CN103520147A - Application of puerarin or medicinal composition containing puerarin in preparation of medicament with effect of preventing or treating senile dementia - Google Patents
Application of puerarin or medicinal composition containing puerarin in preparation of medicament with effect of preventing or treating senile dementia Download PDFInfo
- Publication number
- CN103520147A CN103520147A CN201310311005.1A CN201310311005A CN103520147A CN 103520147 A CN103520147 A CN 103520147A CN 201310311005 A CN201310311005 A CN 201310311005A CN 103520147 A CN103520147 A CN 103520147A
- Authority
- CN
- China
- Prior art keywords
- puerarin
- senile dementia
- group
- triptolide
- galantamine
- 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.)
- Granted
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses application of puerarin or a medicinal composition containing the puerarin in preparation of a medicament with an effect of preventing or treating senile dementia. The puerarin can be singly used as a medicament or can be used together with other senile dementia medicaments with different mechanisms of action when used for treating or preventing the senile dementia of people or mammals, wherein the puerarin not only can reduce side or toxic effects of medicaments but also can achieve an effective of collaborative treatment when used for treating the senile dementia together with a medicinal composition consisting of triptolide, galantamine and borneol. The puerarin can significantly inhibit the deposition of beta-amyloid, and has a definite curative effect and small side effects when used for preventing and treating the senile dementia, so that the puerarin has a wide medical application prospect.
Description
Technical field
The invention belongs to puerarin technical field, the pharmaceutical composition that is specifically related to puerarin or contains puerarin has the purposes in prevention or treatment senile dementia in preparation.
Background technology
Senile dementia, claim again Alzheimer (Alzhimer ' s Disease, AD), it is a kind of central nervous system's degenerative disease, its clinical manifestation is the continuous deterioration of cognitive and memory ability, and carrying out property of activity of daily living goes down and occurs various schizophrenia symptoms and behavior disorder.Along with advancing of disease, patient can lose self care ability gradually, brings white elephant to patient's individual family and society.Prevalence studies show that, the U.S. is 4,500,000 examples at the Alzheimer case load of 2000, every increase of age 5 years old, and Alzheimer patient's percent will rise 2 times, that is to say, and 60 years old crowd's prevalence is 6%, and 85 years old crowd's prevalence is 30%.The old man of China over 60 years old approximately has 1.29 hundred million at present, accounts for 10.15% of total population.Thereby prevention and the treatment of paying attention to senile dementia have very important social meaning and clinical meaning.
The pathogenesis of senile dementia is still indefinite at present, about the pathogenetic main flow theory of senile dementia, is amyloid beta cascade hypothesis.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, reaction causes inflammation, lesion wire plastochondria causes energy metabolism impairment, generate polyoxy freely, caused the oxidative stress infringement of body, 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 cascade enlarge-effect of positive feedback, finally cause neuronic minimizing and mediator to discharge abnormal.
At present the drug main for the treatment of AD will comprise the following aspects: 1. acetylcholinesteraseinhibitors inhibitors, for AD patient's brain Cholinergic Neurons, lose in a large number, acetylcholine mediator famine, use acetylcholinesteraseinhibitors inhibitors, the content that can increase acetylcholine in brain, promotes neuronic recovery.The medicine of this class mainly contains this 2. anti-inflammatory drug such as bright of tacrine, donepezil, profit now, because the surrounding in senile plaque amyloidosis core exists reactive glial cell, therefore someone propose the chronic inflammatory disease theory of AD, and utilize suitable anti-inflammatory drug to reach the object of prevention and treatment.The medicine of this class has aspirin etc.3. irritability glutamate receptor antagonists, Cell protection is avoided the attack of excitatory transmitter cytotoxic effect.The medicine of this class has memantine etc.4. nerve generates the factor, the specific neuron that acts on of its energy, and the plasticity of stimulating neuronal, promotes neuronic growth, survival, safeguards the function of cell.5. other, as estrogenic alternative medicine, the agent of brain cell metabolic activation, the utilization of calcium ion antagonist etc.Although said medicine has shown certain curative effect in clinical practice, in life-time service process, exist serious inevitable side effect.As tacrine has serious hepatotoxicity, need periodic monitoring liver function, therefore tacrine is now seldom for patient.
When the toxic and side effects of chemical synthetic drug is seriously perplexing medical circle, people start more to pay close attention to natural drug, in recent years, the control that natural drug is applied to AD has accumulated a large amount of invaluable experiences, uses natural drug treatment AD to mainly contain 2 advantages: (1) acts on many target spots can the adjusting through row globality to function of human body; (2) side effect is little.Therefore,, for the treatment of AD, the exploitation of natural drug and utilization have larger advantage and more wide prospect.
Puerarin is the effective ingredient in pulse family platymiscium Radix Puerariae.Its chemistry 8-C-β-D-Glucose by name base-7,4-dihydroxy-isoflavone (8-C-β-D-Glucopyranosyl-7,4-hydroxy-isoflavone) acicular crystal that is white in color, can be water-soluble, but dissolubility is little, its aqueous solution is colourless or micro-yellow.Have the immunity of raising, strengthen myocardial contraction, protecting myocardial cell, reduces blood pressure, and has the effects such as antiplatelet aggregation.
From puerarin in 1993, by Ministry of Public Health approval, for clinical, due to it, to have very strong resisting cardiovascular hypoxic-ischemic active, can coronary artery dilator and cerebrovascular, reduction myocardial oxygen consumption, improve myocardium shrinkage function, improve microcirculation and improve the effects such as learning and memory.This medicine is clinical is mainly used in the diseases such as allevating angina pectoris, treatment heart infarction, high blood viscosity, arrhythmia and cerebrovascular.This medicine annual turnover of the whole nation reaches approximately 500,000,000 RMB at present has become one of important treating cardiovascular disease.Total flavones in Radix Puerariae can increase brain and blood flow coronarius.Puerarin has obvious facilitation to the cerebral circulation of animal and human's body and peripheral circulation.Radix Puerariae total flavones improve the cerebrovascular tension force of hypertension and patients with coronary heart disease, elasticity and pollex for because of etc. aspect all have gentle facilitation.Puerarin not only improves the normal brain activity microcirculation of human body, and microcirculation disturbance is also improved significantly, and main manifestations is that the amplitude of local blood capillary blood flow and motion increases.Puerarin is also improved effect to the Microcirculation of Nailfold of patients with sudden sensorineural hearing loss, can accelerate microvascular blood flow velocity, removes blood vessel loop congestion, improves patient's audition.Puerarin has protective effect to hypoxic cardiac muscle, and puerarin can obviously reduce the oxygen consumption of ischemic myocardium, and cardioprotection is avoided the ischemia ultrastructure damage due to port perfusion again.
Patent application 200610046076.3 discloses a kind of pueraria flavonid composition and for the preparation of the application in control cardiovascular and cerebrovascular disease, senile dementia, cerebral infarction, cerebral ischemia and the other diseases that caused by cerebral ischemia thereof, the compositions that these drug regimen species contain Radix Puerariae total flavones and Herba Ixeritis Sonchifoliae total flavones and saponin, or the compositions of pueraria flavonid composition and Fructus Hippophae total flavones, in its pharmaceutical composition, contain multiple not clear composition, do not meet the principle of medication of modern medicine, and in use very easily produce violent untoward reaction.And it does not carry out the test of pesticide effectiveness to the application in the other diseases of preventing and treating cardiovascular and cerebrovascular disease, senile dementia, cerebral infarction, cerebral ischemia and being caused by cerebral ischemia yet, and do not know whether this pueraria flavonid composition has the application described in it, and the effect described in it, being the coefficient effect of each component in pueraria flavonid composition, is not the effect that Radix Puerariae total flavones brings as unique active component.
Summary of the invention
The pharmaceutical composition that the object of the present invention is to provide puerarin or contain puerarin has the purposes in the medicine that prevents or treat senile dementia effect in preparation.This puerarin or the pharmaceutical composition that contains puerarin determined curative effect during for the treatment of senile dementia or prevention, poisonous side effect of medicine is little, has medical application prospect widely.
Above-mentioned purpose of the present invention is achieved by the following technical solution: puerarin or the pharmaceutical composition that contains puerarin have the purposes in the medicine that prevents or treat senile dementia effect in preparation.
Puerarin can be used as medicine for prevention or treatment senile dementia.Present inventor finds through investigative test, puerarin has the effect that suppresses significantly amyloid beta deposition, therefore between the generation of the gathering of A β and the formation of senile plaque and senile dementia and progress, there is very close relationship, can predict puerarin in the present invention and can improve patient's the state of an illness or delay playing a positive role of disease for prevention or the treatment of senile dementia.Drug effect embodiment 11 in the specific embodiment of the invention and drug effect embodiment 12 confirm that puerarin high dose group and puerarin low dose group are to A β
25-35due to rat Senlie dementia model and D-galactose induced mice Senlie dementia model there is good treatment or preventive effect.
For the better effect of the prevention of performance puerarin or treatment senile dementia, the present patent application people has further studied some pharmaceutical compositions that contain puerarin, puerarin of the present invention is mainly due to its inhibitory action to the gathering of A β to the therapeutical effect of senile dementia, and it adopts the machine-processed senile dementia coupling of different treatments can obtain beyond thought treatment or preventive effect from other.The drug combination that experiment showed, in the specific embodiment of the invention not only can strengthen the therapeutic effect of medicine, and can reduce adverse effect and the drug resistance of body to medicine.
Based on this, the invention provides the pharmaceutical composition of a kind of prevention that contains puerarin or treatment senile dementia, in this pharmaceutical composition that contains puerarin, contain puerarin, triptolide and/or Borneolum Syntheticum.
Wherein triptolide (Triptolide, TPL) is one of main active of Radix Tripterygii Wilfordii.Triptolide is one and has multiple bioactive natural product, derives from the root of Chinese herb triperygium wilfordii, and research shows that it has antioxidation, resisting rheumatoid disease, anti-senile dementia, the effect such as anticancer.Applicant finds, when triptolide and puerarin are combined the treatment for senile dementia, two kinds of medicines can embody significant synergism (referring to the embodiment of the present invention 11 and embodiment 12), not only can delay the generation process of senile dementia, more embody significant therapeutic effect, strengthen patient's reminiscence ability.
Wherein Borneolum Syntheticum has the effect of " brain in tying-in ", and it can further improve speed and content that pharmaceutical composition Chinese medicine active component of the present invention sees through blood brain barrier, plays the effect that reduces the drug effect time and strengthen medication effect.
Preferably, in the pharmaceutical composition that contains puerarin triptolide and/or Borneolum Syntheticum, the mass ratio of puerarin and triptolide is 1: 0.1～1, is preferably 1: 0.5.
Preferably, in the pharmaceutical composition that contains puerarin, triptolide and/or Borneolum Syntheticum, the mass ratio of puerarin and Borneolum Syntheticum is 1: 0.1～0.5.
As a modification of the present invention: also contain galantamine in the pharmaceutical composition that contains puerarin of the present invention.Galantamine is at first by the Bulgarian research of Sopharma drugmaker and production, and starting is most separation and Extraction from the bulb of snowdrops, a plurality of countries listing in the whole world at present, and commodity are by name: Nivalin.A little less than its anticholinergic effect, easily see through blood brain barrier, therefore central action is stronger, can be used for the treatment of myasthenia gravis.Prior art confirms that it can be for AD(senile dementia) treatment, be AD treatment drug of first choice clinically at present.On aforementioned pharmaceutical compositions basis, add with galantamine and not only can strengthen the therapeutic effect of pharmaceutical composition, embody significant synergism, more can reduce the probability of happening and the motion function of improving patients of senile dementia of senile dementia complication.
Preferably, in the pharmaceutical composition that contains puerarin of the present invention, the mass ratio of puerarin and galantamine is 1: 0.1～10, be preferably 1: 1～and 5, more preferably 1: 2.
Due to the raising of modern animal welfare and the complexity of diet, the ill disease probability of animal also obviously increases.Purposes treatment target of the present invention can be people or animal, and described animal is preferably mammal.In the medicinal usage of puerarin of the present invention or the pharmaceutical composition that contains puerarin, puerarin can individually dosedly also can be combined other senile dementia administrations, it can select suitable route of administration according to the state of an illness and pharmaceutical properties when preventing or treating senile dementia, be preferably oral administration, people is 0.1mg/kgd ~ 5mg/kgd by dosage, be preferably 0.5mg/kgd ~ 3.5mg/kgd, the dosage of other animals can convert and obtain according to man and animal body surface area, and this is known for those skilled in the art.The present invention is used for the treatment of or prevents the form of administration of senile dementia can be for the present invention's pharmaceutical preparation described above, as tablet, capsule, and slow releasing capsule, slow releasing tablet, suspensoid etc.
In above-described medicinal usage, the present patent application people has preferably been prepared into more stable oral formulations by the test in specific embodiment, as tablet, capsule, and slow releasing capsule, slow releasing tablet, suspensoid etc.Wherein tablet contains two or more following adjuvants: 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 adjuvants: amylum pregelatinisatum, lactose, low-substituted hydroxypropyl cellulose, microcrystalline Cellulose and micropowder silica gel; Described suspensoid contains two or more following adjuvants: zinc sulfate, camphor spirit, sodium carboxymethyl cellulose, glycerol, carbomer; In described slow releasing tablet or slow releasing capsule, contain two or more following adjuvants: microcrystalline Cellulose, lactose, methylcellulose (MC), ethyl cellulose (EC), hydroxyethyl-cellulose (HEC), hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), carboxymethyl cellulose (CMC), pregelatinized starch.In the above-mentioned pharmaceutical preparation that contains puerarin, the effective dose that puerarin is contained in each preparation unit is 0.1mg～200mg.
Compared with prior art, the present invention has following outstanding advantage:
(1) puerarin of the present invention can suppress amyloid beta deposition significantly, determined curative effect when its prevention for senile dementia or treatment, dosage is clear and definite, when the independent treatment for senile dementia or prevention, can significantly delay the Development process of senile dementia, greatly improve patient's cognitive competence and quality of life;
(2) puerarin of the present invention is the active component extracting in natural plants, when its treatment for senile dementia or prevention, side effect is low, patient's compliance is high, the chemicals coupling of itself and other treatment senile dementia can significantly reduce the consumption of chemicals, thereby reduces the toxic and side effects of chemicals.
(3) puerarin of the present invention and other mechanism of action when senile dementia is played to the drug combination of therapeutical effect, its mechanism of drug action is complementary, itself and triptolide coupling can be played the synergism to senile dementia prevention or treatment, on above-mentioned coupling basis, add motion function and the therapeutic effect that can improve patients of senile dementia with galantamine, add onset speed and the therapeutic effect that with Borneolum Syntheticum, can significantly improve medicine.
The specific embodiment
Each raw material adopting in following examples, if no special instructions, is commercially available prod.
embodiment 1 puerarin tablet preparation
Puerarin 0.1g
Starch 25g
Dextrin 35g
Low-substituted hydroxypropyl cellulose 5g
60% appropriate amount of ethanol
Magnesium stearate 1g
Preparation technology: the puerarin, starch, dextrin and the low-substituted hydroxypropyl cellulose mix homogeneously that take recipe quantity.Separately get the 60%(volumn concentration of Sq, lower same) ethanol, being incorporated in mixed-powder, soft material processed after mix homogeneously, granulates by 16 mesh sieves, and 60 ℃ are following dry.After completing after dry, use 18 mesh sieves carry out granulate, sift out the fine powder in dry granular, mix, and then be mixed evenly with dry granule with the magnesium stearate of sieving, and tabletting, obtains.The content that contains puerarin in each preparation unit is 0.1mg～200mg, and medicine people is 0.1mg/kgd ~ 5mg/kgd by dosage.
embodiment 2 puerarin tablet preparations
Puerarin 25g
Microcrystalline Cellulose 180g
Hydroxypropyl cellulose 15g
8%(quality percentage composition) starch slurry is appropriate
Magnesium stearate 1.5g
Preparation technology: the puerarin, microcrystalline Cellulose and the hydroxypropyl cellulose mix homogeneously that take recipe quantity.The 8% starch slurry solution of separately getting Sq, adds in mixed-powder, and soft material processed after mix homogeneously, granulates by 16 mesh sieves, and 60 ℃ following dry.After completing after dry, use 18 mesh sieves carry out granulate, sift out the fine powder in dry granular, mix, and then be mixed evenly with dry granule with the magnesium stearate of sieving, and tabletting, obtains.
The content that contains puerarin in each preparation unit is 0.1mg ~ 200mg, and medicine people is 0.1mg/kgd ~ 5mg/kgd by dosage.
embodiment 3 puerarin tablet preparations
Puerarin 25g
Triptolide 2.5g
Starch 25g
Dextrin 35g
Low-substituted hydroxypropyl cellulose 5g
60% appropriate amount of ethanol
Magnesium stearate 1g
Preparation technology: take recipe quantity, puerarin, triptolide starch, dextrin and low-substituted hydroxypropyl cellulose mix homogeneously.60% ethanol of separately getting Sq, is incorporated in mixed-powder, and soft material processed after mix homogeneously, granulates by 16 mesh sieves, and 60 ℃ following dry.After completing after dry, use 18 mesh sieves carry out granulate, sift out the fine powder in dry granular, mix, and then be mixed evenly with dry granule with the magnesium stearate of sieving, and tabletting, obtains.The content that contains puerarin in each preparation unit is 0.1mg～200mg, and medicine people is 0.1mg/kgd ~ 5mg/kgd by dosage.
embodiment 4 puerarin tablet preparations
Puerarin 100g
Triptolide 50g
Starch 80g
Dextrin 90g
Low-substituted hydroxypropyl cellulose 8g
60% appropriate amount of ethanol
Magnesium stearate 1.5g
Preparation technology: take recipe quantity, puerarin, triptolide starch, dextrin and low-substituted hydroxypropyl cellulose mix homogeneously.60% ethanol of separately getting Sq, is incorporated in mixed-powder, and soft material processed after mix homogeneously, granulates by 16 mesh sieves, and 60 ℃ following dry.After completing after dry, use 18 mesh sieves carry out granulate, sift out the fine powder in dry granular, mix, and then be mixed evenly with dry granule with the magnesium stearate of sieving, and tabletting, obtains.The content that contains puerarin in each preparation unit is 0.1mg～200mg, and medicine people is 0.1mg/kgd ~ 5mg/kgd by dosage.
embodiment 5 puerarin tablet preparations
Puerarin 50g
Triptolide 25g
Galantamine 5g
Lactose 80g
Mannitol 10g
Micropowder silica gel 20g
Microcrystalline Cellulose 100g
Cross-linking sodium carboxymethyl cellulose 25g
Crospolyvinylpyrrolidone 25g
60%(volumn concentration) appropriate amount of ethanol
Magnesium stearate 2g
preparation technology: each adjuvant in prescription is crossed to 100 mesh sieves, after taking puerarin, triptolide, galantamine and mixing homogeneously with lactose, mannitol, the micropowder silica gel, microcrystalline Cellulose, crospolyvinylpyrrolidone and the cross-linking sodium carboxymethyl cellulose that add respectively again recipe quantity, mix homogeneously, adds 60% alcoholic solution soft material processed, 18 mesh sieve granule processed, wet granular in 60 ℃ dry, 16 mesh sieve granulate, add magnesium stearate mix homogeneously, tabletting, obtains.
The content that contains puerarin in each preparation unit is 0.1mg～200mg, and medicine people is 0.1mg/kgd ~ 5mg/kgd by dosage.
embodiment 6 puerarin capsule preparations
Puerarin 25g
Triptolide 25g
Galantamine 25g
Amylum pregelatinisatum 40g
Lactose 30g
Low-substituted hydroxypropyl cellulose 5g
60% appropriate amount of ethanol
Preparation technology: each adjuvant in prescription is crossed to 100 mesh sieves, after taking puerarin, triptolide, galantamine and mixing homogeneously with amylum pregelatinisatum, lactose and low-substituted hydroxypropyl cellulose, add 60% alcoholic solution soft material processed, 18 mesh sieve granule processed, dry in 60 ℃, 16 mesh sieve granulate, filling capsule, obtains.
The content that contains puerarin in each preparation unit is 0.1mg～200mg, and medicine people is 0.1mg/kgd ~ 5mg/kgd by dosage.
the preparation of embodiment 7 puerarin suspensoids
Puerarin 100g
Triptolide 50g
Galantamine 200g
Zinc sulfate 30g
Camphor spirit 250mL
Sodium carboxymethyl cellulose 5g
Glycerol 100mL
Distilled water 1000mL
Preparation technology: the puerarin, triptolide and the galantamine that take recipe quantity are put in mortar, glycerol adding grinds to form thin pasty state, and zinc sulfate is dissolved in 200ml water, separately sodium carboxymethyl cellulose is made to rubber cement with 200ml water, under agitation slowly add in mortar, move in measuring device, under stirring, add solution of zinc sulfate, stir evenly, under agitation with the thread fine wine that camphorates, adding distil water, to full dose, stirs evenly, and obtains.
The content that contains puerarin in each preparation unit is 0.1mg～200mg g, and medicine people is 0.1mg/kgd ~ 5mg/kgd by dosage.
the preparation of embodiment 8 puerarin sustained-release sheets
Puerarin 100g
Borneolum Syntheticum 10g
Carboxylic propyl methocel 30g
Lactose 2.5g
80% appropriate amount of ethanol
Magnesium stearate 0.12g
Preparation technology: rear 80 mesh sieves of crossing of puerarin, lactose and the pulverizing of carboxylic propyl methocel that take respectively recipe quantity are placed on mix homogeneously in mortar, add appropriate 80% ethanol to prepare soft material, the wet grain of the preparation of sieving, granulate after 60 ~ 70 ℃ of dry granules of dry preparation, adds magnesium stearate tabletting can obtain puerarin sustained-release tablet.The content that contains puerarin in each preparation unit is 0.1mg～200mg, and medicine people is 0.1mg/kgd ~ 5mg/kgd by dosage.
the preparation of embodiment 9 puerarin sustained-release capsules
Puerarin 200g
Triptolide 100g
Borneolum Syntheticum 40g
Carboxylic propyl methocel 30g
Ethyl cellulose 6g
50% appropriate amount of ethanol
Microcrystalline Cellulose 4.5g
Preparation technology: took after recipe quantity puerarin was pulverized respectively 80 mesh sieves with adjuvant and mix homogeneously, add 50% appropriate amount of ethanol and make soft material, through extruding sieve plate (aperture 0.8mm), be extruded into the fine strip shape that diameter is suitable, then make strip-shaped materials enter spheronizator and make it completely round as a ball, take out micropill, in 60 ℃ of oven dry 3h left and right, make moisture be controlled at 1%～4%, get 18～24 object micropills.Measure the content of micropill, determine the loading amount of capsule, with filling machine, carry out capsule charge.The content that contains puerarin in each preparation unit is 0.1mg～200mg, and medicine people is 0.1mg/kgd ~ 5mg/kgd by dosage.
the preparation of embodiment 10 puerarin sustained-release capsules
Puerarin 50g
Triptolide 50g
Galantamine 150g
Borneolum Syntheticum 25g
Carboxylic propyl methocel 30g
Ethyl cellulose 6g
50% appropriate amount of ethanol
Microcrystalline Cellulose 4.5g
Preparation technology: took after recipe quantity puerarin was pulverized respectively 80 mesh sieves with adjuvant and mix homogeneously, add 50% appropriate amount of ethanol and make soft material, through extruding sieve plate (aperture 0.8mm), be extruded into the fine strip shape that diameter is suitable, then make strip-shaped materials enter spheronizator and make it completely round as a ball, take out micropill, in 60 ℃ of oven dry 3h left and right, make moisture be controlled at 1%～4%, get 18～24 object micropills.Measure the content of micropill, determine the loading amount of capsule, with filling machine, carry out capsule charge.
The content that contains puerarin in each preparation unit is 0.1mg～200mg, and medicine people is 0.1mg/kgd ~ 5mg/kgd by dosage.
embodiment 11 puerarin pair of the present inventiona β
25-35 due to the therapeutical effect of rat Senlie dementia model
Also do not find at present AD uniqueness, animal model that generally acknowledge, desirable.Existing AD animal model has 2 classes: damaging animal model and transgenic animal model.Damaging animal model mainly comprises physics, chemistry, Organic substance damage and autoimmune damage model.Transgenic animal model mainly refers to single transgene or many transgenic animal models of the related genes such as the precursor sample albumen (APP) relevant with AD, apolipoprotein (Apo) E4, senilism albumen 1 (PSI), senilism albumen 2 (psII).Transgenic models is the focus of studying at present, but modeling process is complicated, somewhat expensive, and deficient in stability goes down to posterity.One of neuropathological feature that AD patient 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, can cause neuronal damage and cognitive function decline, be the key factor of AD formation and development, and the AD rat model that hippocampal injection A sets up is observed the multiple pathological changes such as Abnormal Phosphorylation (being neurofibrillary tangles) of neuronal damage, A β deposition, Protein tau.
1 materials and methods
1.1 experiment material
Laboratory animal is male SD rat, and in 8～12 weeks ages of Mus, body weight 250～300 g ，You The 2nd Army Medical College Experimental Animal Center provide.A β
25-35purchased from U.S. 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, making A β concentration is 10 mmol/L, puts in 37 ℃ of calorstats, to hatch 3 d and carry out aging.
1.2.2 the making of animal model: raise under standard environment, be divided at random 2 groups: matched group and model group, 10 every group.2 groups of there was no significant differences in Mus age and body weight.Animal gives adaptability and feeds after 1 week, by 2% pentobarbital sodium intraperitoneal anesthesia for rat (40～50 mg/kg weight), be fixed on stereo brain orienting instrument, cut off head hair, after iodine tincture disinfection, cut skin, with reference to " rat brain stereotaxic atlas ", select right side tricorn for injection target area, in bregma 1.0 mm backward, the other 1.7 mm places that open of center line, with three edged needle, bore and open skull, expose cerebral dura mater, then use microsyringe with the speed of 15 μ m/s from vertical inserting needle 4.0 mm in brain surface, by 10 mmol/L A β
25-35solution 5 μ l slowly inject, and after let the acupuncture needle remain at a certain point 2 min, slowly remove pin, sew up the incision.Matched group injects equal-volume physiological saline solution.
1.2.3 Morris water maze behavioristics measures: 2 groups of rats are respectively within postoperative the 10th day, starting to carry out the test of Morris water maze.Test program is orientation navigation test: last 5 d, front 2 d are the training adaptation phase, and rear 3 d record achievement, if rat is found platform in 1 min, record its actual escape latency; If do not find yet platform in 1 min, by experimenter, to be drawn upper mounting plate and stopped 20 S, escape latency is recorded as 1 min.
1.2.4 the evaluation of animal model
By following table, can be found out, the escape latency of model group just obviously extends (P < 0.05 or P < 0.01) from the matched group that starts for the 1st day of experimental record, and escape latency no significant difference between escape latency between model group 3 days and matched group 3 days, show that the Senlie dementia model that adopts the method to set up is reliably accurate, can be for the evaluating drug effect of curing senile dementia medicine.
2 animal models and grouping administration
According to above-mentioned modeling method modeling, and matched group, normal group are set, 10 every group, under standard environment, raise.It is as described below that each organizes administering mode:
Normal group: gavage gives the normal saline of same volume;
Matched group: gavage gives the normal saline of same volume;
Model group: gavage gives the normal saline of same volume;
High group of puerarin: gavage gives puerarin 28mg/kg/d;
Low group of puerarin: gavage gives puerarin 0.5 mg/kg/d;
High group of triptolide: gavage gives triptolide 5.6mg/kg/d;
Low group of triptolide: gavage gives triptolide 2.8mg/kg/d;
High group of galantamine: gavage gives galantamine 6mg/kg/d;
Low group of galantamine: gavage gives galantamine 3mg/kg/d;
Borneolum Syntheticum group: gavage gives Borneolum Syntheticum 0.6 mg/kg/d;
One group of compound recipe: gavage gives puerarin 28mg/kg/d and triptolide 5.6mg/kg/d;
Two groups of compound recipes: gavage gives puerarin 28mg/kg/d and triptolide 2.8mg/kg/d;
Three groups of compound recipes: gavage gives puerarin 0.5 mg/kg/d and triptolide 5.6mg/kg/d;
Four groups of compound recipes: gavage gives puerarin 0.5 mg/kg/d and tritolide 2.8mg/kg/d;
Five groups of compound recipes: gavage gives puerarin 0.5 mg/kg/d, triptolide 5.6mg/kg/d and galantamine 6 mg/kg/d;
Six groups of compound recipes: gavage gives puerarin 28mg/kg/d, triptolide 2.8mg/kg/d and galantamine 3mg/kg/d;
Seven groups of compound recipes: gavage gives puerarin 0.5 mg/kg/d, triptolide 2.8mg/kg/d and galantamine 3mg/kg/d;
Eight groups of compound recipes: gavage gives puerarin 28mg/kg/d and Borneolum Syntheticum 0.6mg/kg/d;
Nine groups of compound recipes: gavage gives puerarin 0.5 mg/kg/d, triptolide 2.8mg/kg/d and Borneolum Syntheticum 0.6mg/kg/d;
Ten groups of compound recipes: gavage give puerarin 0.5 mg/kg/d, triptolide 2.8mg/kg/d, galantamine 3mg/kg/d and and Borneolum Syntheticum 0.6mg/kg/d;
Above-mentioned administration group respectively at modeling after administration after 10 days, within the 11st day, be recorded as the 1st day, be administered once every day, 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, the escape latency of rat is measured in administration for 20 days with Morris water maze behavioristics assay method.Measured for the last time rear execution rat.Ge Zu treated rats in Morris water maze performance behavioristics measurement result is as shown in the table.
Each administration group of table 1 is to A β
25-35due to the therapeutic effect of rat Senlie dementia model
| Group | The 1st day | The 5th day | The 10th day | The 15th day | The 20th day |
| Normal group | 10.25±1.24 | 9.54±1.16 | 10.14±0.98 | 10.21±1.26 | 10.31±2.15 |
| Matched group | 20.34±10.31 | 19.57±4.42 | 21.08±5.28 | 20.16±6.24 | 19.95±5.64 |
| Model group | 41.26±10.24 | 42.16±6.97 | 41.25±9.24 | 39.15±6.25 | 40.27±7.15 |
| High group of puerarin | 40.16±9.61 | 38.25±7.85 | 34.47±6.24 | 30.12±5.68 | 27.65±6.58 |
| Low group of puerarin | 40.86±10.13 | 38.64±8.65 | 35.25±6.35 | 31.45±5.64 | 29.64±4.26 |
| High group of triptolide | 40.74±8.59 | 40.16±8.24 | 39.25±6.35 | 39.04±6.58 | 38.64±5.26 |
| Low group of triptolide | 40.85±9.52 | 40.38±8.26 | 40.28±5.28 | 39.89±7.54 | 39.05±4.28 |
| High group of galantamine | 41.06±8.34 | 38.74±7.68 | 37.48±5.98 | 35.16±5.34 | 33.64±4.26 |
| High group of galantamine | 41.16±8.34 | 39.16±7.52 | 38.42±5.63 | 37.65±5.61 | 35.62±4.17 |
| Borneolum Syntheticum group | 40.79±9.24 | 40.49±8.12 | 40.08±5.16 | 39.57±7.94 | 39.05±4.24 |
| One group of compound recipe | 40.28±10.35 | 36.27±4.65 | 33.47±5.34 | 29.54±2.16 | 25.46±4.86 |
| Two groups of compound recipes | 40.23±9.34 | 37.27±4.48 | 32.69±4.84 | 28.64±3.45 | 25.67±3.94 |
| Three groups of compound recipes | 40.15±9.56 | 37.58±4.52 | 33.86±3.24 | 30.12±2.95 | 26.21±3.12 |
| Four groups of compound recipes | 40.26±8.65 | 38.04±4.26 | 34.15±3.45 | 30.25±2.64 | 26.18±3.15 |
| Five groups of compound recipes | 40.05±8.62 | 36.15±3.86 | 32.18±3.26 | 27.58±2.46 | 24.59±3.08 |
| Six groups of compound recipes | 40.12±7.95 | 36.18±3.54 | 32.14±2.97 | 28.12±2.61 | 24.21±2.68 |
| Seven groups of compound recipes | 40.09±8.06 | 35.84±3.67 | 31.58±4.92 | 26.18±3.26 | 23.95±2.38 |
| Eight groups of compound recipes | 40.27±8.35 | 39.27±4.65 | 33.49±5.24 | 29.74±2.66 | 26.46±4.86 |
| Nine groups of compound recipes | 40.22±7.34 | 35.27±4.48 | 29.69±4.84 | 25.64±3.45 | 22.67±3.94 |
| Ten groups of compound recipes | 40.16±8.21 | 35.04±4.21 | 28.62±3.65 | 24.58±2.95 | 20.16±3.04 |
As can be seen from Table 1: each administration group escape latency thing significant difference of the 1st day, but the prolongation along with administration time, the escape latency difference of each administration group rat strengthens, and wherein each administration group of puerarin and the compound recipe group that contains puerarin all have positive therapeutical effect.Be embodied in:
1) the rat escape latency of each treatment group of puerarin is compared and is had significant difference with model group, and no matter low group of the high group of puerarin or puerarin are compared with positive drug galantamine group, all significantly shorten the escape latency of rat, wherein Drug therapy is after 15 days, and the escape latency of its escape latency and positive drug has significant difference.Puerarin is to A β
25-35due to the therapeutic effect of rat Senlie dementia model present dose dependent.
2) the rat escape latency of each treatment group of compound recipe is compared and is had significant difference with model group, and compound recipe group is compared with puerarin list medicine group or is compared with positive drug galantamine group, the escape latency of its rat all obviously shortens, wherein compound medicine treatment is after 15 days, and its escape latency is compared and had significant difference with single therapy group escape latency.This shows that puerarin is to A β
25-35due to therapeutical effect and the galantamine of rat Senlie dementia model its therapeutical effect is not repelled, to senile dementia rat model, there is synergism in two kinds of medicines.
3) each treatment group of compound recipe single medicine group corresponding with it compared and had significant difference, this show puerarin of the present invention can with triptolide or with the combination of triptolide galantamine, or there is significant synergism with the combination of triptolide galantamine Borneolum Syntheticum, wherein the combination of puerarin and triptolide galantamine Borneolum Syntheticum not only significantly strengthens on medication effect, more can improve the motion function of patients of senile dementia, and effect rapidly, accelerates patient's recovery from illness process.
the therapeutical effect of embodiment 12 puerarin of the present invention to D-galactose induced mice Senlie dementia model
1 material
D-galactose is Shanghai reagent two factory's products; The self-control of puerarin You Zhe research department.Keeping away dark auto testing instrument is Chengdu TME Technology Co., Ltd.'s product.
2 experimental techniques
The foundation of 2.1 Senlie dementia model mices: get kunming mouse and be divided at random every group of 12 mices of following drug treatment group.Except matched group, each treatment group mice is pressed 120mg/kg lumbar injection D-galactose every day, injects continuously 4 weeks.Each treatment group gives respectively following medicine:
Normal group: gavage gives the normal saline of same volume;
Model group: gavage gives the normal saline of same volume;
High group of puerarin: gavage gives puerarin 28mg/kg/d;
Low group of puerarin: gavage gives puerarin 0.5 mg/kg/d;
High group of triptolide: gavage gives triptolide 5.6mg/kg/d;
Low group of triptolide: gavage gives triptolide 2.8mg/kg/d;
High group of galantamine: gavage gives galantamine 6mg/kg/d;
Low group of galantamine: gavage gives galantamine 3mg/kg/d;
Borneolum Syntheticum group: gavage gives Borneolum Syntheticum 0.6 mg/kg/d;
One group of compound recipe: gavage gives puerarin 28mg/kg/d and triptolide 5.6mg/kg/d;
Two groups of compound recipes: gavage gives puerarin 28mg/kg/d and triptolide 2.8mg/kg/d;
Three groups of compound recipes: gavage gives puerarin 0.5 mg/kg/d and triptolide 5.6mg/kg/d;
Four groups of compound recipes: gavage gives puerarin 0.5 mg/kg/d and tritolide 2.8mg/kg/d;
Five groups of compound recipes: gavage gives puerarin 0.5 mg/kg/d, triptolide 5.6mg/kg/d and galantamine 6 mg/kg/d;
Six groups of compound recipes: gavage gives puerarin 28mg/kg/d, triptolide 2.8mg/kg/d and galantamine 3mg/kg/d;
Seven groups of compound recipes: gavage gives puerarin 0.5 mg/kg/d, triptolide 2.8mg/kg/d and galantamine 3mg/kg/d;
Eight groups of compound recipes: gavage gives puerarin 28mg/kg/d and Borneolum Syntheticum 0.6mg/kg/d;
Nine groups of compound recipes: gavage gives puerarin 0.5 mg/kg/d, triptolide 2.8mg/kg/d and Borneolum Syntheticum 0.6mg/kg/d;
Ten groups of compound recipes: gavage give puerarin 0.5 mg/kg/d, triptolide 2.8mg/kg/d, galantamine 3mg/kg/d and and Borneolum Syntheticum 0.6mg/kg/d;
2.2 keep away dark experiment behavioristics detects
Keep away between the active box minute light and shade two ，Liang chambers, Room of dark auto testing instrument and have a hole, at the bottom of case, pass to copper grid.Before formal experiment, each group mice is trained, mice head is carried to Fang Renming chamber, hole. the 3min that first conforms, then give darkroom copper grid logical 36V electric current, mice enters and is subject to electric shock behind darkroom and runs away to bright chamber, and copper grid continue energising 5min, and this is training process.After 24h, carry out the test of memory of mice, record the time (keeping away dark incubation period) that mice enters darkroom for the first time, if do not enter yet darkroom in mice 5min.Count its incubation period and make 300s.
3 statistical methods
Experimental data is used<img TranNum="435" file="DEST_PATH_IMAGE003.GIF" he="42" img-content="drawing" img-format="GIF" inline="no" orientation="portrait" wi="20"/>± s represents, with SPSS11.5 software kit, carries out statistical analysis, adopts ANOVA and LSD ' S posthoc test to carry out statistical analysis, with P<0.05, indicates significant difference.
4 experimental results
The impact that puerarin is kept away dark experiment to Senlie dementia model mice is as shown in table 2.
Table 2 puerarin on Senlie dementia model mice keep away dark preclinical impact (
± s)
Compare ##P < 0.01 with normal group; Compare * P < 0.05, * * P < 0.01 with model group;
As can be seen from Table 2, puerarin for treating group is kept away dark significant prolongation incubation period (P < 0.01) with respect to model group mice, prompting puerarin has significant prevention and therapeutic effect to senile dementia mouse model, and its therapeutic effect is better than galantamine group.Be embodied in:
(1) mice of each treatment group of puerarin is kept away dark incubation period and compares and have significant difference with model group, and no matter low group of the high group of puerarin or puerarin are compared with positive drug galantamine group, all significantly shorten mice and keep away dark incubation period, have significant difference.Puerarin presents dose dependent to the therapeutic effect of mice Senlie dementia model.
(2) one group of compound recipe is kept away dark incubation period with the mice of two groups of compound recipes and is compared and have significant difference with model group, and compound recipe group is compared with puerarin list medicine group or is compared with positive drug galantamine group, its mice is kept away and all obviously shortens dark incubation period, has significant difference.This shows that puerarin does not repel its therapeutical effect the therapeutical effect of mice Senlie dementia model and galantamine, and two kinds of medicines exist synergism to senile dementia mouse model.
(3) each treatment group of compound recipe single medicine group corresponding with it compared and had significant difference, this show puerarin of the present invention can with triptolide or with the combination of triptolide galantamine, or there is significant synergism with the combination of triptolide galantamine Borneolum Syntheticum, wherein the combination of puerarin and triptolide galantamine Borneolum Syntheticum not only significantly strengthens on medication effect, more can improve the motion function of patients of senile dementia, and effect rapidly, accelerates patient's recovery from illness process.
In the embodiment of the present invention 11 or embodiment 12, show that the mechanism that puerarin acts on alzheimer disease do not conflict with the medicine that other drug acts on senile dementia, it can combine use, and can obtain the synergism in treatment.
Above-described embodiment is preferably embodiment of the present invention; but embodiments of the present invention are not restricted to the described embodiments; other any do not deviate from change, the modification done under spirit of the present invention and principle, substitutes, combination, simplify; all should be equivalent substitute mode, be included in protection scope of the present invention.
Claims (10)
1. puerarin or the pharmaceutical composition that contains puerarin have the purposes in the medicine of prevention or the effect for the treatment of senile dementia in preparation.
2. purposes according to claim 1, is characterized in that: described in contain puerarin pharmaceutical composition in contain puerarin, triptolide and/or Borneolum Syntheticum.
3. purposes according to claim 2, is characterized in that: the mass ratio of described puerarin and triptolide is 1: 0.1～1.
4. according to the purposes described in claim 2 or 3, it is characterized in that: the mass ratio of described puerarin and Borneolum Syntheticum is 1: 0.1～0.5.
5. according to the purposes described in claim 2 or 3, it is characterized in that: described in contain puerarin pharmaceutical composition in also contain galantamine.
6. purposes according to claim 5, is characterized in that: the mass ratio of described puerarin and galantamine is 1: 0.1～10.
7. purposes according to claim 4, is characterized in that: in described pharmaceutical composition, also contain galantamine.
8. purposes according to claim 7, is characterized in that: the mass ratio of described puerarin and galantamine is 1: 0.1～10.
9. according to the purposes described in claim 1,2,5 or 7, it is characterized in that: the people of described medicine is 0.1mg/kgd ~ 5mg/kgd by dosage.
10. purposes according to claim 9, is characterized in that: described medicine is oral formulations, and in each preparation unit, the content of puerarin is 0.1mg～200mg; Wherein said oral formulations is tablet, slow releasing tablet, capsule, slow releasing capsule or suspensoid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310311005.1A CN103520147B (en) | 2013-07-23 | 2013-07-23 | Puerarin or the pharmaceutical composition that contains Puerarin have the purposes in the medicine that prevents or treat senile dementia effect in preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310311005.1A CN103520147B (en) | 2013-07-23 | 2013-07-23 | Puerarin or the pharmaceutical composition that contains Puerarin have the purposes in the medicine that prevents or treat senile dementia effect in preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103520147A true CN103520147A (en) | 2014-01-22 |
| CN103520147B CN103520147B (en) | 2016-05-11 |
Family
ID=49922738
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310311005.1A Active CN103520147B (en) | 2013-07-23 | 2013-07-23 | Puerarin or the pharmaceutical composition that contains Puerarin have the purposes in the medicine that prevents or treat senile dementia effect in preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103520147B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104248750A (en) * | 2014-09-25 | 2014-12-31 | 中山大学 | Usage of FWW tripeptide in preparation of drug for treating Alzheimer's disease |
| CN104305192A (en) * | 2014-10-23 | 2015-01-28 | 贡岳松 | Functional food for improving memory of Alzheimer's Disease patient and preparation method of functional food |
| CN114470038A (en) * | 2022-03-28 | 2022-05-13 | 北京诺迪博尔医药科技有限公司 | Composition for treating Alzheimer disease-senile cognitive disorder |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1321500A (en) * | 2001-04-23 | 2001-11-14 | 王维林 | Method for preventing and curing diseases by using kakonein preparation |
-
2013
- 2013-07-23 CN CN201310311005.1A patent/CN103520147B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1321500A (en) * | 2001-04-23 | 2001-11-14 | 王维林 | Method for preventing and curing diseases by using kakonein preparation |
Non-Patent Citations (3)
| Title |
|---|
| 李海 等: "葛根素对阿尔茨海默病模型大鼠疗效的观察", 《郑州大学学报(医学版)》 * |
| 雷德亮 等: "雷公藤甲素对APP/PS1双转基因AD模型小鼠海马内Aβ沉积和老年斑形成的影响", 《第五届全国雷公藤学术会议论文汇编》 * |
| 马宏达 等: "中药活性成分治疗阿尔茨海默病的研究进展", 《药学服务与研究》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104248750A (en) * | 2014-09-25 | 2014-12-31 | 中山大学 | Usage of FWW tripeptide in preparation of drug for treating Alzheimer's disease |
| CN104248750B (en) * | 2014-09-25 | 2016-01-20 | 中山大学 | The purposes of FWW tripeptides in preparation treatment Alzheimer disease drug |
| CN104305192A (en) * | 2014-10-23 | 2015-01-28 | 贡岳松 | Functional food for improving memory of Alzheimer's Disease patient and preparation method of functional food |
| CN104305192B (en) * | 2014-10-23 | 2016-05-04 | 贡岳松 | Improve functional food of patients of senile dementia memory and preparation method thereof |
| CN114470038A (en) * | 2022-03-28 | 2022-05-13 | 北京诺迪博尔医药科技有限公司 | Composition for treating Alzheimer disease-senile cognitive disorder |
| CN114470038B (en) * | 2022-03-28 | 2023-10-24 | 北京诺迪博尔医药科技有限公司 | Composition for treating Alzheimer's disease-senile cognitive dysfunction |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103520147B (en) | 2016-05-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101342259B (en) | Method for extracting alkaloid valid parts from hooked uncaria leaf, with hook stem branch or full grass and uses thereof | |
| CN104768540A (en) | Anticholinergic neuroprotective composition and methods | |
| CA2873891C (en) | Pharmaceutical composition for the prophylaxis and treatment of psychological, behavioral and cognitive disorders | |
| 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 | |
| CN104622930A (en) | Application of babao (Chinese character) pill in treatment of senile dementia and pharmaceutical composition of babao pill | |
| CN104225167B (en) | Purposes of the LIUWEI DIHUANG TANG extract in treatment dementia or cognition dysfunction | |
| CN103690581B (en) | A kind of pharmaceutical composition for the treatment of senile dementia | |
| CN102727484A (en) | Use of silymarin in preparations of drugs for treatment of Alzheimer's disease | |
| Moushome et al. | Phytochemical screening and antinociceptive and antidiarrheal activities of hydromethanol and petroleum benzene extract of Microcos paniculata barks | |
| CN101317867B (en) | Application of standard extract of pseudo-ginseng in preparing medicament for preventing and controlling senile dementia | |
| CN103156876A (en) | Medicine composition for treating central nervous system diseases and preparation method and application 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 | |
| CN108743593B (en) | A kind of antidepressant and its oral granular formulation and pharmaceutical applications | |
| CN103860532B (en) | Compound medicine compounds of memantine and metformin and preparation method thereof | |
| CN105832872A (en) | Pharmaceutical composition for treating depression and application of pharmaceutical composition for treating depression | |
| CN107569506A (en) | Ligustrum lucidum Ait, Rhoifolin composition and application thereof | |
| CN107536841A (en) | Ligustrum lucidum Ait, Rhoifolin, Hyperoside composition and application thereof | |
| CN107441105B (en) | Application of panaxadiol saponin Rb component in preparing medicine for preventing and treating pain | |
| CN1593391A (en) | Application of biphenyl cyclooctene containing substance in the process for preparing Alzheimer disease treating medicine | |
| CN102813646A (en) | Application of homomangiferin in preparing pharmaceuticals for preventing senile dementia and hypomnesis, homomangiferin pharmaceutical compositions and homomangiferin preparations | |
| CN107281203A (en) | Application of the Horse chest Nut P.E in preventing and treating medicine for senile dementia is prepared | |
| CN104324359A (en) | Application of RRY tripeptide in preparation of drug for treating Alzheimer's disease | |
| CN105832737B (en) | A kind of pharmaceutical composition and its application comprising vilazodone | |
| CN104248750B (en) | The purposes of FWW tripeptides in preparation treatment Alzheimer disease drug |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |