CN1275620C - Medicine for treating senile dementia - Google Patents

Abstract

The present invention relates to a medicine for treating senile dementia, particularly to a Chinese patent medicine for treating senile dementia. At present, effective medicines and preventing and treating methods are lacked at home and abroad for treating senile dementia. Medicines for treating senile dementia on clinic, such as cholinesterase inhibitor-donepezil, calcium ion antagonist-nimodipine, aniracetam, etc., cause patients to suffer from nausea, vomit and bradycardia, have serious toxicity on the liver and kidney, etc.; thereby, the applications of the medicines are greatly limited. The medicine is prepared from traditional Chinese medicine according to the following weight proportioning: 10 to 70 portions of manyprickle acanthopanax root, 10 to 60 portions of epimedium herb, 10 to 40 portions of red peony root and 1 to 10 portions of borneol. The medicine is used for treating senile dementia comprising Alzheimer disease (AD), vascular dementia, mixed dementia with coexistence of the Alzheimer disease and the vascular dementia, and for senile dementia patients who clinically have the symptoms of dementia, foolishness, stupidity, etc.

Description

The medicine of treatment alzheimer disease

Technical field: the present invention relates to a kind of old light dull-witted Chinese patent medicine for the treatment of.

Background technology: the Combination dementia that senile dementia can be divided into Alzheimer (Alzheimers disease) AD and vascular dementia and the two and deposit.Show as symptoms such as slow-witted, stupid, stupid, stupid clinically.

Epidemiological study shows that the annual male of the sickness rate of senile dementia is 30.5% in the world at present, and the women is 48.2%, the height of visible sickness rate.Senile dementia seriously affects whole world old people's health, and especially China just will step into aged society, and the trend that increases is year by year also arranged in recent years.

At present, both at home and abroad the treatment of senile dementia is still lacked effectively medicine and prevents and treats method.The piperazine of the medicine of treatment primary disease commonly used clinically such as cholinesterase inhibitor-how how is strange, calcium ion antagonist-nimodipine and aniracetam etc., but has nauseating, vomiting, bradycardia and untoward reaction such as serious liver, nephrotoxicity limit its application greatly because of said medicine.

Summary of the invention: the purpose of this invention is to provide a kind of kidney and spleen invigorating is arranged, reduce phlegm invigorate blood circulation, the medicine of consciousness-restoring and orifice-opening, reach the purpose of treatment senile dementia by the kidney invigorating, beneficial marrow, promoting blood circulation.

Above-mentioned purpose realizes by following technical scheme:

The medicine of treatment alzheimer disease, it is the medicament of being made by the Chinese medicine of following weight proportioning:

Radix Et Caulis Acanthopanacis Senticosi 10～70 Herba Epimedii 10～60

Radix Paeoniae Rubra 10～40 Borneolum Syntheticums 1～10.

The medicine of above-mentioned treatment senile dementia, wherein the weight proportion of each raw material is:

Radix Et Caulis Acanthopanacis Senticosi 40 Herba Epimedii 35 Radix Paeoniae Rubra 24 Borneolum Syntheticums 1.

This technical scheme has following beneficial effect:

1. solution of the present invention is based on the Therapeutic Principle of motherland's medical science to senile dementia, achievement with reference to modern pharmacology research, filtered out from the medical treasure-house of motherland that vital energy benefiting and the kidney invigorating, refreshment are sensible, Chinese medicine such as invigorate blood circulation reduces phlegm, by the theory of Chinese medical science prescription, method according to modern galenic pharmacy, extract its elite, make its performance improve the function of cholinergic nerve of centrum system, promote the synthetic of the interior neurotrophic factor of body, prevent neuronal apoptosis, improve neuron antioxidative ability and alleviate and treat alzheimer disease. In this product, be equipped with Radix Et Caulis Acanthopanacis Senticosi and can obviously promote ARA, RNA in the cerebral tissue and proteinic synthetic, improve the learning and memory ability; In compatibility, added Herba Epimedii and can promote the growth promoter of brain cell have tangible potentiation can reach the effect of dementia by the NGF receptor agonism to nerve growth factor (NGF) receptor; Be equipped with scheme after the Radix Paeoniae Rubra according to the proportioning that provides, obvious microcirculation, expansion of cerebral vascular strengthens blood flow in the brain, can reduce normal mouse and the dementia mice diving tower errors number in reacting, and mice and learning and memory function are had tangible potentiation.

2. the present invention proves nontoxic, safety through zoopery, and senile dementia is had certain therapeutical effect.

(1). animal acute toxicity test: give mouse stomach 1 time with Cmax, the maximum gastric capacity of irritating of mice, fail to try to achieve the LD of mice ₅₀With Cmax, the administration of the maximum filling of mice gastric capacity 3 times, each 8 hours at interval, the maximum tolerated dose that records mice was 36.99g/kg, is equivalent to 1027.50 times of clinical consumption per day approximately.The consumption per day that shows medicine of the present invention thus is safe.

(2). long term toxicity test: with 1g/kg, 2g/kg, 4g/kg (be equivalent to approximately clinical consumption per day 27.8,55.5,111.1 times), give the administration of Wistar rat oral gavage respectively, every day 1 time, continuous 60 days, do not find tangible toxic reaction.The result shows: the general state of animal, behavioral activity and diet situation and matched group no significant difference.The equal no significant difference of hematology, histopathology, liver function and organ index and matched group.It is safe and reliable that prompting is taken for a long time.

(3). to influence: get Male Kunming strain mice, be divided into 6 groups at random by the mouse memory obstacle due to the scopolamine (Scoloplamine).1,2 groups gavage distilled water 0.2ml/10g, 3～5 groups gavage medicine of the present invention (0.4g/kg, 0.2g/kg, 0.1g/kg) respectively, the 6th group gavages piracetam 0.1g/kg, every day 1 time, successive administration 7d, behind last administration 1h, 1 group of ip normal saline 0.1ml/10g, 2～6 groups give scopolamine hydrobromide 3mg/kg, carry out the diving tower training behind the 10mim, test behind the 24h, the results are shown in Table 1.

Table 1

Group	Dosage (g/kg)		Example number (only)	The mistake number (X ± S)	The P value
						Medicine	Scopolamine
	Normal control group model group piracetam investigational agent	- - 0.1 2.0 1.0 0.3						- 0.003 0.003 0.003 0.003 0.003	10 10 10 10 10 10	0.50±0.53 4.00±1.71 2.00±0.63 1.50±0.71 1.45±0.93 3.45±2.73	＜0.001 ＜0.01 ＜0.001 ＜0.001

The result shows: scopolamine hydrobromide group mice test period errors number significantly increases than normal group, and trial drug and piracetam group have significantly reduced mice test period errors number, has resisted the mouse memory obstacle due to the hydrobromic acid Rhizoma Scopoliae Japonicae.

(4). to the influence of the rat Memorability obstacle due to the scopolamine:

The Wistar rat is divided into 6 groups at random: (1) normal control group, (2) model fine horse, (3) positive drug nimodipine group, (4)～(6) be medicine 0.25g/kg of the present invention, 0.5g/kg, 1.0/kg, successive administration 8d, administration 7d (2～6) gives scopolamine 1mg/kg, 1 group of normal saline that is waited capacity.After 30 minutes, adopt the passive avoidance reflectometer to keep away dark test training, measure rat enters the darkroom from bright chamber incubation period behind the 24h.The results are shown in Table 2.

Table 2 pair scopolamine brings out the amnemonic influence of rat

Group	Dosage (g/kg)	Example number (only)	Keep away dark incubation period (X ± S)	The P value
					Normal control group model group nimodipine investigational agent investigational agent investigational agent	- - 0.015 0.25 0.5 1.0	9 9 9 9 9 9	222.0±132.9 91.9±131.9 120.0±136.7 130.1±155.3 171±129.7 212.4±132.3	＜0.01 ＜0.01

The result shows: medicine of the present invention (1.0g/kg) obviously lengthening model rat is kept away dark incubation period, improves the rat dysmnesia of being brought out by scopolamine.

(5). to the influence of the mouse memory obstacle due to the reserpine

The elder brother plants male mice and be divided into 4 groups at random behind the water maze primary dcreening operation, normal control group, model group, medicine group of the present invention (0.1g/kg, 0.2g/kg), successive administration 14d, 9d begins normal group and gives normal saline, all the other each groups give reserpine 0.001g/kg, carry out water maze training 2 times/day behind the 1h, increase a cecum every day, for three days on end.1h measures rat/mouse labyrinth incubation period, the accuracy of observing response after the administration in the 14th day.The results are shown in Table 3.

Table 3 medicine of the present invention brings out the influence of mouse memory obstacle to reserpine

Group	Dosage (g/kg)	Accuracy (%)	Incubation period (X ± SD, S)	The P value
					The normal control group	-	84.50	46.6±41.1

Model group investigational agent investigational agent

- 0.1 0.2

51.65 84.00 55.60

93.1±36.9 66.1±35.4 76.6±44.8

＜0.05 ＜0.05

By table 3 as seen, medicine matched group of the present invention (0.1g/kg) can significantly shorten the incubation period of the mice water maze that reserpine causes, the reaction accuracy returns to normal level, shows that this gallbladder medicine can obviously improve the mouse memory damage due to the reserpine.

(6). to the influence of mouse brain and whole blood cholinesterase activity

Divide 4 groups at random with Kunming mouse, gavage medicine 0.1g/kg of the present invention, 0.2g/kg and isometric(al) distilled water respectively, every day 1 time, successive administration 7d, after last administration 1h and positive controls are given physostigmine 0.75mg/kg 30mim, win eyeball and get blood and get brain, make 10% homogenate, measure the cholinesterase activity of brain and whole blood.The results are shown in Table 4.

Table 4

Group	Dosage (g/kg)	Example number (only)	Cholinesterase activity		The P value
						Blood Δ	Full brain ΔΔ
			Normal control group model group investigational agent investigational agent	- 0.0075 0.1 0.2				10 10 10 10	34.865±6.557 26.617±6.133 24.210±6.747 27.912±5.910	232.89±29.81 162.60±33.15 198.44±33.44 205.27±27.57	＜0.001 ＜0.01 ＜0.05

Annotate: ^ΔHydrolyze Ach μ M.g ^-1Blood

^ΔΔHydrolyze Ach μM.g ^-1 wet tissue

Medicine of the present invention can significantly suppress the activity of the acetylcholine esterase in whole blood and the brain.

Embodiment 1:

Medicine of the present invention is made (consumption is a weight portion) by following component

Radix Et Caulis Acanthopanacis Senticosi 10,20,30,40,50,60 or 70

Herba Epimedii 10,20,30,40,50 or 60

Radix Paeoniae Rubra 10,20,30 or 40

Borneolum Syntheticum 1,3,5,7 or 10.

Above-mentioned each component is made medicine production method of the present invention is:

1. get Borneolum Syntheticum earlier, it is standby to be ground into fine powder.

2. get three flavor medicines such as Radix Et Caulis Acanthopanacis Senticosi, Herba Epimedii, Radix Paeoniae Rubra, with boiling water extraction, filter, residue discards, and filtrate is concentrated into the clear paste shape.

3. ethanol is joined in 2 in the clear paste, make pure content reach 75%, adding hydrochloric acid, to transfer PH be 5, treats that precipitation fully.

4. inclining supernatant in 3, filter, and filtrate recycling ethanol, it is 1.05～1.08 clear paste that filtrate is concentrated into density, one-step palletizing makes granule.

5. the Borneolum Syntheticum fine powder is joined in the granule, make tablet.It also can be said dosage form on any pharmaceutics.

Embodiment 2:

The optimum weight proportioning of above-mentioned invention medicine is:

Radix Et Caulis Acanthopanacis Senticosi 40 Herba Epimedii 35 Radix Paeoniae Rubra 24 Borneolum Syntheticums 1.

Embodiment 3

Above-mentioned invention medicine claims with raw material (g) by following proportioning

Radix Et Caulis Acanthopanacis Senticosi 800 Herba Epimedii 700 Radix Paeoniae Rubra 500 Borneolum Syntheticums 15.

Production method is as follows: get Borneolum Syntheticum earlier, pulverize standby.Get Radix Et Caulis Acanthopanacis Senticosi, Herba Epimedii, Radix Paeoniae Rubra three flavors then with boiling water extraction, filter, residue discards.Filtrate is concentrated into the clear paste shape, adds a certain amount of ethanol in clear paste, makes the concentration of alcohol reach 75%, adds HCl and transfers PH to be 5, and is static, treat that precipitation fully after, filter.Concentrated filtrate also reclaims ethanol, and it is 1.05～1.08 clear paste that filtrate is concentrated into density, then with clear paste, auxiliary materials and mixing, granulates with one-step-granulating method, adds the Borneolum Syntheticum fine powder, makes tablet.

Oral dose during use is 3 times on the 1st each 3-5 sheets.

The present invention has announced a kind of medicine of new treatment alzheimer disease, it is to be raw material with Radix Et Caulis Acanthopanacis Senticosi, Herba Epimedii, Radix Paeoniae Rubra and Borneolum Syntheticum, according to the different qualities of every flavor Chinese medicine, give processed such as cataclasm, solvent extraction respectively after, preparation in proportion, and make corresponding dosage forms as required.The present invention's uniqueness of filling a prescription, therapeutic effect is remarkable.

Claims (3)

1. medicine for the treatment of alzheimer disease is characterized in that it is the medicament of being made by the Chinese medicine of following weight proportioning:

Radix Et Caulis Acanthopanacis Senticosi 10～70 Herba Epimedii 10～60

Radix Paeoniae Rubra 10～40 Borneolum Syntheticums 1～10.

2. the medicine of treatment senile dementia according to claim 1, wherein the weight proportion of each raw material is:

Radix Et Caulis Acanthopanacis Senticosi 40 Herba Epimedii 35 Radix Paeoniae Rubra 24 Borneolum Syntheticums 1.

3, the medicine of treatment senile dementia according to claim 1 and 2 is characterized in that being that said medicament is a tablet.