficult look into, doctor trained in Western medicine curative effect, the extremely difficult illness for the treatment of
Or symptom carries out control of withering, more preferable than Western medicine, more thorough therapeutic effect can be obtained, and this curative effect is built upon the above-mentioned traditional Chinese medical science
On the original theoretical definite guidance of tradition, prescription of the present invention have followed this principle.
Under tcm theory instructs, alcoholic strength is wet, is the dry strong product of pungent-warm, long-term alcohol, easy gas consumption blood trouble, damages cloudy and positive,
Involve kidney, the Yang-function insufficiency of kidneyzang, the formation of its habituation mechanism relation dirty with spleen, kidney two is the closest.Wine be damp evil, spleen happiness hot-tempered and
Dislike wet, in the initial stage damp evil of drinking enters, spleen soil is first hindered, conversion of dampness into old, then spleen sun does not rise, the clinical visible disease such as forgetful, dizzy.Simultaneously
Taste are source of generating QI and blood again, are the foundation of acquired constitution, and kidney hides congenital essence, is life basis, is the congenital foundation, kidney essense and its change
Constantly supplementing nutrition and cultivating of the gas of raw yin-Yang, the foodstuff essence of bad temper transporting and its essence derived from food of metaplasia, can fill Sheng.
Insufficiency of the spleen water paddy, cold-damp affecting spleen, it is impossible to nourish congenital, it is foster that disease can cause kidney to lose to lucid yang failing to raise long, the Yang-function insufficiency of kidneyzang, and asthenia in origin and asthenia in superficiality is mutual
See, gas, blood, water are all sick.Often tinnitus heartbeat in later phase clinical in habituation patient, muscle arthrosis, the small of the back diffusivity pain,
Four limbs are sleepy, become thin, constipation or diarrhoea, early ageing, impotence, alliteration dizziness, insomnia, uncomfortable in chest, palpitaition, and apocleisis is hydrophobic, the sound of vomiting of vomitting, and arteries and veins is slow
Or string slides, the insufficiency of both the spleen and the kindey such as the fat tongue of tongue is weak is white, the clinical manifestation of retention of water-damp.
Medicine of the present invention is made up of monkshood or the rhizome of Chinese monkshood, ginseng two taste medicine, and wherein monarch is tonifying spleen and kidney with monkshood or rhizome of Chinese monkshood effect
Sun, change cold clearing damp, direct at the primary symptom of alcohol addiction, minister is replenished qi to invigorate the spleen with ginseng, tonifying spleen kidney qi blood, two medicines share plays Wen Yang altogether
The work(of invigorating the spleen.Full square preparation prescription is rigorous, determined curative effect.Pharmaceutical composition of the present invention can effectively eliminate the psychology of alcohol addiction
With " Drug addiction " of behavior, there is the effect of good withdrawal alcohol addiction, be that clinical application provides a kind of new selection.
Brief description
Fig. 1：The autonomic activities test baseline of each group mouse laundering period, as seen from the figure, is compared with Normal group, Chinese medicine
The autonomic activities baseline of group, alcohol group, Chinese medicine+alcohol group each group mouse does not have significant difference, P>0.05.
Fig. 2,10 days 5 times mouse autonomic activities test results of experience show：Alcohol group is compared with salt solution during 5 times are tested
Mouse autonomic activities number of times is respectively provided with notable significant difference,*The 4th, 5 test phases of P ＜ 0.01., the autonomic activities of mouse
Number is higher than 3 times,#P<0.05；Test the phase at the 4th, 5 times, Chinese medicine+alcohol group and saline control group, Chinese medicine group have statistics poor
It is different,▲P<0.05；Compared with Chinese medicine+alcohol group, there is notable significant difference in the 2nd, 3,4,5 test phase alcohol model group,▼P<
0.01.
Fig. 3：Mouse accepts alcohol (2.2g/kg), Chinese medicine (1.8g/kg), Chinese medicine+alcohol, salt solution respectively in excitation phase
Excite, result shows：Model group alcohol excites and excites otherness notable * P ＜ 0.01 with salt solution, model group alcohol excite with
Medicine+alcohol excites with the significance difference opposite sex▲P<0.01, and Chinese medicine+alcohol group is accepting to excite phase with salt solution group after alcohol excites
The autonomic activities number of times of mouse does not have to be increased ratio, does not have significant difference (P>0.05).
Fig. 4：Express phase, alcohol group mouse dopamine (DA), glutamic acid (GLU) content and salt solution group in mouse locomotor sensitivity
Compare notable rising (*P<0.01), compared with alcohol model group, the dopamine (DA) of Chinese medicine compound prescription intervention group mouse, glutamic acid
(GLU) level significantly reduce (#P<0.01). it has been found that and salt in comparing between three groups of groups in γ mono- aminobutyric acid (GABA)
Water control group is compared, alcohol model group (GABA) reduce more significant (*P<0.01), Chinese medicine intervention group and alcohol model group phase
Than, by increasing capacitance it is possible to increase mouse intracerebral (GABA) release (#P<0.01).
Fig. 5, in mouse locomotor sensitivity expression phase alcohol group mouse dopamine (DA), glutamic acid (GLU) content and salt solution group
Compare still significantly raise (*P<0.01), compared with alcohol model group, the dopamine (DA) of Chinese medicine compound prescription intervention group mouse, paddy ammonia
Sour (GLU) level significantly reduce (#P<0.01). same three groups in comparing between the group of γ mono- aminobutyric acid (GABA), we
Find compared with saline control group, alcohol model group (GABA) reduce more significant (*P<0.01), Chinese medicine intervention group and alcohol mould
Type group is compared, by increasing capacitance it is possible to increase the release of mouse intracerebral (GABA) (#P<0.01).
Fig. 6：Mouse is 599.97 scholar 4..466 (S) in the black box time of staying, and the white box time of staying is
265.75 scholar 67.686 (s) (P<0.01).
Fig. 7：After 10 days 5 cycles of training, test phase result shows, Chinese medicine group in white with the medicine-chest time of staying is
269.58 scholar 20.586S, salt solution group is compared for two groups of 288.33. scholar 41.033S does not have significant difference (P>0.05). and alcohol
Group mouse is 553.67 scholar 57.917S in test phase white with the medicine-chest time of staying, has conspicuousness with respect to physiological saline group
Difference (*P<0.01).
Fig. 8, Chinese medicine intervention group and alcohol group all can significantly inhibit the mouse CPP's that alcohol induces 3 test phases
Formed (*P<0.05), and to the 3rd test phase show, Chinese medicine intervention group is formed for the CPP that alcohol induces to be had significantly
Inhibitory action (#P<0.01).
Specific embodiment
The preparation of embodiment 1 pharmaceutical composition of the present invention
Take monkshood 10g, ginseng 30g.Each flavour of a drug weigh according to quantity, mix and enough water purification, boil monkshood or rhizome of Chinese monkshood 1h by slow fire
With up fiber crops, after enter ginseng and decoct.Collect decocting liquid；The dregs of a decoction add water decoction 2 times, merge each decocting liquid, obtain final product decoction.
In we, tag consumption is slightly larger, takes the work(of its temperature sun dampness elimination.
The preparation of embodiment 2 pharmaceutical composition of the present invention
The decoction of Example one preparation, after concentration, plus pelletizes after the mixing of proper starch, dextrin.
The preparation of embodiment 3 pharmaceutical composition of the present invention
Take rhizome of Chinese monkshood 10g, ginseng 30g.Each flavour of a drug weigh according to quantity, mix and appropriate water purification, boil monkshood or rhizome of Chinese monkshood 1h by slow fire
With up fiber crops, after enter ginseng and decoct.Collect decocting liquid；The dregs of a decoction add water decoction 2 times, merge each decocting liquid, after concentration, do
Dry, after adding appropriate dextrin, soluble starch to pelletize, compressing tablet, obtain final product tablet.
The preparation of embodiment 4 pharmaceutical composition of the present invention
Take monkshood 10g, ginseng 30g.Each flavour of a drug weigh according to quantity, and be decocted first monkshood or the rhizome of Chinese monkshood, boil by slow fire 1h go fiber crops, after enter people
Ginseng is decocted 1 hour, collects decocting liquid；The dregs of a decoction add water decoction 2 times, merge each decocting liquid, after concentration, after being dried plus micro- in right amount
Crystalline cellulose, after mixing, encapsulated, obtain final product capsule.
Prove beneficial effects of the present invention below by way of pharmacodynamic experiment.
Test example 1 medicine of the present invention affects on alcohol addiction mouse locomotor sensitivity animal model and Conditioned place preference model
Experimental study.
1. experiment material
1.1 animal used as test：3 months macrandry cleaning grade Kunming mice, enter between the body weight 25～30g in laboratory.
Mouse and feed are provided by by Chengdu Da Shuo zoopery company, and the animal quality certification is numbered：SCXK(11)2013-24.Buy
After be placed in Chengdu University of Traditional Chinese Medicine's TCM Zang-fu laboratory (country two grades) and raise.
1.2 Experimental agents：Raw material dosage described in embodiment 1 method and method preparation, by Chengdu University of Traditional Chinese Medicine's pharmacy
Chinese medicine preparation research department of institute provides.Lot number：20130111；Clinic drafts dosage for daily primary crude drug 40g, by adult body
The general 60kg of weight calculates, and people's dosage is primary crude drug 0.66g/kg body weight.Laboratory is made into respectively 5.94g/kg/d (quite
Draft dosage in clinic 9 times).Administered volume 0.1ml/10g body weight.
1.3 experiment equipment：Mouse feeder device, gastric perfusion needle (Chengdu University of Traditional Chinese Medicine laboratory), Mice brain tissues cut
Device and nitrogen storage tank (Chengdu Li Lai bio tech ltd), CPP--100 condition position preference experiment instrument, ZZ-6 are certainly
Send out movable tester (Chengdu TME Technology Co., Ltd.), computer：Model：(AOC shows scientific and technological limited public affairs to TFT185W80PS
Department), ELIASA：Model：MultlskanMk3 (match Mo Feishier Instrument Ltd.), electronic thermostatic water-bath：Model DZKW-
4 (Beijing Zhong Xing great achievement Instrument Ltd.).
1.4 experiment reagent：Dopamine (DA) ELISA detection kit:Abcam company produces, Beijing Pfizer biotechnology
Co., Ltd dispenses, product batch number：E-30236.
Glutamic acid (GLU) ELISA detection kit:Abcam company produces, and Beijing bio tech ltd of Pfizer divides
Dress, product batch number：E-30324.
GABA (GABA) ELISA detection kit:Abcam company produces, the limited public affairs of Beijing Pfizer biotechnology
Department's packing, product batch number：E-31033.
2. experimental design and scheme
2.1 locomotor sensitivity experiments
2.1.1 experimental provision ZZ-6 spontaneous activity in mice analysis system：The six palace lattice spontaneous activity box of 2 row X3 are (simultaneously
Six spontaneous activity in mice of measurement, high-resolution 36 infrared array probe apparatus and PC data communication collection analysis work(
Energy.Material is double-deck aluminium-plastic panel, and sound insulation, every light, has ventilation unit.By infrared probe record animal activity situation, calculate animal
Assay of spontaneous activity.
2.1.2 experimental technique and experiment flow
Laundering period:While adaptability is fed one week, all of experiment mice of weighing, the physiological saline of gavage equivalent
After be immediately placed in autonomic activities tester, make mouse can adapt to test experimental situation, the time be 15 minutes.Fit within 7th day
Ying Hou, all of mouse puts into the autonomic activities baseline testing mouse in autonomic activities tester, is subsequently randomly divided into 4 greatly
Group.The purpose of laundering period is to allow KM mouse adaptive testing device, the shadow to mouse autonomic activities for the factor such as exclusion environment, gavage
Ring, and record their normal number of activities.
Formation stages：After test autonomic activities baseline, mouse gavage Chinese medicine or salt solution before half an hour, subsequently fill
The alcohol of stomach (2.2g/kg) or physiological saline, that is, form salt solution group+salt solution group (S+S group, n=40, Chinese medicine group+salt solution group (Z
+ S, n=40), salt solution group+alcohol group (S+E, n=40.), Chinese medicine group+alcohol group (Z+E, N=40) is in alcohol or physiology salt
It is immediately placed in after water gavage 5min in tester and tests 15 minutes, experiment is carried out once every other day, 10 days altogether, carry out 5 times.In warp
After going through 48 hour transition period, excitation phase starts.
Excitation phase：Each tests big group of group, is randomly divided into 4 subgroups in group again.Medicine divides by excitation phase mouse
Do not accept salt solution (s), alcohol group (e), Chinese medicine group (z), Chinese medicine+alcohol group (z+e) excites, and is immediately placed in and independently lives after 5min
In dynamic tester, test 15 minutes.After the completion of test, by salt solution+salt solution+alcohol group (s+s+e, n=10), salt solution+alcohol group+
Alcohol group (s+e+e, n=10) mouse, salt solution+alcohol group+Chinese medicine group+alcohol group (s+e+z+e, n=10) mouse, Chinese medicine group+
Alcohol group+alcohol group (z+e+e, n=10) mouse, the mouse sacrificed by decapitation immediately of this 4 subgroups, take brain tissue, detect midbrain
The dopamine (DA) of (NAC) of edge ventral tegmental area (VTA) and its projection area nucleus accumbens septi, hippocampus, the paddy ammonia in amygdaloid nucleus area
Sour (GLU), this 3 neurotransmitter Chinese medicine patients before and after intervention of GABA (GABA) in ventral tegmental area (VTA) and NAC area
Change.
2.2 condition position preferences experiment (CPP)
2.2.1 experimental provision CPP-100 Conditioned place preference tester：It is seen by the grey that mouse is placed in test box
Examine region, then observation experiment animal is in three (white case length × width × height=280 × 210 × 210mm, grey of test box
Case length × width × height=120 × 210 × 210mm, black case length × width × height=280 × 210 × 21mm) region activity feelings
Condition, thus obtaining animal used as test is that hobby stays in dark areas or the quantitative result data in light colour region, is for evaluating medicine
The rewarding effect of thing and the effective foundation finding anti-drug-seeking behavior.
2.2.2 this experiment of experimental procedure adopts bias experimental arrangement.Experiment is divided into pre-adaptation phase, training period, expression test 3
In the individual stage, in guard box in whole experiment process, the environmental condition such as light, tone, smell is consistent.
The pre-adaptation phase (the -3rd～-1 day), mouse is put in CPP case, is put into by intermediate box, open gate by it freely
Shuttle 15 minutes, once a day, for three days on end, and daily gavage physiological saline, to eliminate the impact to mouse for the experimental implementation,
3rd day record mouse residence time in black, white, intermediate box, in the record 15min time, mouse stops in the different areas
Time, as the index of the natural CPP effect of mouse, the side of time of staying length as non-with medicine-chest, the time of staying short side
As with medicine-chest.And reject has the mouse of obvious preference (will be in the side time of staying to black box and white box>The rejecting of 650S).
Under this experiment condition, mouse natural preference black, still using excess kurtosis experimental design, select white box to be with medicine-chest, black
Case is non-with medicine-chest.
The formation phase (the 1st～10 day), the daily acceptance of every mouse is once trained, and alcohol is every other day administered once.Specifically
For, if first day abdominal cavity gavage alcohol (2.2g/kg) or Chinese medicine, put into and train 15 minutes with medicine-chest, then subcutaneous filling in second day
The physiological saline (NS) of stomach same volume, puts into non-companion's medicine-chest and trains 15 minutes.The equal injecting normal saline of saline control group, Chinese medicine
Compound half an hour before alcohol gavage is administered in advance.The like, 5 cycles of training, form 4 each groups, i.e. salt solution group
(S+S), alcohol control group (E+S), Chinese medicine group (Z+S), Chinese medicine intervention group (Z+E).Training time is fixed as 8 points of every morning
To between 9 points.
The test phase (the 11st day), therefore we were at the 5th day it is considered to training early stage mouse natural preference difference is not notable
After training starts, it is condition training period after each pair alcohol and physiological saline training, therefore 24 hours after each condition training period,
Respectively in the expression of the 6th, 8,10 days test CPP.In the test phase of the 11st day, during before test, mouse is not administered and is directly placed into
Between case open dividing plate, measure in 15min mouse with medicine-chest and the non-time of staying with medicine-chest, the feelings that measurement mouse CPP obtains
Condition.
2.3 observation index and detection method
2.3.1 ZZ-6 spontaneous activity in mice tester is adopted to measure the spontaneous activity time in the experiment of locomotor sensitivity experiment mice
Number.
2.3.2 CPP-100 condition position preference tester is adopted to measure CPP experimental group each group mouse with medicine-chest and non-companion
The time of staying of medicine-chest.
2.3.3 adopt elisa assay method measure Mice brain tissues, detection dopamine, glutamic acid, GABA dense
Degree level.
3. statistical method
Each group experimental data all withRepresent, statistical analysis is carried out using SPSS 17.0 software, relatively adopts for two groups
Checked with t；Multigroup is compared using One-Way ANOVA analysis, is then compared two-by-two with LSD method；Locomotor sensitivity is tested
Multigroup of stimulating phase compares and adopts Covariance Analysis Technique.
4. experimental result
The experimental result of 4.1 locomotor sensitivity
4.1.1 the autonomic activities baseline of experiment laundering period each group mouse compares：It is illustrated in figure 1 each group mouse laundering period
Autonomic activities tests baseline, as seen from the figure, compares with Normal group (s+s), and Chinese medicine group (z+s), alcohol group (e+s), Chinese medicine+
The autonomic activities baseline of alcohol group (z+e) each group mouse does not have significant difference, P>0.05.
4.1.2 the impact to mouse autonomic activities for the Chinese medicine compound prescription repeat administration of the present invention:Fig. 2 show mouse 10 days 5 times
During test, salt solution group, Chinese medicine group, alcohol group (2.2g/kg), the comparison of autonomic activities between Chinese medicine+alcohol group each group.Repeat
Result display interaction time × process (F=19.473, the P of measurement variance analysis<0.01, give Huynh-Feldt method and rectify
Just), time factor (F=41.098, P<0.01, give Huynh-Feldt method and correct), process factor (F=198.030, P<
0.01), connecting trend with the change with test number of days between each treatment group has significant difference.Bonferroni
The result that posttests method carries out Multiple range test shows, the 4th, 5 times the total autonomic activities number of times of test mouse is significantly higher than first three
Group (P<0.01).Between Chinese medicine group and saline control group, the autonomic activities of mouse does not have significant difference (P>0.05), in prompting
Medicine compound itself does not have an impact to the autonomic activities of mouse.Alcohol model group is compared with salt solution group control group 5 test phases
Between the autonomic activities of mouse there is obvious significant difference (P<0.01), prompting alcohol group mouse autonomic activities apparently higher than
Saline control group, alcohol can cause the high activity of mouse.Show in the 1st, 2,3 test results, Chinese medicine+alcohol group and salt
Water group, Chinese medicine group compare the not variant (P of autonomic activities of mouse>0.05), and in the 4th, 5 Chinese medicine+alcohol group mouse
Number of activities is higher than saline control group, Chinese medicine group (P<0.05).Chinese medicine+alcohol group compared with alcohol model group, the 2nd, 3,4,5
The autonomic activities number of times of secondary test phase mouse is significantly lower than alcohol model group, points out, before alcohol gavage, to give Chinese medicine compound prescription
The mouse autonomic activities number of times of alcohol induction can be reduced, i.e. the shape of the mouse locomotor sensitivity that explanation Chinese medicine compound prescription induces to alcohol
One-tenth process has effect.
4.1.3 Chinese medicine compound prescription of the present invention itself forms the impact (Fig. 3) of phase and expression phase to mouse locomotor sensitivity
4.1.3.1 Chinese medicine compound prescription of the present invention itself forms the impact with expression to mouse locomotor sensitivity.
As shown in figure 3-1, Chinese medicine compound prescription, accept respectively alcohol (2.2g/kg), Chinese medicine (1.8g/kg), Chinese medicine+alcohol swash
Give the not variant (P of autonomic activities number of times of each group mouse>0.05), prompting Chinese medicine compound prescription is to mouse locomotor sensitivity model
Formed not having with expression and act on.
4.1.3.2 the foundation of the mouse locomotor sensitivity animal model of alcohol induction.
As shown in figure 3-2, alcohol model group accepts after alcohol excites, excite with salt solution compared with mouse autonomic activities table
Reveal the notable (P of otherness<0.01), show that the mouse locomotor sensitivity animal model being induced by alcohol has built up.
4.1.3.3 the impact that Chinese medicine compound prescription joint alcohol intervention of the present invention is expressed to mouse locomotor sensitivity.As Fig. 3 -- 3 institutes
Show：Alcohol model group autonomic activities number of times of mouse compared with accepting after Chinese medicine excites, exciting group with salt solution does not have statistics
Difference (P>0.05), prompting compound can not affect the expression of alcohol group mouse locomotor sensitivity.And give alcohol in mouse and excite
Half an hour before, we give Chinese medicine compound prescription and shift to an earlier date gavage, compared with result shows and excites group with simple alcohol, Chinese medicine+alcohol group
The expression to mouse locomotor sensitivity is excited to have significant inhibitory action, two groups have the significance difference opposite sex (P<0.01), in prompting
Medicine compound and alcohol use in conjunction can significantly inhibit the expression of the mouse locomotor sensitivity of alcohol induction.
4.1.3.4 the impact that Chinese medicine compound prescription joint alcohol intervention of the present invention is formed to mouse locomotor sensitivity.
As shown in Figure 3-4, Chinese medicine+alcohol group is compared with accepting to excite with salt solution group after alcohol excites, the autonomous work of mouse
Dynamic number of times does not have to be increased, and does not have significant difference (P>0.05).Prompting is combining with alcohol through 10 days Chinese medicine, repeat administration
Afterwards, Chinese medicine+alcohol group mouse does not form locomotor sensitivity, and the mouse accepting after same dose alcohol gavage excites in alcohol
Afterwards, show significant mouse locomotor sensitivity it was demonstrated that the formation of the locomotor sensitivity to mouse for the Chinese medicine compound prescription is inhibited.
4.1.4 Chinese medicine compound prescription of the present invention forms phase dopamine to the mouse locomotor sensitivity animal model being induced by alcohol
(DA), glutamic acid (GLU), the change (Fig. 4) of γ mono- aminobutyric acid (GABA) content.In the mouse locomotor sensitivity being induced by alcohol
The formation phase, alcohol locomotor sensitivity group mouse dopamine (DA), glutamic acid (GLU) content are notable compared with salt solution group to raise (P<
0.01).The dopamine (DA) of Chinese medicine compound prescription intervention group, glutamic acid (GLU) level (P not variant compared with saline control group>
0.05), and compared with alcohol model group, the dopamine (DA) of Chinese medicine compound prescription intervention group mouse, glutamic acid (GLU) level substantially subtract
Few (P<0.01).Likewise, it has been found that and saline control group in comparing between the group of three groups of γ mono- aminobutyric acid (GABA)
Compare, alcohol model group (GABA) reduces more significant (P<0.01), and compared with Chinese medicine intervention group and alcohol sensitization model group, can
Increase the release of mouse intracerebral (GABA).
4.1.5 Chinese medicine compound prescription of the present invention is to the mouse locomotor sensitivity animal model expression phase dopamine being induced by alcohol
(DA), glutamic acid (GLU), the change (Fig. 5) of γ mono- aminobutyric acid (GABA) content.In the mouse locomotor sensitivity being induced by alcohol
The expression phase, the dopamine (DA) of Chinese medicine compound prescription intervention group mouse, glutamic acid (GLU) level compared with alcohol model group hence it is evident that
Reduce (P<0.01).Likewise, in comparing between the group of three groups of γ mono- aminobutyric acid (GABA), Chinese medicine intervention group is sensitized with alcohol
Model group is compared, by increasing capacitance it is possible to increase the release of mouse intracerebral (GABA).
The experimental result of 4.2 condition position preferences experiment (CPP)
4.2.1 the natural preference effect experiment (Fig. 6) of mouse：As shown in Figure 6, mouse is in the pretest time of 900S,
It is 609.97 scholar 4..466S, 365.75 scholar 67.686 (P in the black case time of staying<0.01).Result is pointed out, and mouse is to four
Week has natural preferences for black, bottom surface for coarse netted box, therefore, we using excess kurtosis experimental design by white
, as with medicine box, black case is as non-with medicine box for box.
4.2.2 the foundation (Fig. 7) of the mouse CPP of the Place Preference of Chinese medicine compound prescription of the present invention itself and alcohol induction：As Fig. 7
Shown, after 10 days 5 training periods, testing interim medicine group in white companion's medicine-chest time of staying is 249.58 scholar 20.586S, salt
Water group is compared for two groups of 268.33. scholar 41.033S does not have significant difference (P>0.05), prompting Chinese medicine compound prescription group itself is to mouse
Natural place preference select not affecting.And alcohol group mouse is 533.67 scholars in test phase white with the medicine-chest time of staying
57.917S, has significant difference (P with respect to physiological saline group<0.01), result prompting alcohol (2.2g/kg) can induce
Mouse conditioned place preference is formed.
4.2.3 Chinese medicine compound prescription of the present invention on alcohol inducing mouse CPP formed the phase impact (Fig. 8) as shown in figure 8, with alcohol group
Compare, Chinese medicine compound prescription is in the forming process that time-histories correlation suppresses the mouse Conditioned place preference of alcohol induction.Chinese medicine compound prescription is 3
The result of individual test phase shows the formation (P of the mouse CPP that all can significantly inhibit alcohol induction<0.05), test to the 3rd
Stage shows, Chinese medicine is formed for the CPP that alcohol induces has obvious inhibitory action (P<0.01).
5. conclusion
Compound of the present invention can not only reduce the high activity of mouse that alcohol causes, to the mouse locomotor sensitivity that alcohol induces
Formed and expression significantly inhibits, show that compound of the present invention can intervene the formation of alcohol addiction mouse body dependence
And the multiple drink behavior occurring after abstinence from alcohol.In CPP experiment, compound of the present invention has prevents the mouse condition position that alcohol induces inclined
The formation of good model, can intervene mouse for psychological dependence formation.Most it is essential that compound of the present invention can subtract
When young in mouse limbic brain reward system DA, Glu neurotransmitter release, increase inhibitory neurotransmitter GBBA transmission, thus
The neurobiological basis that the present invention prevents and treats the Changes of Plasticity of central nervous system of mice are established, thus playing withdrawal alcohol
The effect that habituation psychology is relied on behavior, is traditional Chinese medicine prevention alcohol addiction and alcohol dependence provides new therapy and preparation.
Claims (6)
1. the medicine being prepared from by the bulk drug of following weight proportioning is in the medicine of preparation treatment alcohol addiction or/and dependence
Purposes：
Monkshood or 10 parts of the rhizome of Chinese monkshood, 35 parts of ginseng；
Wherein, the preparation method of described medicine is：Each flavour of a drug weigh according to quantity, mix and enough water purification, boil by slow fire monkshood or
Rhizome of Chinese monkshood 1h with up fiber crops, after enter ginseng and decoct, collect decocting liquid；The dregs of a decoction add water decoction 2 times, merge each decocting liquid, add
Pharmaceutically acceptable auxiliary material is prepared into the preparation pharmaceutically commonly used.
2. purposes according to claim 1 it is characterised in that：Described monkshood is RADIX ACONITI LATERALIS PREPARATA and/or unprocessed Radix Aconiti Lateralis, and the rhizome of Chinese monkshood is
Monkshood and/or radix aconiti agrestis；Described ginseng is made a living ginseng and/or moxibustion ginseng.
3. purposes according to claim 1 and 2 it is characterised in that：Described preparation is oral formulations.
4. purposes according to claim 3 it is characterised in that：Described oral formulations are granule, powder, pill, glue
Wafer, tablet or oral liquid.
5. purposes according to claim 4 it is characterised in that：Described capsule is soft capsule.
6. purposes according to claim 1 it is characterised in that：Described medicine is that treatment long-term alcohol leads to taste wet
Heat, with the passing of time conversion of dampness into old, damage yang-energy, the medicine of the card of the insufficiency of both the spleen and the kindey of formation.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1891265A (en) * | 2005-07-08 | 2007-01-10 | 张晴龙 | Ginseng-aconite orally disintegrating tablet and its preparing method |
| CN1899400A (en) * | 2006-07-14 | 2007-01-24 | 天津市轩宏医药技术有限公司 | Medicinal preparation containing ginseng and aconite root in raw material and its preparing method and quality control method |
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2014
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1891265A (en) * | 2005-07-08 | 2007-01-10 | 张晴龙 | Ginseng-aconite orally disintegrating tablet and its preparing method |
| CN1899400A (en) * | 2006-07-14 | 2007-01-24 | 天津市轩宏医药技术有限公司 | Medicinal preparation containing ginseng and aconite root in raw material and its preparing method and quality control method |
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