CN104224817A - Application of panaxadiol saponin component in preparing antischizophrenic drug - Google Patents

Application of panaxadiol saponin component in preparing antischizophrenic drug Download PDF

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CN104224817A
CN104224817A CN201410436367.8A CN201410436367A CN104224817A CN 104224817 A CN104224817 A CN 104224817A CN 201410436367 A CN201410436367 A CN 201410436367A CN 104224817 A CN104224817 A CN 104224817A
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panaxadiol saponin
drug
schizophrenia
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component
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CN104224817B (en
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连晓媛
钱恒
张治针
周广骏
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Zhejiang University ZJU
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Abstract

The invention provides an application of a panaxadiol saponin component in preparing an antischizophrenic drug. The application comprises treatment of schizophrenia and resistance of toxic side effect, namely an extrapyramidal symptom and the like which are caused by the antischizophrenic drug, wherein the antischizophrenic drug comprises the panaxadiol saponin component independently or with other medicines and other active compounds and pharmaceutically acceptable carriers. The invention proves that the panaxadiol saponin component (Rb) can improve the cognitive ability of a schizophrenia animal model, resist the nerve toxic side effect of multiple schizophrenia drugs, improve the negative symptoms (such as cognition impairment) of the schizophrenia and is applied to preparing the antischizophrenic drug.

Description

The schizophrenia medical usage of Panaxadiol saponin component
Technical field
The invention belongs to field of medicaments, relate to the application of Panaxadiol saponin active component (being called for short Rb below) in preparation control mental sickness medicine.More particularly, utilize Panaxadiol saponin component to comprise pharmaceutical preparation that known antipsychotic drug particularly makes together with chlorpromazine, haloperidol, clozapine in the application for the treatment of mental sickness medicine separately or with other material, the pharmaceutical preparation that Panaxadiol saponin component is made separately and existing psychosis conbined usage play potentiation and Attenuation.
Background technology
existing antipsychotic drug has many defects, needs safer, more effective medicine.
Along with the quickening of social rhythm, the pressure spirit aspect that people face from each side is in sub-health state for a long time, develops into mental sickness in the course of time, as treatment will have a strong impact on the productive life activity even life threatening of people not in time.Schizophrenia is major psychosis, the clinical syndrome be made up of one group of syndrome, and it is multifactorial disease.Although at present still not bery clear and definite to the understanding of its cause of disease, the effect that the susceptible quality of individual mind and the undesirable element of outside social environment develop the generation of disease know together by everybody.Be susceptible quality or outside undesirable element all can cause disease generation by inherent biological factor combined effect, factor of its morbidity of different patient may with outbalance in a certain respect.Schizoid clinical symptoms complexity is various, and can relate to the aspects such as sensory perception, thinking, emotion, volitional behavior and cognitive function, between individuality, symptom is widely different, even if same patient also may show different symptoms in different phase or stadium.
Anti-schizophrenia medicine is better to the schizoid positive symptom (comprising disturbance in thinking, vain hope, hallucination, the dyskinesia etc.) therapeutic effect, but to negative symptoms (bradykinesia consciousness, lack interest blank etc. and cognitive impairment, aprosexia, dysmnesia n-back test obstacle etc.) is invalid or effectiveness is low and can damage the cognitive function of patient.From first psychosis (chlorpromazine) be applied to clinical since, through the struggle of decades, nowadays anti-schizophrenia medicine there has been the third generation, not only has good curative effect simultaneously can also improve its negative symptoms to the positive symptom.But six during the last ten years, we still cannot overcome numerous shortcomings (the extrapyramidal symptoms, muscular rigidity, cognitive dysfunction, metabolism syndrome, neuroendocrine disorders etc.) of anti-schizophrenia medicine, and the anti-schizophrenia medicine social activity of patient that needed long-term taking to have a strong impact on, Most patients because its a series of side reaction cannot be stood voluntarily drug withdrawal cause aggravation.
Chlorpromazine (Chlorpromazine, CHL) have great importance as first anti-schizophrenia medicine, which opens the mankind by unbalance for chemical substance in mental sickness and the brain new page connected, up to the present chlorpromazine relies on rapid-action, cheap, the advantage such as drug effect is obvious still in wide clinical application, but the toxic and side effects of its many side reactions drug effect as adjoint in the extrapyramidal symptoms, muscular rigidity etc. is that he cannot overcome self, there is not yet the effective ways that can alleviate its toxic and side effects so far.
Haloperidol (Haloperidol, HAL) is the anti-schizophrenia medicine of a kind of typical butyrophenones, its pharmacological action and phenothiazines anti-schizophrenia medicine similar, also can be used for treating acute think of and feel imbalance and wildly arrogant disease.Action principle is similar with chlorpromazine is all dopamine receptor-blocking agent.Its more serious the extrapyramidal symptoms same, only just can be controlled when reducing dosage, but can reduce drug effect again when reducing dosage.
Clozapine (clozapine, CLO) is the Typical Representative of the anti-schizophrenia medicine of the second filial generation, not only effective to psychosis positive symptom, also has certain effect to negative symptoms.Be applicable to each hypotype that is acute and chronic schizophrenia, effective to hallucinatory paranoid form, hebephrenictype.Also the affective symptom (as: depression, sense of guilt, anxiety) relevant with schizophrenia can be alleviated.To fail to respond to any medical treatment with traditional antipsychotics to some or patient that curative effect is bad, using clozapine instead may be effectively.This medicine is also used for the treatment of the restless and hallucination vain hope of the excitement of mania or other psychotic disorders.Because causing granulocytopenia, generally should not as choice drug; Sedation is strong and anticholinergic untoward reaction is more, and common have dizziness, unable, drowsiness, hyperhidrosis, sialorrhea, Nausea and vomiting, xerostomia, constipation, postural hypotension, tachycardia; Common appetite increases and body weight increases; Electrocardiographic abnormality can be caused to change, electroencephalogram can be caused to change or schizophrenia outbreak.
The side reaction that a certain medicine can reduce said medicine is yet there are no in current world wide, and often there is more serious side reaction and some other more serious reaction in associating other drug, as levodopa and phenothiazines medicine and the used time, the latter can suppress the former Antiparkinsonian effect; Haloperidol and methyldopa share, and can produce disturbance of consciousness, retardation of thinking, disorientation etc.; Clozapine and macrolide antibiotics share and plasma clozapine can be made significantly to raise, and have report to bring out schizophrenia outbreak.The present invention relates to the application of Panaxadiol saponin component in treatment schizophrenia, a kind of and other anti-schizophrenia Drug combination will be provided just, the anti-schizophrenia curative effect that not only greatly can strengthen existing anti-schizophrenia medicine but also the medicine of the toxic and side effects that can reduce them, thus overcome the defect that current anti-schizophrenia curative effect of medication is not enough and safety is low.
the clinical therapeutic efficacy of Radix Ginseng or Radix Panacis Quinquefolii is disturbed in panoxadiol's type saponin and the meeting used in combination of three alcohol type saponin mutually.
Radix Ginseng and Radix Panacis Quinquefolii are rare Chinese medicine, the two the property of medicine, effect and clinical application are then obviously different, are not thisly both different by their principle active component and determine.The Radix Ginseng property of medicine is warm, is temperature compensation medicine, has strongly invigorating primordial QI, Gu de-, and the effects such as recuperating depleted YANG; And the Radix Panacis Quinquefolii property of medicine belongs to cool property, there is effect of nourishing lung yin, the raw rule of yin nourishing, clearind deficient heat, be considered to mend and not dry, so be more suitable for the symptoms such as insomnia, agitation, hypomnesis and senile dementia.Ginsenoside comprises panaxatriol and panoxadiol's type saponin and is considered to the primary pharmacological activity composition that Radix Ginseng and Radix Panacis Quinquefolii act on central nervous system.Radix Ginseng comparatively Radix Panacis Quinquefolii contains more protopanaxatriol ginsenoside, and Radix Panacis Quinquefolii is then containing more diol type saponin.There are some researches prove, Radix Ginseng can promote that central excitatory is dynamic while still alive and Radix Panacis Quinquefolii has maincenter sedation, this drug effect difference mainly contained by them the difference of ginsenoside determined.
Visible, Panaxadiol saponin and saponin triol and the property of medicine and drug effect closely related, should be used respectively; Otherwise the two mixes application, when needing the central excitatory drug effect of triol saponins, the maincenter sedation of glycols saponin will weaken or offset the central excitatory drug effect of triol saponins, vice versa.But Radix Ginseng and Radix Panacis Quinquefolii are mainly directly used as medicine with rhizome for a long time; And the health medicine of the extract of Radix Ginseng and Radix Panacis Quinquefolii or product mainly Radix Ginseng total saponins comprise glycol and saponin triol.This is just difficult to realize the medical value that Radix Ginseng or Radix Panacis Quinquefolii or their total saponins product effectively treat central excitatory or inhibition Symptom and disease.
Summary of the invention
The object of this invention is to provide the application of a kind of Panaxadiol saponin component in preparation antipsychotic drug, comprise treatment schizophrenia and to toxic and side effects such as the extrapyramidal symptoms that antipsychotic drug causes; Described medicine to be Panaxadiol saponin component be active component separately or with other medicines as together with chlorpromazine, haloperidol or clozapine, the medicine formed with pharmaceutically acceptable carrier.
The active component of described Panaxadiol saponin component is ginsenoside Rb 1, Rb 2, Rb 3, Rc and Rd, these five kinds of Panaxadiol saponin.Panaxadiol saponin structural formula is as follows.
The Panaxadiol saponin component that the present invention uses prepares with reference to CN2012102429281 embodiment 1 method, Panaxadiol saponin constituent content 70-90%.Panaxadiol saponin and existing anti-schizophrenia medicine (as clozapine) are share, and can strengthen the curative effect of existing antipsychotic drug and reduce the common toxic and side effects (as the extrapyramidal symptoms) of existing anti-schizophrenia medicine and improve the negative symptoms (as cognitive dysfunction) of schizophrenia.
Comprise with the pharmaceutical preparation that Panaxadiol saponin component is made: oral formulations, injection, slow releasing agent, controlled release agent, targeting preparation or effervescent, oral formulations comprises oral tablet, buccal tablet, chewable tablet, pill, drop pill, capsule, soft capsule, granule, oral liquid, syrup, Emulsion, mixture; Injection comprises small-volume injection, large injection, injectable powder, Emulsion, suspension.
The present invention contains and is reducing the research of side reaction drug effect difference of anti-schizophrenia medicine to Panaxadiol saponin and saponin triol, confirms that Panaxadiol saponin component (Rb) can improve the cognitive competence of schizophrenia animal pattern and can resist the Nervous toxicity side effect of multiple schizophrenia drug; Protopanaxatriol ginsenoside (Rg), then without the Nervous toxicity side effect alleviating schizophrenia drug and cause, on the contrary, also can offset the toxic and side effects of Panaxadiol saponin antagonism schizophrenia medicine when share with Panaxadiol saponin.This just supports the medical usage of Panaxadiol saponin in treatment schizophrenia.
Detailed description of the invention
The invention will be further described in conjunction with specific embodiments in the present invention.But, the invention is not restricted to these embodiments.
embodiment one prepares Panaxadiol saponin component from rhizome of Radix Ginseng medical material
The Isolation and purification method preparation of embodiment 1 in Panaxadiol saponin component application number 201210242928.1 of the present invention.Radix Ginseng or Radix Panacis Quinquefolii rhizome or base of leaf to be ground into after coarse powder with 50% ethanol water seepage pressure effects to extracting liquid colourless, after merging percolate decompression recycling ethanol, to obtain extractum through lyophilization.Be dissolved in by extractum in 45% ethanol water, sample liquid macroporous adsorbent resin column chromatography is separated, and first reacts without obvious saponin to eluent with 45% ethanol water eluting, then reacts without obvious saponin to eluent with 70% ethanol water eluting.Radix Ginseng total saponins (236.8 grams) will be obtained through lyophilization after 70% ethanol elution decompression recycling ethanol.Radix Ginseng total saponins is dissolved in 50% ethanol water, sample liquid octadecylsilane chemically bonded silica column chromatography for separation, first reacts without obvious saponin to eluent with 50% ethanol water eluting, rear use 75% ethanol water eluting.Divide Fraction collection 75% ethanol elution, detect ginsenoside Rb in each component by HPLC method 1, Rc, Rb 2, Rb 3with the content of Rd, will containing ginsenoside Rb 1, Rc, Rb 2, Rb 3to merge with each component of Rd, after amalgamation liquid decompression recycling ethanol, obtain Panaxadiol saponin component through lyophilization.
embodiment two Panaxadiol saponin component and protopanaxatriol ginsenoside are on the impact of the nervimotion toxicity of haloperidol
1. Panaxadiol saponin resists the nervimotion toxic and side effects that haloperidol causes
By pole-jump test observation Panaxadiol saponin component (Rb) to the reducing effect of the nervimotion toxic action of haloperidol (HAL).
To conform 6-7 days at laboratory, the male ICR adult mice of body weight 30 ± 5g, evenly be divided into haloperidol (2.0mg/kg at random, lumbar injection ip) group, Panaxadiol saponin (is called for short Rb, 40mg/kg, ip) (being called for short Rb40+HAL) group is share with haloperidol (2.0mg/kg), Panaxadiol saponin (is called for short Rb, 60mg/kg, ip) (being called for short Rb60+HAL) group is share and Panaxadiol saponin (is called for short Rb with haloperidol (2.0mg/kg), 80mg/kg, ip) (being called for short Rb40+HAL) group is share with haloperidol (2.0mg/kg), often organize 8 animals.Rb intraperitoneal administration (ip) carries out at haloperidol intraperitoneal administration (ip) front 45min; 45min after 45min and administration before haloperidol administration; use the method for neurotoxicity and cognitive function toxicity test and Grasping clubglass test to observe sports coordination ability and the cognitive function of each treated animal, judge that the nervus motorius toxicity that haloperidol produces and Panaxadiol saponin component are to the protective effect of this toxicity by the reduction of the animal movement coordination ability.
Pole-jump test measures neurovirulent condition: experimental provision is the long wooden stick for 50cm of the wooden base of band, and upper end is the little wooden shot of diameter 3cm, and wooden stick becomes 90 degree with base.Experimental procedure: by experiment mice head upwards vertically extremity be entirely placed in little wooden shot, record mice head rotates to be the head downward time (Tturn) and climbs the time (Ttotal) to ground completely from above, whole experimental period is 90s, if do not complete above action in 90s, is considered as 90s.Before experiment starts, 4 days mices need carry out the training stage to guarantee to complete pole-climbing every day, carry out according to the method described above during formal experiment.
Result of study (table 1) shows, Panaxadiol saponin component can reduce the neurotoxicity of haloperidol.As seen from Table 1, haloperidol lumbar injection (ip, 2mg/kg) have before 45min and administration afterwards significant difference ( aMP.AMp.Amp & &p<0.001), illustrate that model is successfully established; Each group before administration numerical value closely, difference that there are no significant, it is feasible for illustrating that the data after administration compare; Tturn and Ttotal of HAL+Rb60 group and HAL+Rb80 group is starkly lower than HAL group (* * P<0.01).As can be seen here, Rb can reduce HAL nervus motorius toxicity significantly, and Rb60mg/kg is dose,optimum.So all adopt the dosage of 60mg/kg at ensuing experiment Panaxadiol saponin.
protopanaxatriol ginsenoside component, to the reduction unprotect effect of the sports coordination ability that haloperidol is induced, weakens the protective effect of Panaxadiol saponin on the contrary
Whether this example is probed into protopanaxatriol ginsenoside component by pole-jump test and whether is had Attenuation to the nervimotion toxic and side effects that haloperidol causes, and measure protopanaxatriol ginsenoside component and can share with Panaxadiol saponin component.
To conform 6-7 days, the male ICR adult mice of body weight 30 ± 5g at laboratory, evenly be divided into HAL(2.0mg/kg at random, ip) group, HAL+Rb60 (60mg/kg, ip) group, HAL+ protopanaxatriol ginsenoside component (are called for short Rg, 30mg/kg, ip) group, HAL+Rg (60mg/kg, ip) group, HAL+Rb30+Rg30 group, HAL+Rb60+Rg60 group, often organizes 8 animals.Rb and Rg all before HAL administration 45min carry out intraperitoneal injection (ip), and the Behaviors survey (pole-jump test) in use-case one (1) carries out observing (assay method is the same).
As seen from Table 2, giving, piperidine alcohols (HAL) is front, each group mice head rotates to be the downward time (Tturn) and climbs completely to ground time (Ttotal) there was no significant difference from above, and before administration is described, each treated animal is homogeneous; After HAL 45 min, HAL model group mice head rotate to be the downward time (Tturn) from above and the time (Ttotal) of climbing completely to ground be all significantly longer than to before HAL ( aMP.AMp.Amp & &p<0.001), illustrate that HAL causes obvious nervimotion toxic and side effects.Rb group or Rg group compare with HAL group, Tturn and the Ttotal time of HAL+Rb60 group significantly shortens (* * * P<0.001), illustrate that Panaxadiol saponin (Rb) can resist the nervimotion toxicity of piperidine alcohols induction; And HAL+Rg30 group and HAL+Rg60 and HAL group compare, there is the trend of prolongation their Tturn and Ttotal time, protopanaxatriol ginsenoside (Rg) is described to the toxicity of HAL without reducing effect, may aggravates chlorpromazine neurotoxicity on the contrary; HAL+Rb30+Rg30 group and HAL+Rb60+Rg60 group compared with HAL+Rb60 group, their Ttotal and Tturn time equal significant prolongation ( ##p<0.01), illustrate that protopanaxatriol ginsenoside can weaken the nervimotion toxic and side effects that causes of Panaxadiol saponin antagonism piperidine alcohols.It can thus be appreciated that comprise in the neurovirulent medical usage of piperidine alcohols in reduction schizophrenia drug, it is necessary for Panaxadiol saponin component and protopanaxatriol ginsenoside component being carried out being separated.In related experiment afterwards, the present invention mainly measures the effect of Panaxadiol saponin component.
embodiment three
1. the dosage of Panaxadiol saponin component to the nervimotion Attenuation that chlorpromazine causes is groped
First grope by the experiment of the grip of mice the suitable dose that chlorpromazine causes nervimotion toxicity, then by this dosimetry Panaxadiol saponin component on the impact of the nervimotion toxicity that chlorpromazine causes.
To conform 6-7 days, the male ICR adult mice of body weight 30 ± 5g at laboratory, evenly be divided into chlorpromazine 4,6,8 mg/kg(lumbar injection at random, ip) three Concentraton gradient groups, to seek the dosage be applicable to, often organize 3 mices.The device of grip measuring myasthenia toxicity is YLS-13A type large mice grip analyzer.Condition determination: every mice parallel assay 3 times, every minor tick 5min; Date processing: grip reduces grip (g) × 100% before (%)=[ grip (g) after the grip (g) before administration-administration ]/administration, the myasthenia state that grip reduces the rear mice of larger explanation process is more obvious.As shown in Table 3, groping CHL6 group and CHL4 group in experiment at dosage and there is obvious significant difference (* * P<0.01), there is significant difference in CHL8 group and CHL4 group; CHL6 group and CHL8 group there was no significant difference.It can thus be appreciated that CHL is the suitableeest test dose when 6mg/kg.
From table 3, the grip of CHL6 group and CHL8 group reduces obviously than being greater than CHL4 group in this experiment, and there is significant difference (* P<0.05, * P<0.01), the standard deviation of CHL6 treated animal grip reduction is less simultaneously, is more suitable for as model related experiment later.
panaxadiol saponin component is to the Attenuation of the nervimotion toxicity that chlorpromazine causes
Seek Panaxadiol saponin component by the experiment of the grip of mice, to chlorpromazine, whether there is the effect that neurotoxicity reduces.
To conform 6-7 days, the male ICR adult mice of body weight 30 ± 2g at laboratory, random evenly point chlorpromazine 6mg/kg(lumbar injection, ip) group, Rb60+CHL6 group, often organize 8 animals.Rb 45 min before CHL administration carry out intraperitoneal injection, and chlorpromazine (CHL) group gives equal-volume normal saline.Before Rb administration, after 45 min and CHL administrations, 45min measures the forelimb grip of animal respectively, and each group of statistical analysis is to the change before and after CHL.
On example two (1) basis, measure Panaxadiol saponin component (Rb) further to the impact of the nervimotion toxicity that chlorpromazine causes.Experiment grouping comprises chlorpromazine (CHL, 6 mg/kg, ip) group and Rb 60 mg/kg (ip) group, often organizes 8 animals, and Rb 45 min before giving CHL carry out intraperitoneal injection, and CHL group gives isopyknic normal saline.45 min after 45 min and medicine CHL before giving Rb or normal saline, measure animal forelimb grip.
From table 4, CHL6 group is giving the 45 min right fore grips reductions by 42% of CHL 6 mg/kg, and Panaxadiol saponin (Rb60+CHL6) prevention group reduction by 21%, there is the difference (* * P<0.01) of highly significant between two groups, illustrate that Panaxadiol saponin has obvious inhibitory action to the neuromuscular toxicity that chlorpromazine causes.This result of study supports the neurovirulent clinical practice that Panaxadiol saponin reduces schizophrenia drug.
embodiment four Panaxadiol saponin component is to the Attenuation of the nervimotion toxic and side effects that clozapine is induced
Measure as index Panaxadiol saponin to cause nervimotion toxicity abated effect to clozapine by the stiff experiment of mouse muscle.
To conform 6-7 days, the male ICR adult mice of body weight 30 ± 5g at laboratory, evenly be divided into clozapine (CLO 20,30mg/kg at random, ig) two groups and Panaxadiol saponin associating clozapine (Rb60+CLO20, Rb40+CLO30) individual group, often organize 8 animals by totally 6 groups.In drug combination group, Rb is prior to clozapine 45min administration, and CLO various dose treated animal gives equal-volume normal saline, and muscular rigidity is tested 30min before Rb administration and after clozapine administration and measured.
Muscular rigidity experimental provision: be fixed on horizontal plane, high 50 millimeters, the wood chip of wide 3 millimeters.Experiment condition and method: mice forelimb is positioned over wood chip upper end, record mice forelimb keeps the stiff time, and experimental period is 30s, if be greater than 30s, is considered as 30s.Dead time (T1, S) before dead time (T2, S) after stiff time (S)=administration 30min-experiment, difference larger explanation stiffness is more serious, and namely the nervus motorius toxicity of clozapine is stronger.
From table 5 experimental result, to clozapine (CLO 20 or 30, mg/kg) 30 min afterwards, the dead time significant prolongation of animal ( aMP.AMp.Amp & &p<0.001), illustrate that CLO causes the toxic and side effects of muscular rigidity; CLO20+Rb60 group and CLO30+Rb60 group compared with respective CLO matched group, its dead time all significantly reduces ( *p<0.05).Illustrate thus, Panaxadiol saponin when dosage is 60mg/kg to dosage be 20, the nervus motorius toxicity of the clozapine of 30mg/kg has obvious inhibitory action, this just supports.
embodiment five Panaxadiol saponin is to the improvement result of the cognitive dysfunction of mice schizophrenia model
This experiment is by the improvement result of nouveaut identification measuring Panaxadiol saponin component to cognitive dysfunction in mice schizophrenia model.
To conform 6-7 days, the male ICR adult mice of body weight 30 ± 5g at laboratory, use biphenyl Horizon (MK 801) within continuous 6 days, to carry out intraperitoneal administration to cause schizophrenia model.After last administration, for eliminating the experimental error that in body, remaining MK801 causes, carry out the eluting phase of three days.Through eluting after date, carry out open field experiment (open field) and be evenly divided into Normal group, MK801 model, Rb40 (40 mg/kg), Rb60 (60 mg/kg) with its result, arranging according to group and carry out administration 7 days; Set Normal group simultaneously.After last administration 1h, carry out nouveaut experiment.
Open field test principle: spacious field experiment (open field test), also known as Open field test, is a kind of method of evaluation experimental animal inner directed behavior, exploratory behavior and tensity in strange environment.With the occurrence frequency of laboratory animal some behavior among novel environment and persistent period etc. for index, the inner directed behavior of reaction experiment animal in foreign environment and exploratory behavior.Device: self-control specification be 150*150*40 without bottom surface box, ground can be replaced by ground, draws the square 25(5*5 of 10*10 on the ground) individual.Condition and parameter: room temperature; Artificial lighting; Total move distance.Before step: a, experiment, mice removes to experimental room by 1h, to adapt to spacious field experimental provision in surrounding b, toy behavior analysis system from upper left, 25 identical little lattice are numbered with different colours by left-to-right order, wherein 7,8,9,12,13,14 and 19 is middle section, all the other are periphery lattice, No. 13 lattice put into center lattice for pinching mousetail when center lattice are tested at every turn, observe its active situation, each mensuration terminates animal excrements to remove totally, and with 70% alcohol wipe device, every only measures 1 time, each 5min.
The box of the square of nouveaut experimental provision: 50*50*50; Condition and parameter: carry out under room temperature condition; To touch or nose touches time (Tn) of new object going to smell near new object 1 centimeters nose, be similarly recorded in the reference material place time (Tf).Step: a, carrying out testing or train front 24h, animal to be placed in the room of test, adaptive testing environment.B, experiment are divided into two stages, the interval 1h in two stages.First stage is adaptive phase, places two identical objects, by the midpoint of two objects in mice embedding device, make it adapt to 3min in device; Second stage is experimental stage, one of them object is changed into the object not identical with it and repeats above step.Formula: ratio=(Tn-Tf)/(Tn+Tf) contacting the new object time.
Result of study (table 6) shows, the new object time scale of contact of MK801 model group be starkly lower than Normal group ( aMP.AMp.Ampp<0.05), show that MK801 model group reduces the interest of new things, instruction modeling success; The new object time scale of contact of Rb40 group and Rb60 group apparently higher than MK801 model group ( *p<0.05, * * P<0.01), and respectively close to and higher than Normal group.As can be seen here, Rb has significant improvement result to the cognitive dysfunction that schizophrenia model causes, and can return to normal level and be even better than normal level.This just supports the clinical application that Panaxadiol saponin can improve the cognitive disorder of schizophrenic further.

Claims (4)

1. the application of Panaxadiol saponin active component in preparation antipsychotic drug, described Panaxadiol saponin component mainly comprises ginsenoside Rb 1, Rb 2, Rb 3, Rc and Rd five kinds of Panaxadiol saponin, their structural formula is:
It is characterized in that, the excipient that described medicine is allowed by Panaxadiol saponin component and preparation or carrier are made.
2. the application of Panaxadiol saponin active component according to claim 1 in preparation antipsychotic drug, it is characterized in that, described medicine by Panaxadiol saponin component and other treat schizophrenia drug or with other reactive compound, the excipient allowed with preparation or carrier are made, other treatment schizophrenia drug described selects chlorpromazine, haloperidol or clozapine, and other reactive compound described selects active Chinese drug component material, natural product, artificial-synthetic compound and activity in vivo material.
3. application according to claim 1 and 2, is characterized in that, the dosage form of described medicine is liquid preparation, solid preparation.
4. application according to claim 1 and 2, is characterized in that, the administering mode of described medicine is oral administration or drug administration by injection or through mouth and nose spray delivery.
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CN107441104A (en) * 2017-08-24 2017-12-08 浙江大学 PDS Rb components prevent and treat the medical usage of diabetic complication and metabolic disorder relevant disease
CN116019819A (en) * 2022-12-20 2023-04-28 浙江大学 Active ginsenoside composition and preparation method and application thereof

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