CN106727898B

CN106727898B - Pharmaceutical composition for preventing and treating Alzheimer disease and preparation method thereof

Info

Publication number: CN106727898B
Application number: CN201710093641.XA
Authority: CN
Inventors: 阮时宝; 苏志诚; 褚克丹; 徐伟
Original assignee: Individual
Current assignee: Individual
Priority date: 2017-02-21
Filing date: 2017-02-21
Publication date: 2020-07-31
Anticipated expiration: 2037-02-21
Also published as: CN106727898A

Abstract

The invention discloses a pharmaceutical composition for preventing and treating Alzheimer's disease, which is a preparation prepared from the following raw material medicines in parts by weight: 8-12 parts of epimedium, 4.8-7.2 parts of American ginseng, 4.8-7.2 parts of pseudo-ginseng, 2.4-3.6 parts of antrodia camphorata and 2.4-3.6 parts of liquorice. Animal experiments and clinical research results show that the pharmaceutical composition has a remarkable effect of preventing and treating the Alzheimer disease, can effectively improve the cognitive ability of patients, improves the self-care ability of the patients in daily life, and has a wide clinical application prospect.

Description

Pharmaceutical composition for preventing and treating Alzheimer disease and preparation method thereof

Technical Field

The invention relates to a pharmaceutical composition for preventing and treating Alzheimer's disease and a preparation method thereof, belonging to the field of medicines.

Background

Alzheimer's disease is a degenerative disease of the central nervous system that occurs in the elderly characterized primarily by progressive dementia. It was first described in 1907 by the german doctor Alois Alzheimer. Its main clinical manifestations are progressive cognitive dysfunction and memory decline, character and behavior changes, confusion, loss of thinking and judgment, loss of self-care ability of life and ultimately death. This devastating degenerative disease deprives the victim of the most human-characterized qualities of memory, reasoning, abstraction and language. The international society for alzheimer's disease published a famous "debar non-research consensus" on lancets at month 12 2005, which states: 2430 million people all over the world suffer from dementia, and 460 million new dementia cases are generated every year (1 new patient is generated every 7 seconds). The number of patients increases 1 time every 20 years, and the number of global dementia reaches 8110 ten thousand by 2040 years.

The specific pathogenesis of the Alzheimer disease is not completely researched at present, and various hypotheses exist, including cholinergic neuron hypothesis, A β toxicity hypothesis, Tau protein hypothesis, insulin hypothesis, free radical damage hypothesis and the like.

Disclosure of Invention

The invention aims to provide a pharmaceutical composition for preventing and treating Alzheimer disease and a preparation method thereof.

The invention provides a pharmaceutical composition for preventing and treating Alzheimer's disease, which is prepared from the following raw material medicines in parts by weight: 8-12 parts of epimedium, 4.8-7.2 parts of American ginseng, 4.8-7.2 parts of pseudo-ginseng, 2.4-3.6 parts of antrodia camphorata and 2.4-3.6 parts of liquorice.

Further, the traditional Chinese medicine is prepared from the following raw material medicines in parts by weight: 10 parts of epimedium, 6 parts of American ginseng, 6 parts of pseudo-ginseng, 3 parts of antrodia camphorata and 3 parts of liquorice.

Further, the pseudo-ginseng is Sichuan pseudo-ginseng; the licorice is prepared licorice.

Furthermore, the preparation is prepared by mixing crude drug powder of raw drug materials, water or an extract of an organic solvent in weight ratio and adding pharmaceutically acceptable auxiliary materials or auxiliary components.

Further, the preparation is an oral preparation.

Further, the preparation is powder, granules, capsules, tablets, pills, decoction or mixture.

The invention provides a preparation method of the pharmaceutical composition, which comprises the following steps: directly pulverizing the raw materials in weight ratio, or extracting with water or organic solvent, and adding pharmaceutically acceptable adjuvants or auxiliary components.

Further, the preparation method comprises the following steps:

a. preparing an epimedium inclusion compound;

b. weighing powder of Antrodia camphorata, American ginseng and Sichuan pseudo-ginseng, powder of honey-fried licorice root or extractum thereof and an epimedium inclusion compound according to the weight ratio, and adding pharmaceutically acceptable auxiliary materials or auxiliary components to obtain the medicine.

Further, the preparation method of the epimedium inclusion compound comprises the steps of dissolving epimedium extract by using ethanol, dripping the dissolved epimedium extract into β -cyclodextrin saturated aqueous solution, stirring the mixture for 3 hours at the temperature of 60 ℃, stirring the mixture for 1 hour at the temperature of 15-20 ℃, cooling the mixture for 18 hours at the temperature of 0 ℃, carrying out suction filtration and drying, and obtaining the epimedium inclusion compound.

The invention provides application of the pharmaceutical composition in preparing a medicament for treating and/or preventing Alzheimer disease.

The invention provides an application of the pharmaceutical composition and piracetam in preparing a combined medicament for treating and/or preventing Alzheimer disease.

The invention provides application of the pharmaceutical composition in preparing a medicament for enhancing immunity.

The invention provides granules for preventing and treating Alzheimer's disease, which are prepared from the following raw and auxiliary materials in parts by weight: the pharmaceutical composition comprises the following raw material medicines, 16.86 parts of microcrystalline cellulose, 1.686 parts of sodium alginate and 0.1686 parts of magnesium stearate.

The invention provides granules for preventing and treating Alzheimer's disease, which are prepared from the following raw materials and auxiliary materials in parts by weight, wherein the raw materials comprise 21.86 parts of microcrystalline cellulose, 2.186 parts of sodium alginate, 0.2186 parts of magnesium stearate and 8 parts of β -cyclodextrin.

The invention provides a combined medicament for preventing and treating Alzheimer's disease, which contains the pharmaceutical composition and piracetam which are prepared from unit preparations with the same or different specifications and are used for simultaneous or separate administration, and a pharmaceutically acceptable carrier; the pharmaceutical composition comprises the following raw material medicines and piracetam in a weight ratio: (1.5-2): 3.

the invention provides a pharmaceutical composition for preventing and treating Alzheimer's disease, which comprises the following pharmacological bases:

the main active component of the medicine is Icariin (ICA), the ICA can improve the activity of acetylcholinesterase (AChE) and acetylcholinesterase (ChAT) by inhibiting tau protein phosphorylation, and reduce oxidative stress reaction, and the microglial-cortical neuron co-culture technology discovers that the ICA can obviously inhibit the neuron degeneration induced by lipopolysaccharide (L PS), so that the pathological improvement of the Alzheimer disease is realized.

The total saponin (PQS) of the stem and leaf of American ginseng has the function of enhancing the TB lymph function of a human body and can improve the specific immunologic function of the human body. The expression of endothelin-1 (ET-1) can be reduced by inducing the expression of Vascular Endothelial Growth Factor and (VEGF), so as to strengthen the formation of new vessels and the establishment of collateral circulation of patients with cerebral infarction, improve cerebral blood supply and cerebral ischemia and anoxia, achieve the effects of calming heart and concentrating attention, eliminating fatigue, enhancing memory and the like, and can be suitable for symptoms such as insomnia, dysphoria, memory loss, senile dementia and the like.

Antrodia camphorata contains abundant polysaccharides and terpenoids, can be combined with macrophages through cell surface glycoprotein to activate the macrophages, absorb, destroy and eliminate damaged, aged and dead self cells in vivo and pathogenic microorganisms invading in vivo through phagocytosis of the macrophages, and induce the organism to generate a series of cellular immunity and humoral immunity. The mycelium extract has a good repairing effect on vascular endothelial cell injury induced by free radicals, and the fruiting body extract has an inhibiting effect on the expression of Inducible Nitric Oxide Synthase (iNOS), so that the mycelium extract has a certain anti-inflammatory activity in vivo.

The panax notoginseng saponins have the effects of stopping bleeding, and the effective component of panax notoginseng saponins can promote the proliferation of hematopoietic cells, regulate and control the up-regulation of gene expression related to the proliferation and differentiation of the hematopoietic cells, and have good blood enriching effect; it also has effects in resisting myocardial ischemia due to hypophysis posterior lobe, improving myocardial cell anoxia resistance and resisting damage caused by oxygen supply, dilating coronary artery, increasing coronary blood flow, improving myocardial microcirculation, increasing myocardial oxygen consumption, and protecting cardiovascular system.

The composition has the effects of tonifying spleen and kidney, promoting blood circulation to remove blood stasis, refreshing mind and benefiting intelligence. It is used for treating dementia due to spleen and kidney deficiency and brain collateral obstruction caused by blood stasis. The clinical manifestations are as follows: sudden onset, mainly cognitive dysfunction, staged development, symptoms and signs of neurological impairment, hypomnesis, judgment reduction, agnosia, language ambiguity, word inadequacy, decline of daily living ability, dizziness, numbness of limbs, difficulty in walking, pale complexion, cold limbs, salivation in the mouth, tinnitus and deafness, binaural hearing, absence of spirit in eyes, teeth withering and burning, soreness and weakness of waist and knees, muscle atrophy, anorexia, shortness of breath and disinclination to speaking, abdominal pain and massage, malcomplexion, pale and swollen tongue, white fur, sublingual collateral blood stasis or ecchymosis, deep and weak pulse with petechia, and very much more on both feet. The method is characterized in that: the location of this syndrome is mainly in the brain, and closely related to the dysfunction of heart, liver, spleen and kidney. The term "essential deficiency" refers to the deficiency of the spleen and kidney, while the term "essential excess" refers to the obstruction of blood stasis in the brain collaterals. The treatment aims at promoting blood circulation and removing blood stasis, tonifying deficiency and strengthening body resistance, and nourishing marrow and brain.

In the medicinal composition, the epimedium herb is pungent, sweet and warm in nature, has the effects of tonifying kidney and yang, is warm and can assist blood circulation, and is a monarch medicament. The American ginseng is bitter and sweet in taste and cool in nature, can tonify lung qi, nourish yin, promote fluid production, soothe nerves and benefit intelligence, and can restrict the warm and dry nature of the epimedium and the pseudo-ginseng. Chuan san Qi is sweet and bitter in taste and warm in nature, mainly enters Yangming and jueyin channels, and has the characteristics of promoting blood circulation to remove blood stasis, stopping bleeding without retaining blood stasis and not damaging healthy qi. For long-term stasis and easy heat transformation, it is combined with pungent, bitter and slightly cold Zhi Antrodia camphorata to clear heat and purge fire, and also with inducing resuscitation, which are used as adjuvant drugs. Prepared licorice root, radix Glycyrrhizae Praeparata, as a guiding drug, has the effects of replenishing qi, regulating the middle warmer, and harmonizing the effects of the other drugs in the recipe.

Animal experiments and clinical research results show that the pharmaceutical composition has a remarkable effect of preventing and treating the Alzheimer disease, can effectively improve the cognitive ability of patients, improves the self-care ability of the patients in daily life, and has a wide clinical application prospect.

Furthermore, the preparation process of the pharmaceutical composition dosage form is investigated, a granule formula with good taste, high molding rate and good stability is provided, and the pharmaceutical composition has great clinical application value.

Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.

The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.

Drawings

FIG. 1 is a graph showing the staining of CA1 region HE in hippocampal tissue;

FIG. 2 is a graph showing the comparison of the molding rates of the auxiliary materials;

FIG. 3 is a graph comparing the angles of repose of various excipients;

FIG. 4 is a comparison graph of hygroscopicity of various excipients;

FIG. 5 is a plot of the sedimentation surface at various times.

Detailed Description

The raw materials and equipment used in the embodiment of the present invention are known products and obtained by purchasing commercially available products.

The instrument comprises the following steps: an ultra-pure water machine (Milli-Q Advantage, model: Milli-Q Advantage, Michibo China Co., Ltd.); an electric heating forced air dryer (Shanghai Jing hong experiment equipment Co., Ltd., model: DHG-9030); one in ten thousand electronic balances (mettler toledo, model: XS105 Du). And other glassware, screens, etc.

Reagent testing: antrodia camphorata (taiwan); american ginseng (Fujian Tongchun pharmaceutical Co., Ltd., lot number; 20150402); notoginseng radix powder (Anhui Dechang pharmaceutical tablet Co., Ltd., lot number: 20150205); epimedium extract (Saanen Tianrui Biotechnology Co., Ltd., batch No: TR 20150406); radix Glycyrrhizae Preparata extract (Baoji King pharmaceutical Co., Ltd., lot number: 20150303); microcrystalline cellulose, soluble starch, lactose, mannitol, sucrose, sodium lauryl sulfate, sodium carboxymethylcellulose, sodium alginate and magnesium stearate; absolute ethanol (A.R), experimental water was ultrapure water.

Example 1 preparation of granules of the pharmaceutical composition of the invention

Prescription: 3g of antrodia camphorata, 6g of American ginseng, 6g of Sichuan pseudo-ginseng, 1g of epimedium extract (the extract rate of the epimedium is 10 percent based on 10g of crude drug), 0.86g of honey-fried licorice extract (the extract rate of the honey-fried licorice extract is 28.57 percent based on 3g of crude drug), 16.86g of microcrystalline cellulose, 1.686g of sodium alginate and 0.1686g of magnesium stearate.

The preparation process comprises the following steps: weighing powder of radix Panacis Quinquefolii, radix Notoginseng, radix Glycyrrhizae Preparata extract, herba Epimedii extract and Antrodia Camphorata, adding adjuvants, mixing (sieving with 80 mesh sieve), adding 80% ethanol dropwise to obtain soft material, sieving with 14 mesh sieve, granulating by wet method, and oven drying at 60 deg.C for 2 hr. Sieving the dry granules with a first sieve for finishing granules, sieving the dry granules with a fourth sieve for removing fine powder, preparing the dry granules into granules of 35.55g, and subpackaging, sealing and storing for later use.

Example 2 preparation of granules of the pharmaceutical composition of the invention

The prescription comprises 3g of antrodia camphorata, 6g of American ginseng, 6g of Sichuan pseudo-ginseng, 1g of epimedium extract (the extract rate of the epimedium extract is 10 percent based on 10g of original medicine), 0.86g of honey-fried licorice extract (the extract rate of the honey-fried licorice extract is 28.57 percent based on 3g of original medicine), 21.86g of microcrystalline cellulose, 2.186g of sodium alginate, 0.2186g of magnesium stearate and 8g of β -cyclodextrin.

The preparation process comprises the steps of crushing antrodia camphorata, American ginseng, radix notoginseng and honey-fried licorice root into fine powder, dissolving 1g of epimedium extract with 10ml of absolute ethyl alcohol, slowly dripping the dissolved solution into β -cyclodextrin saturated aqueous solution by a dropper, stirring the solution for 3 hours at 60 ℃, stirring the solution for 1 hour at 15-25 ℃, cooling the solution for 18 hours at 0 ℃, carrying out suction filtration and drying to obtain 6g of epimedium inclusion compound, weighing 6g of antrodia camphorata, American ginseng, radix notoginseng, honey-fried licorice root fine powder and epimedium inclusion compound according to the prescription amount, adding microcrystalline cellulose, sodium alginate and magnesium stearate, mixing the mixture evenly, adding a proper amount of 80% ethanol, granulating and drying to prepare 46.12g of granules, thus obtaining the shengbai granules, subpackaging, sealing and storing.

The beneficial effects of the present invention are demonstrated by the following experimental examples. The liter hundred granules described below were granules prepared according to example 1 of the present invention.

Experimental example 1 therapeutic Effect of the pharmaceutical composition of the present invention on rat model of Alzheimer's disease

1. Establishment of Alzheimer disease rat model

2mg of A β 25-35 peptide fragments are dissolved in 400 mu l of sterilized distilled water, the concentration is 5 mu g/mu l of sealing film is sealed, the solution is incubated for 72h at 37 ℃ to be changed into an A β in an aggregation state, after 3.5ml/kg of chloral hydrate with 10 percent is subjected to intraperitoneal injection anesthesia, the rat is fixed on a small animal stereotaxic apparatus, hair is cut and disinfected, a longitudinal incision is made in the middle of the skull, the skull is exposed, a hole is drilled at the corresponding position of the skull (3.6 mm behind bregma and 2.1mm on the right side of the midline) according to a rat brain stereotactic map, except for a sham group rat, the rat in the right side is injected with A β 25-35 oligomers (the concentration is 2 mu g/mu l) under the aseptic condition, the rat is vertically injected into the right side hippocampus at a constant speed (3.96 mm below the hippocampus), 5min is continuously injected at a speed of 0.2 mu l/min, a needle is reserved after the injection, the injection is slowly withdrawn for 2min, the solution is fully dispersed, and a small amount of physiological saline is injected at the operative site of the upper operation, and a small amount of continuous.

2. Grouping and administration of drugs

The molded rats were randomly divided into: model group, pseudo-operation group, positive medicine group, Shengbai granule high, middle and low dose group, each group has 12. The next day after animal modeling, the gavage treatment is carried out (1.31 g/(kg.d), 2.63 g/(kg.d) and 5.26/(kg.d) are respectively carried out on the high, medium and low dose components of the Ligbe granules, 0.525 mg/(kg.d) of aricept is carried out on the positive drug component, and the equal dose of normal saline is carried out on the model group and the sham operation group). Once daily for 14 days.

3. Learning memory capacity determination

The learning and memory ability of rats is measured by a Morris water maze tester. The Morris test system consists of a circular water pool, a movable platform and an automatic recording system. The automatic recording system includes a camera, a monitor, and a computer. A camera is mounted about 2m above the water pool and is connected to a monitor and a computer. The whole movement of the rat in the water pool is tracked by using computer software, and the movement track of the rat in the whole period is displayed. When the rat climbs the platform or the set time is up, the computer stops tracking and skillfully records the swimming track of the rat, including the total route of swimming in the pool, the time required for finding the platform (escape latency), the strategy adopted for finding the platform, the orientation error angle and the like, so as to observe the spatial learning and memory capacity of the rat. Rats were tested for learning and memory according to the Morris water maze protocol. The water maze is a circular water pool with the diameter of 180cm and the height of 55cm, the inner wall of the water pool is painted black, the water depth is 30cm, and a round table with the height of 29cm and the diameter of 10cm is arranged at a position 35cm away from the pool wall.

3.1 hidden platform test

The rats swim freely for 90s in a pool without a platform 1 day before the monitoring experiment, to become familiar with the environment of the water maze. The platform was held constant during the experiment, leaving a distance of 35cm between the midpoint of the platform and the cell wall. Two points equidistant to the opposite side of the platform are selected as water entry points, the animal is gently put into the water facing the pool wall during training, and the total swimming distance from the water entry of the rat to the platform finding and the time (escape latency) required for the platform finding are recorded. If the platform is not reached within 90s, the escape latency of the rat is recorded as 90s, and the monitoring is continued for 5 days, and each day is divided into 2 segments in the afternoon, and each segment is trained 4 times. Statistical analysis was performed with the arithmetic mean of eight latencies per day as the performance of the day. The results are shown in Table 1.

Table 1 effect of liter hundred particles on average escape latency in Morris water maze test in AD rats(s) ((s))

n＝8)

Note: compared with the sham operation group^*P is less than 0.05; compared with model group^#P＜0.05

3.2 space exploration test

After 24h from the end of the concealed platform test, the platform in the pool was removed. The rats were then placed in the water facing the wall of the pool, optionally at the same point of entry. Statistical analysis is carried out on the residence time of the rat in the quadrant of the original platform, and the ratio of the activity time of the rat in the quadrant of the original platform to the total time and the times of crossing the corresponding position of the original platform in 90s are measured. The training is carried out for 4 times in 2 segments in the afternoon, and the results are shown in a table 2.

TABLE 2 Effect of Lily per liter particles on the spatial exploratory Capacity of the Morris Water maze test in AD rats ((

n＝8)

4. Activity detection of rat hippocampal acetylcholinesterase (AChE) and acetylcholine transferase (ChAT)

After the study and memory ability test experiment is finished, fasting is carried out for more than 12 hours, 10% chloral hydrate is used for carrying out intraperitoneal injection on anesthetized rats, blood is taken from abdominal aorta, centrifugation is carried out for 8min at 1500r/min, and serum is separated. During detection, serum is diluted by phosphate buffer solution according to the ratio of 1:9, and AChE and ChAT are detected strictly according to the kit instructions. Cutting head, taking brain, separating hippocampal tissue on ice tray, repeatedly washing with 4 deg.C normal saline, weighing hippocampal tissue, transferring into homogenizing tube, adding normal saline whose tissue mass is g/normal saline volume ml is l:9, homogenizing, fully grinding and homogenizing hippocampal tissue, making into brain tissue liquid whose concentration is 10%, 3000r/min, centrifuging for 10min, extracting supernatant, and strictly detecting AChE and ChAT according to kit instruction. The results are shown in tables 3 and 4.

TABLE 3 Effect of Lily per liter particles on AchE content in hippocampal tissue and serum of AD model rats (S) ((S))

n＝8)

Table 4 effect of hanbai granules on ChAT content in hippocampal tissue and serum of AD model rats: (

n＝8)

5. Method for detecting pathological changes of rat hippocampal tissues by Nissler staining method

After the experiment is finished, instilling the brain through 4% paraformaldehyde perfusion, taking the brain, removing olfactory bulbs, cerebellum and lower brainstem, embedding the brain in paraffin, slicing, dewaxing conventionally, soaking in absolute ethyl alcohol for 2 hours, soaking in tar violet for 1 hour, rapidly differentiating by 95% ethyl alcohol, dehydrating by absolute ethyl alcohol, sealing by neutral gum after xylene is transparent, and observing the pathological change of brain neurons under an optical microscope. As shown in FIG. 1, the nucleus of the pyramidal cells in CA1 area of hippocampus of rat in the sham operated group was large and round, the nucleolus was obvious, the cells were arranged densely and orderly, and the pyramidal cells were found in multiple layers (FIG. 1A). In the model group, pyramidal cells in a CA1 region of a rat hippocampus are sparse, and the level is unclear; partial cell deletion exists; some cells are provided with a vacant area, and the phenomenon of nuclear condensation, cytoplasm thick staining and cell body reduction occurs; inflammatory cell infiltration occurred and glial cells were proliferated to form nodules (fig. 1B). The pyramidal cells in the CA1 area of the rat hippocampal tissue in the drug group are regularly arranged and have clear layers; the phenomenon of nucleus contraction is less likely to occur; no inflammatory cell infiltration was found (fig. 1C).

By combining the experimental results, the shengbai granules have obvious improvement effect on learning and memory function damage of AD model rats caused by A β 1-40, can obviously reduce AchE level in hippocampal tissues and serum, can improve ChAT level, and can inhibit reduction of quantity caused by cell necrosis and loss of CA1 region of hippocampal of AD rats, thereby showing that the shengbai granules have obvious effect of preventing and treating Alzheimer disease.

Experimental example 240 clinical studies of patients with senile dementia using Shengbai granule treatment

Alzheimer's Disease (AD) is a clinically common neurodegenerative disorder, and is also the most common senile dementia, and is characterized clinically by continuous deterioration of cognitive and memory functions, progressive decline of daily living ability, and various neuropsychiatric symptoms and behavioral disorders. The research aims to analyze and explore the condition and clinical curative effect of the shengbaike granules for treating the senile dementia patients.

1. General data

40 AD patients in the group, wherein 22 male patients, 18 female patients, 62-81 years old, 72.13 + -6.53 years old, 2-6 years old dementia and 4.57 + -1.51 years old are referred to the diagnosis standard established by the American neuropathy language disorder stroke research institute for nervous system diseases, ① patients describe or replace the patients with half year history of memory loss, ② patients have obvious cognitive function and can not be corrected by repeated tests, ③ patients have contextual memory impairment related to or independent of cognitive function when the related symptoms of the patients appear, the 3 symptoms simultaneously meet the conditions of definite diagnosis of senile dementia, and differential diagnosis of AD, VD and mixed dementia, excludes benign senile amnesia, senile depression, intracranial space occupation, acute brain trauma and dementia accompanied by the cognitive diseases, patients are randomly divided into a control group and a treatment group according to the ratio of 1:1, and 20 patients in each group, wherein 10 male patients, 10 patients, 5.70 patients, 5 patients, 5.70 patients and 7.5 patients have the average age of severe dementia, 7.7 patients have the data of mild age, 7.7 patients, 7 patients have the average age of severe dementia, 7.5 patients with the moderate dementia and 7.8 patients have the data of moderate dementia, 7.8 patients with the moderate dementia.

2. Method of treatment

Both groups of patients were first given conventional treatment, i.e. oral piracetam tablet treatment 1.2 g/time, 3 times/d in the control group of patients. The patients in the treatment group are treated by the liter hundred particles based on the conventional treatment of the control group, and the dosage is 10 g/time and 3 times/d. 1 month is a treatment course, and the treatment effect is evaluated after 3 months of treatment.

Piracetam tablets (Shandong anti-medicine, Inc., specification: 0.4g per tablet) are used in clinical dose: 2-4 tablets per time, three times a day, and the clinical dosage of the pharmaceutical composition is as follows: 11.85 g/bag, three bags per day. The dosage ratio of the active ingredients is as follows: the piracetam and the pharmaceutical composition provided by the invention have the advantages that the raw material medicine is 3: 2-3: 1.5, and the safe dosage ratio can be 2: 1.

3. Determination of therapeutic effect

After treatment, MMSE (cognitive dysfunction scale) and AD L (daily life capacity scale) are recorded respectively, MMSE detects the cognitive function of a patient and the severity of dementia, AD L detects the self-care capacity of the daily life of the patient, and the curative effect of the patient is judged according to the traditional Chinese medicine diagnosis standard and the curative effect evaluation standard of senile dementia established by the Chinese national academy of traditional Chinese medicine.

CDR and GDS scales were recorded and collated for both groups of patients simultaneously. The CDR scale is an senile dementia rating scale, and the information is collected by the communication between medical personnel and patients and family members thereof, so that the cognitive function, the memory and the basic ability of life of the patients are judged and analyzed. The GDS scale is a comprehensive decline scale that records and analyzes the cognitive abilities of patients by interviewing patients and caregivers. Statistical analysis is carried out by adopting SPSS 13.0 software, and the average value plus or minus standard deviation is used for measuring data

Showing, using t test for comparison between groups, and using χ test for counting data²The test shows that the difference is statistically significant when P is less than 0.05.

4. Results

After the control group and the treatment group are used for 3 treatment courses in comparison, the total effective rate of the treatment group is 75 percent, the total effective rate of the control group is 55 percent, the comparison difference of the two groups has statistical significance (P is less than 0.05), and the clinical effect ratios of the two groups are as follows: treatment group 20 cases: the effective rate is 2 (10%), effective rate is 13 (65%), ineffective rate is 5 (25%), and the total effective rate is 75%. Control 20 cases: 1 (5%) effective, 10 (50%) effective, 9 (45%) ineffective and 55% total effective rate. The results of CDR and GDS scale assessment before and after treatment of two groups of patients are shown in tables 5 and 6:

TABLE 5 comparison of CDR Scale assessment before and after treatment in two groups of patients

Note: compared with the control group after the treatment,^*p is less than 0.05; compared with the group before treatment,^#P＜0.05。

comparison of pre-treatment CDR scale assessment results for both groups of patients showed no significant difference (P > 0.05); compared with the evaluation results of CDR scales after treatment, the evaluation results of the patients in the treatment group are obviously better than those of the patients in the control group, and the difference has statistical significance (P is less than 0.05).

TABLE 6 comparison of GDS Scale assessment before and after treatment for two groups of patients

comparing results of GDS scale assessment before treatment of two groups of patients, no significant difference exists (P is more than 0.05); after treatment, evaluation results of the GDS scale are compared, the evaluation results of the patients in the treatment group are obviously superior to those of the patients in the control group, and the difference has statistical significance (P is less than 0.05).

The data of the group show that after three courses of treatment, the scores of MMSE and AD L of patients in a treatment group are obviously higher than those of a control group, the total effective rate of the patients in the treatment group is obviously higher than that of the control group, the two groups of comparison differences have statistical significance (P < 0.05), the curative effects of the two groups of patients after treatment are recorded and compared by a CDR and GDS scale evaluation method, the evaluation results of the CDR scales after treatment are compared, the evaluation results of the patients in the treatment group are obviously better than those of the patients in the control group, the differences have statistical significance (P < 0.05), the dementia symptoms after treatment, namely the self-care ability of the patients in the treatment group, are obviously better than those of the control group, the evaluation results of the GDS scales after treatment are compared, the evaluation results of the patients in the treatment group are better than those of the patients in the control group, the differences have statistical significance (P < 0.05), the cognitive function of the patients in the treatment group after treatment is proved to be higher than that of the control group, and the Alzheimer' disease treated by the Bai granule for treating.

Experimental example 3 therapeutic action of the pharmaceutical composition of the present invention on mouse model with low immunity

1. Animal grouping and administration method

Mice were randomized into 6 groups: blank group, model group, positive drug group, Shengbai granule high, middle and low dose groups, each group containing 12. Each group is intragastrically administrated once a day, and the high, medium and low dosage components of the shengbai granules are respectively intragastrically administrated for 1.90 g/(kg.d), 3.80 g/(kg.d) and 7.60/(kg.d); 1.30 g/(kg. d) of Zhenqi Fuzheng granules are taken as the positive medicine group for gastric lavage; the model group and blank group were given an equal dose of saline. The administration was continued for 14 d.

Starting on the 10 th day of the gavage, the model group, the positive medicine group, the high, medium and low dose groups of Shengbai granules are injected with 80mg/kg of cyclophosphamide in the abdominal cavity after the gavage, so as to manufacture a low immunity model, and the blank group is injected with normal saline for 4 days continuously. The methods and times of administration are shown in the following table:

TABLE 7 methods of administration and time

2. Evaluation of Immunity-enhancing efficacy

At present, the function test of enhancing immunity of functional food is mainly carried out from 4 aspects: the result is positive in any 2 aspects of 4 aspects of cellular immune function, humoral immune function, monocyte-macrophage function and NK cell activity, and the tested sample can be judged to have the function of enhancing the immunity.

Wherein, the functional index of the mononuclear-macrophage is evaluated by a mouse carbon clearance experiment, and the principle is as follows: the mononuclear-macrophage system in blood has the function of phagocytizing and removing foreign matters entering into the body. After entering the blood by injection, the carbon particles are quickly phagocytized by macrophages in organs such as liver, spleen and the like, so that the concentration of the carbon particles in the blood plasma is reduced, and the function of a mononuclear-macrophage system can be reflected by the phagocytosis rate. Within a certain range, the clearance rate of carbon particles is an exponential function of the dosage, i.e. the phagocytosis speed is proportional to the blood carbon concentration and inversely proportional to the amount of carbon particles that have been phagocytosed.

The cellular immune function index is evaluated by a spleen lymphocyte transformation experiment, and the principle is as follows: t cells, upon stimulation with specific antigens or non-specific mitogens in vitro, develop lymphoblasts with vigorous metabolism, increased protein and nucleic acid synthesis, increased cell volume, and the ability to divide, referred to as lymphocyte transformation. The conversion rate of the lymphocytes can reflect the cellular immune level of the body. Therefore, it can be used as one of the indexes for measuring the cellular immune function of the body.

The humoral immunity function index is evaluated by a serum hemolysin experiment, and the principle is as follows: mice were immunized with SRBC as cellular antigen. B cells proliferate and differentiate into plasma cells under the stimulation of antigens, the plasma cells mature in lymph nodes or lymph tissues (3-4d), antibody-hemolysin corresponding to SRBC is secreted and released into body fluid, and the specific humoral immunity function of the body can be reflected by measuring the hemolysin.

The NK cell killing activity index is evaluated by measuring lactate dehydrogenase (L DH), the principle is that under normal conditions, L DH can not permeate cell membranes, when the cell is killed by the NK cell, the permeability of the cell membrane is increased, L DH is released to the outside of the cell, and the activity of killing the NK cell of an organism can be indirectly reflected by using L DH matrix liquid (containing lithium lactate and the like) to perform colorimetric measurement on the lactate dehydrogenase on an enzyme linked immunosorbent assay instrument.

2.1 mouse carbon clearance test

After 2 hours of intragastric administration on day 14, the mice were injected with ink in a volume ratio of 1:4 according to 5ml/kg of weight of the mice in the tail vein, and the ink was injected into the tail vein2 minutes after injection (t)₂) And 10 minutes (t)₁) 20ul of blood was collected from the retrobulbar capillary plexus by using a quantitative capillary tube and dissolved in 3ml of 0.1% NaCO₃And (3) solution. And (3) uniformly blowing and beating with a capillary, carrying out color comparison with a spectrophotometer at the wavelength of 680nm, and respectively determining optical density values (OD): a. the₁、A₂。

According to the weight m of the mouse and the weight m of the liver₁And spleen weight m₂The clearance index K and the phagocytosis index α were calculated as follows:

clearance index K ═ l ga₁-lgA₂)/(t₂-t₁)

Phagocytosis index α ═ m/(m1+ m2)]×³√K

The results of the experiment are shown in the following table:

table 8 effect of bai granule on clearance index in immunocompromised mouse model: (

n＝10)

Note: compared to blank group^*P is less than 0.05; compared with model group^#P＜0.05

2.2 spleen lymphocyte transformation experiment

2.2.1 preparation of spleen cell suspension after 2 hours of intragastric administration on day 14, mice were sacrificed by dislocation of cervical vertebrae, the spleens were aseptically taken out, placed in a small dish containing a suitable amount of sterile Hanks' solution, gently shredded with forceps, gently twisted with a sterilized rubbing stick, and made into single cell suspension. The red blood cells were removed by filtration through a 200 mesh sieve, hypotonic, washed 3 times with Hanks' solution, centrifuged 10min (1000r/min) each time, and the cells were then suspended in 2ml of complete medium.

2.2.2 counting viable cell number using Trypan blue staining 0.5ml of cell suspension was added to the tube. 0.5ml of 0.4% trypan blue dye solution was added and the mixture was stained for 2 to 3 minutes. Sucking a little suspension, coating the suspension on a slide and adding a cover plate. Taking several random visual fields under the lens to count the number of dead cells and the number of live cells respectively and counting the viability of the cells (the dead cells can be stained by trypan blue, dark blue cells can be seen under the lens, the live cells are not stained, and the cells are colorless and transparent under the lens). The number of the counted living cells is more than 95%.

2.2.3 adjustment of cell concentration to 2 × 10⁷The hemocytometer and cover plate were wiped clean and the cover plate was placed on the counting plate. The cell suspension was aspirated a little and dropped onto the edge of the coverslip to fill the suspension between the coverslip and the counting plate. And standing for 3 minutes. Observing under a mirror, calculating the total number of the four lattices of the counting plate, and recording the line pressing cells only on the left side and the upper side. Calculated as follows:

cell number/ml ═ (total of four cells/4) × 10000 (see occasionally under the mirror cell clumps consisting of more than two cells, calculated as single cells.)

2.2.4 lymphocyte proliferation reaction the cell suspension was added to 96-well plates in two wells, 1ml per well, 100. mu.g/ml ConA 50. mu. L (equivalent to 5. mu.g) in one well and no ConA in the other well as 3 wells each as a control, and 5% CO was placed in each well as a replicate₂And cultured at 37 ℃ for 72 hours.

4 hours before the end of the incubation, 0.7ml of the supernatant was gently aspirated from each well, and 0.7ml of calf serum-free RPM11640 medium was added simultaneously with MTT (5mg/ml) at 50. mu.l/well, and the incubation was continued for 4 hours. After the culture is finished, 1ml of acidic isopropanol is added into each hole, and the mixture is uniformly blown and beaten to ensure that the purple crystals are completely dissolved. The optical density was measured at a wavelength of 570nm using an enzyme linked immunosorbent assay. The optical density of the ConA-added wells minus the optical density of the non-ConA-added wells represents the proliferative capacity of lymphocytes. The results are shown in the following table:

TABLE 9 Effect of Lily granule on spleen lymphocyte transformation in immunocompromised mouse model: (

n＝10)

2.3 serum hemolysin assay

2.3.1 animal grouping and dosing methods mice were randomly divided into 6 groups: blank group, model group, positive drug group, Shengbai granule high, middle and low dose groups, each group containing 12. Each group is intragastrically administrated once a day, and the high, medium and low dosage components of the shengbai granules are respectively intragastrically administrated for 1.90 g/(kg.d), 3.80 g/(kg.d) and 7.60/(kg.d); 1.30 g/(kg. d) of Zhenqi Fuzheng granules are taken as the positive medicine group for gastric lavage; the model group and blank group were given an equal dose of saline. The administration was continued for 14 d.

Starting on the 10 th day of the gavage, the model group, the positive medicine group, the high, medium and low dose groups of Shengbai granules are injected with 80mg/kg of cyclophosphamide in the abdominal cavity after the gavage, so as to manufacture a low immunity model, and the blank group is injected with normal saline for 4 days continuously. Starting on the 9 th day of gavage, 5% (V/V) sheep red blood cells, 0.2ml each, were intraperitoneally injected at the same time, and immunized for 6 days.

2.3.2 measurement of half-maximal hemolytic value (HC50) mice were enucleated and bled, left for 1h, centrifuged at 2000r/min for 10min, and serum was separated and diluted 1:2 with physiological saline.

Preparing Sheep Red Blood Cell (SRBC) suspension (collecting blood from jugular vein of healthy young (half-year-old) sheep, adding twice of Alsever's blood cell preservation solution, storing at 4 deg.C. taking preserved sheep blood during experiment, washing with normal saline for 3 times, centrifuging at 2000r/min for 5min each time, removing fibrin, leukocyte, platelet, etc., and preparing into desired concentration with normal saline); guinea pig serum was prepared (guinea pig heart was bled, serum was separated, serum was added to packed Sheep Red Blood Cells (SRBC) and haemolysis involving non-specific complement was removed by placing guinea pig serum SRBC 5:1(V/V) in a refrigerator at 4 ℃ for 30min, centrifuged at 2000r/min for 10min, supernatant was aspirated, and diluted with physiological saline to 1:10 serum for use).

To the test tube were added 125. mu.l of 10% SRBC (V/V), 250. mu.l of complement (diluted guinea pig serum) and 250. mu.l of diluted serum sample in this order; control 1 tube 125. mu.l 10% SRBC (V/V), 250. mu.l complement (diluted guinea pig serum) and 250. mu.l physiological saline were added sequentially; control 2 tubes were sequentially added 125. mu.l of 10% SRBC (V/V), 250. mu.l of physiological saline, and 250. mu.l of diluted serum sample. After incubation at 37 ℃ for 30min, the reaction was stopped in an ice bath for 10min and centrifuged at 2000r/min for 10 min. 250. mu.l of the supernatant was added to a 96-well plate, and the value of absorbance (A) at a wavelength of 540nm was measured by an enzyme-linked immunosorbent assay. The control tube absorbances (control 1 tube and control 2 tube) were subtracted from the experimental tube absorbances and the results are given in the following table:

TABLE 10 Effect of Lily per liter particles on serum hemolysin levels in immunocompromised mouse models: (

n＝10)

2.4 lactate dehydrogenase (L DH) assay experiments

2.4.1 preparation of spleen cell suspension (Effector cells) spleen was taken aseptically, placed in a small dish containing a suitable amount of sterile Hanks 'solution, the spleen was gently shredded with forceps, gently crushed with a sterile pestle to make a single cell suspension, filtered through a 200 mesh sieve, hypotonic to remove erythrocytes, washed 3 times with Hanks' solution, centrifuged 10min (1000r/min) each time, the cells were then suspended in 2ml of complete culture medium, the number of viable cells (above 95%) was counted by trypan blue staining, and finally the cell concentration was adjusted to 2 × 10 with RPMI1640 complete culture medium⁷One per ml.

2.4.2 subculture of target cells 24h before subculture experiment, 3 washes with Hanks solution before application, and adjusting cell concentration to 4 × 10 with RPMI1640 complete medium⁵One per ml.

2.4.3NK cell Activity detection 100. mu.l each of target cells and effector cells (50: 1 ratio of effective to target) was added to a U-shaped 96-well plate; target cell natural release holes are filled with 100 mul of target cells and culture solution respectively, and target cell maximum release holes are filled with 100 mul of target cells and 1% NP40 or 2.5% Triton respectively; all the above-mentioned materials are equipped with three composite holes, at 37 deg.C and 5% CO₂Culturing in an incubator for 4 h. Centrifuging 96-well culture plate at 1500r/min for 5min, sucking 100 μ l of supernatant per well, placing into 96-well culture plate with flat bottom, and addingAdding L DH matrix solution 100 μ l, reacting for 3min, adding 1 mol/L mol HCl 30 μ l per well, and measuring absorbance (A) value with an enzyme linked immunosorbent assay device at 490 nm.

The NK cell activity is X, and the calculation formula is as follows:

X＝[(A_f-A_n)/(A_m-A_n)]×100

in the formula: a. the_f- -reaction well Absorbance

A_n- -Natural Release pore Absorbance

A_m- -maximum release pore absorbance

The results are shown in the following table:

TABLE 11 Effect of Lily Bai granule on NK cell Activity in immunocompromised mouse model (II)

n＝10)

The results of a mouse carbon clearance experiment, a spleen lymphocyte transformation experiment, a serum hemolysin determination experiment and a lactate dehydrogenase determination experiment are integrated, and the shengbai granules are proved to have obvious improvement effects on the mononuclear-phagocyte function, the cellular immune function, the humoral immune function and the NK cell activity of a model mouse with low immunity caused by cyclophosphamide.

Experimental example 4 Effect of Filler and its amount on the quality of the granules of the present invention

The inventor previously investigated the concentration of the wetting agent, and the wetting agent is preferably 80% ethanol in view of the ease of granulation and the cost of the material.

Soluble starch, lactose, mannitol, microcrystalline cellulose, dextrin and xylitol are respectively selected as fillers, granules are prepared according to the process of example 1, and the influence of the fillers on the quality of the granules is mainly examined from the aspects of forming rate, hygroscopicity, flowability, properties and the like.

4.1 formability test

Weighing the prepared particles, firstly sieving the particles by a first sieve and then sieving the particles by a fifth sieve, and collecting the particles which can pass through the first sieve but can not pass through the fifth sieve. The 5 batches were tested repeatedly for particle formation. The results are shown in FIG. 2.

The molding ratio (mass (g) of granules after sieving/mass (g) of granules before sieving) was × 100%

As is clear from fig. 2, the molding rate of microcrystalline cellulose was the highest (82.05%) among the 5 types of excipients that were evaluated. From this, it can be seen that microcrystalline cellulose is most suitably added as a filler to the Shengbai granule of the present invention from the viewpoint of moldability.

4.2 Angle of repose detection

The method comprises the steps of connecting 3 funnels in series by a fixed funnel method, fixing the funnels at a certain height (H is 1.5cm) on horizontally placed filter paper, carefully pouring particles into the uppermost funnel along the funnel wall until the tip of a particle cone formed on the filter paper contacts with a funnel opening, calculating the angle of repose (tga) according to the diameter (2R) of the bottom of the cone measured on the filter paper, and averaging 5 tests in each group, wherein the figure is 3.

Angle of repose value (tga) ═ H/R

4.3 moisture absorption test

3g of the prepared granules are taken and placed in an oven with the temperature of 25 ℃ for constant weight of 48 h. NaCl was periodically placed in a glass desiccator with a saturated solution of NaCl at the bottom until a supersaturated solution was formed, at which time the relative humidity in the desiccator was 75%. Spreading the granules in a flat weighing bottle dried to constant weight, the thickness is not more than 3mm, precisely weighing, and placing in the dryer (the flat weighing bottle cap is opened). After 48h the weight was taken to calculate the percent moisture absorption. Two sets of mean values were made, see FIG. 4.

Moisture absorption rate (weight after moisture absorption-weight before moisture absorption)/weight before moisture absorption) × 100%

4.4 bulk Density detection

The sieved granulate was weighed 10g (m) into a dry measuring cylinder (50ml cylinder) and the number of scales (V) m L was read by gentle shaking, 5 trials each, averaged, see table 12:

TABLE 12 bulk Density measurements

4.5 characterization of the traits

TABLE 13 description of the properties

As can be seen from table 13, the properties of the granules are summarized, and the granules made of microcrystalline cellulose are considered to have the best effect in combination with the uniformity and hardness of the granules and whether the granules are agglomerated during the granulation process.

Taking the above indexes into comprehensive consideration, the microcrystalline cellulose with the dosage of 1:1 of the original drug amount of the prescription is used as a filling agent, 80% ethanol is used as a wetting agent for granulation, and the obtained granules have high forming rate, good properties and good mobile phase and hygroscopicity.

Experimental example 5 influence of the selection of the auxiliary materials on the taste of the granule of the present invention

1. Sweetening agent

The sweetening agent aspartame is added on the basis of the prescription in the example 1, the dosage of the sweetening agent aspartame is respectively 0.3 percent, 0.5 percent and 0.7 percent of the total prescription dosage, and the sweetness of the sweetening agent cannot cover the bitterness of the medicine after tasting, but forms a bitter and sweet taste, and the taste is more strange and is not considered finally.

2. Bag and material

The inventor researches and discovers that the bitter taste of the granule is mainly caused by epimedium, β -cyclodextrin is selected as an inclusion material, and experiments are carried out under the conditions that the ratio of epimedium extract powder to β -cyclodextrin is 1:4, 1:6, 1:8 and 1: 10.

Weighing β -cyclodextrin 8g, adding water at 60 ℃ by using a magnetic stirrer to prepare a saturated solution (β -cyclodextrin 8g is saturated in 100ml of water at 60 ℃), precisely weighing herba epimedii extract with a corresponding proportion, adding ten times of ethanol to dissolve, slowly dripping β -cyclodextrin saturated solution at 60 ℃, stirring at constant temperature for 3h, cooling to room temperature, stirring for 1h, taking out, refrigerating for 12h, carrying out suction filtration, washing a filter cake with a small amount of ethanol, then washing with a small amount of water, drying in an oven at 60 ℃ for 4h, obtaining, weighing the weight, and calculating the yield (see table 14).

TABLE 14 Epimedium β -Cyclodextrin inclusion Compound yield

Epimedium extract (g)	β -Cyclodextrin (g)	Clathrate (g)	Yield (%)
				2	8	6.34	63.40
1.33	8	6.16	66.02
				1	8	6.13	68.11
0.8	8	5.92	67.27

Finally determining that the epimedium extract is β -cyclodextrin ═ 1:8, namely precisely weighing 1g of the epimedium extract, dissolving the extract in 10ml of ethanol, slowly dripping β -cyclodextrin saturated solution at 60 ℃, stirring at constant temperature for 3h, then cooling to room temperature, stirring for 1h, taking out, refrigerating for 12h, carrying out suction filtration, washing a filter cake with a small amount of ethanol, then washing with a small amount of water, drying in an oven at 60 ℃ for 4h, obtaining 6g of epimedium inclusion compound on average, and adding 6g of the product into the prescription under the condition that the inclusion rate is not calculated.

After the epimedium is wrapped, the taste is not bitter before, the improved prescription is tried to drink, the taste is better than before, and the bitter taste is completely acceptable, which indicates that the method is feasible.

Experimental example 6 Effect of the selection of auxiliary materials on the settling time of suspension granules according to the present invention

Because the main component of shengbai granules is American ginseng and the crude drug of panax notoginseng is directly pulverized and is insoluble in water, the granules have poor solubility, thereby causing poor taste and appearance. Because the powder amount is too large, the settling time is prolonged by adding suspending agent to increase the viscosity of the solution (making into suspension granule). Different amounts of sodium carboxymethylcellulose (4%, 5%, 6%) and sodium alginate (4%, 5%, 6%) are respectively adopted, and meanwhile, the suspending property of the sodium alginate is enhanced by magnesium stearate with the amount of 0.5% of the prescription amount. The suspending property of the sodium carboxymethyl cellulose and the suspending property of the sodium alginate with different dosages are determined by comparing the sedimentation volume ratio through experimental measurement.

Weighing 6 parts of sample (sodium carboxymethylcellulose with the addition of prescription amounts of 4%, 5% and 6% is respectively prescription No. 1, prescription No. 2 and prescription No. 3; sodium alginate with the addition of prescription amounts of 4%, 5% and 6% is respectively prescription No. 4, prescription No. 5 and prescription No. 6; magnesium stearate with the addition of prescription amount of 0.5% is respectively added in the prescription No. 1-6; pure prescription medicinal material without adding a suspending agent is prescription No. 7), placing the 5g of sample in a measuring cylinder with a plug, adding distilled water to 50ml of scale, sealing the plug, shaking forcibly for 1min, supplementing distilled water to 50ml of scale according to the falling liquid level, then shaking forcibly for 1min, standing, recording the starting height Ho of the suspension, then recording the height H of the sedimentation surface after standing for 5min, 10min, 30min, 1H, 2H, 3H and 12H respectively, and calculating according to the following formula:

sedimentation volume ratio (F) ═ H/Ho

Compared with experiments (see figure 5), the suspending effect of the sodium alginate is better than that of the sodium carboxymethyl cellulose, and the suspending effect is that the sodium alginate with the amount of 6 percent of the prescription amount is added and the magnesium stearate with the amount of 0.5 percent of the prescription amount is added. But 5 percent of sodium alginate and 0.5 percent of magnesium stearate in the prescription amount can meet the requirement of suspending aid, the material cost and the total prescription amount are comprehensively considered, and finally 5 percent of sodium alginate and 0.5 percent of magnesium stearate in the prescription amount are selected as suspending aids.

Claims

1. A pharmaceutical composition for preventing and treating Alzheimer disease is characterized in that: the traditional Chinese medicine is prepared from the following raw materials in parts by weight: 10 parts of epimedium, 6 parts of American ginseng, 6 parts of Sichuan pseudo-ginseng, 3 parts of antrodia camphorata and 3 parts of honey-fried licorice root.

2. The pharmaceutical composition of claim 1, wherein: the preparation is prepared by mixing crude drug powder of raw drug materials, water or an extract of an organic solvent in a weight ratio and adding pharmaceutically acceptable auxiliary materials or auxiliary components.

3. The pharmaceutical composition of claim 2, wherein: the preparation is an oral preparation.

4. The pharmaceutical composition of claim 3, wherein: the preparation is powder, granules, capsules, tablets, pills, decoction or mixture.

5. A process for the preparation of a pharmaceutical composition according to any one of claims 1 to 4, characterized in that: the method comprises the following steps: directly pulverizing the raw materials in weight ratio, or extracting with water or organic solvent, and adding pharmaceutically acceptable adjuvants or auxiliary components.

6. The method of claim 5, wherein: the method comprises the following steps:

a. preparing an epimedium inclusion compound;

b. weighing Antrodia Camphorata, radix Panacis Quinquefolii and Notoginseng radix powder, Glycyrrhrizae radix or its extract powder and herba Epimedii clathrate at a certain weight ratio, and adding pharmaceutically acceptable adjuvants or auxiliary components.

7. The preparation method of claim 6, wherein the epimedium inclusion compound is prepared by dissolving epimedium extract in ethanol, dripping into β -cyclodextrin saturated aqueous solution, stirring at 60 deg.C for 3 hours, stirring at 15-20 deg.C for 1 hour, cooling at 0 deg.C for 18 hours, filtering, and drying.

8. Use of the pharmaceutical composition of any one of claims 1 to 4 in the manufacture of a medicament for the treatment and/or prevention of alzheimer's disease.

9. Use of a pharmaceutical composition according to any one of claims 1 to 4 in combination with piracetam for the preparation of a medicament for the treatment and/or prevention of alzheimer's disease.

10. Use of the pharmaceutical composition of any one of claims 1 to 4 in the preparation of a medicament for enhancing immunity.

11. A granule for preventing and treating Alzheimer disease is characterized in that: the medicament is prepared from the following raw and auxiliary materials in parts by weight: the pharmaceutical composition of claim 1 comprises bulk drug, 16.86 parts of microcrystalline cellulose, 1.686 parts of sodium alginate and 0.1686 parts of magnesium stearate.

12. A granule for preventing and treating Alzheimer's disease is characterized by being prepared from the following raw and auxiliary materials in parts by weight, 21.86 parts of microcrystalline cellulose, 2.186 parts of sodium alginate, 0.2186 parts of magnesium stearate and 8 parts of β -cyclodextrin in the pharmaceutical composition of claim 1.

13. A combined medicine for preventing and treating Alzheimer disease is characterized in that: the pharmaceutical composition and piracetam in the dosage forms, which contain unit preparations with the same or different specifications and are used for simultaneous or separate administration, and a pharmaceutically acceptable carrier; the pharmaceutical composition comprises the following raw material medicines and piracetam in a weight ratio: (1.5-2): 3.