CN104622930A - Application of babao (Chinese character) pill in treatment of senile dementia and pharmaceutical composition of babao pill - Google Patents
Application of babao (Chinese character) pill in treatment of senile dementia and pharmaceutical composition of babao pill Download PDFInfo
- Publication number
- CN104622930A CN104622930A CN201510018702.7A CN201510018702A CN104622930A CN 104622930 A CN104622930 A CN 104622930A CN 201510018702 A CN201510018702 A CN 201510018702A CN 104622930 A CN104622930 A CN 104622930A
- Authority
- CN
- China
- Prior art keywords
- pill
- treasures
- senile dementia
- pharmaceutical composition
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the field of medicines, relates to a new application of know medicines and a pharmaceutical composition, and in particular relates to application of a babao (Chinese character) pill in preparation of medicines for treatment of senile dementia and a pharmaceutical composition of the babao pill. A pharmacological experiment proves that the babao pill is capable of significantly inhibiting deposition of beta-amyloid protein, can be combined with other medicines with different drug action mechanisms for treatment of senile dementia, is capable of reducing the toxic and side effects of chemotherapeutic drugs and obtaining a collaborative treatment effect, and is accurate in curative effect when being applied to prevention or treatment of senile dementia, and small in side effect, so that the babao pill has a wide medical application prospect.
Description
Technical field
The invention belongs to field of medicaments, relate to a kind of novelty teabag and pharmaceutical composition of known drug, relate to the pill of Eight Treasures treatment purposes of senile dementia and the pharmaceutical composition of pill of Eight Treasures thereof specifically.
Background technology
Senile dementia is the degenerative disease of a kind of central nervous system, and its clinical manifestation is continuous deterioration that is cognitive and memory ability, and activity of daily living Progressive symmetric erythrokeratodermia goes down and occurs various all schizophrenic symptoms and behavior disorder.Along with advancing of disease, patient can lose self care ability gradually, brings white elephant to the individual family of patient and society.Health status shows, and senile dementia is more common in the old people of more than 60 years old, and the old man of current China more than 60 years old about has 1.29 hundred million, accounts for 10.15% of total population.Thus, the prevention and therapy paying attention to senile dementia has very important social meaning and clinical meaning.
The pathogenesis of senile dementia is still indefinite at present, is amyloid beta cascade hypothesis about the pathogenetic main flow theory of senile dementia.This hypothesis thinks that the abnormal degraded of amyloid beta sample precursor (APP) generates excessive aβ protein, and in brain the core of formation of deposits senile plaque, it can activate microglia, cause inflammation reaction, lesion wire plastochondria causes energy metabolism impairment, generate polyoxy freely, and cause the oxidative stress of body to damage, active cell apoptosis pathway.On the other hand, A β can also activated protein kinase, impels Protein tau Abnormal Phosphorylation, and damage cholinergic neuron, causes the pathological changes of central cholinergic system.These pathological changes promote again generation and the abnormal stacking of A β, produce the Cascaded amplification effect of positive feedback, finally cause neuronic minimizing and tramsmitter release extremely.
When the toxic and side effects of chemical synthetic drug seriously annoyings medical circle, people start more to pay close attention to natural drug, in recent years, the control that natural drug is applied to senile dementia have accumulated a large amount of invaluable experiences, uses natural drug treatment senile dementia to mainly contain 2 advantages: (1) acts on Mutiple Targets and can to the adjustment of function of human body through row globality; (2) side effect is little.Therefore, for the treatment of senile dementia, the exploitation of natural drug and utilization have larger advantage and more wide prospect.
Pill of Eight Treasures has eliminating damp-heat, promoting blood circulation and detoxication, the effect of de-etiolation pain relieving.Be applicable to the caused heating of damp-heat accumulation, jaundice, yellowish or reddish urine, nausea and vomiting, indigestion and loss of appetite, hypochondriac pain abdominal distention, yellowish fur or thick greasy extra dry white wine, or urethra scorching hot twinge, lower abdominal distention pain caused by damp invasion of lower energizer, and the symptom such as spreading venereal diseases toxicity hepatitis, acute cholecystitis, the infection of acute urinary system.Have and protect the liver, obviously reduce glutamate pyruvate transaminase; Function of gallbladder promoting, significantly promotes the advantage of bile secretion; Pill of Eight Treasures antiinflammatory action is remarkable, and safety is high, and immunoregulation effect is remarkable, antipyretic, analgesia and sedation remarkable, no side effects, widely used medicine Chinese patent medicine.There are some researches show: pill of Eight Treasures has therapeutical effect in protection memory function and anti-cerebral ischemia, for treatment senile dementia provides a new research direction.
Summary of the invention
In order to overcome the feature that current curing senile dementia medicine effect is indefinite, poisonous side effect of medicine is large, improve cognitive competence and the viability of vast patients of senile dementia, the invention provides a kind of novel curing senile dementia medicine, the present invention relates to a kind of medicinal usage of pill of Eight Treasures, namely pill of Eight Treasures is for the preparation of the purposes in prevention or treatment senile dementia.Determined curative effect when medicine provided by the present invention is used for the treatment of senile dementia or prevents, poisonous side effect of medicine is little, has medical application prospect widely.
An object of the present invention is that open pill of Eight Treasures is for preventing or preparing the application in the medicine for the treatment of senile dementia.Inventor finds through investigative test, and pill of Eight Treasures compound has the effect suppressing amyloid beta deposition significantly.The generation of the gathering of A β and the formation of senile plaque and senile dementia and have very close relationship between being in progress, therefore can predict pill of Eight Treasures in the present invention and can improve the state of an illness of patient for the prevention of senile dementia or treatment or delay playing a positive role of disease.Test examples 9 of the present invention and test examples 10 confirm that pill of Eight Treasures is to A β
25-35caused by caused rat Senlie dementia model and D-galactose, rat Senlie dementia model has well treatment or preventive effect.
Two of the object of the invention is that providing a kind of treats the pharmaceutical composition of senile dementia also containing pill of Eight Treasures.Pill of Eight Treasures of the present invention is to the therapeutical effect of senile dementia mainly because it is to the inhibitory action of the gathering of A β, and it adopts the senile dementia coupling of different therapy mechanism can obtain beyond thought treatment or preventive effect from other.Experiment proves, drug combination not only can strengthen the therapeutic effect of medicine, and can reduce adverse effect and body to the drug resistance of medicine.Based on this, the invention provides a kind of pharmaceutical composition for the treatment of senile dementia, containing pill of Eight Treasures powder and bilobalide in this pharmaceutical composition, the ratio of weight and number of described pill of Eight Treasures powder and bilobalide is (1-50): 1, preferably (6-10): 1.Bilobalide is considered to the natural paf receptor antagonists having potential applicability in clinical practice most at present, and its antagonism is active closely related with chemical constitution.When R3 in lactone structure is hydroxyl or hydroxy number increases, the antagonistic activity of PAF is weakened; And when R2 is hydroxyl and R3 is H, then active significantly enhancing, wherein with ginkalide B, the strongest applicant of behaviour's antagonism that PAF produces is found, when bilobalide and pill of Eight Treasures powder combine the treatment for senile dementia, two kinds of medicines can embody significant synergism (see the embodiment of the present invention 9 and embodiment 10), not only can delay the generation process of senile dementia, more embody significant therapeutic effect, strengthen the reminiscence ability of patient.
As a kind of embodiment for the treatment of senile dementia compositions preferred for this invention, described pharmaceutical composition active component can also contain donepezil further, in described pharmaceutical composition, the ratio of weight and number of pill of Eight Treasures powder and donepezil is (1-50): 1, preferably (30-50): 1.Donepezil is a kind of symptomatic treatment medicine of long-acting senile dementia.Senile dementia is a kind of is main manifestations with hypomnesis, with the acquired hypophrenia of other Cognitive function damagies.Donepezil hydrochloride is second filial generation acetylcholine esterase (ChE) inhibitor, and its therapeutical effect is that the acetyl gallbladder acyl that reversibly acetylcholine esterase inhibition (AchE) causes is hydrolyzed and increases the acetyl choline content of acceptor site.Donepezil may also have other mechanism, comprises the disposal to peptide, neurotransmitter receptor or Ca
2+the direct effect of passage.Donepezil is applicable to gently, moderate senile dementia.Aforementioned pharmaceutical compositions basis adds the therapeutic effect that not only can strengthen pharmaceutical composition with donepezil, embodies significant synergism, more can reduce the probability of happening of senile dementia complication and improve the motion function of patients of senile dementia.
Purposes treatment target of the present invention can be people or animal, and described animal is preferably mammal.In the pharmaceutical composition of the medicinal usage of pill of Eight Treasures of the present invention or the treatment senile dementia containing pill of Eight Treasures, pill of Eight Treasures individually dosedly also can combine other senile dementia administrations, suitable route of administration can be selected according to the state of an illness and pharmaceutical properties when it is for preventing or treating senile dementia, be preferably oral administration, people's dosage, for being 1 mg/kgd-500 mg/kgd, is preferably 10mg/kgd-400 mg/kgd.
Three of the object of the invention openly also can realize the pharmaceutical preparation of said medicine purposes and the drug combination preparation containing pill of Eight Treasures containing pill of Eight Treasures.In above-described medicinal usage, inventor has been prepared into more stable oral formulations by test, as tablet, capsule, and slow releasing capsule, slow releasing tablet, suspensoid.Wherein tablet contains two or more following adjuvant: starch, dextrin, low-substituted hydroxypropyl cellulose, magnesium stearate, microcrystalline Cellulose, hydroxypropyl cellulose, starch slurry lactose, mannitol, micropowder silica gel, cross-linking sodium carboxymethyl cellulose and crospolyvinylpyrrolidone; Described capsule contains two or more following adjuvant: amylum pregelatinisatum, lactose, low-substituted hydroxypropyl cellulose, microcrystalline Cellulose and micropowder silica gel; Described suspensoid contains two or more following adjuvant: zinc sulfate, camphor spirit, sodium carboxymethyl cellulose, glycerol, carbomer; Two or more following adjuvant is contained: microcrystalline Cellulose, lactose, methylcellulose (MC), ethyl cellulose (EC), hydroxyethyl-cellulose (HEC), hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), pregelatinized starch in described slow releasing tablet or slow releasing capsule.Above-mentioned containing in the pharmaceutical preparation of pill of Eight Treasures, the effective dose that each preparation unit contains pill of Eight Treasures is 0.1mg-200mg.
The invention discloses pill of Eight Treasures for the preparation of the purposes in treatment senile dementia and the pharmaceutical composition of senile dementia prevention and cure, it compared with prior art has following outstanding advantage:
1) pill of Eight Treasures can suppress amyloid beta to deposit significantly, determined curative effect when its prevention for senile dementia or treatment, dosage is clear and definite, separately for the treatment of senile dementia or when preventing, significantly can delay the Development process of senile dementia, greatly improve cognitive competence and the quality of life of patient.
2) when pill of Eight Treasures is used for the treatment of senile dementia or prevents, side effect is low, the compliance of patient is high, the chemicals coupling of itself and other treatment senile dementia significantly can reduce the consumption of chemicals, thus reduces the toxic and side effects of chemicals.
3) pill of Eight Treasures and other mechanism of action when senile dementia being played to the drug combination of therapeutical effect, its mechanism of drug action is complementary, itself and bilobalide coupling can play the synergism preventing senile dementia or treat, and above-mentioned coupling basis adds motion function and the therapeutic effect that can improve patients of senile dementia with donepezil.
Detailed description of the invention
The present invention is further illustrated below by way of specific embodiment; but those skilled in the art should know specific embodiments of the invention and not limit the present invention in any way, and any equivalent replacement done on basis of the present invention all falls into protection scope of the present invention.
embodiment 1 compound tablet preparation of the present invention
Preparation technology: the pill of Eight Treasures taking recipe quantity grinds to form fine powder, mixs homogeneously pill of Eight Treasures powder with bilobalide, starch, dextrin and low-substituted hydroxypropyl cellulose.Separately get 60% ethanol of Sq; be incorporated in mixed-powder; soft material processed after mix homogeneously, is granulated by 16 mesh sieves, and less than 60 DEG C dry; after drying completes, use 18 mesh sieve carries out granulate; sift out the fine powder in dry granular, mix with the magnesium stearate of sieving, and then be mixed evenly with dry granule; tabletting, to obtain final product.
embodiment 2 compound tablet preparation of the present invention
Preparation technology: the pill of Eight Treasures taking recipe quantity grinds to form fine powder, mixs homogeneously pill of Eight Treasures powder with bilobalide, starch, dextrin and low-substituted hydroxypropyl cellulose, separately gets 60% ethanol of Sq; be incorporated in mixed-powder; soft material processed after mix homogeneously, is granulated by 16 mesh sieves, and less than 60 DEG C dry; after drying completes, use 18 mesh sieve carries out granulate; sift out the fine powder in dry granular, mix with the magnesium stearate of sieving, and then be mixed evenly with dry granule; tabletting, to obtain final product.
embodiment 3 compound tablet preparation of the present invention
preparation technology: pill of Eight Treasures in prescription is ground to form fine powder, above-mentioned each raw material crossed 100 mesh sieves, takes pill of Eight Treasures powder, after bilobalide, donepezil mix homogeneously with lactose, mannitol, then add the micropowder silica gel of recipe quantity, microcrystalline Cellulose, crospolyvinylpyrrolidone and cross-linking sodium carboxymethyl cellulose respectively, mix homogeneously, add 60% alcoholic solution soft material, 18 mesh sieve granules, wet granular is in 60 DEG C of dryings, 16 mesh sieve granulate, add magnesium stearate mix homogeneously, tabletting, to obtain final product.
embodiment 4 compound capsule preparation of the present invention
Preparation technology: pill of Eight Treasures in prescription is ground to form fine powder by prescription, above-mentioned each raw material is crossed 100 mesh sieves, take pill of Eight Treasures powder, after bilobalide, donepezil mix homogeneously with amylum pregelatinisatum, lactose and low-substituted hydroxypropyl cellulose, add 60% alcoholic solution soft material, 18 mesh sieve granules, in 60 DEG C of dryings, 16 mesh sieve granulate, filling capsule, to obtain final product.
the preparation of embodiment 5 compound recipe suspensoid of the present invention
Preparation technology: the pill of Eight Treasures taking recipe quantity grinds to form fine powder, puts in mortar by pill of Eight Treasures powder, bilobalide and donepezil, and glycerol adding grinds to form thin pasty state, zinc sulfate is dissolved in 200ml water, separately sodium carboxymethyl cellulose 200ml water is made rubber cement, under agitation slowly add in mortar, move in measuring device, solution of zinc sulfate is added under stirring, stir evenly, under agitation to camphorate fine wine with thread, adding distil water is to full dose, stir evenly, to obtain final product.
the preparation of embodiment 6 compound slow-release tablet of the present invention
Preparation technology: the pill of Eight Treasures taking recipe quantity grinds to form fine powder, cross 80 mesh sieves after pill of Eight Treasures powder, bilobalide, lactose and carboxylic propyl methocel being pulverized and be placed on mix homogeneously in mortar, add appropriate 80% ethanol and prepare soft material, the wet grain of preparation of sieving, granulate after the 60-70 DEG C of dry granule of dry preparation, adds magnesium stearate tabletting and can obtain pill of Eight Treasures slow releasing tablet.
the preparation of embodiment 7 compound sustained release capsules agent of the present invention
Preparation technology: take recipe quantity pill of Eight Treasures and grind to form fine powder, pill of Eight Treasures powder, donepezil and bilobalide and adjuvant were pulverized after 80 mesh sieves respectively and mixed homogeneously, add 50% appropriate amount of ethanol and make soft material, the suitable fine strip shape of diameter is extruded into through extruding sieve plate (aperture 0.8mm), then make strip-shaped materials enter spheronizator and make it completely round as a ball, take out micropill, about 3h is dried in 60 DEG C, moisture is made to control 2% ~ 3%, get 18 ~ 24 object micropills, measure the content of micropill, determine the loading amount of capsule, carry out capsule charge with filling machine.
the preparation of embodiment 8 compound sustained release capsules agent of the present invention
Preparation technology: take recipe quantity pill of Eight Treasures and grind to form fine powder, pill of Eight Treasures powder, donepezil and bilobalide and adjuvant were pulverized after 80 mesh sieves respectively and mixed homogeneously, add 50% appropriate amount of ethanol and make soft material, the suitable fine strip shape of diameter is extruded into through extruding sieve plate (aperture 0.8mm), then make strip-shaped materials enter spheronizator and make it completely round as a ball, take out micropill, dry about 3h in 60 DEG C, make moisture control 2% ~ 3%, get 20 ~ 24 object micropills.Measure the content of micropill, determine the loading amount of capsule, carry out capsule charge with filling machine.
embodiment 9 pill of Eight Treasures pair of the present inventiona β
25-35 the therapeutical effect of caused rat Senlie dementia model
That also do not find senile dementia uniqueness at present, generally acknowledged, desirable animal model.Existing senile dementia animal model has 2 classes: damaging animal model and transgenic animal model.Damaging animal model mainly comprises physics, chemistry, Organic substance damage and autoimmune lesions model.Transgenic animal model mainly refers to the single transgene of the related genes such as the precursor sample albumen (APP) relevant with senile dementia, apolipoprotein (Apo) E4, Presenilin 1 (PSI), Presenilin 2 (psII) or many transgenic animal models.Transgenic models is the focus of research at present, but modeling process is complicated, and somewhat expensive, go down to posterity deficient in stability.One of neuropathological feature that patients of senile dementia is main is senile plaque (sP) deposition, and A β is the main component in senile plaque.All oneself confirms the neurotoxic effect of A β to the inside and outside test of body, neuronal damage and cognitive function decline can be caused, the key factor of senile dementia formation and development, and the multiple pathological changes such as the senile dementia rat model that hippocampal injection A sets up observes neuronal damage, A β deposits, the Abnormal Phosphorylation (i.e. neurofibrillary tangles) of Protein tau.
1 materials and methods
1.1 experiment material
Laboratory animal is male SD rat, 9 ~ 11 weeks ages of Mus, and body weight 260-310 g, is provided by The 2nd Army Medical College Experimental Animal Center.A β
25-35purchased from American Sigma company, Morris water maze is purchased from Shanghai Ji Liang company.
The foundation of 1.2 rat Senlie dementia models and evaluation
1.2.1 intracerebral ventricle injection A β
25-35the preparation of solution: by A β
25-35be dissolved in physiological saline solution, make A β concentration be 10 mmol/L, put and hatch 3 d in 37 DEG C of calorstats and carry out aging.
1.2.2 the making of animal model: raise under standard environment, is divided into 2 groups at random: matched group and model group, often organizes 10.2 groups of there was no significant differences on Mus age and body weight.Animal gives after adaptability feeds 1 week, by rat with 2% pentobarbital sodium intraperitoneal anesthesia (40 ~ 50 mg/kg weight), be fixed on stereo brain orienting instrument, cut off head hair, skin is cut after iodine tincture disinfection, select right side tricorn for injection target area with reference to " rat brain stereotaxic atlas ", in bregma 1.0 mm backward, center line is other opens 1.7 mm places, bore with three edged needle and open skull, expose cerebral dura mater, then use microsyringe with the speed of 15 μm/s from vertical inserting needle 4.0 mm in brain surface, by 10 mmol/L A β
25-35solution 5 μ l slowly injects, and slowly removes pin, sew up the incision after let the acupuncture needle remain at a certain point 2 min.Matched group injects equal-volume physiological saline solution.
1.2.3 Morris water maze behavioristics measures: 2 groups of rats started to carry out the test of Morris water maze respectively at postoperative 10th day.Test program is orientation navigation test: last 5 d, front 2 d are the training adaptation phase, rear 3 d
Record achievement, if rat finds platform in 1 min, records its actual escape latency; If find platform not yet in 1 min, then drawn upper mounting plate by experimenter and stop 20 S, escape latency is recorded as 1 min.
1.2.4 the evaluation of animal model
As can be seen from following table, escape latency matched group from the 1st day of experimental record of model group just obviously extends (P < 0.05 or P < 0.01), and escape latency between model group 3 days and escape latency no significant difference between matched group 3 days, show that the Senlie dementia model adopting the method to set up is reliably accurate, may be used for the evaluating drug effect of curing senile dementia medicine
| Group | First day | Second day | 3rd day |
| Matched group | 19.94±9.92 | 20.06±6.44 | 20.98±5.34 |
| Model group | 40.88±10.04 | 39.94±6.32 | 40.04±7.20 |
2 animal models and grouping administration
According to above-mentioned modeling method modeling, model group, pill of Eight Treasures group, bilobalide group, donepezil group, compound recipe one group, compound recipe two groups are set, and matched group is set, often organize 10, raise under standard environment.Each group of administering mode is as described below:
Matched group: gavage gives the normal saline of same volume;
Model group: gavage gives the normal saline of same volume;
Pill of Eight Treasures group: gavage gives pill of Eight Treasures capsule (the accurate word Z10940006 of traditional Chinese medicines) 50 mg/kg/d that the Xiamen pharmaceutical factory of traditional Chinese medicine produces;
Bilobalide group: gavage gives bilobalide 2.8mg/kg/d;
Donepezil group: gavage gives donepezil 3mg/kg/d;
Compound recipe one group: gavage gives pill of Eight Treasures 50 mg/kg/d+ bilobalide 2.8mg/kg/d;
Compound recipe two groups: gavage gives pill of Eight Treasures 50 mg/kg/d+ bilobalide 2.8mg/kg/d+donepezil 3mg/kg/d;
Above-mentioned administration group is respectively at administration afterwards in 10 days after modeling, within 11st day, be recorded as the 1st day, every day is administered once, observe drinking water for animals and diet situation every day, respectively at administration the 1st day, administration the 5th day, administration the 10th day, administration the 15th day, administration measures the escape latency of rat for 20 days with Morris water maze behavioristics assay method.Rat is put to death after last mensuration completes.Ge Zu treated rats in Morris water maze performance behavioristics measurement result is as shown in the table.
The each administration group of table 1 is to A β
25-35the therapeutic effect of caused rat Senlie dementia model
| Group | 1st day | 5th day | 10th day | 15th day | 20th day |
| Matched group | 21.04±9.98 | 20.02±4.38 | 20.78±5.18 | 20.92±6.18 | 20.00±5.58 |
| Model group | 42.06±9.88 | 42.14±7.00 | 41.08±8.84 | 39.26±6.34 | 40.32±6.88 |
| Pill of Eight Treasures group | 40.16±9.54 | 38.32±7.82 | 35.42±6.24 | 34.12±6.22 | 29.64±6.58* |
| Bilobalide group | 40.68±8.60 | 40.24±8.18 | 36.42±6.36 | 35.14±6.58 | 30.46±5.26* |
| Donepezil group | 41.00±8.36 | 39.04±7.68 | 37.62±6.00 | 36.16±5.42 | 30.72±4.32* |
| Compound recipe one group | 40.08±8.12 | 35.84±3.68 | 32.00±5.02 | 30.22±3.32* | 26.82±2.38* |
| Compound recipe two groups | 40.02±8.62 | 35.18±3.96 | 32.18±3.34 | 27.52±2.38* | 22.58±2.40** |
Compared with model group, * P < 0.05, * * P < 0.01;
As can be seen from Table 1: each administration group escape latency thing significant difference of the 1st day, but along with the prolongation of administration time, the escape latency difference of each administration group rat strengthens, wherein pill of Eight Treasures administration group and the compound recipe group containing pill of Eight Treasures all have positive therapeutical effect, 15th day, compound recipe one group has significant difference with the rat escape latency of compound recipe two groups compared with model group, at the 20th day, pill of Eight Treasures group, bilobalide group, donepezil group all has significant difference with compound recipe group compared with the rat escape latency of model group, wherein the rat escape latency of compound recipe two groups has pole significant difference compared with model group.This shows that pill of Eight Treasures is to A β
25-35the treatment of caused rat Senlie dementia model has remarkable effect, and pill of Eight Treasures does not repel its therapeutical effect with bilobalide and donepezil, and two kinds of medicines exist synergism to senile dementia rat model, strengthen the therapeutic effect to senile dementia.
embodiment 10 pill of Eight Treasures of the present invention is to the therapeutical effect of rat Senlie dementia model caused by D-galactose
1 material
D-galactose is Shanghai reagent two factory product; Pill of Eight Treasures is provided (market is bought) by Xiamen Chinese Medicine Co., Ltd.Keeping away dark auto testing instrument is Chengdu TME Technology Co., Ltd.'s product.
2 experimental techniques
The foundation of 2.1 Senile Dementia Model Rats: getting Kunming is 98 rats, is divided into 7 groups at random, matched group, model group, bilobalide group, donepezil group, compound recipe one group and compound recipe two groups, often organize 14 rats.Except matched group, all the other respectively organize rat every day by 120mg/kg lumbar injection D-galactose, continuously injection 4 weeks.Each treatment group gives following medicine respectively:
Matched group: gavage gives the normal saline of same volume;
Model group: gavage gives the normal saline of same volume;
Pill of Eight Treasures group: gavage gives pill of Eight Treasures 50 mg/kg/d;
Bilobalide group: gavage gives bilobalide 2.8mg/kg/d;
Donepezil group: gavage gives donepezil 3mg/kg/d;
Compound recipe one group: gavage gives pill of Eight Treasures 50 mg/kg/d+ bilobalide 2.8mg/kg/d;
Compound recipe two groups: gavage gives pill of Eight Treasures 50 mg/kg/d+ bilobalide 2.8mg/kg/d+donepezil 3mg/kg/d;
2.2 step-through test behavioristicss are detected
Keep away active box point light and shade two Room of dark auto testing instrument, have a hole between two Room, at the bottom of case, pass to copper grid.Before formal experiment, each group of rat is trained, rat head is carried Fang Renming room, hole. first conform 3min, and lead to 36V electric current then to darkroom copper grid, rat is subject to electric shock and namely runs away to bright room after entering darkroom, and copper grid continue energising 5min, and this is training process.Carry out the test of memory of rat after 24h, record rat enters the time (keeping away dark incubation period) in darkroom for the first time, if enter darkroom not yet in rat 5min.Its incubation period, 300s made by meter.
3 statistical methods
Experimental data represents with ± s, carries out statistical analysis with SPSS11.5 software kit, adopts ANOVA and LSD ' S posthoc test to carry out statistical analysis, indicates significant difference with P<0.05.
4 experimental results
The impact of pill of Eight Treasures on Senile Dementia Model Rats step-through test is as shown in table 2.
Table 2 pill of Eight Treasures keeps away dark preclinical impact (± s) to Senile Dementia Model Rats
| Group | n | Keep away dark incubation period (s) |
| Matched group | 14 | 23.02±5.58 |
| Model group | 14 | 104.18±10.94 ## |
| Pill of Eight Treasures group | 14 | 78.84±9.58* |
| Bilobalide group | 14 | 91.04±12.68 |
| Donepezil group | 14 | 90.26±8.02 |
| Compound recipe one group | 14 | 52.74±8.26* |
| Compound recipe two groups | 14 | 48.08±7.02** |
Compared with normal group,
##p < 0.01; Compared with model group, * P < 0.05, * * P < 0.01;
As can be seen from Table 2, pill of Eight Treasures group, compound recipe one group and compound recipe two groups keep away dark significant prolongation incubation period (P < 0.05) relative to model group rats, prompting pill of Eight Treasures has significant prevention and therapy effect to senile dementia rat model, and its therapeutic effect is better than donepezil group.Be embodied in:
1) rat of pill of Eight Treasures group is kept away and has significant difference compared with model group dark incubation period, compared with positive drug donepezil group, all significantly shortens rat and keeps away dark incubation period, there is significant difference.
2) compound recipe one group is kept away with the rat of compound recipe two groups and is had significant difference compared with model group dark incubation period, and compound recipe group is compared with pill of Eight Treasures list medicine group or compared with positive drug donepezil group, its rat is kept away and all obviously shortens dark incubation period, has significant difference.This shows that pill of Eight Treasures does not repel its therapeutical effect the therapeutical effect of rat Senlie dementia model and bilobalide and donepezil, and three kinds of medicines exist synergism to senile dementia rat model.
Show in the embodiment of the present invention 9 or embodiment 10 that the mechanism that pill of Eight Treasures acts on alzheimer disease is not conflicted with the medicine that other drug acts on senile dementia, it can conbined usage, and can obtain the synergism in treatment.
Claims (9)
1. the purposes of pill of Eight Treasures in preparation prevention or treatment senile dementia.
2. purposes as claimed in claim 1, it is characterized in that, pill of Eight Treasures is oral formulations, and its people is with dosage 1 mg/kgd-500 mg/kgd.
3. purposes as claimed in claim 1, it is characterized in that, pill of Eight Treasures is oral formulations, and its people's dosage is 10mg/kgd-400 mg/kgd.
4. treat a pharmaceutical composition for senile dementia, it is characterized in that, described pharmaceutical composition contains pill of Eight Treasures powder and bilobalide.
5. pharmaceutical composition as claimed in claim 4, it is characterized in that, in described pharmaceutical composition, the ratio of weight and number of pill of Eight Treasures powder and bilobalide is (1-50): 1.
6. pharmaceutical composition as claimed in claim 4, is characterized in that, containing donepezil in described pharmaceutical composition.
7. pharmaceutical composition as claimed in claim 6, it is characterized in that, in described pharmaceutical composition, the ratio of weight and number of pill of Eight Treasures powder and donepezil is (1-50): 1.
8. the pharmaceutical composition as described in as arbitrary in claim 4-7, it is characterized in that, the dosage form of described pharmaceutical composition is oral formulations.
9. pharmaceutical composition as claimed in claim 8, it is characterized in that, described oral formulations makes tablet, capsule, slow releasing capsule, slow releasing tablet or suspensoid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510018702.7A CN104622930A (en) | 2015-01-15 | 2015-01-15 | Application of babao (Chinese character) pill in treatment of senile dementia and pharmaceutical composition of babao pill |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510018702.7A CN104622930A (en) | 2015-01-15 | 2015-01-15 | Application of babao (Chinese character) pill in treatment of senile dementia and pharmaceutical composition of babao pill |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104622930A true CN104622930A (en) | 2015-05-20 |
Family
ID=53202492
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510018702.7A Withdrawn CN104622930A (en) | 2015-01-15 | 2015-01-15 | Application of babao (Chinese character) pill in treatment of senile dementia and pharmaceutical composition of babao pill |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104622930A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105963332A (en) * | 2016-06-29 | 2016-09-28 | 厦门中药厂有限公司 | Application of Babao Dan in preparation of migraine medicine |
| CN108339037A (en) * | 2018-05-23 | 2018-07-31 | 唐水金 | Pill of Eight Treasures treats the purposes of rhinitis and its pharmaceutical composition of pill of Eight Treasures |
| CN110420226A (en) * | 2019-09-18 | 2019-11-08 | 厦门中药厂有限公司 | Pill of Eight Treasures is preparing the purposes in the drug for preventing or treating disease relevant to IL-6 inflammatory factor storm |
| CN110478375A (en) * | 2019-09-18 | 2019-11-22 | 厦门中药厂有限公司 | Pill of Eight Treasures is preparing the purposes in the drug for preventing or treating acute lung injury |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101015592A (en) * | 2007-03-05 | 2007-08-15 | 昆明制药集团股份有限公司 | Compound Chinese medicine preparation of breviscapine |
| CN101062211A (en) * | 2007-06-19 | 2007-10-31 | 翟航荣 | Chinese medicinal preparation for senile dementia |
| CN101357136A (en) * | 2008-09-04 | 2009-02-04 | 广东药学院 | Composition of traditional Chinese medicine effective constituent for preventing and treating diseased associated with cerebral ischemia injury |
| CN101766703A (en) * | 2006-03-27 | 2010-07-07 | 深圳市生物谷科技有限公司 | Medicinal combination containing borneol and musk |
| CN103393753A (en) * | 2013-07-16 | 2013-11-20 | 侯晓峰 | Traditional Chinese medicinal composition for treating cardiovascular and cerebrovascular diseases |
-
2015
- 2015-01-15 CN CN201510018702.7A patent/CN104622930A/en not_active Withdrawn
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766703A (en) * | 2006-03-27 | 2010-07-07 | 深圳市生物谷科技有限公司 | Medicinal combination containing borneol and musk |
| CN101015592A (en) * | 2007-03-05 | 2007-08-15 | 昆明制药集团股份有限公司 | Compound Chinese medicine preparation of breviscapine |
| CN101062211A (en) * | 2007-06-19 | 2007-10-31 | 翟航荣 | Chinese medicinal preparation for senile dementia |
| CN101357136A (en) * | 2008-09-04 | 2009-02-04 | 广东药学院 | Composition of traditional Chinese medicine effective constituent for preventing and treating diseased associated with cerebral ischemia injury |
| CN103393753A (en) * | 2013-07-16 | 2013-11-20 | 侯晓峰 | Traditional Chinese medicinal composition for treating cardiovascular and cerebrovascular diseases |
Non-Patent Citations (2)
| Title |
|---|
| 笪志民 宋钟娟: "治疗老年痴呆药", 《精神神经科药物手册》 * |
| 詹益兴: "银杏内酯", 《绿色精细化工：天然产品制造法》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105963332A (en) * | 2016-06-29 | 2016-09-28 | 厦门中药厂有限公司 | Application of Babao Dan in preparation of migraine medicine |
| CN108339037A (en) * | 2018-05-23 | 2018-07-31 | 唐水金 | Pill of Eight Treasures treats the purposes of rhinitis and its pharmaceutical composition of pill of Eight Treasures |
| CN110420226A (en) * | 2019-09-18 | 2019-11-08 | 厦门中药厂有限公司 | Pill of Eight Treasures is preparing the purposes in the drug for preventing or treating disease relevant to IL-6 inflammatory factor storm |
| CN110478375A (en) * | 2019-09-18 | 2019-11-22 | 厦门中药厂有限公司 | Pill of Eight Treasures is preparing the purposes in the drug for preventing or treating acute lung injury |
| CN110420226B (en) * | 2019-09-18 | 2021-11-09 | 厦门中药厂有限公司 | Application of Babaodan in preparation of medicine for preventing or treating diseases related to IL-6 inflammatory factor storm |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Watt et al. | Chronic Treatment with 50 mg/kg Cannabidiol Improves Cognition and Moderately Reduces Aβ 40 Levels in 12-Month-Old Male AβPP swe/PS1ΔE9 Transgenic Mice | |
| Liu et al. | Silibinin ameliorates STZ-induced impairment of memory and learning by up-regulating insulin signaling pathway and attenuating apoptosis | |
| Yi et al. | Direct pharmacological Akt activation rescues Alzheimer's disease like memory impairments and aberrant synaptic plasticity | |
| CN104622930A (en) | Application of babao (Chinese character) pill in treatment of senile dementia and pharmaceutical composition of babao pill | |
| Huang et al. | The neuroprotective effect of deep brain stimulation at nucleus basalis of Meynert in transgenic mice with Alzheimer's disease | |
| CA2873891C (en) | Pharmaceutical composition for the prophylaxis and treatment of psychological, behavioral and cognitive disorders | |
| Yamamoto et al. | Differential activity of drugs to induce emesis and pica behavior in Suncus murinus (house musk shrew) and rats | |
| Chen et al. | Tacrine (10)-hupyridone prevents post-operative cognitive dysfunction via the activation of BDNF pathway and the inhibition of AChE in aged mice | |
| JP2022511785A (en) | Compositions and Methods for Treating Dementia | |
| CN103690581B (en) | A kind of pharmaceutical composition for the treatment of senile dementia | |
| CN103520147B (en) | Puerarin or the pharmaceutical composition that contains Puerarin have the purposes in the medicine that prevents or treat senile dementia effect in preparation | |
| Tzankova et al. | Cytisine—from ethomedical use to the development as a natural alternative for smoking cessation | |
| CN102727484A (en) | Use of silymarin in preparations of drugs for treatment of Alzheimer's disease | |
| Asalgoo et al. | The effect of saffron aqueous extract and crocin on PTSD rat models: The focus on learning and spatial memory | |
| CN103735761B (en) | A kind of pharmaceutical composition preventing and treating Alzheimer disease and preparation method thereof | |
| CN104116740B (en) | The medical usage of tetrandrine treatment senile dementia and the pharmaceutical composition containing tetrandrine | |
| WO2015060746A1 (en) | Combination for treating and/or preventing manifestations of psychiatric, cognitive, behavioral and neurological disorders in the case of organic diseases of the central nervous system having various origins | |
| Zhang et al. | (m) RVD-hemopressin (α) and (m) VD-hemopressin (α) improve the memory-impairing effect of scopolamine in novel object and object location recognition tasks in mice | |
| CN102813646B (en) | Application of homomangiferin in preparing pharmaceuticals for preventing senile dementia and hypomnesis, homomangiferin pharmaceutical compositions and homomangiferin preparations | |
| CN111494379A (en) | Application of piperine in improving early olfactory disorder of Parkinson's disease | |
| CN107569506A (en) | Ligustrum lucidum Ait, Rhoifolin composition and application thereof | |
| CN1593391A (en) | Application of biphenyl cyclooctene containing substance in the process for preparing Alzheimer disease treating medicine | |
| CN108743593A (en) | A kind of antidepressant and its oral granular formulation and pharmaceutical applications | |
| CN104130232B (en) | The method of purification of a kind of EGCG and the EGCG of acquisition and pharmaceutical composition | |
| KR102527194B1 (en) | Composition for cognitive function improvement, memory improvement, stress relief and anti-anxiety |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20150520 |
|
| WW01 | Invention patent application withdrawn after publication |