CN116726138B

CN116726138B - Traditional Chinese medicine composition for treating senile parkinsonism and complications, and preparation method and application thereof

Info

Publication number: CN116726138B
Application number: CN202311013415.8A
Authority: CN
Inventors: 杨明会; 李绍旦; 张印; 崔艺馨; 陈琦
Original assignee: 6th Medical Center of PLA General Hospital
Current assignee: 6th Medical Center of PLA General Hospital
Priority date: 2023-08-11
Filing date: 2023-08-11
Publication date: 2023-11-24
Anticipated expiration: 2043-08-11
Also published as: CN116726138A

Abstract

The invention provides a traditional Chinese medicine composition for treating senile parkinsonism and complications thereof. The traditional Chinese medicine composition provided by the invention can fill the market gap of medicines for treating parkinsonism. Clinical test data show that the compound kidney-tonifying and blood-activating particles can delay the early stage development speed of PD and realize synergistic effect of PD in middle and late stages, and have definite curative effect. Experiments prove that the compound kidney-tonifying and blood-activating particles can regulate and control the expression of the nerve cell factor in the nigrostriatal body and play a therapeutic role. The traditional Chinese medicine composition provided by the invention has definite curative effect on non-exercise symptoms, has high effectiveness, high safety and small adverse reaction, has no obvious adverse reaction in clinical practice, and can realize long-term health care and prevention effects on kidney deficiency and blood stasis symptoms such as high-altitude parkinsonism, senile vascular dementia, cerebral infarction sequelae and the like of senile groups.

Description

Traditional Chinese medicine composition for treating senile parkinsonism and complications, and preparation method and application thereof

Technical Field

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating senile parkinsonism and complications, and a preparation method and application thereof.

Background

Parkinson's Disease (PD) is a slowly progressive neurodegenerative disease of the central nervous system that is common in the middle aged and elderly, with progressive degeneration of the substantia nigra dopamine neurons of the midbrain as the primary, multiple system involvement. PD is mainly characterized by motor symptoms such as bradykinesia, resting tremor, muscle stiffness and postural gait disorder, and non-motor symptoms such as cognitive mood disorder, sleep disorder, abnormal urination, pain and fatigue. Epidemiological investigation shows that the incidence rate of the disease of people over 65 years old reaches 1.7%, and certain younger trend is presented, and the average new PD patients in China reach 10 ten thousand per year. Motor symptoms and non-motor symptoms of PD patients cause a series of dysfunctions of varying severity, severely affecting the patient's ability to exercise in daily life, resulting in reduced quality of life and loss of work. The treatment of PD is mainly carried out by using medicines, the early disease of PD progresses rapidly, and no treatment method or medicine has sufficient evidence at present that the disease can be delayed. The efficacy of the traditional effective medicines for treating the diseases gradually decreases, and side effects such as the catabolism and the like are also larger and larger, so that patients are difficult to tolerate the traditional effective medicines; surgical treatment such as deep brain electrical stimulation (DBS) may partially improve the symptoms of dyskinesia in patients, but there are complications associated with nerve stimulation after surgery. The fact that PD patients have an average life expectancy of up to 17 years after self-diagnosis is sufficient to underscore the necessity and importance of developing long-term treatment strategies. The morbidity, the prevalence and the disability rate of PD are obviously increased, and become the difficulty of important public health and health problems of the aging society in China. How to delay the early stage development speed of PD, how to improve the western medicine synergy of middle and late stage PD patients, improve the western medicine sensitivity and the like is a core problem which is difficult to overcome in the current PD treatment.

Disclosure of Invention

In view of the above, the technical problem to be solved by the invention is to provide a traditional Chinese medicine composition for treating senile parkinsonism and complications, and a preparation method and application thereof.

The invention provides a traditional Chinese medicine composition for treating senile parkinsonism and complications, which is prepared from the following raw materials in parts by mass:

15-30 parts of cistanche salsa, 15-20 parts of red sage root, 15-20 parts of grassleaf sweetflag rhizome, 15-20 parts of dogwood fruit, 10-20 parts of leech, 15-20 parts of szechuan lovage rhizome, 15-20 parts of roasted polygala tenuifolia, 15-20 parts of prepared fleece-flower root, 10-15 parts of ginger, 6-15 parts of centipede, 15-30 parts of astragalus membranaceus, 15-20 parts of red paeony root, 15-20 parts of Chinese angelica, 10-15 parts of morinda officinalis, 10-15 parts of glossy privet fruit, 10-15 parts of raspberry, 10-15 parts of radix angelicae pubescentis, 10-15 parts of Chinese taxillus twig, 10-15 parts of achyranthes root, 10-15 parts of vinegar turtle shell, 10-15 parts of figwort root, 6-10 parts of cassia twig, 10-15 parts of kudzuvine root, 10-15 parts of radix bupleuri, 6-10-15 parts of bitter orange, 10-15 parts of dried chicken gizzard-skin and 10-15 parts of chicken's gizzard-skin.

The invention also provides a preparation method of the traditional Chinese medicine composition, which comprises the following steps:

a) Pulverizing rhizoma Acori Graminei and radix Polygoni Multiflori Preparata to obtain medicinal powder;

B) Pulverizing rhizoma Ligustici Chuanxiong, extracting with ethanol solution, filtering the extractive solution, and concentrating to obtain rhizoma Ligustici Chuanxiong dry extract;

c) Mixing Corni fructus, cistanchis herba, hirudo, saviae Miltiorrhizae radix, cortex et radix Polygalae, rhizoma Zingiberis recens, scolopendra, radix astragali, radix Paeoniae Rubra, radix Angelicae sinensis, radix Morindae officinalis, fructus Ligustri Lucidi, rubi fructus, radix Angelicae Pubescentis, herba Taxilli, achyranthis radix, carapax Trionycis Vinegar, radix scrophulariae, ramulus Cinnamomi, radix Puerariae, bupleuri radix, fructus Aurantii, radix rehmanniae and endothelium corneum Gigeriae Galli with water, soaking, decocting to obtain decoction;

filtering the decoction, and concentrating to obtain mixed dry extract;

d) Mixing the medicinal powder, rhizoma Ligustici Chuanxiong dry extract and the mixed dry extract to obtain the Chinese medicinal composition.

Preferably, in the step A), the crushed granularity is that the powder is crushed to pass through a 80-mesh screen;

in the step B), the volume concentration of the ethanol solution is 60% -80%, and the mass volume ratio of the ligusticum wallichii to the ethanol solution is 1: (6-10);

in the step C), the soaking time is 0.5-2 hours, the times of decoction are two times, and the feed liquid ratio of the first decoction is 1: (8-15), wherein the decoction time is 1.5 hours; the second decoction liquid is 1: (6-12), wherein the decoction time is 1.5 hours; mixing the water extracts obtained by the two times of decoction to obtain decoction;

Concentrating at 50-60 ℃ under reduced pressure to obtain thick paste with the relative density of 1.25-1.4.

The invention also provides application of the traditional Chinese medicine composition in preparing medicines for treating and/or preventing senile parkinsonism and complications.

Preferably, the senile parkinson's disease and complications are early senile parkinson's disease and complications.

Preferably, the dosage of the traditional Chinese medicine composition is 20-30 g/day.

The invention also provides a pharmaceutical composition comprising the metaba and the traditional Chinese medicine composition.

The invention also provides application of the pharmaceutical composition in preparing medicines for treating and/or preventing senile parkinsonism and complications.

Preferably, the senile parkinsonism and complications thereof are middle-late senile parkinsonism and complications thereof.

Preferably, the dosage of the methoamub and the traditional Chinese medicine composition is 375-500 mg methoamub/day and 20-30 g traditional Chinese medicine composition/day.

Compared with the prior art, the invention provides a traditional Chinese medicine composition for treating senile parkinsonism and complications, which is prepared from the following raw materials in parts by mass: 15-30 parts of cistanche salsa, 15-20 parts of red sage root, 15-20 parts of grassleaf sweetflag rhizome, 15-20 parts of dogwood fruit, 10-20 parts of leech, 15-20 parts of szechuan lovage rhizome, 15-20 parts of roasted polygala tenuifolia, 15-20 parts of prepared fleece-flower root, 10-15 parts of ginger, 6-15 parts of centipede, 15-30 parts of astragalus membranaceus, 15-20 parts of red paeony root, 15-20 parts of Chinese angelica, 10-15 parts of morinda officinalis, 10-15 parts of glossy privet fruit, 10-15 parts of raspberry, 10-15 parts of radix angelicae pubescentis, 10-15 parts of Chinese taxillus twig, 10-15 parts of achyranthes root, 10-15 parts of vinegar turtle shell, 10-15 parts of figwort root, 6-10 parts of cassia twig, 10-15 parts of kudzuvine root, 10-15 parts of radix bupleuri, 6-10-15 parts of bitter orange, 10-15 parts of dried chicken gizzard-skin and 10-15 parts of chicken's gizzard-skin. The traditional Chinese medicine composition provided by the invention can fill the market gap of medicines for treating parkinsonism. Clinical test data show that the compound kidney-tonifying and blood-activating particles can delay the early stage development speed of PD and realize synergistic effect of PD in middle and late stages, and have definite curative effect. Experiments prove that the compound kidney-tonifying and blood-activating particles can regulate and control the expression of the nerve cell factor in the nigrostriatal body and play a therapeutic role. The traditional Chinese medicine composition provided by the invention has definite curative effect on non-exercise symptoms, has high effectiveness, high safety and small adverse reaction, has no obvious adverse reaction in clinical practice, and can realize long-term health care and prevention effects on kidney deficiency and blood stasis symptoms such as high-altitude parkinsonism, senile vascular dementia, cerebral infarction sequelae and the like of senile groups.

Drawings

Fig. 1 is a flow chart of a preparation process of a traditional Chinese medicine composition for treating senile parkinsonism and complications, which is provided by the invention;

FIG. 2 is a rat midbrain striatal dopamine transporter (DAT) PET imaging;

FIG. 3 shows the expression of Bcl-2 and Bax proteins in the brain substantia nigra of rats of each group;

FIG. 4 shows the expression of Bcl-2 and Bax proteins from the striatum of rats in each group;

FIG. 5 shows Fas and FADD expression in the brain of each group of rats;

FIG. 6 shows Fas and FADD expression in the striatum of the rat brain of each group;

FIG. 7 shows striatal adenosine A in groups of rats _2A Percentage of protein expression%±s)；

FIG. 8 shows the percentage expression of DMT1 protein in the striatum of each group of rats±s)；

FIG. 9 shows the percentage expression of the striatal Nrf2 protein of each group of rats±s)；

FIG. 10 shows the percentage expression of the striatum VMAT2 protein in each group of rats±s)；

FIG. 11 is a rat brain striatal adenosine A _2A Protein immunofluorescence results (×20);

FIG. 12 shows immunofluorescence of rat brain striatal adenosine DMT1 protein (x 20);

FIG. 13 shows immunofluorescence of rat brain striatal adenosine Nrf2 protein (. Times.20);

FIG. 14 shows the immunofluorescence of rat brain striatal adenosine VMAT2 protein (x 20).

Detailed Description

The preparation raw materials of the traditional Chinese medicine composition provided by the invention comprise 15-30 parts of cistanche deserticola, preferably 15, 20, 25, 30 or any value between 15-30 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 15-20 parts of red sage root, preferably 15, 16, 17, 18, 19, 20 or any value between 15-20 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 15-20 parts of grassleaf sweelflag rhizome, preferably 15, 16, 17, 18, 19, 20 or any value between 15-20 parts.

The preparation raw materials of the traditional Chinese medicine composition further comprise 15-20 parts of cornus officinalis, preferably 15, 16, 17, 18, 19, 20 or any value between 15-20 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 10-20 parts of leech, preferably 10, 12, 14, 15, 16, 18, 20 or any value between 10-20 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 15-20 parts of ligusticum wallichii, preferably 15, 16, 17, 18, 19, 20 or any value between 15-20 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 15-20 parts of roasted polygala tenuifolia, preferably 15, 16, 17, 18, 19, 20 or any value between 15-20 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 15-20 parts of prepared fleece flower root, preferably 15, 16, 17, 18, 19, 20 or any value between 15-20 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 10-15 parts of ginger, preferably 10, 11, 12, 13, 14, 15 or any value between 10-15 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 6-15 parts of centipedes, preferably 6, 8, 10, 12, 14, 15 or any value between 6 and 15 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 15-30 parts of astragalus, preferably 15, 20, 25, 30 or any value between 15-30 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 15-20 parts of red paeony root, preferably 15, 16, 17, 18, 19, 20 or any value between 15 and 20 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 15-20 parts of angelica, preferably 15, 16, 17, 18, 19, 20 or any value between 15-20 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 10-15 parts of morinda officinalis, preferably 10, 11, 12, 13, 14, 15 or any value between 10-15 parts.

The preparation raw materials of the traditional Chinese medicine composition further comprise 10-15 parts of glossy privet fruits, preferably 10, 11, 12, 13, 14 and 15 parts or any value between 10 and 15 parts.

The preparation raw materials of the traditional Chinese medicine composition further comprise 10-15 parts of raspberry, preferably 10, 11, 12, 13, 14, 15 or any value between 10-15 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 10-15 parts of radix angelicae pubescentis, preferably 10, 11, 12, 13, 14, 15 or any value between 10-15 parts.

The preparation raw materials of the traditional Chinese medicine composition further comprise 10-15 parts of mistletoe, preferably 10, 11, 12, 13, 14, 15 or any value between 10-15 parts.

The preparation raw materials of the traditional Chinese medicine composition further comprise 10-15 parts of radix achyranthis bidentatae, preferably 10, 11, 12, 13, 14, 15 or any value between 10-15 parts.

The preparation raw materials of the traditional Chinese medicine composition further comprise 10-15 parts of vinegar turtle shell, preferably 10, 11, 12, 13, 14, 15 or any value between 10-15 parts.

The preparation raw materials of the traditional Chinese medicine composition further comprise 10-15 parts of radix scrophulariae, preferably 10, 11, 12, 13, 14, 15 or any value between 10-15 parts.

The preparation raw materials of the traditional Chinese medicine composition also comprise 6-10 parts of cassia twig, preferably 6, 7, 8, 9, 10 or any value between 6 and 10 parts.

The preparation raw materials of the traditional Chinese medicine composition further comprise 10-15 parts of radix puerariae, preferably 10, 11, 12, 13, 14, 15 or any value between 10-15 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 10-15 parts of bupleurum, preferably 10, 11, 12, 13, 14, 15 or any value between 10-15 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 6-10 parts of fructus aurantii, preferably 6, 7, 8, 9, 10 or any value between 6 and 10 parts.

The preparation raw materials of the traditional Chinese medicine composition provided by the invention also comprise 10-15 parts of radix rehmanniae, preferably 10, 11, 12, 13, 14, 15 or any value between 10-15 parts.

The preparation raw materials of the traditional Chinese medicine composition also comprise 10-15 parts of chicken's gizzard-membrane, preferably 10, 11, 12, 13, 14, 15 or any value between 10-15 parts.

filtering the decoction, and concentrating to obtain mixed dry extract;

Wherein, in the step A), the crushed granularity is that the powder is crushed to pass through a 80-mesh screen;

In the step B), the peak number and the total peak area of the extract are greatly different along with the change of the concentration of the ethanol solvent; the volatile oil, alkaloid, phenolic component, organic acid and phthalide lactone component contained in rhizoma Ligustici Chuanxiong are mostly fat-soluble components and are easily dissolved in ethanol. The ethanol extract with the volume concentration of 60-80% has the maximum peak, the maximum total peak area and the great difference compared with other concentrations, so that the ethanol solution with the volume concentration of 60-80% is preferable for extracting the ligusticum wallichii. Preferably 60%, 65%, 70%, 75%, 80%, or any value between 60% and 80%, wherein the mass volume ratio of the ligusticum wallichii to the ethanol solution is 1: (6-10), preferably 1:6, 1:7, 1:8, 1:9, 1:10, or 1: any value between (6) and (10);

in the step C), the soaking time is 0.5-2 hours, preferably any value between 0.5, 1, 1.5, 2 or 0.5-2 hours, the times of the decoction are two times, and the feed liquid ratio of the first decoction is 1: (8-15), preferably 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, or 1: any value between (8) and (15), and the decoction time is 1.5 hours; the second decoction liquid is 1: (6-12), preferably 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, or 1: any value between (6) and (12), and the decoction time is 1.5 hours; mixing the water extracts obtained by the two times of decoction to obtain decoction;

Finally, the medicinal powder, the Ligusticum wallichii dry extract and the mixed dry extract are mixed to obtain the traditional Chinese medicine composition. And the traditional Chinese medicine composition can be prepared into granule preparations, paste preparations, oral liquid, micropills, dripping pills, honeyed pills, watered pills, capsules and tablets according to the dosage form requirement.

The preparation prepared from the traditional Chinese medicine composition is prepared from medicinal powder and extract, so that more excipients are not required to be added, and dextrin is used as an additive due to the fluctuation of medicinal materials and extraction rate. The taste of the traditional Chinese medicine is bitter in most of the prescription, so that the taste is difficult to adjust. Sodium cyclamate and stevioside are selected as flavoring agents, and the flavoring agents are repeatedly adjusted by a plurality of people, and the stevioside is selected as the flavoring agents.

The senile parkinsonism and complications thereof are early senile parkinsonism and complications thereof.

For early PD patient treatment, the compound kidney-tonifying and blood-activating particles can effectively improve non-motor symptoms such as constipation, depression, sleep disorder, dysosmia and the like, and improve the levels of brain neurotransmitters DA, NE and 5-HT and indexes of upper limb muscular tension, TUGT and 10 MWT; the compound kidney-tonifying and blood-activating particles can effectively relieve exercise symptoms, reduce muscle tension, enhance exercise capacity of patients and obviously delay early PD progression speed.

In the invention, the dosage of the traditional Chinese medicine composition is 20-30 g/day, and the dosage can be appropriately increased or decreased according to the illness state.

In the present invention, the pharmaceutical composition further comprises one or more of antane, amantadine, tah Shu Da.

Wherein the senile parkinsonism and complications thereof are middle-late senile parkinsonism and complications thereof.

For the treatment of PD patients in middle and late stages, the compound kidney-tonifying and blood-activating particles can effectively improve non-motor symptoms such as dysosmia and the like, and improve indexes such as the level of brain neurotransmitters DA, NE and 5-HT, the tension of upper limb muscles, TUGT and 10 MWT; the compound kidney-tonifying and blood-activating particles are added on the basis of the methoamum, so that the exercise symptoms can be effectively relieved, the muscle tension can be effectively relieved, the exercise capacity of a patient can be enhanced, and the progress of the illness can be delayed due to the synergistic effect of the compound kidney-tonifying and blood-activating particles.

In the invention, the dosage of the methoamub and the traditional Chinese medicine composition is 375-500 mg methoamub/day and 20-30 g traditional Chinese medicine composition/day, and the dosage can be appropriately increased or decreased according to the illness state.

One of the action mechanisms of the traditional Chinese medicine composition for treating the parkinsonism is possibly related to inhibiting Fas and FADD expression, blocking activation of Fas-FADD-caspase-8 pathway and playing a role in inhibiting apoptosis.

One of the action mechanisms of the traditional Chinese medicine composition for treating the parkinsonism is to inhibit apoptosis by up-regulating the expression of PD rat black matrix Bcl-2 protein and down-regulating the expression of Bax protein.

The invention deduces that the traditional Chinese medicine composition plays roles in enhancing DAR2 activity, regulating GABA energy neuron network in striatum, enhancing activity of middle acanthose neuron, inhibiting indirect pathway, enhancing direct pathway and playing a role similar to adenosine A _2A Receptor antagonists, thereby treating parkinson's disease.

The invention concludes that the traditional Chinese medicine composition plays a role in reducing abnormal deposition of iron in brain, resisting oxidative stress, reducing damage of dopamine neurons and protecting the dopamine neurons.

The invention concludes that the traditional Chinese medicine composition plays roles of resisting oxidative stress, inhibiting inflammatory reaction, resisting apoptosis and protecting dopaminergic neurons and astrocytes.

The invention concludes that the traditional Chinese medicine composition plays a role in resisting free radicals and reducing damage of dopamine neurons.

In conclusion, the traditional Chinese medicine composition provided by the invention can regulate and control the expression of the nerve cell factor in the nigrostriatal body.

The invention is deepened and optimized through long-term clinical practice of the past proved recipe, and centipede, astragalus root, red paeony root, angelica, morinda officinalis, glossy privet fruit, raspberry, radix angelicae pubescentis, mistletoe, radix achyranthis bidentatae, vinegar turtle shell, radix scrophulariae, cassia twig, kudzuvine root, radix bupleuri, fructus aurantii, radix rehmanniae and chicken's gizzard-membrane are added on the basis of taking kidney-tonifying and blood-activating particles as main materials (cistanche, radix salviae miltiorrhizae, rhizoma acori graminei, fructus corni, leech, ligusticum wallichii, radix polygala tenuifolia preparata, radix polygoni multiflori preparata and ginger). The recipe takes cistanche salsa, red sage root, cornus officinalis, prepared fleece flower root, centipede, red paeony root, angelica, morinda root, glossy privet fruit, raspberry, achyranthes root and dried rehamnnia root as the main medicine, and the large-dose kidney tonifying medicine and the blood circulation activating, stasis removing and vein relaxing medicine are combined to tonify kidney and activate blood; astragalus root is a key medicine for tonifying qi, and has the effects of invigorating qi, promoting blood circulation, and benefiting qi, i.e. invigorating qi, promoting blood circulation, removing blood stasis, and benefiting qi circulation. Astragalus root Wu Shuizhi, the middle warmer is good; tonify without congestion, attack without hurting the healthy energy. The centipede has brain on the node, which is the other species, is characterized by entering the brain with the property of nourishing brain marrow nerve, ensuring that the heart is not lost, having slightly pungent taste and slightly warm nature, strong channeling ability, and being capable of opening viscera and collaterals at all qi and blood coagulation places, and being capable of entering the brain, the above-mentioned medicines are taken as main medicines, focusing on the effects of tonifying kidney and activating blood, simultaneously adding turtle shell to nourish yin and subdue yang to quench liver wind, adding grassleaf sweelflag rhizome and thinleaf milkwort root to resolve phlegm and resuscitate, matching centipede to strengthen sleep and cognition disorder, cassia twig and kudzuvine root to strengthen yang and relieve muscle to strengthen and alleviate limb pain, astragalus root, chinese thorowax root and bitter orange to dredge qi-activating machine to strengthen and improve body position hypotension, achyranthes root, radix angelicae pubescentis, parasitic liver and kidney to strengthen tendons and bones, cistanche, dried rehabilitating rehmannia root and figwort to strengthen the effect of relieving constipation, and chicken's gizzard membrane to strengthen spleen and digestion and transportation medicine. The Chinese medicinal composition has the effects of tonifying kidney and promoting blood circulation, promoting blood circulation and removing obstruction in collaterals, nourishing blood and yin, tonifying yang and qi, promoting qi circulation and eliminating phlegm, and can be used for improving non-motor symptoms such as postural hypotension, constipation, limb pain and cognitive dysfunction just in accordance with the pathogenesis of parkinsonism. Aiming at the 'deficiency stagnation' core pathogenesis of the old population, the prescription is more focused on tonifying kidney, tonifying qi and activating blood compared with kidney-tonifying blood-activating granules from the aspect of 'deficiency stagnation caused by deficiency', aggravates the kidney-tonifying blood-activating force, ensures that qi-blood deficiency is balanced, and the whole prescription has the effects of tonifying kidney and activating blood so that kidney essence is enriched and brain marrow is nourished, and the mind is self-calm.

Modern medical research shows that the effective components of the pulp of dogwood fruit can enhance the total antioxidant capacity of rat cortex and play a role in neuroprotection, and the salvia miltiorrhiza injection has a survival promoting effect on transplanted neurons of parkinsonism; the polygonum multiflorum can also increase the contents of monoamine transmitter 5-HT, dopamine and NE in the brain tissue of the mice, the angelica sinensis main volatile oil component, namely angelica sinensis, has the effects of scavenging free radicals and resisting oxidation, has good scavenging effects on DPP H and oH, and the centipede can obviously reduce the contents of lipofuscin in the brain tissue of the mice and peroxidized lipid in serum, increase the contents of SoD and No in the serum of the rabbits, and reduce the contents of malondialdehyde and endothelin, thereby playing an antioxidant role; the radix astragali extract can influence the expression of ERK1/2, bax, bcl-2, caspase-3, IL-6, IL-10, TNF-alpha target proteins to play a role in treating Parkinson's disease. Radix Angelicae Pubescentis and radix Angelicae Pubescentis extract (including radix Angelicae Pubescentis alcohol extract, radix Angelicae Pubescentis total coumarin and cnidium lactone coumarin monomer) have protective effect on dementia (Alzheimer disease and vascular dementia) and nerve system degeneration disease (Parkinson disease and multiple sclerosis), and the mechanism may be related to their effects of resisting apoptosis, resisting oxidation, resisting immunity inflammation, regulating cytoprotective factor, etc.; the glossy privet fruit can inhibit PD rat oxidative stress injury and relieve inflammatory reaction of rats; the rehmannia contains catalpol, rehmannia glycoside, prepared rehmannia polysaccharide, calycosin and other active pharmacological components, and plays roles in resisting oxidative stress, inhibiting monoamine oxidase expression, reducing excitatory toxicity, inhibiting apoptosis, regulating neurotrophic factor expression, inhibiting proinflammatory factor release and the like. Therefore, the modern pharmacology provides the basis for treating the Parkinson for the compound kidney-tonifying and blood-activating particles.

In order to further understand the present invention, the following examples are provided to illustrate the traditional Chinese medicine composition for treating senile parkinson's disease and complications, and the preparation method and application thereof, and the scope of the present invention is not limited by the following examples.

In the following examples, meadobe (dopa-hydrazine tablet), national drug standard H10930198. The components are as follows: each tablet contains 200mg of levodopa and 50mg of benserazide.

The composition of the kidney-tonifying and blood-activating granule comprises the following components: 20 parts of cistanche, 20 parts of red sage root, 15 parts of grassleaf sweetflag rhizome, 15 parts of dogwood fruit, 10 parts of leech, 15 parts of szechuan lovage rhizome, 15 parts of roasted polygala root, 15 parts of prepared fleece-flower root and 10 parts of ginger;

the preparation method comprises the following steps: pulverizing rhizoma Acori Graminei and radix Polygoni Multiflori Preparata to 80 mesh. Soaking 6 medicines of dogwood, cistanche, polygala tenuifolia, leech, red sage root and ginger in water for 0.5h, decocting for 2 times, 1.5 hours each time, adding 8 times of water for the first time and 6 times of water for the second time, filtering, combining the decoction of the two times with the water extract, concentrating under reduced pressure to thick paste with the relative density of 1.25-1.4 (60 ℃), and drying under reduced pressure (80 ℃) to obtain dry paste (1) for standby. Pulverizing rhizoma Ligustici Chuanxiong, reflux-extracting with 10 times of 80% ethanol twice for 1 hr each time, mixing extractive solutions, concentrating under reduced pressure (60deg.C), and vacuum drying to dry (50deg.C) to obtain dry extract (2); mixing the above dry extract, dextrin and medicinal powder, pulverizing, and sieving with 60 mesh sieve.

Example 1

(1) The compound kidney-tonifying and blood-activating granule comprises the following components: 20 parts of cistanche, 20 parts of red sage root, 15 parts of grassleaf sweetflag rhizome, 15 parts of dogwood fruit, 10 parts of leech, 15 parts of szechuan lovage rhizome, 15 parts of prepared polygala root, 15 parts of prepared fleece flower root, 10 parts of ginger, 6 parts of centipede, 20 parts of astragalus root, 20 parts of red paeony root, 15 parts of Chinese angelica, 10 parts of morinda root, 10 parts of glossy privet fruit, 10 parts of raspberry, 10 parts of pubescent angelica root, 10 parts of mistletoe, 10 parts of twotooth achyranthes root, 10 parts of vinegar turtle shell, 10 parts of figwort root, 6 parts of cassia twig, 10 parts of kudzuvine root, 10 parts of Chinese thorowax root, 6 parts of bitter orange, 10 parts of dried rehmannia root and 10 parts of chicken's gizzard-skin.

(2) The manufacturing process comprises the following steps:

a) Mixing rhizoma Acori Graminei and radix Polygoni Multiflori Preparata, pulverizing to 80 mesh.

b) Soaking 19 medicines such as dogwood, cistanche, polygala tenuifolia, leech, red sage root, ginger and the like in water for 0.5h, decocting for 2 times, 1.5 h each time, adding 8 times of water for the first time and 6 times of water for the second time, filtering, combining the decoction of the two times with the water extract, concentrating under reduced pressure to thick paste with the relative density of 1.25-1.4 (60 ℃), and drying under reduced pressure (80 ℃) to obtain dry paste (1) for standby.

c) Pulverizing rhizoma Ligustici Chuanxiong, reflux-extracting with 10 times of 80% ethanol twice for 1 hr each time, mixing extractive solutions, concentrating under reduced pressure (60deg.C), and vacuum drying to dry (50deg.C) to obtain dry extract (2);

d) Mixing 6.5 dry extract, 3.5g dextrin and the medicinal powder, adding 0.2% stevioside, pulverizing, and sieving with 60 mesh sieve.

Referring to fig. 1, fig. 1 is a flow chart of a preparation process of a traditional Chinese medicine composition for treating senile parkinson's disease and complications.

Example 2

(1) The compound kidney-tonifying and blood-activating granule comprises the following components: 20 parts of cistanche, 20 parts of red sage root, 20 parts of grassleaf sweelflag rhizome, 20 parts of dogwood fruit, 20 parts of leech, 20 parts of szechuan lovage rhizome, 20 parts of prepared polygala root, 20 parts of prepared fleece-flower root, 15 parts of ginger, 15 parts of centipede, 30 parts of astragalus, 20 parts of red paeony root, 20 parts of Chinese angelica, 15 parts of morinda officinalis, 15 parts of glossy privet fruit, 15 parts of raspberry, 15 parts of pubescent angelica root, 15 parts of Chinese taxillus twig, 15 parts of twotooth achyranthes root, 15 parts of vinegar turtle shell, 15 parts of figwort root, 10 parts of cassia twig, 15 parts of kudzuvine root, 15 parts of Chinese thorowax root, 10 parts of bitter orange, 15 parts of dried rehmannia root and 15 parts of chicken's gizzard-skin.

(2) The manufacturing process comprises the following steps:

as in example 1.

Example 3

(1) The compound kidney-tonifying and blood-activating granule comprises the following components: 15 parts of cistanche, 18 parts of red sage root, 18 parts of grassleaf sweelflag rhizome, 18 parts of dogwood fruit, 12 parts of leech, 18 parts of szechuan lovage rhizome, 18 parts of prepared polygala root, 18 parts of prepared fleece-flower root, 12 parts of ginger, 12 parts of centipede, 18 parts of astragalus root, 18 parts of red paeony root, 18 parts of Chinese angelica, 12 parts of morinda root, 12 parts of glossy privet fruit, 12 parts of raspberry, 12 parts of pubescent angelica root, 12 parts of Chinese taxillus twig, 12 parts of twotooth achyranthes root, 12 parts of vinegar turtle shell, 12 parts of figwort root, 8 parts of cassia twig, 12 parts of kudzuvine root, 12 parts of Chinese thorowax root, 8 parts of bitter orange, 12 parts of dried rehmannia root and 12 parts of chicken's gizzard-skin.

(2) The manufacturing process comprises the following steps:

as in example 1.

Comparative example 1

The formulation is as in example 1, in the preparation process, the rhizoma acori graminei adopts a steam distillation method to extract rhizoma acori graminei volatile oil (HD method):

pulverizing rhizoma Acori Graminei, soaking in water, and collecting total volatile oil in a volatile oil extractor for 8 hr. A pale yellow oil was obtained in 0.31% yield. This method is not suitable because of the practical mass production, difficult availability. Because rhizoma Acori Graminei is rhizome medicinal material, contains a large amount of starch, is easy to gelatinize after heating, and prevents the extraction of volatile oil, so direct powdering and drug taking are considered.

Comparative example 2

The formula is as in example 1, and in the preparation process, the prepared fleece-flower root adopts the following method:

extraction of prepared fleece flower root

Decocting the medicinal materials with water for 30 min to obtain 10g of extract, precisely weighing, placing in a flask, precisely adding distilled water 100-150ml, weighing, heating, boiling, refluxing for 30-50 min, cooling, weighing again, adding diluted ethanol to the reduced weight, shaking, adding distilled water 2ml of supernatant to volume of 25-35ml, filtering with microporous membrane (0.45-0.55 μm), concentrating the filtrate, and drying to obtain Polygoni Multiflori radix extract powder.

Decocting the medicinal materials with water for 120 min to obtain 10g of extract, precisely weighing, placing in a flask, precisely adding distilled water 100-150ml, weighing, heating, boiling, refluxing for 90-120 min, cooling, weighing again, adding diluted ethanol to the reduced weight, shaking, adding distilled water 2ml of supernatant to volume of 25-35ml, filtering with microporous membrane (0.45-0.55 μm), concentrating the filtrate, and drying to obtain Polygoni Multiflori radix extract powder.

Chromatographic conditions and system suitability test: octadecylsilane chemically bonded silica is used as a filler; acetonitrile-water (15:85) as mobile phase; the detection wavelength is 320nm. The theoretical plate number is not less than 2000 calculated according to the peak of 2,3,5,4' -tetrahydroxy stilbene-2-O-beta-D-glucoside.

Preparation of a control solution: precisely weighing 2,3,5,4' -tetrahydroxy stilbene-2-O-beta-D-glucoside reference substance, adding diluted ethanol, and making into solution containing 35 μg per 1 ml.

Preparing a medicinal material sample solution: taking 0.2g of medicine powder (sieving with a fourth sieve), precisely weighing, placing into a conical flask, precisely adding 25-35ml of diluted ethanol, weighing, heating and refluxing for 30-45 min (60-80 ℃), cooling, weighing again, supplementing the reduced weight with diluted ethanol, shaking, and filtering supernatant with microporous membrane (0.45-0.55 μm).

Assay: respectively precisely sucking 10 μl of the reference solution and the sample solution, and injecting into a liquid chromatograph for measurement. The results are shown in Table 1 below.

TABLE 1 influence of temperature on 2,3,5,4' -tetrahydroxy stilbene-2-O-beta-D-glucoside in prepared fleece flower root

From the above data, it is known that 2,3,5,4' -tetrahydroxy stilbene-2-O-beta-D-glucoside in prepared fleece flower root is easily dissolved in water and can be effectively extracted as clinical decoction, but because of the characteristic of unstable heat, the extraction process is longer in the mass production process, and the effective components are destroyed, so that the prepared fleece flower root is not suitable for being mixed with other medicines for decoction. It is suitable to treat with rhizoma Acori Graminei alone or in combination.

Animal experiment

(1) Animals: SD rats, 190-230g, male rats, 65 SPF grade, health eligibility, provided by the national institute of military medical science laboratory animal center, animal eligibility number: SCXK 2007-004. And during the test, observing and feeding in the medical laboratory animal center of the general hospital of the liberation army (the animal experiment condition accords with the barrier environment standard).

(2) The daily dosage of the kidney-tonifying and blood-activating granule is about 24 g. Accordingly, the gastric lavage dose of the rat is designed according to 5 times of the daily dosage of the human, and the administration doses of the rat are respectively as follows: 2g/kg, 2g/kg. Positive drug: the dose of Meadopa (135 mg/kg.d). 10 animals are randomly taken out according to the weight to be used as a normal control group (NS), and the rest animals are subjected to modeling, and after successful modeling is confirmed, the animals are randomly subdivided into: (2) compound kidney-tonifying and blood-activating particles (FBS); (3) a kidney-tonifying and blood-activating granule group (BS); (4) the compound kidney-tonifying and blood-activating granule removes astragalus root and centipede group (FBSL) (the astragalus root and centipede components are removed based on the formula of the example 1) (5) the Meadoba group (A) (6) MODEL group (MODEL).

(3) Test procedure

Rats were weighed, numbered, and were intraperitoneally injected (5 ml/kg) with 10% chloral hydrate solution, dehaired on top of the head, fixed on an SN22 brain stereotactic apparatus, sterilized with iodine, alcohol, incised skin and fascia, and exposed the skull. The brain nucleus positioning selects the right substantia nigra coordinate as follows according to the rat brain stereogram: the incisor line is lower than horizontal-3.3 mm, A/P (posterior to the center of the bregma) -4.8 mm, L/R (left and right from the center of the bregma) 1.6 mm, O/V (depth from the meningeal surface) -8.2 mm. After the right substantia nigra coordinates are positioned, the right skull is drilled, 6-OHDA 8 mug is dissolved in 2 mu L of physiological saline (containing 2 g/L vitamin C), microinjection is carried out on a substantia nigra compact part or/and a substantia nigra striata pathway at the side, the injection speed is 1 mu L/min, the needle is left for 10min, then the needle is slowly withdrawn (2-3 min), the wound is closed, the skin is closed, the blood is stopped, the iodine is disinfected, penicillin is injected into the abdominal cavity (10 ten thousand U/kg), 1 time/d, local wound iodine is disinfected for 1 time/d, and the suture is removed after 7 d. DA-capable neuronal degeneration occurred 24 h after general injection and reduction in striatal DA levels occurred 2-3 days later, with 80% -90% reduction in successful model DA levels. 2 weeks after operation, 0.01% apomorphine is injected into the abdominal cavity (1 ml/dose), rotation occurs after 1-5 minutes, and when in rotation, the body is bent towards the healthy side by taking the healthy side hind limb as a fulcrum, and the body is connected end to end and rotates in situ. Some even flip occurs and some rotate in a small circle. Observing and recording the rotation times to the healthy side every 5 min and the total rotation times of 40min, wherein the rotation times are more than or equal to 7 circles every min and the rotation times are more than or equal to 280 circles every 40min, and the positive result is obtained. The positive subjects were eligible PD model rats 1 time a week for 4 weeks.

(4) Administration and observation index

After successful modeling, 60 PD model rats that were successfully modeled were randomly divided into 6 groups. Normal control group (NS), MODEL group (MODEL), compound kidney-invigorating and blood-activating granule (FBS), kidney-invigorating and blood-activating granule group (BS), compound kidney-invigorating and blood-activating granule with astragalus root, centipede group (FBSL), and mecobab group (a). The administration was performed once daily for 8 weeks. The body mass was weighed 1 time per week, and the dosage was adjusted according to the body mass, and the administration was continued for 8 weeks.

Changes in behavior were observed from week 5 of dosing, and the drinking water control, mecobab and model groups were given daily amounts of drinking water or mecobab lavage by mass, as observed in the treatment group (compound kidney-invigorating and blood-activating granule (FBS) group).

(5) Observation index

(1) Behavioral observation: at various time points after the operation, apomorphine 0.5 mg/kg was injected intraperitoneally, and after 5 min of drug injection, the rotation direction of the rats was recorded and the number of rotations within 40 min was measured with a parkinsonism rat rotation recorder.

(2) Midbrain striatum dopamine transporter (DAT) PET imaging: after 8 weeks of treatment, 4 rats were randomly withdrawn from each of the 3 groups, the tail vein was injected with the radiotracer 11C- β -CFT, the rats were anesthetized and placed on an acquisition bed for irradiation, and the scan field of view included the entire brain and neck of the rats, and images were acquired. Then, a region of interest (ROI) is measured, radioactivity is measured on the left striatum, the right striatum and the cerebellum of the rat brain by using ROI software, and the ipsilateral striatum/cerebellum ratio is calculated.

(6) Experimental results

(1) Behavioral observations

Normal control group (NS), compound kidney-tonifying and blood-activating granule (FBS), kidney-tonifying and blood-activating granule (BS), compound kidney-tonifying and blood-activating granule excluding astragalus root, centipede group (FBSL), and mecobab group (a)

The kidney-tonifying and blood-activating particles/compound kidney-tonifying and blood-activating particles remove the influence of astragalus, centipede and compound kidney-tonifying and blood-activating particles on the behavior of PD rats: as can be seen from table 2, the behavioral changes of the BS, FBS, FBSL group rats were significantly improved with the treatment time, but the improvement of the traditional Chinese medicine FBS group was most significant. Observing the change of the rotation behavior of the rats from the 5 th week of the intragastric administration, the number of rotation turns of the rats is obviously reduced (P < 0.01) from the 5 th week after the treatment of the treatment group compared with the number of rotation turns before the treatment; compared with the simultaneous points of the model group, the difference of the number of the 5 th and 8 th rotation circles has statistical significance (P < 0.01); the differences were statistically significant (P < 0.01) compared to the control group at the same time point.

TABLE 2 influence of the rotating behavior of the Parkinson's disease model rats (40 min)

Note that: p <0.001 compared to model set; * Comparison of P <0.001 with control group

(2) Midbrain striatum dopamine transporter (DAT) PET imaging:

DAT imaging agent 11C- β -CFT in model rats showed significant radioconcentration in normal (left) striatal areas, whereas the uptake was significantly reduced in destructive (right) striatal areas; the control group treated the bilateral striatum area DAT showed symmetry in the degree of radioconcentration; the radioactive uptake of striatum DAT on both sides of the treatment group is basically symmetrical, the destroyed side (right side) is close to the non-destroyed side (left side) in a concentrated manner (see figure 2), and three graphs in figure 2 are sequentially from left to right in a model group (post-treatment R/L), a control group (post-treatment R/L) and a treatment group (post-treatment R/L).

ROI measurement: the left striatum/cerebellum ratio and the right striatum/cerebellum ratio of the control group are 2.46+/-0.39,2.51 +/-0.32 respectively, and no obvious difference (P > 0.05) exists; treatment groups were 2.43± 0.41,2.34 ±0.29, respectively, with no significant difference (P > 0.05); the model groups were 2.29± 0.42,1.89 ±0.34, respectively, with no significant difference (P > 0.05). The right side (damaged side) of the treatment group is obviously increased compared with the same side of the model group (P < 0.01), and the same side of the treatment group is not obviously different from the control group (P > 0.05). The right side (damaged side) of the model group is obviously reduced (P < 0.01) compared with the same side of the control group.

Conclusion: the results show that the kidney-tonifying and blood-activating particles/the compound kidney-tonifying and blood-activating particles have obvious effect of treating parkinsonism and centipede groups, are capable of promoting the release of DAT, but the compound kidney-tonifying and blood-activating particles have obvious curative effects superior to the kidney-tonifying and blood-activating particles groups and the compound kidney-tonifying and blood-activating particles remove the astragalus and centipede groups, and the difference has statistical significance.

(3) Treatment protocol:

1) Study medication:

(1) compound kidney-tonifying and blood-activating granule: prepared in example 1.

(2) Kidney tonifying and blood circulation activating granule: cistanche, red sage root, grassleaf sweelflag rhizome, dogwood fruit, leech, szechuan lovage rhizome, roasted polygala root, prepared fleece flower root and ginger.

(3) Western medicine for treating PD: meadobe (dopa-sequin), national drug standard H10930198. The components are as follows: each tablet contains 200mg of levodopa and 50mg of benserazide.

2) Clinical data:

according to Hoehn & Yahr standard, early PD patients are divided into a kidney-tonifying and blood-activating particle group and a Meadobe control group through layering test design; the patients with middle and late stage PD are divided into kidney tonifying and blood activating particles, meadoba groups and Meadoba control groups for clinical study.

A first part: research on delayed progression effect of compound kidney-tonifying and blood-activating particles on treatment of early parkinsonism

(1) Test group

According to the order of the doctor's visit, subjects randomly acquire random numbers on line and enter groups in sequence. The subjects were randomly assigned to control and treatment groups, and divided into 30 cases of compound kidney-tonifying and blood-activating particles, 30 cases of kidney-tonifying and blood-activating particles treatment group, and 30 cases of Meadoba control group.

(2) Inclusion criteria

(1) Meets the Western diagnosis standard of PD; (2) Hoehn & Yahr scale grading is less than or equal to grade 2; (3) PD course is less than or equal to 15 years; (4) age 60-80 years old;

(5) voluntarily attending the study and signing informed consent.

(3) Treatment protocol:

1) Study medication:

(1) compound kidney-tonifying and blood-activating particles (example 1): cistanche, red sage root, grassleaf sweelflag rhizome, dogwood fruit, leech, szechuan lovage rhizome, baked polygala root, prepared fleece flower root, ginger, centipede, astragalus root, red paeony root, chinese angelica, medicinal indianmulberry root, glossy privet fruit, raspberry, pubescent angelica root, chinese taxillus twig, twotooth achyranthes root, vinegar turtle shell, figwort root, cassia twig, kudzuvine root, chinese thorowax root, bitter orange, dried rehmannia root and chicken's gizzard-skin.

2) Treatment time:

according to the past study experience of the project group and referring to domestic related documents, the treatment is carried out for 12 weeks.

3) The administration mode is as follows:

(1) treatment 1 group: the compound kidney-tonifying and blood-activating granule is used for treatment, and the administration method comprises the following steps: orally taken 2 times a day, 1 bag each time. 10g per bag;

(2) treatment group 2: the application of the kidney-tonifying and blood-activating granule treatment comprises the following administration method: orally taken 2 times a day, 1 bag each time. 10g per bag;

(3) control group: the methoamum therapy is taken by the following steps: orally taking 125mg each time, 3 times a day; the daily dosage is 375mg. Patients were examined at 4 points prior to treatment, on the 4 th weekend, on the 8 th weekend, and on the 12 th weekend. Re-diagnosis was performed at 4 time points and related examinations were completed. The subject is asked to fill out the medication diary daily and return the package of spent drug and the remaining drug at the follow-up. The viewing physician fills out the drug delivery registry and carefully inquires the subject about the medication and records adverse events.

(4) Detection index

1) And (3) measuring:

the NMSS scale, the CSS scale, the PDSS scale, the MoCA scale and the HAMD scale are adopted. Detection was performed at 2 points prior to treatment, at the end of week 12.

2) Instrument inspection:

(1) central neurotransmitter changes in the brain: the levels of DA, acetylcholine, norepinephrine, 5-hydroxytryptamine, and gamma-aminobutyric acid in the brain were determined using an ultra slow rise and fall analyzer (EFG). Detection was performed at 2 intervals prior to treatment, at the end of week 12.

(2) Changes in muscle tone: using muscle state testing systems (myotometers) ^® ) And measuring the tension change of the biceps brachii and quadriceps femoris in the resting state and the maximum autonomous contraction state. Detection was performed before treatment, at the end of week 12.

(3) Olfactory change condition: the olfactory examination suit mainly comprises 3 parts, wherein the Olfactory Threshold (OT), the olfactory recognition threshold (OD) and the olfactory recognition threshold (OI) are respectively tested, and after the end of the test, OT, OD and OI values are added to obtain TDI total score for evaluating the olfactory function. Detection was performed at 2 points prior to treatment, at the end of week 12.

(5) Test results:

(1) three sets of baseline data were compared: the three groups of basic data are not statistically significant.

TABLE 3 Table 3

(2) Non-motor symptom score (NMSS) comparison: NMSS scores were significantly reduced in both treatment 1 and treatment 2 groups after treatment and were significantly different from the control group (P < 0.05), and the reduction in scores was more significant in treatment 1 than in treatment 2 groups and was significantly different (P < 0.05).

Table 4 three sets of pre-treatment and post-treatment NMSS score comparisons (score,)

comparing with pre-treatment, treatment 1 group with treatment 2 group, and #P <0.05; treatment group 2 was compared to control group, & P <0.05.

(3) Comparing the curative effects:

efficacy assessment criteria: NMSS score = (pre-treatment score-post-treatment score)/pre-treatment score x 100.00%.

Recovery is that the NMSS percent reduction is less than or equal to 100 percent;

the obvious effect is that the NMSS percent reduction is less than or equal to 95 percent;

the effective rate is that the NMSS percent reduction is less than 20 percent and less than or equal to 50 percent;

the NMSS percent reduction is less than or equal to 20 percent.

The total effective rate of the treatment group 1 and the treatment group 2 is obviously higher than that of the control group, and the total effective rate of the treatment group 1 is obviously higher than that of the treatment group 2.

Table 5 comparative patient efficacy of three groups (examples)

(4) Sleep Scale (PDSS) score comparison: post-treatment group 1 and treatment group 2 had significant increases in PDSS scores and significant differences from the control group (P < 0.05), treatment group 1 was more significant than treatment group 2 in score increase and significant differences (P < 0.05).

Table 6 three sets of pre-treatment and post-treatment PDSS score comparisons (score,)

(5) Constipation scale (CSS) score: post-treatment 1 and treatment 2 had significant reductions in CSS scores and significant differences (P < 0.05) from the control group, with treatment 1 being more significant than treatment 2 and significant differences (P < 0.05).

Table 7 three sets of pre-treatment and post-treatment CSS score comparisons (score,)

(6) Depression scale (HAMD) score comparison: both treatment 1 and treatment 2 had significantly reduced HAMD scores and significantly different from the control (P < 0.05), with treatment 1 being significantly more reduced than treatment 2 and significantly different (P < 0.05).

Table 8 three sets of pre-treatment and post-treatment HAMD score comparisons (score,)

(7) Brain neurotransmitter level comparison: post-treatment groups 1 and 2 had significantly elevated DA, NE, 5-HT and significantly different (P < 0.05) from the control group, and treatment group 1 DA, NE, 5-HT levels were elevated more significantly than treatment group 2 and significantly different (P < 0.05).

TABLE 9 comparison of DA, NE, 5-HT measurements before and after three treatment groups)

Note that: comparing with pre-treatment, treatment 1 group with treatment 2 group, and #P <0.05; treatment group 2 was compared to control group, & P <0.05.

(8) Patient sniffing score comparison: 1-normal smell; 2-mild lesions; 3-moderate lesions; 4-severe lesions; 5-complete loss

The olfactory function scores were significantly reduced in both treatment 1 and treatment 2 following treatment, with significant differences (P < 0.05) from the control group, and the score reduction was more significant in treatment 1 than in treatment 2, with significant differences (P < 0.05).

Table 10 three sets of pre-treatment and post-treatment HAMD score comparisons (score,)

(9) Comparison of cognitive assessment scale (MoCA) scores three groups of patients were in early PD, no significant cognitive impairment, no difference in MoCA scores before and after treatment.

Table 11 three sets of pre-treatment and post-treatment MoCA score comparisons (score,)

Three groups of comparisons of pre-and post-treatment muscle tone levels and motor function: the indexes of the upper limb muscular tension, TUGT, 10MWT and the like of the treatment group 1 and the treatment group 2 are improved, and the treatment group 1 has statistical significance compared with the control group, and has better effect compared with the treatment group 2.

Table 12 three sets of pre-and post-treatment myotonic levels and motor function comparisons M (P ₂₅ ，P ₇₅ )

6) Conclusion of clinical trial: clinical researches on early PD patients show that the compound kidney-tonifying and blood-activating particles can effectively improve non-motor symptoms such as constipation, depression, sleep disorder, dysosmia and the like, improve the levels of brain neurotransmitters DA, NE, 5-HT, improve indexes such as upper limb muscular tension, TUGT, 10MWT and the like, have better effects than kidney-tonifying and blood-activating particle groups and control groups, and indicate that the disease progress cannot be delayed by pure western medicine treatment; the compound kidney-tonifying and blood-activating particles can effectively relieve exercise symptoms, reduce muscle tension, enhance exercise capacity of patients and obviously delay early PD progression speed.

A second part: synergistic effect research of compound kidney-tonifying and blood-activating particles for treating middle-late parkinsonism

(1) Test group

According to the order of the doctor's visit, subjects randomly acquire random numbers on line and enter groups in sequence. The subjects were randomly assigned to control, treatment 1 and treatment 2 groups, and divided into 30 cases of compound kidney-tonifying and blood-activating particles + methodbag treatment 1 group, kidney-tonifying and blood-activating particles + methodbag treatment 2 group, 30 cases of methodbag control group, 30 cases.

(2) Inclusion criteria

(1) Meets the Western diagnosis standard of PD;

(2) the Hoehn & Yahr scale grades > 2 and 4;

(3) PD course is less than or equal to 15 years;

(4) Age 60-80 years old;

(5) voluntarily attending the study and signing informed consent.

(3) Exclusion criteria:

(1) with serious diseases such as severe liver and kidney dysfunction, severe infection, etc.;

(2) allergic constitution;

(3) patients with other clinical trials were enrolled in approximately 3 months;

(4) Treatment regimen

1) Study medication:

(3) Western medicine for treating PD: based on the administration of Meadobe, other PD therapeutic drugs such as antane, amantadine, tay Shu Da and the like can be taken together according to the clinical practice of patients.

2) Treatment time:

3) The administration mode is as follows:

(1) treatment 1 group: the compound kidney-tonifying and blood-activating granule is used for treatment, and the administration method comprises the following steps: orally taken 2 times a day, 1 bag each time. 10g per bag; the methodolb is taken for treatment, and the taking method is as follows: orally taking 125mg each time, 3 times a day; the daily dosage is 375mg.

(2) Treatment group 2: the application of the kidney-tonifying and blood-activating granule treatment comprises the following administration method: orally taken 2 times a day, 1 bag each time. 10g per bag; the methodolb is taken for treatment, and the taking method is as follows: orally taking 125mg each time, 3 times a day; the daily dosage is 375mg.

(3) Control group: the methoamum therapy is taken by the following steps: orally taking 125mg each time, 3 times a day; the daily dosage is 375mg.

Patients were examined at 4 points prior to treatment, on the 4 th weekend, on the 8 th weekend, and on the 12 th weekend. Re-diagnosis was performed at 4 time points and related examinations were completed. The subject is asked to fill out the medication diary daily and return the package of spent drug and the remaining drug at the follow-up. The viewing physician fills out the drug delivery registry and carefully inquires the subject about the medication and records adverse events.

(4) Detection index

1) And (3) measuring: the UPDRS scale, the NMSS scale, the PDSS scale, the MoCA scale and the HAMD scale are adopted. Detection was performed at 2 points prior to treatment, at the end of week 12.

2) Instrument inspection:

(2) Changes in muscle tone: using muscle state testing systems (myotometers) ^® ) And measuring the tension change of the biceps brachii and quadriceps femoris in the resting state and the maximum autonomous contraction state. Detection was performed at 2 intervals prior to treatment, at the end of week 12.

(3) Olfactory change condition: the olfactory examination suit mainly comprises 3 parts, wherein the Olfactory Threshold (OT), the olfactory recognition threshold (OD) and the olfactory recognition threshold (OI) are respectively tested, and after the end of the test, OT, OD and OI values are added to obtain TDI total score for evaluating the olfactory function. Detection was performed at 4 points prior to treatment, on the 4 th weekend, on the 8 th weekend, and on the 12 th weekend.

(4) Exercise ability assessment: "standing-walking" timing test (TUGT), 10m walking test (10 MWT).

(5) Clinical test results:

TABLE 13

Table 14 three groups of pre-and post-treatment NMSS scoresThe comparison of the fractions (the fraction, )

(3) Comparing the curative effects: efficacy assessment criteria:

NMSS score = (pre-treatment score-post-treatment score)/pre-treatment score x 100.00%.

the NMSS percent reduction is less than or equal to 20 percent.

TABLE 15

(4) Brain neurotransmitter level comparison: post-treatment groups 1 and 2 had significantly elevated DA, NE, 5-HT and significantly different (P < 0.05) from the control group, and treatment group 1 DA, NE, 5-HT levels were elevated more significantly than treatment group 2 and significantly different (P < 0.05).

TABLE 16 comparison of DA, NE, 5-HT measurement values before and after three treatment groups)

(5) Patient sniffing score comparison: 1-normal smell; 2-mild lesions; 3-moderate lesions; 4-severe lesions; 5-complete loss. The olfactory function scores were significantly reduced in both treatment 1 and treatment 2 following treatment, with significant differences (P < 0.05) from the control group, and the score reduction was more significant in treatment 1 than in treatment 2, with significant differences (P < 0.05).

Table 17 three sets of pre-treatment and post-treatment HAMD score comparisons (score,)

(6) Comparison of cognitive assessment scale (MoCA) scores there was no difference between MoCA scores before and after treatment for three groups, as cognitive impairment rarely occurred in early PD patients.

Table 18 three sets of pre-treatment and post-treatment MoCA score comparisons (score,)

(7) Three groups of pre-treatment and post-treatment UPDRS scale scores were compared:

table 19 three sets of pre-treatment and post-treatment UPDRS scale score comparisons M (P ₂₅ ，P ₇₅ )

(8) Three groups of pre-and post-treatment myotonic levels and motor function comparisons: the indexes of the upper limb muscular tension, TUGT, 10MWT and the like of the treatment group 1 and the treatment group 2 are improved, and the treatment group 1 has statistical significance compared with the control group, and has better effect compared with the treatment group 2.

Table 20 three sets of pre-and post-treatment myotonic levels and motor function comparisons M (P ₂₅ ，P ₇₅ )

(6) Conclusion: clinical researches on patients with middle and late PD show that the UPDRS-III score of a control group is increased compared with that of the control group before treatment, the compound kidney-tonifying and blood-activating particles can effectively improve non-motor symptoms such as olfactory disorder, and improve the levels of brain neurotransmitters DA, NE and 5-HT, and indexes such as upper limb muscle tension, TUGT and 10MWT are all improved, and the effect is superior to that of the kidney-tonifying and blood-activating particle group and the control group, so that the disease progress cannot be delayed by pure western medicine treatment; the compound kidney-tonifying and blood-activating particles can effectively relieve exercise symptoms, and the synergistic effect of the compound kidney-tonifying and blood-activating particles can effectively relieve exercise symptoms, reduce muscular tension, enhance exercise capacity of patients and delay disease progress.

Third section: experimental research on treating parkinsonism by using compound kidney-tonifying and blood-activating particles-influence on expression of nerve cell factor in nigrostriatal body

1. Materials and methods

1.1 Animals

SPF-grade male SD rats were 60, and had a body weight (200.+ -.20) g.

1.2 Medicament and reagent

The compound kidney-tonifying and blood-activating granule (prepared in example 1) comprises 6% chloral hydrate, 6-hydroxydopamine (6-OHDA), apomorphine, 4% paraformaldehyde, bax rabbit polyclonal antibody, bcl-2 rabbit polyclonal antibody and DAB chromogenic kit.

1.3 Model preparation

60 rats were housed in an independent ventilated cage system 5 per cage. Feeding conditions: the temperature (22+/-1) DEG C and the humidity (50+/-5) percent are alternately changed for 12 hours every day, and the special people are responsible for adding feeds, changing water and the like. After 2 weeks of feeding, the model preparation groups are randomly divided into 2 groups, 50 model preparation groups and 10 model preparation groups, the model preparation groups are randomly divided into 44 modeling groups, 6 artificial operation groups, and modeling is performed after the behavioural test has no rotation. Fasted, not forbidden, weighed, 6% chloral hydrate after intraperitoneal injection (350 mg/kg) anesthesia for 12 hours before molding, dehairing the top of the head, fixing the prone position on a rat brain stereotactic instrument, sterilizing with iodine and alcohol, exposing the skull along the median sagittal line, adjusting a door tooth bar to enable the front and back fontanes to be positioned on the same horizontal plane, determining the position of the right forebrain inner bundle (MFB) according to the rat brain stereotactic map, and selecting MFB coordinates: 4.3mm behind bregma, 1.5mm beside sagittal line, 7.7mm in depth, carefully drilling skull with dental drill, sucking 6-OHDA 8 μl with microinjection pump, slowly injecting at 1 μl/min, retaining needle for 5 min after injection, slowly taking out needle, and locally sterilizing and suturing scalp. The sham operation group is injected with the same amount of physiological saline, the other conditions are the same as the modeling operation, and the normal group is not treated.

The rotation behavior test is carried out 2 weeks after operation, 0.01% apomorphine is injected into the abdominal cavity (0.5 mg/kg), the rats are put on a binding sleeve and then are placed in a rotation detector, and the rotation times are uniformly recorded by the rotation detector after 5 minutes, wherein the recording time is 30 minutes. The successful parkinsonian rat model was obtained with constant turns to the left and greater than 210 rpm/30.

1.4 model grouping and administration

The 23 parkinsonian rats successfully molded are randomly divided into 13 treatment groups (compound kidney-tonifying blood-activating particles) and 10 model groups, and 10 normal groups are provided, wherein the treatment groups are given 2.7g/kg of compound kidney-tonifying blood-activating particles (according to the conversion formula of the drug dosage of the rats and the human beings, and the drug is administered according to the weight of 10 times of the clinical dosage of the rats and the human beings), and are administered by a stomach infusion method once daily, the administration time is 10:00 am, and the administration time is once daily, and the administration amount is weighed once weekly, and is adjusted for 8 weeks continuously, and the normal groups and the model groups are given with equal physiological saline to perform stomach infusion.

1.5 Sampling and treatment

After behavioural examination of each group of rats, 20% uratam (5 ml/kg) was used for intraperitoneal injection anesthesia, a needle point-cut perfusion needle was pushed into the ascending aorta from the left ventricle to fix, the thoracic aorta was clamped, isotonic saline (37 ℃) was perfused, the right auricle was cut off, when the outflow liquid was clear, fixation was performed with 4% paraformaldehyde (4 ℃), 50ml was rapidly perfused, then 50ml was slowly perfused, and fixation was completed after neck stiffness. Immediately breaking the head and taking the brain, placing the brain tissue into 4% paraformaldehyde, placing the brain tissue into a refrigerator at 4 ℃ for fixing for 4 hours, taking the midbrain and striatum part for conventional paraffin embedding, and using a paraffin slicer to carry out crown continuous slicing on the paraffin blocks, wherein each paraffin block is 5 pieces, and the paraffin slice thickness is 5 mu m. Bcl-2, bax immunohistochemical staining was performed (staining steps were performed according to kit instructions).

1.6 Observation index

Detecting the expression of Bcl-2, bax, fas, FADD, A A receptor and the like in neurophysiologic, neurobiochemical, neuropathological aspects and the like.

(II) results of experimental study

1.1 Bcl-2, bax expression

1.1.1 Bcl-2 and Bax expression in the substantia nigra

The results are shown in Table 21 and FIG. 3. The model group had significantly reduced Bcl-2 expression (P < 0.01) compared to the normal group, and the treatment group had significantly enhanced Bcl-2 expression (P < 0.01) compared to the model group; the Bax expression was significantly increased in the model group compared to the normal group (P < 0.01), and the Bax expression was significantly decreased in the treatment group compared to the model group (P < 0.01).

TABLE 21 PI value comparison of rat brain substantia nigra Bcl-2 and Bax protein expression @)

Note that: in comparison with the set of models, ^* P<0.01

1.1.2 Striatal Bcl-2 and Bax expression

The results are shown in Table 22 and FIG. 4. The model group had significantly reduced Bcl-2 expression (P < 0.01) compared to the normal group, and the treatment group had significantly enhanced Bcl-2 expression (P < 0.01) compared to the model group; the Bax expression was significantly increased in the model group compared to the normal group (P < 0.01), and the Bax expression was significantly decreased in the treatment group compared to the model group (P < 0.01).

TABLE 22 comparison of PI values of rat brain striatum Bcl-2 and Bax protein expression)

Note that: in comparison with the set of models, ^* P<0.01

1.2Fas, FADD expression

1.2.1 Rat brain substantia nigra Fas, FADD expression

The results are shown in Table 23 and FIG. 5. The Fas expression was significantly increased in the model group compared to the normal group (P < 0.01), and the Fas expression was significantly decreased in the treatment group compared to the model group (P < 0.01); the FADD expression was significantly increased in the model group compared to the normal group (P < 0.01), and the FADD expression was significantly decreased in the treatment group compared to the model group (P < 0.01).

TABLE 23 comparison of PI values expressed by rat brain black matter Fas and FADD)

Note that: in comparison with the set of models, ^* P<0.01

1.2.2 Rat brain striatum Fas and FADD expression

The results are shown in Table 24 and FIG. 6. The normal group has less Fas expression, the protein expression of the model group is obviously enhanced compared with that of the normal group (P < 0.01), and the Fas expression of the treatment group is obviously reduced compared with that of the model group (P < 0.01); the normal group has less FADD expression, the model group has obviously enhanced protein expression compared with the normal group (P < 0.01), and the treatment group has obviously reduced FADD expression compared with the model group (P < 0.01).

TABLE 24 comparison of PI values expressed by rat brain striatum Fas and FADD)

Note that: in comparison with the set of models, ^* P<0.01

1.3 Adenosine A _2A protein/DMT 1 protein/Nrf 2 protein/VMAT 2 protein

The results are shown in Table 25 and FIGS. 7-10, which are rat brain striatal region adenosine A _2A Percentage of positive area of DMT1, nrf2, VMAT2 protein, specifically, FIG. 7 shows the striatal adenosine A of each group of rats _2A Percentage of protein expression%) The method comprises the steps of carrying out a first treatment on the surface of the FIG. 8 shows the percentage expression of the DMT1 protein in the striatum of the rats of each group (/ -for the group)>) The method comprises the steps of carrying out a first treatment on the surface of the FIG. 9 shows the expression percentage of the striatal Nrf2 protein of each group of rats (/ -for each group>) The method comprises the steps of carrying out a first treatment on the surface of the FIG. 10 shows the percentage expression of the striatal VMAT2 protein in each group of rats (++>)。

Rat brain striatum region, normal group adenosine A _2A The protein expression is less, the expression of the treatment group is lower than that of the control group, and the expression of the treatment group is higher than that of the normal group. The expression of DMT1 protein in the normal group is less, the expression in the treatment group is lower than that in the control group and higher than that in the normal group. The normal group has more Nrf2 protein expression, the treatment group has higher expression than the control group and has lower expression than the normal group. The VMAT2 protein expression in the normal group is more, the expression in the treatment group is higher than that in the control group, and the expression in the treatment group is lower than that in the normal group.

Table 25 rat brain striatal region adenosine A _2A Percentage of positive area of DMT1, nrf2 and VMAT2 protein)

Note that: comparison of the treated group with the Normal group ^△ p<0.05, compared with the control group ^※ p<0.05

1.3.1 groups of rats brainstem A _2A Protein expression

The results are shown in FIG. 11. FIG. 11 is a rat brain striatal adenosine A _2A Protein immunofluorescence results (x 20).

Immunofluorescence display: adenosine A _2A The protein is expressed in the cytoplasm and the cell membrane of the striatum area, the immunofluorescence staining is red, and the normal striatum area is adenosine A _2A The protein expression is less, the expression of the control group is obviously increased, and the treatment group is between the control group and the control group.

1.3.2 Expression of rat paleo striatum DMT1 protein in each group

The results are shown in FIG. 12, and FIG. 12 shows the results of immunofluorescence of rat brain striatal adenosine DMT1 protein (. Times.20).

Immunofluorescence display: DMT1 protein is mainly expressed in the cytoplasm of the striatum region, and the nucleus is also expressed, so that immunofluorescent staining is green. The normal striatum area DMT1 protein expression is less, the control group expression is obviously increased, and the treatment group expression is intermediate to the control group expression and the control group expression.

1.3.3 expression of the rat striatum Nrf2 protein from groups

The results are shown in FIG. 13, and FIG. 13 shows the immunofluorescence of rat brain striatal adenosine Nrf2 protein (. Times.20).

Immunofluorescence display: nrf2 protein is expressed in the striatum region cytoplasm, and immunofluorescent staining is green. The normal striatum region Nrf2 protein expression is more, the control group expression is obviously reduced, and the treatment group expression is between the normal striatum region Nrf2 protein expression and the control group expression.

1.3.4 expression of the rat striatum VMAT2 protein in groups

The results are shown in FIG. 14, and FIG. 14 shows the results of immunofluorescence of rat brain striatal adenosine VMAT2 protein (. Times.20).

Immunofluorescence display: VMAT2 protein is expressed in the striatum region cytoplasm, and immunofluorescent staining is green. The expression of the VMAT2 protein in the normal striatum area is more, the expression of the control group is obviously reduced, and the expression of the treatment group is between the two.

Results: (1) The expression of Fas and FADD in the brain substantia nigra and striata of a parkinsonism model rat is obviously enhanced, the expression of Fas and FADD in the brain substantia nigra and striata of the parkinsonism rat is weakened compared with that of a model group, and after the intervention of the compound kidney-tonifying and blood-activating particles, the expression of Fas and FADD in the brain substantia nigra and striata of the parkinsonism rat is weakened, so that one of the action mechanisms of the compound kidney-tonifying and blood-activating particles for treating parkinsonism is possibly related to inhibiting the expression of Fas and FADD, blocking the activation of Fas-FADD-caspase-8 pathway, and playing a role in inhibiting apoptosis.

(2) Detecting the expression conditions of the brain substantia nigra and striata Bcl-2 and Bax of the rat, wherein the expression of the Bcl-2 of the model group is obviously weakened compared with that of the normal group, and the expression of the Bcl-2 of the treatment group is obviously enhanced compared with that of the model group; compared with a normal group, the Bax expression of the model group is obviously enhanced, and compared with the model group, the Bax expression of the treatment group is obviously weakened, and the result shows that the Bax expression in the brain substantia nigra and striatum of the parkinsonism rats is weakened after the compound kidney-tonifying and blood-activating particles are dried, and the Bcl-2 expression is enhanced, so that one of the action mechanisms of the compound kidney-tonifying and blood-activating particles for treating the parkinsonism diseases is possibly to inhibit apoptosis by up-regulating the Bcl-2 protein expression of the black substantia nigra of the PD rats and down-regulating the Bax protein expression.

(3) Compound kidney-tonifying and blood-activating granule for reducing brain striatal adenosine A of PD model rat _2A Protein expression, deducing that the compound kidney-tonifying and blood-activating particles play a role in enhancing DAR2 activity, regulating GABA energy neuron network in striatum, increasing activity of middle acanthose neurons, inhibiting indirect pathway, enhancing direct pathway and playing a role similar to adenosine A _2A Receptor antagonists, thereby treating parkinson's disease.

(4) The compound kidney-tonifying and blood-activating particles can reduce the expression of brain DMT1 protein of a PD model rat. It is inferred that the compound kidney-tonifying and blood-activating granule plays a role in reducing abnormal deposition of iron in brain, resisting oxidative stress, reducing damage of dopamine neurons and protecting the dopamine neurons.

(5) The compound kidney-tonifying and blood-activating particles can improve the expression of the brain Nrf2 protein of the PD model rat. It is inferred that the kidney-tonifying and blood-activating particles play roles in resisting oxidative stress, inhibiting inflammatory reaction, resisting apoptosis and protecting dopaminergic neurons and astrocytes.

(6) The compound kidney-tonifying and blood-activating particles can raise the expression of the brain VMAT2 protein of the PD model rat, regulate the quantity of DA entering synapse for storage, release and recycling, enhance the removal of endogenous and exogenous toxins, play a role in resisting free radicals and reducing the damage of dopamine neurons.

Conclusion: the core pathology of the parkinsonism is changed into progressive loss of nigral dopaminergic neurons, and experiments prove that the compound kidney-tonifying and blood-activating particles can regulate and control the expression of nerve cell factors in the nigral striatum, so that the effectiveness of the compound kidney-tonifying and blood-activating particles in treating the parkinsonism is further verified.

Example 4

Typical cases of cerebral infarction sequela:

ning a certain, 69 years old, 11 months and 20 days of 2022 for initial diagnosis. The patient has history of hypertension and diabetes, and is unconscious, hemiplegia after waking up, and speech incapacity after 15 days, and after intravenous transfusion treatment for 2 weeks in neurology, the patient still has unfavorable limb movement and speech difficulty. Skull CT suggests left ischemic infarction; nuclear magnetism craniocerebral artery imaging prompts scanning is shown on the left side of a cerebral hemisphere, frontotemporal lobe is abnormal in a sheet signal, the left side of the cerebral hemisphere is in a rectangular fan shape, a focus simultaneously affects cortex and subcortical areas, T1WI is a slightly low signal, T2WI is a high signal, a water inhibition sequence is a high signal, a midline is not shifted, and middle cerebral artery branches are thinned. The symptoms are that the blood pressure is 120/80mmhg, the whole body is hypodynamia and drowsiness, the muscle strength of the right upper limb is 0 level, the muscle strength of the right lower limb is level I, the left half body is normal, the memory is reduced, the thinking is difficult, the stool is slightly shaped, the urine is normal, the tongue is pale and fat, the tongue coating is thin and white, the ecchymosis exists, the venation of the sublingual vein is detoured, and the pulse is deep and weak. The treatment of the syndrome pertains to qi deficiency and blood stasis and blockage of the channels and collaterals, and should be based on the principle of qi-tonifying, blood-activating and collaterals-dredging.

Prescription: modified Compound BUSHENHUOXUE decoction

Cistanche 20g red sage root 20g grassleaf sweelflag rhizome 15g cornus fruit 15g

Leech 10g, ligusticum wallichii 15g, polygala root 15g, fleece-flower root 15g

10g of ginger, 6g of centipede, 20g of astragalus root, 20g of red paeony root

When 15g of Chinese angelica root, 10g of morinda root, 10g of glossy privet fruit, 10g of raspberry

Single living 10g Loranthus mulberry mistletoe 10g Huaihe achyranthes root 10g vinegar turtle shell 10g

10g of radix scrophulariae, 6g of cassia twig, 10g of radix puerariae, 10g of radix bupleuri and 10g of radix bupleuri

Hovenia dulcis 6g dried rehamnnia root 10g chicken's gizzard-membrane 10g

14 doses of the preparation are prepared into granules which are the same as those of example 1, 10g, and are orally taken for 2/day.

After 2 weeks, the symptoms of hypodynamia, drowsiness and the like of the patient are improved, the stool is basically shaped, the muscle strength of the right upper limb is level I, and the muscle strength of the right lower limb is level I ⁺ A pale tongue with thin and white coating, a lighter ecchymosis, a tortuosity of the sublingual veins and a deep and powerful pulse. Continuing the front symptomatic treatment. After the follow-up visit for 3 months, after the rehabilitation function exercise is assisted by the patient, the muscle strength of the right upper limb and the right lower limb can reach level 4, the speech is clear, but the symptoms such as low speech speed, hypodynamia, drowsiness and the like are obviously improved.

Example 5

Typical cases of senile vascular dementia:

patient Wang Mou, male, 70 years old, had a major "memory decline 2 years, aggravated half a year" at 10 months 3 of 2022 at outpatient with "cognitive dysfunction".

The patients in 2019 gradually show speaking reduction, reaction retardation and forgetfulness, mainly the recent memory disorder, and are not specially treated. After that, the disease slowly progresses, the memory is obviously reduced in the early 2022 years, the walking is needed to be assisted by people, and the urination and defecation are incontinent for about 2 to 3 times per day. The patients have no headache, dizziness, mental abnormality, illusion, limb convulsion and fever in the course of disease. There was no significant decrease in body weight. In the past, the patients have the history of hypertension, type 2 diabetes and coronary heart disease for 20 years, the patients take the medicine regularly, and the blood pressure is 190/120 mm Hg at most. The gas poisoning coma is caused by 28 years ago, and no sequelae exists. Auxiliary inspection: brain CT suggests enlarged ventricles, extensive white matter lesions, and brain atrophy. Brain MRI suggests multiple ischemic infarct foci in the brain, multiple ischemic demyelination changes in the brain, bilateral hippocampal corpus callosum atrophy, brain atrophy. Simple intelligent state table (MMSE): 8 minutes, cognitive impairment; welch adult memory assessment: the patient cannot fit. Hachinski score was 7 points. The symptoms are as follows: the whole body is hypodynamia, drowsiness, weakness of the two lower limbs is obvious, the action is slow, people are assisted to support, the memory is obviously reduced, the eyes are slightly dull, the amnesia is realized, the reaction is slow, the sleeping is still easy, the urine and the feces are easy to cause incontinence, the tongue is pale and white in coating, and the tongue surface is provided with ecchymosis. The treatment of syndromes due to qi deficiency and kidney deficiency, blood stasis and obstruction of the channels and collaterals should be based on the principle of qi invigorating, kidney tonifying, blood circulation promoting and collaterals dredging. Prescription: modified Compound BUSHENHUOXUE decoction

Prescription:

Leech 10g, ligusticum wallichii 15g, polygala root 15g, fleece-flower root 15g

10g of ginger, 6g of centipede, 20g of astragalus root, 20g of red paeony root

Ramulus Cinnamomi 6g radix Puerariae 10g radix bupleuri 10g endothelium corneum Gigeriae Galli 10g

Fructus Aurantii 6g, radix rehmanniae 10g, radix scrophulariae 10g

1 dose per day, and made into granule with the same dosage as in example 1, 10g, and orally taken for 2/day.

After 4 weeks, the symptoms of hypodynamia, drowsiness, weakness of the two lower limbs and the like of the patient are relieved before the patient is in a back examination, the tongue ecchymosis is relieved before the patient is in a back examination, and the front symptomatic treatment is continued. After 6 months of follow-up, the symptoms of hypodynamia, drowsiness and the like are obviously improved after the patient assists in rehabilitation function exercise, and the symptoms of memory, amnesia and the like are better than before, so that the patient can self-care, and can exercise independently for 6000 steps every day. Simple intelligent state table (MMSE): 18 minutes, cognitive impairment; welch adult memory assessment: 89 minutes. Hachinski score was 6 points.

The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating senile parkinsonism and complications, senile vascular dementia or cerebral infarction sequela is characterized by being prepared from the following raw materials in parts by mass:

15-30 parts of cistanche salsa, 15-20 parts of red sage root, 15-20 parts of grassleaf sweelflag rhizome, 15-20 parts of dogwood fruit, 10-20 parts of leech, 15-20 parts of szechuan lovage rhizome, 15-20 parts of roasted polygala tenuifolia, 15-20 parts of prepared fleece-flower root, 10-15 parts of ginger, 6-15 parts of centipede, 15-30 parts of astragalus membranaceus, 15-20 parts of red paeony root, 15-20 parts of Chinese angelica, 10-15 parts of morinda officinalis, 10-15 parts of glossy privet fruit, 10-15 parts of raspberry, 10-15 parts of radix angelicae pubescentis, 10-15 parts of mistletoe, 10-15 parts of achyranthes root, 10-15 parts of vinegar turtle shell, 10-15 parts of figwort root, 6-10 parts of cassia twig, 10-15 parts of kudzuvine root, 10-15 parts of radix bupleuri, 6-10 parts of bitter orange, 10-15 parts of dried chicken gizzard-skin and 10-15 parts of chicken gizzard-skin;

the preparation method of the traditional Chinese medicine composition comprises the following steps:

Filtering the decoction, and concentrating to obtain mixed dry extract;

2. A method of preparing the traditional Chinese medicine composition according to claim 1, comprising the steps of:

filtering the decoction, and concentrating to obtain mixed dry extract;

3. The method according to claim 2, wherein in step a), the pulverized particle size is such that the powder is pulverized to pass through a 80 mesh screen;

4. Use of a Chinese medicinal composition according to claim 1 for the preparation of a medicament for the treatment and/or prophylaxis of senile parkinson's disease and complications, senile vascular dementia or cerebral infarction sequela.

5. The use according to claim 4, wherein the senile parkinson's disease and complications are early stage senile parkinson's disease and complications.

6. The use according to claim 5, wherein the dosage of the Chinese medicinal composition is 20-30 g/day.

7. A pharmaceutical composition comprising metaba and the traditional Chinese medicine composition of claim 1.

8. Use of a pharmaceutical composition according to claim 7 for the preparation of a medicament for the treatment and/or prevention of senile parkinson's disease and complications.

9. The use according to claim 8, wherein the senile parkinson's disease and complications are middle and late senile parkinson's disease and complications.

10. The use according to claim 9, wherein the dosage of said methoamub and said Chinese medicinal composition according to claim 1 is 375-500 mg methoamub/day + 20-30 g Chinese medicinal composition/day.