CN113413439B

CN113413439B - Traditional Chinese medicine formula for treating Alzheimer's disease and preparation method of compound preparation of traditional Chinese medicine formula

Info

Publication number: CN113413439B
Application number: CN202110786360.9A
Authority: CN
Inventors: 孙勉; 凌仕信
Original assignee: Zhongshan Chuangtian Biotechnology Co ltd
Current assignee: Zhongshan Chuangtian Biotechnology Co ltd
Priority date: 2021-07-12
Filing date: 2021-07-12
Publication date: 2022-03-29
Anticipated expiration: 2041-07-12
Also published as: CN113413439A

Abstract

The invention discloses a traditional Chinese medicine formula for treating Alzheimer's disease and a preparation method of a compound preparation thereof, wherein the traditional Chinese medicine formula comprises the following components in parts by weight: 40-50 parts of dendrobium nobile, 15-20 parts of astragalus membranaceus, 15-20 parts of salvia miltiorrhiza, 4-8 parts of polygonatum sibiricum, 4-8 parts of ligusticum wallichii and 2-4 parts of liquorice, wherein the dendrobium nobile is prepared from dendrobium nobile stems and dendrobium nobile flowers in a weight ratio of 5.0-6.5: 1.0-2.0. The dendrobium stem is used as a monarch drug, the astragalus and the salvia are used as ministerial drugs, the ligusticum wallichii and the rhizoma polygonati are used as adjuvant drugs, and the liquorice is used as a conductant drug. The compound traditional Chinese medicine for treating the Alzheimer disease realizes the improvement of the treatment effect of the medicine on the Alzheimer disease through the specific targeting effect and the mutual cross function among the components.

Description

Traditional Chinese medicine formula for treating Alzheimer's disease and preparation method of compound preparation of traditional Chinese medicine formula

Technical Field

The invention relates to a traditional Chinese medicine formula for treating Alzheimer's disease and a preparation method of a compound preparation thereof, belonging to the technical field of modern traditional Chinese medicines.

Background

Alzheimer Disease (AD) is a neurodegenerative disease commonly seen in the elderly, and its main pathological changes are diffuse atrophy of cerebral cortex, neurofibrillary tangles, and formation of a large number of senile plaques among nerve cells, etc., with progressive cognitive impairment and memory hypofunction as its main clinical symptoms.

With the current increase in the life expectancy of the population of society, the incidence of AD in the elderly population tends to rise dramatically. However, no specific pathogenesis or effective therapeutic method is available so far.

The existing drugs for treating mild-to-moderate alzheimer's disease are donepezil (Aricept) from Pfizer and Eisai, rivastigmine (Exelon) from novain, galantamine (remininyl) from Johnson & Johnson, and memantine (Ebixa) from Lundbeck, respectively. However, the side effects of the western medicine are very obvious. Such as nausea, vomiting, diarrhea, dizziness, insomnia, muscle spasm, fatigue; hallucinations, chaos of consciousness; dizziness, headache, tiredness; anxiety, increased muscle tone, vomiting, etc.

Because the etiology and pathogenesis of the Alzheimer disease are unknown, no specific therapy exists for the treatment, and the symptomatic treatment is mainly used. Including drug therapy to improve cognitive function and memory impairment; symptomatic treatment improves mental symptoms; good nursing and disease progress delaying. The medicine and rehabilitation therapy aims at improving cognition and memory functions, maintaining independent living ability of patients and improving living quality.

At present, AD treatment drugs are only used for improving cognitive functions, single-target drug therapy has limited curative effect clinically, no specific drug for treating Alzheimer disease exists, and intelligence-improving drugs or drugs for improving cognitive functions are currently effective drugs for treating Alzheimer disease. Patients with alzheimer's disease all have a combination of cognitive disorders, and the main purpose of using nootropic or cognitive function-improving drugs is to improve cognitive function and delay the progression of the disease.

Alzheimer's disease is treatable and controllable by drugs and can help patients improve cognitive function and delay disease progression. However, if the patient does not receive or adhere to correct diagnosis and treatment in time, the progress of the disease cannot be controlled, the disease condition completely loses the basic self-care ability after the disease condition is developed to be severe, and the disease often dies due to complications such as bedsore, fracture, pneumonia and the like or due to exhaustion of important organ functions.

Alzheimer's disease generally occurs in the elderly, and has a high incidence due to the central nervous degeneration of the elderly and the massive death of body cells. The disease is strongly related to both genetic and environmental factors. Patients develop memory impairment or personality changes after the onset of disease. At present, the representative medicines of the traditional Chinese medicines for treating the Alzheimer disease in China are as follows: 1. compound sea snake capsule: the medicine mainly contains sea snake live peptide, can directly enter damaged neurons through the barrier of blood brain, has single repairing effect on dopamine neurons, but has no obvious effect on the total effect. 2. A ginkgo leaf preparation: is a natural active substance extracted from folium Ginkgo, including flavonoids or ginkgolides. The medicine is beneficial to improving cerebral blood circulation and promoting cell activity, and can relieve symptoms such as dizziness, memory deterioration and dysphoria caused by Alzheimer disease. But has obvious side effect and certain neurotoxicity and nephrotoxicity after long-term large-scale administration. 3. The brain protein hydrolysate tablet is an active peptide medicine, contains various amino acids and peptide nerve growth factors, and has the effects of nourishing nerves, improving insomnia and relieving headache. The patient needs to take two to about 4 tablets each time, and needs to take the medicine three times a day. The medicine is mainly used as a nutrition adjuvant, has large dosage, and is not suitable for direct treatment. 4. Other finished Chinese medicines are various in types, such as Chinese patent medicines for reducing blood sugar, blood fat and cholesterol, Chinese patent medicines for dilating cerebral vessels, improving cerebral vascular perfusion, Chinese patent medicines for resisting aging and fatigue, improving immunity of human bodies, Chinese patent medicines for regulating nervous systems and exciting hematopoietic system functions and the like. The Chinese patent medicines are mainly used in the fields of cardiovascular and cerebrovascular disease treatment, blood pressure reduction and blood sugar reduction, have the main functions of treating cardiovascular and cerebrovascular diseases, and are only used as auxiliary medicines when treating Alzheimer's disease. Although the Chinese patent medicines are various in types, the efficacy and the effect are too single, the Chinese patent medicines only have auxiliary improvement effect on partial single symptoms, the whole treatment effect cannot be realized, and the application defect in the treatment of the Alzheimer disease is very obvious.

Therefore, the invention provides a multi-effect and multi-target-effect traditional Chinese medicine formula for treating the Alzheimer disease and a compound preparation thereof, which can comprehensively improve the memory, the spatial memory, the learning ability, the cognitive ability and the like of the old, thereby achieving the purpose of radically treating the Alzheimer disease and making up the important defect of the current Chinese patent medicine for treating the Alzheimer disease.

Disclosure of Invention

The invention aims to solve the problems that the existing medicine for treating the Alzheimer disease has unobvious drug effect and more side effects, only has single-target property, lacks of immunoregulation property and the like, and provides a traditional Chinese medicine formula for treating the Alzheimer disease, which has the advantages of remarkable effect, short treatment course, quick response, safety and no toxic or side effect.

The invention also aims to provide a preparation method of the traditional Chinese medicine formula compound preparation.

In order to achieve the purpose, the invention adopts the following technical scheme:

a traditional Chinese medicine formula for treating Alzheimer's disease is characterized by comprising the following components in parts by weight:

40-50 parts of dendrobium nobile, 15-20 parts of astragalus membranaceus, 15-20 parts of salvia miltiorrhiza, 4-8 parts of rhizoma polygonati, 4-8 parts of ligusticum wallichii and 2-4 parts of liquorice, wherein the dendrobium nobile consists of dendrobium stem and dendrobium nobile flowers, and the weight ratio of the dendrobium stem to the dendrobium nobile flowers is 5.0-6.5: 1.0-2.0.

Preferably, the formula consists of the following components in parts by weight:

48 parts of dendrobium nobile, 18 parts of astragalus mongholicus, 18 parts of salvia miltiorrhiza, 7 parts of rhizoma polygonati, 7 parts of ligusticum wallichii and 2 parts of liquorice.

Preferably, the dendrobium nobile lindl in the invention is composed of dendrobium nobile stems and dendrobium nobile flowers, and the weight ratio of the dendrobium nobile stems to the dendrobium nobile flowers is 5.5: 1.5.

the dendrobium nobile lindl is a monarch drug, namely a drug which plays a main treatment role on the main symptoms or main diseases of the prescription in the prescription, is the main attack direction of the prescription, and the efficacy of the dendrobium nobile lindl is the first of the prescription and is an indispensable drug in the prescription. The astragalus and the salvia are ministerial drugs, one is a drug for assisting monarch drug to strengthen treatment of principal disease or principal symptoms, and the other is a drug for treating concurrent disease or concurrent symptoms, and the potency of the drug is smaller than that of the monarch drug. The rhizoma ligustici wallichii and the rhizoma polygonati are adjuvant drugs, namely assisting monarch drugs and ministerial drugs to strengthen the treatment effect, or directly treating secondary concurrent symptoms. The liquorice is a messenger drug, and has the effects of guiding the channels and guiding the medicines in the formula to reach the focus, and is a blending drug, namely a drug with the effect of blending the medicines, and simultaneously the taking taste of the blending drug.

The compound of the invention is a compound traditional Chinese medicine medicament screened based on the modern traditional Chinese medicine pharmacology by adopting the modern new traditional Chinese medicine technology according to the traditional Chinese medicine theory, and the medicament improves the brain cognitive function and prevents the development process of the Alzheimer disease through the ways of neurotransmitter, cerebral vasodilatation, brain metabolism promoting medicaments and the like. The invention realizes the improvement of the treatment effect of the medicine on the Alzheimer disease by the specific directional action and the mutual cross function among the components, and the interaction and the cross effect among the components are realized based on the basic principle, the action and the effect of the traditional Chinese medicine formula and the analysis of the components of the modern traditional Chinese medicine, the targeting action of the medicine, the efficacy and the toxicological evaluation and the like.

Furthermore, the efficacy and action principles of the traditional Chinese medicine components are explained as follows:

dendrobium nobile: dendrobine is one of the marking components of dendrobium nobile. The dendrobium nobile lindl has the highest dendrobium alkaloid content in all dendrobium nobile, and particularly, the dendrobium nobile lindl produced by Guizhou red water has the average dendrobium alkaloid content of more than 0.8 percent and the highest dendrobium alkaloid content of 1.82 percent through detection. (Chinese pharmacopoeia stipulated not less than 0.4%). The dendrobium nobile lindl contains dendrobium nobile lindl alkali, and also contains various effective components such as dendrobium nobile lindl polysaccharide, flavonoid, phenols, phenanthrenes and bibenzenes, fluorenones, sesquiterpenes and the like. The dendrobine is a pyrrolizidine derivative alkaloid which is extracted and separated from stems of dendrobium nobile (Dendro bium nobile Lindl) belonging to the family Orchidaceae, and has a molecular formula of C16H25NO2, a molecular weight of 263.27 and a melting point of 134.5-136 ℃. Experiments prove that the component has the effects of relieving pain and fever, reducing blood sugar, lowering blood pressure, regulating heart rate, treating Alzheimer's disease and the like. The polysaccharides of herba Dendrobii have effects of enhancing organism immunity and enhancing phagocytosis of abdominal cavity macrophage on chicken erythrocyte. The dendrobium nobile lindl has the functions of improving the nonspecific immunity of organisms and antagonizing the immunosuppression effect of cyclophosphamide, and the phagocytic function of macrophages is restored to a normal level. The dendrobium nobile lindl total alkali can obviously reduce the blood sugar level of patients with light and incipient diabetes, restore the blood sugar to normal, effectively reduce the blood sugar and the level of glycosylated hemoglobin, can dilate blood vessels, can reduce the vascular resistance of femoral artery and carotid artery, obviously improve the blood stasis symptom, reduce blood cholesterol and triglyceride, and improve the high-density lipoprotein cholesterol level, and is used for treating cardiovascular and cerebrovascular diseases and Alzheimer's disease. Herba Dendrobii can significantly increase SOD (superoxide dismutase) level, reduce LPO (lipid peroxide) to delay aging and resist oxidation, and has certain effects of improving intelligence and memory, and can be used for treating presenile dementia, neurasthenia and amnesia; one ester component contained in herba Dendrobii has effects of promoting blood circulation, removing blood stasis, treating thromboangiitis obliterans, cerebral thrombosis, and arteriosclerotic occlusion, and preventing organic change. In addition, the dendrobium alkaloid also has the effect of inhibiting or correcting the abnormal change of enzyme activity caused by galactose, and the dendrobium alkaloid has obvious improvement effect on tau protein abnormal hyperphosphorylation, GSK-3beta and inflammation at a site induced by lipopolysaccharide, so that the apoptosis of peripheral nerve cells of the hippocampus can be reduced, and the dendrobium alkaloid has obvious curative effect on the presenile dementia.

Astragalus root: the radix astragali contains saponin, flavone, etc., the saponin comprises radix astragali saponin I and II, radix astragali contains radix astragali saponin A, B, and radix astragali contains radix astragali saponin IV and soybean saponin I; the main components of the flavone are formononetin, calycosin and the like. Further contains amino acids, betaine, etc.; mongolian milkvetch root also contains astragalus polysaccharide I, II, III, etc. Radix astragali has effects of enhancing and regulating immunity, dilating blood vessel, inhibiting platelet aggregation, reducing blood viscosity, and improving blood circulation and brain perfusion, and contains microelements such as zinc. The astragalus has good effect of treating AD, the astragalus can induce BMSCs to differentiate into nerve cells in vitro, and the astragalus can induce BMSCs in vivo to treat AD, and has certain effect of preventing senile dementia.

Red sage root: is dried root and rhizome of Salvia miltiorrhiza Bge (Salvia militaria Bge.) belonging to Labiatae. The main functions are as follows: the function of the cardiovascular system, strengthening heart, enhancing myocardial contractility, improving cardiac function, without increasing myocardial oxygen consumption; has effects in dilating coronary artery and increasing myocardial blood flow; peripheral vessel dilation, increased blood flow; a decrease in cerebral blood flow; antithrombotic enhancement of plasmin activity; prolonged bleeding and clotting time; inhibition of platelet aggregation (increase of cAMP levels in platelets inhibits TXA2 synthesis); improving the rheological properties of blood (reduced blood viscosity, shortened time for red cell electrophoresis); improving microcirculation. The Saviae Miltiorrhizae radix is dried root and rhizome of Salvia miltiorrhiza Bunge (Salvia millirrhiza Bunge) of Salvia of Labiatae, and is frequently used in clinical treatment of AD. The salvia miltiorrhiza volatile oil has in-vitro antioxidant activity, an AD mouse model is built by adopting a method of intraperitoneal injection of D-gal and intragastric administration of AlCl _3, the anti-AD effect of the salvia miltiorrhiza volatile oil is explored, the learning capacity and the space memory capacity of an experimental AD model mouse are respectively determined by applying a Morris water maze experiment and a probe test on a behavioral level, the contents of Abeta, GFAP, BACE-1 and NEP related to the AD morbidity in the mouse brain are determined by applying western blot analysis (WB) and immunohistochemical analysis (IHC) on a protein level, the contents of MDA, ROS, SOD, GSH, AchE and Ach in the brain homogenate of the AD mouse are investigated by using Biochemical determinations on a molecular biological level, and the expression change of related inflammatory factors and Abeta related proteins in the AD mouse brain is investigated by applying an RT-PCR technology on a gene level. The mouse-like symptoms of AD caused by D-gal combined with AlCl 3 are inspected on the individual behavioral level, the molecular biological level, the protein level and the gene level, and the results show that the salvia volatile oil can obviously improve the learning ability and the memory ability of mice, obviously inhibit the expression abilities of Abeta, BACE-1 and GFAP related to the AD onset in hippocampal regions and cortical regions of the brains of the mice, promote the distribution of NEP in the hippocampal regions and cortical regions, obviously increase the contents of Ach and GSH and the activities of antioxidant enzymes SOD and CAT, and promote the gene expression levels of inflammatory reactions, inflammatory factors related to oxidative damage and related enzymes generated by Abeta in the brains of the mice to be reduced. The results show that in vivo and in vitro pharmacological experiments prove that the salvia miltiorrhiza volatile oil has stronger anti-inflammatory and antioxidant capabilities and can play a certain role in relieving and treating AD mouse-like symptoms caused by the combination of D-gal and AlCl _ 3.

Rhizoma polygonati: the rhizome contains steroid saponin, and 2 furostanol type saponins and 2 spirostanol type saponins are separated. The former is that: 26-O-beta-D-glucopyranosyl-22-O-methyl- (25) S-furost-5-ene-3 beta, 26-diol 3-O-beta-lycoris tetraglucoside (26-O-beta-D-glucopyranosyl-22-O-methyl-25 (S) -furost-5-ene-3 beta, 26-diol 3-O-beta-lycotetraoside) namely sibirian polygodide A (sibirioside-A) and 26-O-beta-glucopyranosyl-22-O-methyl-25 (S) -furost-5-ene-3 beta, 14 alpha, 26-triol 3-O-beta-lycoris tetraglucoside (26-O-beta-D-glucopyranosyl-22-O-beta-lycosyltetraoside) methyl-25(S) -fruost-5-ene-3 beta, 14 alpha, 26-triol 3-O-beta-lycotetraoside) namely 14 alpha-hydroxysibirioside A (14 alpha-hydroxysibirioside A); the ones belonging to the latter are: ((23S, 25R) spirost-5-ene-3 beta, 14 alpha, 23-triol 3-O-beta-lycotetraside), i.e., polyuria sibirica glycoside B (sibiricoside B) and neoparadiosgenin-A3-O-beta-lycoris tetraoside. The sealwort polysaccharide A, B, C is prepared by condensing glucose (glucose), mannose (mannose) and galacturonic acid (galacturonic acid) according to a molar ratio of 6:26: 1; and oligosaccharide A, B, C with relative molecular mass of 1630, 862 and 472, which is prepared by condensing fructose (fructose) and glucose at molar ratio of 8:1.4:1 and 2: 1. Rhizoma Polygonati has effects of increasing coronary blood flow, regulating blood lipid, lowering blood sugar, resisting aging and enhancing immunity. The modern clinic is used for treating coronary heart disease, hyperlipoidemia, diabetes, leukopenia, pulmonary tuberculosis, chronic hepatitis, mental and sleep deficiency, headache, senile dementia, deficiency of heart and spleen, deficiency of liver and kidney, weak muscles and bones, anorexia, dry mouth and other symptoms.

Ligusticum wallichii: it can be used for treating senile dementia, and is especially suitable for patients with stagnation of qi and blood stasis, and obstruction of cerebral collaterals. (1) The chemical components are as follows: containing ligustrazine (tetramethylpyrazine), loline or perindopril (1- (5-hydroxymethyl-2-furyl) -9h-pyrido [3, 4-b)]Indole [1- (5 hydroxymethy-2-furyl) -9H-pyrido [3,4-b ]]indole]Ligustilide, 3-butylidenephthalide, 3-butylidenebenzthalide-7-hydroxyphthalide, butylphthalide, (3S) -3-n-butyl-4-hydroxyphthalide [ (3S) -3-butyl-4-hydroxyphenylidenebenzthalide)]Namely (3S) -chuanxiongol ((3S) -chunxiongol), 3-n-butyl-3, 6,7-trihydroxy-4,5,6,7-tetrahydrophthalide (3-n-butyl-3, 6,7-trihydroxy-4,5,6,7-tetrahydrophthalide), neocnidide (neocin-dilide), senkyunolide (senkyunolide), B, C, D, E, F, G, H [ cis-6, 7-dihydroxy-ligustilide (cis-6, 7-dihydroxy-origniside ]]I [ trans-6, 7-hydroxyligustilide (trans-6, 7-dihydrox-yliggustilide) ]]、J[4]、K、L、M[6]、N[4]、O、P[8](E) -senkyunolide]E[4]Senkyunone, 2-methoxy-4- (3-methoxy-1-propenyl) phenol (2-methoxy-4- (3-methoxy-1-propenyl) phenol), 2-pentanoyl-benzyl ester [2- (1-oxypentyl) -benzoic acid methyl ester]5-hydroxymethyl-6-endo-3-methoxy-4-hydroxyphenyl-8-oxabicyclo [3.2.1]Oct-3-en-2-one [ 5-hydroxymethy-l-6-endo-3-methoxy-4-hydroxyphenyl-8-oxa-bicyclo (3.2.1) -oct-3-one][5]4-hydroxy-3-methoxyphenylhexene(4-hydroxy-3-methoxy styrene), 1-hydroxy-1- (3-methoxy-4-hydroxyphenyl) hexane [1-hydroxy-1- (3-methoxy-4-hydroxyphenyl) ethane]4-hydroxybenzoic acid (4-hydroxybenzoic acid), vanillic acid (vanillic acid), caffeic acid (coffeic acid), protocatechuic acid (protocatholic acid), ferulic acid (ferulic acid), chrysophanol (chrysophanic acid), sedanonic acid (sedanonic acid), L-isoleucyl-L-valine anhydride (L-isoleucyl-L-valine anhydride), L-valyl-L-valine anhydride (L-valyl-L-valinic acid anhydride), lol-valyl-L-valinic acid, loline (perlulaine), cnidium rhizome phenol, uracil (uracil), trimethylamine hydrochloride (trimethyamine-HCL), choline chloride (chlorinate), palmitic acid (palivitytic acid), vanillin (vanillin), 1-acyl-beta-carboline (1-beta-carboline), eudesmol (eudesmol), 1-acyl-beta-carboline (beta-carboline), eudesmol (eudesmol), linoleic acid (linoleic acid), dilinoleyl palmityl glyceride (dilinoyl palmityl glyceride), sucrose (sucrose), and the like. (2) The rhizome of Ligusticum wallichii contains volatile oil about 1%. The oil was identified to have 40 kinds of components, which accounted for 93.64% of the volatile oil, of which the main component was ligustilide (ligustilide) 58%, 3-butylidenephthalide 5.29%, and sabinene 6.08%, lactone compounds contained in the rhizome, including butenolide (butylidenephthalide), ligustilide (senkyunolide), neocnidilide (neocnidilide), 4-hydroxy-3-butylphthalide (4-hydroxy-3-buthyl phthalide), ligustilide (Chuanxingingol), ligustilide (2, 2' -diligurtilide), and 3-butyl-3, 6, ⒎ -4,5,6,7-tetrahydrophthalide, etc., in addition to the above-mentioned two kinds. The nitrogen-containing compounds include tetramethylpyrazine (tetramethylpyrazine, ligustrazine, chuanxinong gzine), perlyrine, trimethylamine hydrochloride, choline hydrochloride, L-isoleucyl-L-valine anhydride (L-isobutryl-L-valine anhydride), L-valyl-L-valine anhydride, 1-acetyl-beta-carboline, uracil, adenine and adenosine. the acidic or phenolic compounds include 4-hydroxy-3-methoxystyrene, 1-hydroxy-1- (3-methoxy-4-hydroxybenzene) -ethane, 4-hydroxybenzoic acid, caffeic acid, vanillic acid, ferulic acid (ferulaic acid), danamic acid (sadanic acid), rhein (chrysophanic acid), palmitic acid, vanillin and linoleic acid Sixteen kinds of,5,5 '-bifuranyl ether (bis-5, 5' -formyl furfuryl ether), sporular eucalyptol (spathulenol), beta-sitosterol, sucrose and a fatty acid glyceride. (3) Toxicity of Ligusticum wallichii: the LD50 of ligustrazine intravenous injection to mice is 239 mg/kg. The LD50 of the crude water-soluble preparation of chuanxiong rhizome to mice ip and im is 65.86 g/kg and 66.42g/kg respectively. The LD50 of ligustrazine mouse iv was 239 mg/kg. The mouse po ligustrazine is 5 mg/kg or 10mg/kg daily for 4 weeks, and no obvious abnormality is found in animal body weight, hemogram, liver and kidney function and pathological histological examination. (4) The pharmacological action of the ligusticum wallichii is as follows: a. has obvious tranquilizing effect on central nervous system, and small amount of volatile oil of rhizoma Ligustici Chuanxiong has effects of inhibiting animal brain activity, and exciting brain-extending respiratory center, blood vessel movement center and spinal cord reflex center, and the decoction of rhizoma Ligustici Chuanxiong can inhibit spontaneous activity of mouse ig and mouse ig, respectively, so that sleep time of mouse caused by pentobarbital sodium is prolonged, and caffeine (20mg/kg) can be resisted with exciting effect. But not against the convulsions of rats caused by pentaerythrine. The stomach is drenched with 25-50g/kg of rhizoma ligustici wallichii decoction, so that the spontaneous activity of a rat can be inhibited, and the sedation of the mouse is more obvious than that of the rat; it can also prolong the sleep time of pentobarbital, but can not antagonize the excitation of caffeine, and can not prevent the convulsion or lethal effect of pentamethylene tetrazole and cocaine. b. For treating cardiovascular diseases, rhizoma Ligustici Chuanxiong decoction is used for treating isolated Bufo siccus and frog heart at concentration of 10^-5-10^-4The amplitude of contraction is increased and the heart rate is slightly slower.

Licorice root: sweet and neutral in nature and flavor, enter heart, spleen, lung and stomach meridians. The liquorice contains various chemical components, the main components comprise glycyrrhizic acid, liquiritin and the like, the chemical composition of the liquorice is very complex, and the compounds separated from the liquorice at present comprise dozens of compounds such as glycyrrhizin, glycyrrhetinic acid, liquiritin, isoliquiritin, neoliquiritin, neoisoliquiritin, liquiritigenin, liquiritin, glyceol, isoliquiritigenin, 7-methyl coumarine, umbelliferone and the like, but the components and the quantity generally vary according to the type, planting area, harvesting time and other factors of the liquorice. A large number of researches show that glycyrrhizin and flavonoids are the most important physiological active substances in liquorice and mainly exist in the part inside the epidermis of liquorice root. The liquorice has the functions of regulating body immunity, resisting aging, inflammation and pathogenic microorganism, calming, resisting tumor, improving cardiovascular, tonifying spleen and qi, moistening lung and relieving cough, clearing heat and detoxicating, relieving pain, moderating drug property, eliminating phlegm and the like, and is used for treating weakness of spleen and stomach, shortness of breath and weakness, palpitation and severe palpitation, cough with little phlegm, toxic heat and pyocutaneous disease, medicine and food poisoning, abdominal and acute pain and limb contracture pain.

A Chinese medicinal composition for treating Alzheimer's disease and its preparation method are provided, which is characterized in that the dosage forms of the compound preparation include granule, dripping pill, nanometer preparation, decoction, tablet and capsule.

When the granule or the dropping pill is prepared, firstly, a liquorice extract, a mixed extract of astragalus and salvia miltiorrhiza, a mixed extract of polygonatum and ligusticum wallichii and a dendrobium nobile extract are respectively prepared, then the liquorice extract, the mixed extract of astragalus and salvia miltiorrhiza and the mixed extract of polygonatum and ligusticum wallichii are mixed and concentrated into a concentrated solution, and finally the dendrobium nobile extract and the concentrated solution are mixed and then added with an auxiliary agent to prepare a finished product.

Preferably, the preparation method of the liquorice extract comprises the following steps:

crushing liquorice into powder, adding water, performing ultrasonic treatment at low temperature of 0-10 ℃, rotation speed of 15000-30000 rpm and 50-60 Hz for 30-60 min, performing high-speed centrifugation, separating supernatant and precipitate, reserving the supernatant for later use, adding ethanol into the precipitate, performing low-temperature ultrasonic treatment for 15-30 min, performing suction filtration, washing filter residues with ethanol for 3-5 times, respectively collecting the filter residues and filtrate, and combining the filtrate and the supernatant to obtain a liquorice extracting solution.

Preferably, the preparation method of the mixed extract of the astragalus and the salvia comprises the following steps:

pulverizing radix astragali and Saviae Miltiorrhizae radix into powder, and placing the powder and Glycyrrhrizae radix residue for preparing Glycyrrhrizae radix extract in a decocting pot together at a solid-to-liquid ratio of 1: 4-8, adding deionized water, heating and boiling for 60-90 min under a reflux condition, adding ethanol with the same volume as the deionized water into a frying pan when the temperature is reduced to below 65 ℃, heating, carrying out micro-boiling reflux for 60-90 min, cooling to room temperature after the reaction is finished, and filtering with a 2.0-micrometer filter membrane to obtain primary filtrate; filtering the primary filtrate with 0.4 μm filter membrane to obtain mixed extractive solution of radix astragali and Saviae Miltiorrhizae radix.

Preferably, the preparation method of the mixed extract of rhizoma polygonati and ligusticum wallichii comprises the following steps:

pulverizing rhizoma Polygonati and rhizoma Ligustici Chuanxiong into powder, placing the powder and the residue obtained in the preparation of mixed extractive solution of radix astragali and Saviae Miltiorrhizae radix in a decocting pot, adding deionized water, heating to 95-100 deg.C, maintaining the temperature for 110-130 min, cooling to 55-65 deg.C, filtering with 2.0 μm filter membrane to obtain primary filtrate, and filtering with 0.4 μm filter membrane to obtain mixed extractive solution of rhizoma Polygonati and rhizoma Ligustici Chuanxiong.

Preferably, the licorice extract, the mixed extract of the astragalus root and the salvia miltiorrhiza and the mixed extract of the polygonatum rhizome and the ligusticum wallichii are stirred at a high speed, homogenized and mixed, and then concentrated into a mixed concentrated solution for later use. More preferably, the high speed stirring speed is 2900 revolutions per minute.

Preferably, the preparation method of the dendrobium nobile lindl extract comprises the following steps: the stem and flower of dendrobium nobile lindl are mixed according to the weight ratio of 5.0-6.5: 1.0-2.0, and grinding into powder, wherein the weight ratio of the raw materials is preferably 5.5: 1.5, taking the dendrobium nobile lindl powder under the conditions of extraction pressure of 5-l 0Mpa and extraction temperature of 15-25 ℃, and adopting CO₂Performing supercritical extraction to obtain dendrobium nobile volatile oil, adding the residual dendrobium nobile dregs obtained by the supercritical extraction into ethanol, soaking for 90-120 min at 30-50 ℃, performing reflux extraction for 120-180 min at 65-85 ℃, concentrating the extracting solution into dendrobium nobile extract, and mixing the obtained dendrobium nobile volatile oil and the dendrobium nobile extract to obtain the dendrobium nobile mixed extract.

In the invention, the steps for preparing the finished product of the granule are as follows:

and (2) stirring and mixing the mixed concentrated solution of the astragalus, the salvia miltiorrhiza, the polygonatum, the ligusticum wallichii and the liquorice extract with the dendrobium nobile mixed extract at a high speed, wherein the stirring speed is 2900 r/min, adding the auxiliary agent during stirring and mixing, homogenizing again, putting the mixture into an ultrasonic instrument, carrying out ultrasonic treatment at 50-60 Hz for 20-30 min, then feeding the mixture into a granulator for granulation to obtain a semi-finished product of the traditional Chinese medicine granules, and drying the semi-finished product to obtain the finished product of the traditional Chinese medicine granules. Preferably, the auxiliary agent for preparing the granule is a mixture of hydroxypropyl cellulose, maltodextrin and xylitol according to the weight ratio of 0.2-0.5:0.5-1.0:1.0-2.0, and the total weight ratio of the auxiliary agent to the extracts of all the components of the traditional Chinese medicine is 8-9: 1-2.

In the invention, the steps for preparing the finished dripping pill product are as follows:

stirring and mixing the mixed concentrated solution of the astragalus, the salvia, the polygonatum, the ligusticum wallichii and the liquorice extract with the dendrobium nobile mixed extract at a high speed of 2900 r/min, adding an auxiliary agent during stirring and mixing, stirring and mixing uniformly at a high speed, homogenizing again, carrying out ultrasonic treatment at 60-80 Hz for 40-60 min, carrying out melting and heat preservation at the temperature of 60-95 ℃, then putting into a special dripping pill machine, dripping into a condensing agent at the speed of 40-70 drops per minute, forming the dripping pills, taking out, removing the condensing agent, and drying to obtain the dendrobium nobile lindl dripping pill. Wherein the adjuvant for preparing dripping pill is mixture of two or more of polyethylene glycol 6000, polyethylene glycol 4000, sodium stearate, Tween 80, insect wax, and hydrogenated vegetable oil. Preferably, the mixture of adjuvants is polyethylene glycol 6000: polyethylene glycol 4000: the insect wax is prepared by mixing 1.0-2.0: 2.0-3.0:0.1-0.5, wherein the weight ratio of the mixed concentrated solution of the astragalus root, the salvia miltiorrhiza, the sealwort, the ligusticum wallichii and the liquorice extract to the mixed extract of the dendrobium nobile and the auxiliary agent is 15-30: 0.5-1.0: 2.0-5.0, preferably 25: 1.0: 3.5.

the preparation method of the nano preparation, the decoction, the tablet and the capsule in the invention is a conventional technical method in the traditional Chinese medicine industry.

Compared with the prior art, the invention has the following advantages:

the medicine of the invention improves the cognitive function of the brain and prevents the development process of the Alzheimer disease through the ways of neurotransmitter, cerebral vasodilation, brain metabolism promoting drugs and the like. The compound traditional Chinese medicine for treating the Alzheimer disease realizes the improvement of the treatment effect of the medicine on the Alzheimer disease through the specific targeting effect and the mutual cross function among the components.

Detailed Description

The invention will be further described with reference to specific embodiments.

Example 1:

the weight parts of each component are as follows: 48 parts of dendrobium nobile, 18 parts of astragalus mongholicus, 18 parts of salvia miltiorrhiza, 7 parts of rhizoma polygonati, 7 parts of ligusticum wallichii and 2 parts of liquorice. Wherein, the dendrobium nobile lindl is prepared from dendrobium nobile lindl stems and dendrobium nobile flowers according to the weight ratio of 5.5: 1.5.

The preparation method of the granule comprises the following steps:

1) making herba Dendrobii, radix astragali, Saviae Miltiorrhizae radix, rhizoma Polygonati, rhizoma Ligustici Chuanxiong, and Glycyrrhrizae radix into standard Chinese medicinal decoction pieces;

2) preparing a liquorice extracting solution: crushing liquorice into powder, adding water, performing ultrasonic treatment at low temperature of 0-10 ℃, rotation speed of 15000-30000 rpm and 50-60 Hz for 30-60 min, performing high-speed centrifugation, separating supernatant and precipitate, keeping the supernatant for later use, adding ethanol into the precipitate, performing low-temperature ultrasonic treatment for 15-30 min, performing suction filtration, washing filter residues with ethanol for 3-5 times, respectively collecting the filter residues and filtrate, and combining the filtrate and the supernatant to obtain an extracting solution for later use;

3) preparing an extracting solution of astragalus and salvia: pulverizing radix astragali and radix Salviae Miltiorrhizae into powder, and placing the powder and the radix Glycyrrhizae residue obtained in step 2) in a frying pan together at a solid-to-liquid ratio of 1: 4-8, adding deionized water, heating and boiling for 60-90 min under a reflux condition, adding ethanol with the same volume as the deionized water into a frying pan when the temperature is reduced to below 65 ℃, heating, carrying out micro-boiling reflux for 60-90 min, cooling to room temperature after the reaction is finished, and filtering with a 2.0-micrometer filter membrane to obtain primary filtrate; filtering the primary filtrate with 0.4 μm filter membrane to obtain extractive solution;

4) preparing a polygonatum and ligusticum wallichii extracting solution, crushing the polygonatum and ligusticum wallichii into powder, putting the powder and the filter residue obtained in the step 3) into a frying pan together, adding deionized water, heating to 95-100 ℃, keeping the temperature for 110-130 minutes, cooling to 55-65 ℃, filtering with a 2.0 mu m filter membrane to obtain a primary filtrate, and filtering the primary filtrate with a 0.4 mu m filter membrane to obtain an extracting solution for later use;

5) preparing a mixed concentrated solution of astragalus, salvia miltiorrhiza, rhizoma polygonati, ligusticum wallichii and liquorice extract: stirring the extracting solution prepared in the step 2) to the step 4) at a high speed, homogenizing and mixing, and then concentrating to obtain a mixed concentrated solution for later use;

6) preparing a dendrobium nobile mixed extract: herba DendrobiiThe stem and the dendrobium stem flower are 5.5: 1.5 mixing and crushing into powder, taking the dendrobium nobile lindl powder under the conditions of extraction pressure of 5-l 0Mpa and extraction temperature of 15-25 ℃, and adopting CO₂Performing supercritical extraction to obtain dendrobium nobile volatile oil, adding the residual dendrobium nobile dregs obtained by the supercritical extraction into ethanol, soaking for 90-120 min at 30-50 ℃, performing reflux extraction for 120-180 min at 65-85 ℃, concentrating the extracting solution into dendrobium nobile extract, and mixing the obtained dendrobium nobile volatile oil and the dendrobium nobile extract to obtain dendrobium nobile mixed extract for later use;

7) preparing granules: mixing the mixed concentrated solution of the astragalus, the salvia miltiorrhiza, the sealwort, the ligusticum wallichii and the liquorice extract with the dendrobium nobile mixed extract at a high speed, stirring at the rotating speed of 2900 revolutions per minute, adding an auxiliary agent in the stirring and mixing process, wherein the auxiliary agent is a mixture of hydroxypropyl cellulose, maltodextrin and xylitol according to the weight ratio of 0.2-0.5:0.5-1.0:1.0-2.0, and the total weight ratio of the auxiliary agent to all the extracts of the traditional Chinese medicines is 8-9: 1-2, homogenizing again after mixing uniformly, placing the mixture in an ultrasonic instrument for 20-30 min under 50-60 Hz ultrasonic treatment, then feeding the mixture into a granulator for granulation to obtain a semi-finished product of the traditional Chinese medicine granules, and drying the semi-finished product to obtain a finished product of the traditional Chinese medicine granules.

Example 2:

40 parts of dendrobium nobile, 20 parts of astragalus membranaceus, 20 parts of salvia miltiorrhiza, 8 parts of rhizoma polygonati, 8 parts of ligusticum wallichii and 4 parts of liquorice.

Wherein, the dendrobium nobile lindl is prepared from dendrobium nobile stems and dendrobium nobile flowers according to the weight ratio of 6.5: 2.0.

The preparation method of the granule comprises the following steps:

2) preparing a liquorice extracting solution: crushing liquorice into powder, adding water, performing low-temperature ultrasonic treatment for 30-60 min, performing high-speed centrifugation, separating supernatant and precipitate, keeping the supernatant for later use, adding ethanol into the precipitate, performing low-temperature ultrasonic treatment for 15-30 min, performing suction filtration, washing filter residues with ethanol for 3-5 times, respectively collecting the filter residues and filtrate, and combining the filtrate and the supernatant to obtain an extracting solution for later use;

6) preparing a dendrobium nobile mixed extract: the stem and flower of dendrobium nobile lindl are mixed according to the weight ratio of 6.5: 2.0, crushing into powder, taking the dendrobium nobile lindl powder under the conditions of extraction pressure of 5-l 0Mpa and extraction temperature of 15-25 ℃, and adopting CO₂Performing supercritical extraction to obtain dendrobium nobile volatile oil, adding the residual dendrobium nobile dregs obtained by the supercritical extraction into ethanol, soaking for 90-120 min at 30-50 ℃, performing reflux extraction for 120-180 min at 65-85 ℃, concentrating the extracting solution into dendrobium nobile extract, and mixing the obtained dendrobium nobile volatile oil and the dendrobium nobile extract to obtain dendrobium nobile mixed extract for later use;

Example 3:

the weight parts of each component are as follows: 50 parts of dendrobium nobile lindl, 15 parts of astragalus membranaceus, 15 parts of salvia miltiorrhiza, 4 parts of rhizoma polygonati, 4 parts of ligusticum wallichii and 2 parts of liquorice, wherein the dendrobium nobile lindl is prepared from dendrobium nobile lindl stems and dendrobium nobile flowers according to the weight ratio of 5.0: 1.0.

The decoction prepared from the components comprises the following steps:

putting the raw materials in a decocting device according to the total raw materials: the weight ratio of water is 1.0: 3.0, boiling for 30 minutes for the first time, filtering by a filter bag with the diameter of 2.0 mu m, and reserving filtrate for later use; adding water into the first-time boiling filtration residue, boiling for 60 minutes, filtering with a 1.5-micron filter bag, and reserving the filtrate for later use; adding water into the second boiled and filtered decoction dregs, boiling for 90 minutes, filtering by a filter bag with the diameter of 1.0 mu m, and reserving the filtrate for later use; and finally, combining the three filtrates, placing the combined filtrates in a closed container for sterilization and filling, storing the combined filtrates at the temperature of 0-10 ℃, and taking out and heating the combined filtrates when drinking.

Example 4:

the weight parts of each component are as follows: 46.5 parts of dendrobium nobile lindl, 17.5 parts of astragalus membranaceus, 17.5 parts of salvia miltiorrhiza, 7.5 parts of rhizoma polygonati, 7.5 parts of ligusticum wallichii and 3.5 parts of liquorice, wherein the dendrobium nobile lindl is prepared from dendrobium nobile lindl stems and dendrobium nobile flowers according to the weight ratio of 6.5: 1.0.

The steps of preparing the components into the nanometer preparation are as follows: mixing the raw materials, placing the mixture into an ultrafine pulverizer to perform ultrafine grinding to 50-100nm ultrafine powder, and uniformly mixing the ultrafine powder and the powder by a powder mixer to obtain a finished product.

Test example: study on the efficacy of the finished product of the embodiment of the invention

Firstly, the finished product drug granules prepared in the embodiment 1 are used for rat gavage treatment.

1. Modeling for purchasing SPF-grade SD adult rats

Model animal strains: SPF grade SD rats, healthy, 250-300 g in body weight.

Grouping experiments: normal control group, model group, positive medicine group and tested medicine group.

The experimental period is as follows: 4-6 weeks.

2. The modeling method comprises the following steps: abeta perfusion model

2.1 the basic principle in view of the neurotoxic effects of A β, brain perfusion and deposition of A β can replicate the dementia model.

2.2 method of operation

SD rat is anesthetized with 3% sodium pentobarbital (40mg/kg), unhaired, skin sterilized and cut open, two holes (AP-3.5mm, Ml + -2.0 mm, Dv2.7mm) are symmetrically drilled on skull with dental drill to obtain injection point of CA3 region of hippocampus, and Abeta is injected into bilateral hippocampus_1-28Fragments (2uL, 5nmol/uL), also can be injected unilaterally. Filling the empty needle with denture powder, suturing skin and sterilizing. Or perfusing the brain ventricle of the rat with Abeta by using a miniature osmotic pump or injecting Abeta into basal Nucleus (NB) of the rat_1-40A polypeptide.

2.3 Observation of indicators

1) Focal necrosis, neuronal loss and gliosis can be seen at the site of brain injection in experimental animals, leading to neuronal degeneration.

2) Injecting Abeta into human hippocampus to form a dementia model, detecting whether staining positive substances precipitate at an injection part by Congo red staining test, indicating that dystrophic axons appear by silver staining compared with the method of Xiaoshfski, and after injecting Abeta for 1 month, obviously losing neurons in the hippocampus by naked eyes, especially in dentate gyrus.

3) The brain ventricle of the rat is perfused with A beta by a miniature osmotic pressure pump, and the rat cognitive function is proved to be damaged by water maze and passive avoidance test, and the activity of choline acetyltransferase in the anterior cortex of the brain and the hippocampus is obviously reduced, and the results show that the A beta perfusion causes the dysfunction of the central nervous system.

4) Injection of Abeta into basal Nuclei (NB) of rats_1-40The polypeptide is determined to have plaque formation at an injection part through NissL staining and A beta immunoreaction, and is accompanied with cholinergic hypofunction, cholinergic neuron of basal nucleus is reduced, and Ach release is reduced.

5) Unilateral and bilateral hippocampal injection of Abeta_1-28Fragment (2ul, 5 n)mol/uL), the results of behavior experiments show that the injected Abeta reduces the mental motor coordination ability (PMC), and meanwhile, passive avoidance experiments show that the learning acquisition ability is damaged after the Abeta is injected, and the passive avoidance times are reduced. The above results show that a β perfusion is associated with impairment of learning and memory functions and neuronal degeneration and loss.

2.4 model modeling of AD rats is successful

The model not only shows the abnormity of passive reflection behavior, but also has prominent spatial resolution obstacle. Pathologically, the model not only has the characteristics of reduced number of neurons, reduced positive ChAT immunoreaction cells, but also has the characteristics of amyloid deposition of blood vessel walls, nerve fiber filaments, glial cell hyperplasia, increased generation of inflammatory mediators and the like, and is closer to the pathological characteristics of AD to a certain extent. Can be used as a means for researching the pathological mechanism of AD and evaluating therapeutic drugs. The model has short induction period and good repeatability, and can save the dosage of Abeta by injecting into hippocampus.

3. Aiming at AD rat model rats, the dosage of the finished product medicinal granule is calculated according to kilogram body weight for intragastric administration, the dosage is three dosages of low dosage and medium dosage, the dosage is conventional dosage, the dosage is 0.125g/250g, and the dosage is 2 times of the low dosage. The high dose is 4 times of the low dose, the stomach filling is carried out for one week, the stomach filling method uses a disposable syringe to suck medicine and uses a stomach filling needle to fill the stomach according to the conventional method, then the behavior change condition of the rat in the Morry water maze is tested, the space learning memory ability of the rat is tested, the result shows that the low and medium doses can obviously improve the space learning ability of the model rat, particularly the time for the model rat to search a platform is obviously shortened when the Morry water maze is tested, the search strategy is also improved, and the disordered and unchangeable mode is changed into the trend search.

4. Performing heart perfusion on the model rats and the control group, and taking the brains of the model rats and the control group to perform tau protein phosphorylation level, expression levels of methylated PP2Ac and methylase/demethylase, and expression levels of Abeta-40 and Abeta-42; meanwhile, taking the hippocampus of other rats treated in the same way, and detecting the phosphorylation level of each site of tau protein, the expression level of methylated PP2Ac and methylase/demethylase and the expression level of Abeta-40 and Abeta-42 in the hippocampus by using a Western blot experiment technology, thereby discussing and clarifying the treatment mechanism and the treatment effect. NFTs caused by hyperphosphorylation of Tau protein are one of the major pathological features of the brain in AD. The research proves that the phosphorylation sites on the Tau protein molecules are more than 30, the Tau protein molecules in normal brain contain 2-4 phosphate groups, and each Tau protein molecule can contain 6-12 phosphate groups in the brain of AD patients due to hyperphosphorylation of the Tau protein. Hyperphosphorylated Tau protein loses its normal physiological function, resulting in neurofibrillary tangles, causing impaired nerve axonal transport, causing synaptic loss, neuronal damage, and ultimately, cerebral neurodegeneration in AD patients. Post-translational modifications of proteins have a significant impact on protein function. In normal brain, Tau protein phosphorylation and dephosphorylation are in equilibrium under the combined action of protein kinase and protein phosphatase. With the change of the apparent conditions such as age, environment, nutritional status, etc., the balance may be broken, causing the enhancement of the related protein kinase, the weakening of the protein phosphatase, and the hyperphosphorylation of Tau protein. There are a wide variety of protein kinases and protein phosphatases that regulate protein phosphorylation and dephosphorylation. The Tau protein phosphatases are mainly classified into Phosphoprotein Phosphatases (PPs) and phosphotyrosinase (PTPs). Among them, the substrate amino acid residue for dephosphorylation of PPs is serine/threonine residue, and mainly includes various subtypes such as PP1, PP2A, PP2B, PP4, PP5, etc., and plays a major role in the dephosphorylation process of phosphorylated Tau (p-Tau) protein. Therefore, PP2A is considered as a key phosphatase for dephosphorylation of p-Tau protein, and activity change of PP2A is closely related to pathological process of AD.

The result shows that the finished medicine of the invention can reduce the demethylase PME and the demethylation and phosphorylation levels of PP2Ac, and simultaneously can reduce the phosphorylation level of the Thr668 site of APP and inhibit the expression level of Abeta-40. The Tau protein molecule in the model rat is reduced from the original 11 phosphate groups to 4 phosphate groups, reaching the normal level. In the total dephosphorylation of phosphorylated Tau protein, the PP2A action accounted for 69.235% and the sum of the other protein phosphatases accounted for 30.765%. The phosphorylation sites on the Tau protein molecule are reduced from the original 35 to 21, and the value returns to the normal value.

5. A clean SD adult rat is purchased, the dosage of the finished product medicinal granule is calculated according to kilogram body weight, the stomach is irrigated, the blood concentration of the finished product medicinal granule with higher concentration in the blood of the rat is kept, and the aim of treating the Alzheimer disease is fulfilled by using the medicament.

6. Injecting Wortmannine + GFX which is a tool medicine capable of causing the activity of protein kinase GSK-3beta to be increased and 0A which is a tool medicine capable of causing the activity of PP2Ac to be reduced into the ventriculus cerebralis of the SD rat with gastric perfusion, and preparing an Alzheimer disease rat model with the activity of protein kinase GSK-3beta in hippocampal tissues and the activity of protein phosphatase PP2Ac to be reduced.

The above mechanism can illustrate the therapeutic mechanism of the compound preparation of the invention for treating Alzheimer disease.

Secondly, the traditional Chinese medicine formula for treating the Alzheimer disease is added, added or replaced according to the traditional Chinese medicine compound formula, and the contrast test of the effect of treating the Alzheimer disease is carried out

The method for researching the drug effect of the finished product in the embodiment of the invention is adopted to evaluate the drug effect, the components in the formula of the invention are added, subtracted or replaced under the same test method and the same environmental conditions, and the components are prepared into granules or dropping pills, and the change of the research and treatment effect is observed.

The evaluation results of the specific formula addition change or substitution change and the treatment effect on the Alzheimer disease after the formula addition change or substitution change are shown in the following tables (tables 1 and 2):

table 1: prescription addition, subtraction or replacement change table

Wherein, the dendrobium nobile lindl is prepared from dendrobium nobile stems and dendrobium nobile flowers according to the weight ratio of 5.0-6.5: 1.0-2.0. Preferably 5.5: 1.5.

table 2: evaluation of treatment effect of the composition on treating Alzheimer's disease after addition, subtraction or replacement of the composition

The traditional Chinese medicine formula for treating the Alzheimer disease is compounded according to the theory of traditional Chinese medicines and the principle of monarch, minister, assistant and guide, the dendrobium nobile is monarch drug, the astragalus and the red sage root are ministerial drugs, the ligusticum wallichii and the rhizoma polygonati are assistant drugs, and the liquorice is a conductant drug. The compound traditional Chinese medicine is prepared by adopting modern new traditional Chinese medicine technology and based on the pharmacological screening of modern traditional Chinese medicines, and the medicine improves the cognitive function of the brain and prevents the development process of the Alzheimer disease through the ways of neurotransmitter, cerebral vasodilation, brain metabolism promoting medicines and the like. The invention realizes the improvement of the treatment effect of the medicament on the Alzheimer disease through the specific targeting action and the mutual cross function among the components. The interaction and cross effect among the traditional Chinese medicine components are realized based on the basic principle, the action and the efficacy of the traditional Chinese medicine formula and the analysis of the components of the modern traditional Chinese medicine, the targeting action of the medicine, the efficacy and the toxicological evaluation and the like. The traditional Chinese medicine composition has obvious effects of improving and treating symptoms caused by the Alzheimer disease, has short treatment course, quick response, safety and no toxic or side effect, and can be widely applied to clinical treatment of the Alzheimer disease.

Claims

1. The traditional Chinese medicine for treating the Alzheimer disease is characterized by comprising the following components in parts by weight:

2. The traditional Chinese medicine for treating Alzheimer's disease according to claim 1, which is characterized by comprising the following components in parts by weight:

48 parts of dendrobium nobile lindl, 18 parts of astragalus membranaceus, 18 parts of salvia miltiorrhiza, 7 parts of polygonatum sibiricum, 7 parts of ligusticum wallichii and 2 parts of liquorice, wherein the dendrobium nobile lindl consists of dendrobium nobile stems and dendrobium nobile flowers, and the weight ratio of the dendrobium nobile stems to the dendrobium nobile flowers is 5.5: 1.5.

3. a method for preparing a compound Chinese medicine preparation for treating Alzheimer's disease according to claim 1, wherein the dosage form of the compound preparation comprises granules, dripping pills, nano preparations, decoctions, tablets and capsules.

4. The method for preparing a compound Chinese medicinal preparation for treating Alzheimer's disease according to claim 3, wherein the granule or drop pill is prepared by respectively preparing radix Glycyrrhizae extractive solution, radix astragali and radix Salviae Miltiorrhizae extractive solution, rhizoma Polygonati and rhizoma Chuanxiong extractive solution, and herba Dendrobii extract, mixing radix Glycyrrhizae extractive solution, radix astragali and radix Salviae Miltiorrhizae extractive solution, and rhizoma Polygonati and rhizoma Chuanxiong extractive solution, concentrating, mixing herba Dendrobii extract and concentrated solution, and adding adjuvant to obtain the final product.

5. The preparation method of the compound traditional Chinese medicine preparation for treating Alzheimer's disease according to claim 4, wherein the preparation method of the liquorice extract, the mixed extract of radix astragali and Salvia miltiorrhiza, the mixed extract of rhizoma Polygonati and rhizoma Ligustici Chuanxiong, and the Dendrobium nobile extract comprises the following steps:

1) preparing a liquorice extracting solution: crushing liquorice into powder, adding water, performing ultrasonic treatment at low temperature of 0-10 ℃, rotation speed of 15000-30000 rpm and 50-60 Hz for 30-60 min, performing high-speed centrifugation, separating supernatant and precipitate, reserving the supernatant for later use, adding ethanol into the precipitate, performing low-temperature ultrasonic treatment for 15-30 min, performing suction filtration, washing filter residues with ethanol for 3-5 times, respectively collecting the filter residues and filtrate, and combining the filtrate and the supernatant to obtain a liquorice extracting solution;

2) preparing a mixed extracting solution of astragalus and salvia: pulverizing radix astragali and radix salviae miltiorrhizae into powder, putting the powder and the licorice residue obtained in the step 1) into a frying pan together, and mixing the powder and the licorice residue according to a solid-liquid ratio of 1: 4-8, adding deionized water, heating and boiling for 60-90 min under a reflux condition, adding ethanol with the same volume as the deionized water into a frying pan when the temperature is reduced to below 65 ℃, heating, carrying out micro-boiling reflux for 60-90 min, cooling to room temperature after the reaction is finished, and filtering with a 2.0-micrometer filter membrane to obtain primary filtrate; filtering the primary filtrate with 0.4 μm filter membrane to obtain mixed extractive solution of radix astragali and Saviae Miltiorrhizae radix;

3) preparing a mixed extracting solution of rhizoma polygonati and ligusticum wallichii: pulverizing rhizoma polygonati and ligusticum wallichii into powder, putting the powder and the filter residue obtained in the step 2) into a frying pan together, adding deionized water, heating to 95-100 ℃, keeping the temperature for 110-130 minutes, cooling to 55-65 ℃, filtering with a 2.0 mu m filter membrane to obtain primary filtrate, and filtering the primary filtrate with a 0.4 mu m filter membrane to obtain a mixed extract of the rhizoma polygonati and the ligusticum wallichii;

4) preparing the dendrobium nobile extract: the stem and flower of dendrobium nobile lindl are mixed according to the weight ratio of 5.0-6.5: 1.0-2.0, crushing into powder, taking the dendrobium nobile lindl powder under the conditions of extraction pressure of 5-l 0Mpa and extraction temperature of 15-25 ℃, and adopting CO₂Performing supercritical extraction to obtain dendrobium nobile volatile oil, adding the residual dendrobium nobile dregs obtained by the supercritical extraction into ethanol, soaking for 90-120 min at 30-50 ℃, performing reflux extraction for 120-180 min at 65-85 ℃, concentrating the extracting solution into dendrobium nobile extract, and mixing the obtained dendrobium nobile volatile oil and the dendrobium nobile extract to obtain the dendrobium nobile mixed extract.

6. The preparation method of the compound traditional Chinese medicine preparation for treating alzheimer disease as claimed in claim 3, wherein the preparation steps of the compound preparation as a finished granule product are as follows:

mixing and concentrating a liquorice extract, a mixed extract of astragalus and salvia miltiorrhiza and a mixed extract of polygonatum and ligusticum wallichii into a mixed concentrated solution, then stirring and mixing the mixed concentrated solution with the dendrobium nobile at a high speed, wherein the stirring speed is 2900 r/min, adding an auxiliary agent during stirring and mixing, homogenizing again, placing the mixture in an ultrasonic instrument for ultrasonic treatment at 50-60 Hz for 20-30 min, then feeding the mixture into a granulator for granulation to obtain a semi-finished product of traditional Chinese medicine granules, and drying the semi-finished product to obtain a finished product of the traditional Chinese medicine granules.

7. The method for preparing a compound Chinese medicine preparation for treating alzheimer's disease as claimed in claim 6, wherein the adjuvant for preparing the granule is a mixture of hydroxypropyl cellulose, maltodextrin and xylitol in a weight ratio of 0.2-0.5:0.5-1.0:1.0-2.0, and the total weight ratio of the adjuvant to the total extracts of all the Chinese medicinal materials is 8-9: 1-2.

8. The preparation method of the compound traditional Chinese medicine preparation for treating Alzheimer's disease according to claim 3, wherein the preparation method of the compound preparation as a finished product of dripping pills comprises the following steps:

mixing and concentrating a liquorice extract, a mixed extract of astragalus and salvia miltiorrhiza and a mixed extract of polygonatum and ligusticum wallichii into a mixed concentrated solution, then stirring and mixing the mixed concentrated solution with a dendrobium nobile at a high speed of 2900 r/min, uniformly stirring and mixing the added auxiliary agents while stirring, homogenizing again, carrying out ultrasonic treatment for 40-60 min at 60-80 Hz, carrying out melting and heat preservation at the temperature of 60-95 ℃, then putting the mixed solution into a special dropping pill machine, dripping the mixed solution into a condensing agent at the speed of 40-70 drops per minute, forming the dropping pill, taking out, removing the condensing agent, and drying to obtain the finished product.

9. The method for preparing a compound Chinese medicinal preparation for treating alzheimer's disease according to claim 8, wherein the adjuvant for preparing the dripping pill is a mixture of any two or more of polyethylene glycol 6000, polyethylene glycol 4000, sodium stearate, tween 80, insect wax and hydrogenated vegetable oil.

10. The preparation method of the compound traditional Chinese medicine preparation for treating alzheimer disease according to claim 9, characterized in that the weight ratio of each component of the adjuvant is polyethylene glycol 6000: polyethylene glycol 4000: the insect wax is 1.0-2.0: 2.0-3.0:0.1-0.5, wherein the weight ratio of the mixed concentrated solution of the astragalus root, the salvia miltiorrhiza, the sealwort, the szechuan lovage rhizome and the liquorice extract to the mixed extract of the dendrobium nobile and the auxiliary agent is 15-30: 0.5-1.0: 2.0-5.0.