A Chinese medicine composition for slowing down brain degenerative diseases and its preparation method and application

Abstract

The invention discloses a Chinese medicine composition for slowing down brain degenerative lesions and its preparation method and application, which belongs to the field of medical technology, wherein the Chinese medicine composition includes the following components by weight: 15-20 parts of processed Polygonum multiflorum, 15-20 parts of Cistanche deserticola, 10-20 parts of Cornus officinalis, 10-18 parts of Chuanxiong, 15-22 parts of Polygala tenuifolia, 10-20 parts of Acorus calamus, 2-6 parts of Hirudo, 15-22 parts of Salvia miltiorrhiza, and 2-6 parts of ginger. Each component added by the present invention plays the effects of invigorating the kidney, promoting blood circulation and removing blood stasis, clearing phlegm, opening the orifices and dredging the meridians, relieving memory impairment, cognitive impairment, dull expression, taciturnity, vague speech, inexpressible words, sore waist, poor appetite, lack of breath and laziness, and has the effects of improving memory, improving cognitive function, regulating emotions, etc.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a Chinese medicine composition for slowing down brain degenerative diseases, and a preparation method and application thereof. Background Art

[0002] The cognitive function of the human brain reaches its peak at the age of 35, and then begins to decline. After the age of 45, the rate of decline will accelerate significantly. A study published in a sub-journal of Nature magazine by the Capital Medical University research team in 2023 showed that the brain will experience "cliff-like" aging at a certain age. If calculated based on the expected average life expectancy of 80 years old, that is, brain aging begins at the age of 54, and the brain ages faster at the age of 72. Cognitive decline has now become one of the major threats to the aging population; nearly half of people over 85 years old suffer from Alzheimer's disease. Therefore, it is extremely urgent to clarify the mechanism of cognitive decline. The most important risk factor for cognitive decline and Alzheimer's disease in the elderly is age itself, which seriously endangers the quality of life of the elderly. The main diseases related to brain degenerative diseases are: Alzheimer's disease (AD), with memory impairment and cognitive impairment as the main manifestations; small vessel disease (CSVD), which can lead to decreased executive function, cognitive changes, subsequent stroke, and so on. The changes in the brain during brain degenerative diseases are mainly reflected in four aspects: morphology (decreased brain weight and number of neurons, reduced gray and white matter volume; loss of dendritic complexity, reduced number of synapses, decreased plasticity; proliferation of astrocytes and microglia); physiology (absolute cerebral blood flow decreases by about 10%-20%, but cerebral blood flow and brain oxygen metabolism rate are still adapted to age, vascular autoregulation ability still exists, and the response to hypoxemia may be normal); biochemistry (many neurotransmitter systems change with age, such as DA1, 5-HTI, AChI, NA, GABA, etc., but the level of glutamate in the cortex is not affected); cognitive function (mainly manifested in slowed reaction time and cognitive processes, decreased dynamic evaluation, adaptability, and response to new environmental factors, as well as short-term memory impairment). With the aging of the world, the incidence of brain degenerative diseases is high, the disability rate is high, and the family and social burden is heavy.

[0003] With the rise of precision medicine, the treatment of brain degenerative diseases has also begun to develop in a personalized direction. Through genetic testing, brain imaging technology and other means, doctors can more accurately assess the patient's brain function status and potential risks. In terms of drug treatment, by adjusting the balance of neurotransmitters, anti-oxidative stress, anti-inflammatory and other mechanisms, cognitive function can be improved and memory can be enhanced, but the clinical effect is not good. Non-drug therapies such as cognitive training, physical therapy, and music therapy are also widely used in the treatment of brain degenerative diseases. These therapies can stimulate the activity of brain neurons, but the clinical effect is not significant. With the continuous development of cutting-edge technologies such as neuroscience and artificial intelligence, the application of brain-computer interface technology (BMI) provides a new treatment approach for patients with brain degenerative diseases. However, the technology is immature and the long-term effect is poor.

[0004] In short, the effective methods of treating brain degenerative diseases at this stage are showing a trend of diversification and personalization. Although various means such as drug therapy, non-drug therapy, lifestyle intervention and cutting-edge scientific and technological exploration are used, the clinical effects cannot achieve good therapeutic effects, and there are few clinical trials of specific interventions.

[0005] In response to this severe situation, the present invention aims to explore and develop an innovative technical solution to delay or reverse the cognitive decline of the brain during the aging process, especially for the prevention and treatment of Alzheimer's disease and other brain degenerative diseases. Summary of the invention

[0006] The purpose of the present invention is to provide a Chinese medicine composition for slowing down brain degenerative diseases, so as to solve the problems raised in the above background technology.

[0007] To achieve the above object, the present invention provides the following technical solutions:

[0008] A traditional Chinese medicine composition for slowing down brain degenerative diseases comprises the following components in parts by weight: 15-20 parts of processed Polygonum multiflorum, 15-20 parts of Cistanche deserticola, 10-20 parts of Cornus officinalis, 10-18 parts of Ligusticum chuanxiong, 15-22 parts of Polygala tenuifolia, 10-20 parts of Acorus calamus, 2-6 parts of Leech, 15-22 parts of Salvia miltiorrhiza and 2-6 parts of ginger.

[0009] Preferably, the Chinese medicine composition includes the following components in parts by weight: 15-18 parts of processed Polygonum multiflorum, 15-18 parts of Cistanche deserticola, 15-20 parts of Cornus officinalis, 14-16 parts of Ligusticum chuanxiong, 15-18 parts of Polygala tenuifolia, 10-15 parts of Acorus calamus, 4-6 parts of Leech, 20-22 parts of Salvia miltiorrhiza, and 2-4 parts of ginger.

[0010] Preferably, the Chinese medicine composition includes the following components in parts by weight: 15 parts of processed Polygonum multiflorum, 15 parts of Cistanche deserticola, 18 parts of Cornus officinalis, 15 parts of Chuanxiong, 15 parts of Polygala tenuifolia, 12 parts of Acorus calamus, 6 parts of Hirudo, 22 parts of Salvia miltiorrhiza, and 2 parts of ginger.

[0011] Another object of the present invention is to provide a method for preparing the above-mentioned Chinese medicine composition for slowing down brain degenerative diseases, which comprises the following steps:

[0012] According to the weight proportions of the above components, take processed Polygonum multiflorum, Cistanche deserticola, Cornus officinalis, Ligusticum chuanxiong, Polygala tenuifolia, Acorus calamus, Leech, Salvia miltiorrhiza, and ginger;

[0013] Grind Acorus calamus and Rhizoma Chuanxiong, soak them in water, and use a volatile oil extractor to collect volatile oil to obtain a pale yellow oily volatile oil;

[0014] Soak Cistanche deserticola, Cornus officinalis, Polygala tenuifolia, Leech, Salvia miltiorrhiza and ginger in water, boil them for several times, filter and discard the residue to obtain a decoction;

[0015] The decoction is mixed with the volatile oil and processed Polygonum multiflorum, concentrated under reduced pressure to a thick paste, and then dried under reduced pressure to obtain a dry paste;

[0016] The dry paste is mixed with an appropriate amount of additives to obtain the traditional Chinese medicine composition.

[0017] Preferably, the temperature of the reduced pressure concentration is 50-60° C.; and the relative density of the thick paste is 1.25-1.4.

[0018] Preferably, the temperature of the reduced pressure drying is 60-80°C.

[0019] Preferably, the additives include dextrin and sucralose.

[0020] Preferably, the added amount of the dextrin is 0.1%-1% of the mass of the dry paste; the added amount of the sucralose is 0.01%-0.03% of the mass of the dry paste.

[0021] Another object of the present invention is to provide a Chinese medicine composition prepared by the above preparation method.

[0022] Another object of the present invention is to provide a use of the above-mentioned Chinese medicine composition in the preparation of a drug for treating or slowing down brain degenerative diseases.

[0023] The Chinese medicine composition for slowing down brain degenerative lesions provided by the present invention is derived from the empirical prescription of the inventor's long-term clinical practice, wherein the present invention uses Cistanche deserticola, Cornus officinalis, and Polygonum multiflorum processed as the monarch, tonifying the kidney and replenishing essence, yin and yang are both supplemented, and the basic pathogenesis of kidney deficiency and marrow sea malnutrition of brain degenerative diseases is hit; and Salvia miltiorrhiza and Chuanxiong are the ministers, promoting blood circulation and removing blood stasis; Acorus calamus and Polygala tenuifolia are the assistants, and phlegm is opened to the mind, and the blood circulation medicine in the compatibility prescription plays the role of removing phlegm and blood stasis; insect medicine leech is used as the messenger, and its effect of searching and clearing the collaterals is taken, and ginger is used as the messenger, which not only reconciles all medicines, but also warms the middle and promotes drug absorption. The components added by the present invention jointly play the effects of tonifying the kidney, activating blood circulation and removing blood stasis, clearing phlegm, opening the mind and clearing the collaterals, and relieves the symptoms of dull expression, silence, memory loss, vague speech, inexpressible words, sore waist, poor appetite, lack of breath and laziness, and has the effects of improving memory, improving cognitive function, regulating emotions, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is a comparison chart of the changes in brain DA levels in the two groups before and after treatment.

[0025] Figure 2 The present invention provides a Venn diagram of the main active ingredients of the Chinese medicine composition and brain degenerative diseases.

[0026] Figure 3 This is a topological analysis diagram of the core targets of the main active ingredients of the traditional Chinese medicine composition provided by the present invention for treating brain degenerative diseases.

[0027] Figure 4 This is a KEGG analysis diagram of the signaling pathway for the main active ingredients of the traditional Chinese medicine composition provided by the present invention in treating brain degenerative diseases.

[0028] Figure 5 A visualization diagram of the network diagram of active ingredients of the traditional Chinese medicine composition provided by the present invention - brain degenerative lesions - signaling pathways - core targets. DETAILED DESCRIPTION

[0029] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] The pathogenesis of degenerative diseases in traditional Chinese medicine is as follows: when people reach old age, their kidney qi is deficient, the transpiration and gasification function is abnormal, the body fluid cannot be evaporated and becomes phlegm, or the kidney essence is deficient, the yin is deficient and the fire moves, burning the body fluid into phlegm. Blood can block the qi mechanism, and the disorder of qi and the abnormal metabolism of water and body fluid can aggravate the phlegm; on the contrary, the evil of phlegm and turbidity stays inside, blocking the meridians, blood flow is blocked, the meridians are blocked, and the blood gradually becomes more serious. Tang Rongchuan said in "Blood Syndrome Theory": "Blood accumulation in the eyes for a long time can also turn into phlegm and water. It should be known that the congestion of phlegm and water is caused by blood stasis, but if the blood stasis is removed, the phlegm and water will disappear by itself." Therefore, degenerative diseases in the brain are characterized by deficiency of the root and excess of the symptoms. The root deficiency lies in the deficiency of kidney essence and qi, the deficiency of the marrow sea, and the failure of the clear yang to rise; the excess of the symptoms lies in the blood stasis and phlegm that obscure the brain orifices and block the brain meridians. Because it is closely related to aging, on the one hand, the dysfunction of the internal organs mainly caused by kidney deficiency can lead to the production of phlegm, blood stasis, etc., that is, deficiency leads to excess; on the other hand, phlegm and blood stasis can affect the generation and circulation of qi, blood and body fluids, making the original deficiency even worse, so-called excess leads to deficiency. The two are mutually causal, forming a vicious cycle, resulting in a lingering course of the disease and multiple symptoms. Therefore, the main pathogenesis of brain degenerative diseases is kidney deficiency and blood stasis.

[0031] The present invention is based on the theory of traditional Chinese medicine. With the increase of age, the functions of human qi and blood and viscera gradually decline, and the qi and blood flow is not smooth. In addition, the influence of external environmental factors can easily lead to the accumulation of pathological products such as "blood stasis", which in turn hinders the brain network, and the brain marrow is malnourished and functional decline. The team of the present invention is committed to digging out effective prescriptions from traditional classics through modern Chinese medicine research. After long-term clinical verification and animal experiments, the classic prescriptions with good efficacy are verified. Combined with modern science and technology, such as network pharmacology, molecular docking technology, etc., reveal the mechanism of action of Chinese medicine and its compound in protecting neurons, promoting nerve regeneration, improving brain microcirculation, anti-oxidative stress, anti-inflammatory, etc. The multi-component, multi-target, and multi-pathway action characteristics of Chinese medicine, through reasonable compatibility, Chinese medicine can comprehensively adjust the internal environment of the body according to individual differences of patients, so as to achieve the purpose of delaying or reversing brain aging and improving cognitive function. At the same time, the high safety and small side effects of Chinese medicine also provide guarantees for long-term application.

[0032] Specifically, in one embodiment of the present invention, a Chinese medicine composition for slowing down brain degenerative diseases is provided, which comprises the following components in parts by weight: 15-20 parts of processed Polygonum multiflorum, 15-20 parts of Cistanche deserticola, 10-20 parts of Cornus officinalis, 10-18 parts of Chuanxiong, 15-22 parts of Polygala tenuifolia, 10-20 parts of Acorus calamus, 2-6 parts of Hirudo, 15-22 parts of Salvia miltiorrhiza, and 2-6 parts of ginger. Preferably, the Chinese medicine composition comprises the following components in parts by weight: 15-18 parts of processed Polygonum multiflorum, 15-18 parts of Cistanche deserticola, 15-20 parts of Cornus officinalis, 14-16 parts of Chuanxiong, 15-18 parts of Polygala tenuifolia, 10-15 parts of Acorus calamus, 4-6 parts of Hirudo, 20-22 parts of Salvia miltiorrhiza, and 2-4 parts of ginger. More preferably, the Chinese medicine composition includes the following components by weight: 15 parts of processed Polygonum multiflorum, 15 parts of Cistanche deserticola, 18 parts of Cornus officinalis, 15 parts of Chuanxiong, 15 parts of Polygala tenuifolia, 12 parts of Acorus calamus, 6 parts of Hirudo, 22 parts of Salvia miltiorrhiza, and 2 parts of ginger. The above Chinese medicine composition can be made into granule preparations, paste preparations, oral liquids, micropills, dripping pills, honey pills, water pills, capsules, tablets and other dosage forms.

[0033] The method for preparing the above-mentioned Chinese medicine composition for slowing down brain degenerative diseases comprises the following steps:

[0034] S1. According to the weight proportions of the above components, take processed Polygonum multiflorum, Cistanche deserticola, Cornus officinalis, Ligusticum chuanxiong, Polygala tenuifolia, Acorus calamus, Leech, Salvia miltiorrhiza, and ginger;

[0035] S2, crushing Acorus calamus and Rhizoma Chuanxiong, soaking them in water, and collecting volatile oil with a volatile oil extractor to obtain volatile oil in the form of a light yellow oil;

[0036] S3, soaking Cistanche deserticola, Cornus officinalis, Polygala tenuifolia, Leech, Salvia miltiorrhiza, and ginger in water, boiling them for multiple times, filtering and discarding the residue to obtain a decoction;

[0037] S4, mixing the decoction with the volatile oil and processed Polygonum multiflorum, concentrating under reduced pressure to a thick paste, and then drying under reduced pressure to obtain a dry paste;

[0038] S5. Mix the dry paste with an appropriate amount of additives to obtain the Chinese medicine composition.

[0039] Specifically, the temperature of reduced pressure concentration is 50-60°C; the relative density of the thick paste is 1.25-1.4; the temperature of reduced pressure drying is 40-80°C. The additives include dextrin and sucralose. The amount of dextrin added is 0.1%-1% of the mass of the dry paste; the amount of sucralose added is 0.01%-0.03% of the mass of the dry paste.

[0040] The formula of the Chinese medicine composition provided by the present invention is explained as follows:

[0041] Lord: Cistanche deserticola, processed Polygonum multiflorum, Cornus officinalis;

[0042] Minister: Chuanxiong, Salvia miltiorrhiza;

[0043] Auxiliary: Acorus calamus, Polygala tenuifolia;

[0044] Ingredients: leeches, ginger;

[0045] Among them, Cistanche deserticola tastes sweet and salty, is warm in nature, and has the functions of nourishing the kidney and yang, benefiting essence and blood, and moistening the intestines. It is known as the "desert ginseng". "Shennong's Herbal Classic" states: "It tastes sweet and slightly warm, cures five kinds of fatigue and seven kinds of injuries, nourishes the middle, eliminates cold and heat pain in the stem, nourishes the five internal organs, strengthens yin, benefits essence and qi, promotes fertility, treats women's symptoms, and takes it for a long time to lose weight", and lists it as a top grade.

[0046] Cornus officinalis, also known as Cornus officinalis, is sour and astringent in taste, slightly warm in nature, and has the effects of nourishing the liver and kidneys, astringing and consolidating. The Jingyue Complete Works says: "It tastes sour and astringent, and is mainly used for astringency, consolidating yin and replenishing essence."

[0047] Processed Polygonum multiflorum is slightly warm in nature but not dry, bitter and sweet in taste, and belongs to the liver and kidney meridians. It is a good product for nourishing the liver and kidney and benefiting the essence and blood among Chinese medicinal materials. The ancient book "Compendium of Materia Medica" claims that it "can nourish blood and benefit the liver, consolidate essence and benefit the kidney, strengthen tendons and bones, and make hair black. It is a good tonic medicine, not cold and not dry, and its merits are above the medicines of Rehmannia glutinosa and Asparagus cochinchinensis". The production process of processed Polygonum multiflorum is particularly particular. It needs to go through the complicated process of nine steaming and nine drying to remove its toxicity, preserve its essence, and make its drug effect more gentle and lasting. This processing method not only enhances the tonic power of Polygonum multiflorum, but also promotes the generation of essence and blood, and then achieves multiple effects such as strengthening tendons and bones, black hair and eyesight, improving sleep quality, and enhancing immunity. In an embodiment of the present invention, processed Polygonum multiflorum, Fructus Corni and Cistanche deserticola are compatible, and they play the merits of kidney-tonifying, filling essence and benefiting the brain, thereby effectively improving symptoms such as memory loss, sore waist and weak legs, and slow movement.

[0048] Danshen, bitter and slightly cold, has the functions of removing blood stasis and relieving pain, promoting blood circulation and menstruation, clearing the heart and relieving vexation. The "Compendium of Materia Medica" says that it is "good at regulating blood, removing stagnation and promoting new blood, regulating menstruation and smoothing the meridians".

[0049] Chuanxiong is warm and pungent in nature, and is a blood qi medicine that can go up to the head, down to the blood sea, open up depression in the middle, and bypass the collaterals. In the embodiment of the present invention, Chuanxiong is combined with Salvia miltiorrhiza, and the two play the magic of promoting blood circulation and removing blood stasis, promoting qi and relieving pain. Salvia miltiorrhiza is slightly cold in nature, which can control the warm and dry nature of Chuanxiong, so that it can promote qi without hurting yin; the pungent and dispersing nature of Chuanxiong helps Salvia miltiorrhiza to promote blood circulation and remove blood stasis. The two complement each other, and the effects of promoting blood circulation and removing blood stasis and improving microcirculation are significant, which helps to relieve symptoms such as slow movement and promote recovery.

[0050] Acorus calamus is bitter and pungent in taste and warm in nature. It has the effects of clearing phlegm and opening the orifices, refreshing the mind and improving intelligence, removing dampness and stimulating appetite. "Shennong's Herbal Classic" records: "It can cure wind-cold-dampness arthralgia, cough and reverse breathing, open the heart orifices, nourish the five internal organs, open the nine orifices, brighten the ears and eyes, and make sounds. Long-term use will make the body light, prevent forgetfulness, eliminate confusion, and prolong life." Acorus calamus can not only eliminate phlegm and dampness, but also open the orifices, harmonize the stomach qi, and assist the blood-activating drugs to remove phlegm and blood stasis.

[0051] Polygala root is slightly warm in nature, bitter and pungent in taste, and enters the heart, kidney and lung meridians. It is a good product for calming the mind, improving intelligence, and connecting the heart and kidney. The "Ben Jing" says: "Polygala root cures cough, reverses the middle, replenishes deficiency, removes evil spirits, benefits the nine orifices, improves wisdom, sharpens the ears and eyes, keeps memory, strengthens the will and doubles strength." Its uniqueness lies in that it can not only calm the mind and relieve troubles, help sleep and calm the mind, but also guide the heart fire to the kidney, so that water and fire are balanced, and the heart and kidney are connected, thereby relieving insomnia, dreaminess, palpitations and other symptoms caused by the lack of communication between the heart and kidney, and can also strengthen the spleen and improve the diet. In the embodiment of the present invention, Polygala and Acorus calamus are used together as adjuvants. Acorus calamus can open the mind and wake up the spirit, dissipate dampness and soothe the stomach, and can lead the medicinal effects of Radix Polygoni Multiflori, Cistanche deserticola, Polygala, and Salvia miltiorrhiza to reach the mind and reach the subtle places, and open the mind that is obscured by phlegm and turbidity; the two work synergistically, which can not only dispel phlegm and open the mind to treat the symptoms, but also calm the mind and improve intelligence to treat the root cause, and have significant therapeutic effects on amnesia, dementia, and confusion caused by phlegm and turbidity obscuring the mind. Polygala and Acorus calamus can also strengthen the compatibility of blood-activating drugs such as Rhizoma Chuanxiong and Salvia miltiorrhiza to enhance their blood-activating and blood-stasis-removing, opening the mind and awakening the spirit.

[0052] Leeches are salty, bitter and flat. They enter the liver meridian and have unique effects of breaking blood, removing blood stasis, promoting menstruation and eliminating symptoms. The "Ben Jing" states: "Leech can remove bad blood, blood stasis, amenorrhea, blood stasis accumulation, infertility, and promote water flow". Leeches are good at running around, can penetrate into the meridians and veins, search for blood stasis without leaving any remaining evil. For long-term diseases entering the meridians and blood stasis that are difficult to eliminate, leeches, as a guiding drug, not only strengthen the blood circulation and blood stasis-removing power of salvia miltiorrhiza and chuanxiong, but also because of their unique blood-breaking and blood-stasis-removing properties, the whole prescription can penetrate into the lesions, dissolve blood stasis, promote the smooth flow of qi and blood, and restore the normal physiological function of the body while nourishing the liver and kidneys, replenishing essence and filling the marrow. Furthermore, although leeches are fierce in nature, they enter the blood without hurting the body. They are used together with tonic drugs such as processed Polygonum multiflorum and Cistanche deserticola, one attack and one supplement, which complement each other. The addition of leeches makes the whole prescription contain a strong unblocking force in the tonic, which not only conforms to the treatment concept of "tonifying by unblocking" in traditional Chinese medicine, but also avoids the disadvantages of stagnation that may be caused by simple tonic. Ginger is a common adjuvant, pungent and warm, and it is dispersed, and it belongs to the lung, spleen, and stomach meridians. "Pharmacopoeia" praises: "Ginger is mainly used for phlegm and water, and it is used to treat cough, seasonal diseases, and stop vomiting and indigestion." In the embodiment of the present invention, ginger is used as an adjuvant to reconcile various medicines. Its warm and dispersing nature can help Chuanxiong, Danshen and other blood circulation and blood stasis drugs to better warm the blood vessels, promote blood circulation, and accelerate the dissipation of blood stasis. Furthermore, ginger can also warm the middle and strengthen the spleen, promote the spleen and stomach, and make the drugs that nourish the liver and kidney and replenish the essence and fill the marrow better absorbed and utilized, so as to achieve a therapeutic effect with twice the result with half the effort.

[0053] In summary, the Chinese medicine composition provided by the embodiment of the present invention integrates multiple effects such as tonifying the kidney and filling the essence, promoting blood circulation and removing blood stasis, removing phlegm and opening the orifices, calming the mind and improving intelligence, etc., through careful compatibility, each medicine is mutually restricted and promoted, the whole prescription regulates and replenishes the kidney essence to fill the marrow sea, promotes blood circulation to remove blood stasis, opens the orifices and wakes up the mind to benefit the primordial spirit, moistens the intestines and relieves constipation to open the kidney gate, and promotes both tonification and tonification, and plays the merits of tonifying the kidney and promoting blood circulation, removing blood stasis and unblocking the collaterals. Therefore, the medical theory of the present invention for brain degeneration is clear and the syndrome differentiation is clear. The main functions of the side are clear, and multiple groups of medicines are closely linked, the symptoms are matched, the medicines are suitable, and the compatibility is appropriate. The present invention is aimed at the core pathogenesis of "deficiency and stagnation", and delays and improves the symptoms of brain degeneration such as memory loss, vague speech, inarticulate words, dull expression, taciturnity, sore waist and weak legs from the perspective of "stagnation due to deficiency, and deficiency due to stagnation", which greatly improves the quality of life of elderly patients.

[0054] The following embodiments are some specific implementation cases and clinical application cases of the present invention in practical applications, but are not limited thereto.

[0055] Example 1: This example provides a Chinese medicine composition for slowing down brain degenerative diseases, and its preparation method comprises the following steps:

[0056] S1. Weigh 15g of processed Polygonum multiflorum, 15g of Cistanche deserticola, 18g of Cornus officinalis, 15g of Ligusticum chuanxiong, 15g of Polygala tenuifolia, 12g of Acorus calamus, 6g of Hirudo, 22g of Salvia miltiorrhiza, and 2g of ginger, and set aside.

[0057] S2. Crush the Acorus calamus and Rhizoma Chuanxiong weighed above, soak them in water, and use a volatile oil extractor to collect the total volatile oil within 1 hour to obtain the volatile oil in the form of a light yellow oil with a yield of 0.31%, which is set aside.

[0058] S3. Soak Cistanche deserticola, Cornus officinalis, Polygala tenuifolia, Leech, Salvia miltiorrhiza and ginger in water for 1 hour, and decoct them twice continuously. Add 10 times the amount of water for the first time, decoct for 1.5 hours and filter, then add 8 times the amount of water for the second time, decoct for another 1.5 hours, filter and discard the residue, combine the two decoctions to obtain a decoction for later use.

[0059] S4. Grind the prepared Polygonum multiflorum to 100 mesh, and mix it with the above-mentioned decoction and volatile oil, then concentrate it under reduced pressure at 55°C to a thick paste with a relative density of 1.3, and then dry it under reduced pressure at 70°C to obtain a dry paste for later use.

[0060] S5. Mix the above dry paste with appropriate amounts of dextrin and sucralose powder to obtain a Chinese medicine composition; wherein the added amount of dextrin is 0.5% of the mass of the dry paste; and the added amount of sucralose is 0.015% of the mass of the dry paste.

[0061] Example 2: This example provides a Chinese medicine composition for slowing down brain degenerative diseases, and its preparation method comprises the following steps:

[0062] S1. Weigh 15g of processed Polygonum multiflorum, 20g of Cistanche deserticola, 10g of Cornus officinalis, 10g of Ligusticum chuanxiong, 15g of Polygala tenuifolia, 10g of Acorus calamus, 2g of Leech, 15g of Salvia miltiorrhiza, and 2g of ginger, and set aside.

[0063] S2. Crush the Acorus calamus and Rhizoma Chuanxiong weighed above, soak them in water, and use a volatile oil extractor to collect the total volatile oil within 1 hour to obtain the volatile oil in the form of a light yellow oil for later use.

[0064] S3. Soak Cistanche deserticola, Cornus officinalis, Polygala tenuifolia, Leech, Salvia miltiorrhiza and ginger in water for 0.5h, and decoct them twice continuously. Add 8 times the amount of water for the first time, decoct for 1.5 hours and filter, then add 6 times the amount of water for the second time, decoct for another 1.5 hours, filter and discard the residue, combine the two decoctions to obtain a decoction for later use.

[0065] S4. Grind the prepared Polygonum multiflorum to 100 mesh, and mix it with the above-mentioned decoction and volatile oil, then concentrate it under reduced pressure at 50°C to a thick paste with a relative density of 1.25, and then dry it under reduced pressure at 60°C to obtain a dry paste for later use.

[0066] S5. Mix the above dry paste with appropriate amounts of dextrin and sucralose to obtain a Chinese medicine composition; wherein the added amount of dextrin is 0.1% of the mass of the dry paste; and the added amount of stevioside is 0.015% of the mass of the dry paste.

[0067] Example 3: This example provides a Chinese medicine composition for slowing down brain degenerative diseases, and its preparation method comprises the following steps:

[0068] S1. Weigh 20g of processed Polygonum multiflorum, 15g of Cistanche deserticola, 20g of Cornus officinalis, 18g of Ligusticum chuanxiong, 22g of Polygala tenuifolia, 20g of Acorus calamus, 6g of Hirudo, 22g of Salvia miltiorrhiza, and 6g of ginger, and set aside.

[0069] S2. Crush the Acorus calamus and Rhizoma Chuanxiong weighed above, soak them in water, and use a volatile oil extractor to collect the total volatile oil within 1 hour to obtain the volatile oil in the form of a light yellow oil for later use.

[0070] S3. Soak Cistanche deserticola, Cornus officinalis, Polygala tenuifolia, Leech, Salvia miltiorrhiza and ginger in water for 2 hours, and decoct them twice continuously. Add 15 times the amount of water for the first time, decoct for 1.5 hours and filter, then add 12 times the amount of water for the second time, decoct for another 1.5 hours, filter and discard the residue, combine the two decoctions to obtain a decoction for later use.

[0071] S4. Grind the prepared Polygonum multiflorum to 100 mesh, and mix it with the above-mentioned decoction and volatile oil, then concentrate it under reduced pressure at 60°C to a thick paste with a relative density of 1.4, and then dry it under reduced pressure at 80°C to obtain a dry paste for later use.

[0072] S5. Mix the above dry paste with appropriate amounts of dextrin and sucralose to obtain a Chinese medicine composition; wherein the added amount of dextrin is 1% of the mass of the dry paste; and the added amount of stevioside is 0.03% of the mass of the dry paste.

[0073] Example 4: This example provides a Chinese medicine composition for slowing down brain degenerative diseases, and its preparation method comprises the following steps:

[0074] S1. Weigh 18g of processed Polygonum multiflorum, 18g of Cistanche deserticola, 15g of Cornus officinalis, 14g of Ligusticum chuanxiong, 18g of Polygala tenuifolia, 10g of Acorus calamus, 4g of Hirudo, 20g of Salvia miltiorrhiza, and 4g of ginger, and set aside.

[0075] S2. Crush the Acorus calamus and Rhizoma Chuanxiong weighed above, soak them in water, and use a volatile oil extractor to collect the total volatile oil within 1 hour to obtain the volatile oil in the form of a light yellow oil for later use.

[0076] S3. Soak Cistanche deserticola, Cornus officinalis, Polygala tenuifolia, Leech, Salvia miltiorrhiza and ginger in water for 1 hour, and decoct them twice continuously. Add 12 times the amount of water for the first time, decoct for 1.5 hours and filter, then add 10 times the amount of water for the second time, decoct for another 1.5 hours, filter and discard the residue, combine the two decoctions to obtain a decoction for later use.

[0077] S4. Grind the prepared Polygonum multiflorum to 100 mesh, and mix it with the above-mentioned decoction and volatile oil, then concentrate it under reduced pressure at 55°C to a thick paste with a relative density of 1.3, and then dry it under reduced pressure at 70°C to obtain a dry paste for later use.

[0078] S5. Mix the above dry paste with appropriate amounts of dextrin and sucralose to obtain a Chinese medicine composition; wherein the added amount of dextrin is 0.5% of the mass of the dry paste; and the added amount of sucralose is 0.02% of the mass of the dry paste.

[0079] Example 5: This example provides a Chinese medicine composition for slowing down brain degenerative diseases, and its preparation method comprises the following steps:

[0080] S1. Weigh 16g of processed Polygonum multiflorum, 16g of Cistanche deserticola, 20g of Cornus officinalis, 16g of Ligusticum chuanxiong, 16g of Polygala tenuifolia, 15g of Acorus calamus, 5g of Hirudo, 21g of Salvia miltiorrhiza, and 3g of ginger, and set aside.

[0081] S2. Crush the Acorus calamus and Rhizoma Chuanxiong weighed above, soak them in water, and use a volatile oil extractor to collect the total volatile oil within 1 hour to obtain the volatile oil in the form of a light yellow oil for later use.

[0082] S3. Soak Cistanche deserticola, Cornus officinalis, Polygala tenuifolia, Leech, Salvia miltiorrhiza and ginger in water for 1 hour, and decoct them twice continuously. Add 12 times the amount of water for the first time, decoct for 1.5 hours and filter, then add 10 times the amount of water for the second time, decoct for another 1.5 hours, filter and discard the residue, combine the two decoctions to obtain a decoction for later use.

[0083] S4. Grind the prepared Polygonum multiflorum to 100 mesh, and mix it with the above-mentioned decoction and volatile oil, then concentrate it under reduced pressure at 55°C to a thick paste with a relative density of 1.3, and then dry it under reduced pressure at 70°C to obtain a dry paste for later use.

[0084] S5. Mix the above dry paste with appropriate amounts of dextrin and sucralose to obtain a Chinese medicine composition; wherein the added amount of dextrin is 0.5% of the mass of the dry paste; and the added amount of sucralose is 0.02% of the mass of the dry paste.

[0085] Clinical validation: 1. Clinical trials were conducted to observe the efficacy of the Chinese medicine composition prepared in the embodiment of the present invention, as follows:

[0086] 1. The subjects were patients who visited the PLA General Hospital Institute of Traditional Chinese Medicine, the Fourth Military Medical University Xijing Hospital Institute of Traditional Chinese Medicine, the Department of Traditional Chinese Medicine of the Affiliated Tangdu Hospital, and the Guangdong Provincial Hospital of Traditional Chinese Medicine of Guangzhou University of Chinese Medicine from October 2006 to October 2009. The study adopted a multicenter, randomized, double-blind, controlled trial design. A total of 120 cases were diagnosed with "brain degeneration" after screening, and were divided into a treatment group and a control group according to a random number table, and 104 cases completed the endpoint. Inclusion criteria: ① Diagnostic criteria: confirmed as brain degeneration by a medical institution, meeting any of the following diagnoses: Alzheimer's disease (AD), according to DSM-5 or NINCDS-ADRDA criteria; mild cognitive impairment (MCI), and at risk of developing Alzheimer's disease; amyotrophic lateral sclerosis (ALS). ② Age: ≥45 years old, and in the elderly (patients aged 65 and above are preferred). ③ Gender: Both men and women can be included, and stratified analysis is performed by gender. ④ Disease course restrictions: The disease course is between 6 months and 5 years, ensuring that the patient is in the early or middle stages of the disease in order to evaluate the effect of the intervention. ⑤ Cognitive function assessment: The Mini-Mental State Examination (MMSE) score is between 10-24 points, meeting the criteria for mild to moderate cognitive impairment. ⑥ Associated symptoms: Mild depression or anxiety symptoms are allowed, but the score using the relevant scale (such as HAMD or HAMA) must not exceed a mild degree. ⑦ Assessment of living ability: Daily living activities ability (such as Barthel scale score) ≥ 40 points, and able to perform basic daily life care. ⑧ Social support: Patients need family members or caregivers to provide necessary support during the study. ⑨ Informed consent: Patients need to sign an informed consent form to indicate their willingness to participate in the study.

[0087] 2. Intervention method: The two groups of patients continued the basic western medicine treatment regimen before enrollment, and the dosage, method and variety of western medicine in the first 3 months of treatment remained unchanged. The control group took a placebo, and the treatment group took the Chinese medicine composition prepared in Example 1 of the present invention. During the 6-month follow-up observation of the second course of treatment, the dosage of western medicine can be adjusted according to the condition. The treatment group continued the above-mentioned Chinese medicine composition treatment regimen, and the western medicine group took western medicine alone. The placebo is made of starch, dextrin, bittering agent, etc., and the smell and taste are very close to the above-mentioned Chinese medicine composition.

[0088] Method of taking the Chinese medicine composition and placebo: Oral, 1 bag / time, 2 times / day. Observation period: 2 months.

[0089] 3. Observation indicators: Main indicators: UPDRS functional rating scale, NMSS scale, timed movement test, 10-meter reentry movement test. Secondary indicators: DA level (EEG ultra-slow fluctuation analyzer) detection. Safety indicators: blood and urine routine tests, liver and kidney function, electrocardiogram, and adverse event records. Completion of clinical observation for 9 months is the endpoint of efficacy evaluation.

[0090] ① Cognitive function assessment: Montreal Cognitive Assessment (MoCA);

[0091] ② Daily living ability (NMSS scale, UPDRS);

[0092] ③ TCM syndrome scale: This scale is based on the symptoms of poor limb movement, tremor, cramps, soreness of waist and knees, mental depression, forgetfulness, insomnia, tingling, frequent urination at night, constipation, etc. Each symptom is scored from 0 to 3 points according to the severity, as shown in Table 1. The total score of each symptom is calculated, with a full score of 33 points. The higher the score, the more severe the symptom.

[0093] ④ Assessment of walking and dynamic balance ability: (1) Time Up and Go Test (TUGT): The patient sits in a chair and relaxes. When the tester gives the "start" command, the patient stands up and walks to the 5-meter mark at a normal pace, then turns around and returns to the chair to sit firmly. The test time is from the "start" command to the patient sitting firmly (in seconds). To ensure that the patient understands the entire test process, the patient can practice 1-2 times before the formal test. Scoring criteria: record the time taken. (2) 10-meter walk test (10 Meter Walk Test, 10MWT): Ask the patient to walk 10 meters on a flat ground at a comfortable and natural maximum speed, record the time and number of steps required, and calculate the step length (step length = 10 meters / number of steps). The test time is from the "start" command to the patient crossing the mark line with one foot.

[0094] ⑤ Brain neurotransmitter DA detection: ML2001 brain fluctuation graph instrument and analysis software are used. The patient is asked to close his eyes, be awake and keep quiet, collect EEG signals for 18 minutes, and the instrument automatically analyzes and processes and gives the normal value and measured value of the brain neurotransmitter DA. Among them: S11 reflects dopamine (Dopa-mine, DA).

[0095] ⑥Safety indicators: Secondary endpoint indicators: blood pressure, pulse, body temperature, respiratory rate; laboratory indicators: routine blood tests, routine urine tests, routine stool tests, liver and kidney function tests, electrocardiograms, which were measured before and after the study and the changes before and after were compared.

[0096] Table 1

[0097]

[0098] 4. Statistical methods: The data of this study were analyzed using SPSS21.0 statistical software; baseline analysis included basic demographic characteristics and intergroup comparability analysis of factors related to the disease; efficacy analysis was a comparison of the primary and secondary indicators of the two groups; safety analysis included a comparison of abnormal blood routine, urine routine, electrocardiogram, and liver and kidney function indicators and the number of adverse events. Descriptive statistical analysis was performed for quantitative data using the number of cases, mean ± standard deviation (x ± s), or median and interquartile range. Comparative analysis before and after treatment within or between groups; t-test statistics were used for those that conformed to normal distribution and had equal variances; non-parametric tests were used for those that did not conform to normal distribution or had unequal variances; count data were described by frequency and rate, and chi-square test was used; P < 0.05 indicated statistical differences.

[0099] 5. Results: Cognitive function evaluation of the two groups of patients before and after treatment: The MoCA score of the treatment group after treatment was significantly higher than that before treatment, and showed more obvious improvement compared with the control group, which may indicate that the treatment regimen is effective in improving cognitive function, as shown in Table 2.

[0100] Table 2 Comparison of MoCA scores between the two groups before and after treatment (points, )

[0101]

[0102] Daily living ability (NMSS scale, UPDRS scale): After treatment, the NMSS scores of the treatment group were lower than those before treatment. After treatment, the NMSS scores of the treatment group were significantly lower than those of the control group (P<0.05); there was no significant difference in the control group before and after treatment (P>0.05), as shown in Table 3. Before treatment, there was no significant difference in the UPDRS-Ⅱ and UPDRS-Ⅲ scores between the two groups; after treatment, the UPDRS-Ⅱ and UPDRS-Ⅲ scores of the treatment group were lower than those before treatment, and the UPDRS-Ⅱ score was lower than that of the control group during the same period; the UPDRS-Ⅲ score of the control group increased compared with that before treatment, and the differences were statistically significant (P<0.05), as shown in Table 4.

[0103] Table 3 Comparison of NMSS scores between the two groups before and after treatment (points, )

[0104]

[0105] Table 4 Comparison of UPDRS scores between the two groups of patients M (P 25 , P 75 )

[0106]

[0107] TCM syndrome score: A total of 104 patients completed the observation during the follow-up period, including 55 in the treatment group and 49 in the control group. At the time of enrollment: the TCM syndrome score of the treatment group was 24.24±5.39 points, and the control group was 23.06±4.43 points; after 9 months of treatment: the TCM syndrome score of the treatment group was 14.29±4.21 points, and the control group was 18.81±5.13 points. The two-group comparison t-test analysis method was used to statistically analyze the changes in the TCM syndrome scores of the two groups before and after treatment as shown in Table 5:

[0108] Table 5 Changes in TCM syndrome scores in the two groups before and after treatment (points, )

[0109]

[0110] Effectiveness analysis: At the end of treatment (9 months), there were 0 cases of clinical basic recovery in the treatment group, accounting for 0%, and 0 cases in the control group, accounting for 0%; 3 cases of markedly effective treatment group, accounting for 5.45%, and 1 case in the control group, accounting for 2.04%; 17 cases of effective treatment group, accounting for 30.90%, and 2 cases in the control group, accounting for 4.08%; 27 cases of improved treatment group, accounting for 49.09%, and 4 cases in the control group, accounting for 8.16%; 8 cases of ineffective treatment group, accounting for 14.55%, and 42 cases in the control group, accounting for 85.71%. The effective rate of the treatment group was 85.50%, and the effective rate of the control group was 14.30%.

[0111] Use x 2 The rates of markedly effective, effective, improved, ineffective and clinically basically cured in the two groups were compared after treatment. After 9 months of treatment, the effective rate of TCM syndrome score in the treatment group was significantly higher than that in the control group (x 2 The values ​​were 52.578, P=0.000<0.01), as shown in Table 6.

[0112] Table 6 Comparison of improvement rate of TCM syndrome scores in two groups of patients with brain degenerative diseases after 9 months of treatment (cases, %)

[0113]

[0114] Assessment of walking and dynamic balance ability: Before treatment, there was no significant difference in muscle tension level and motor function between the two groups. After treatment, TUGT and 10MWT of the treatment group were lower than those before treatment, and the step length was increased compared with that before treatment. The muscle tension and TUGT of the upper limbs of the treatment group were lower than those of the control group during the same period; the TUGT of the control group was increased compared with that before treatment, and the differences were statistically significant (P < 0.05), as shown in Table 7.

[0115] Table 7 Comparison of muscle tension level and motor function between the two groups of patients M (P 25 , P 75 )

[0116]

[0117] Comparison of brain neurotransmitter DA: There were significant differences between the treatment group and the control group at different times before and after treatment (F=3.112P=0.044); there was an interaction between the time factor and the treatment factor (F=28.883P=0.000), such as Figure 1 shown.

[0118] Safety indicators: There were no significant changes in blood and urine routine tests, liver and kidney function, and electrocardiogram tests before and after the subjects took the Chinese medicine granules.

[0119] Adverse events: A total of 6 cases of adverse events occurred, including 1 case in the treatment group and 5 cases in the control group. One case in the treatment group dropped out due to pneumonia, and the adverse events of the 5 cases in the control group were: 2 cases of stomach pain, 1 case of fever, 1 case of aggravated dyskinesia, and 1 case of mild cerebral infarction. No serious adverse events occurred in the trial, and no adverse reactions related to the trial drugs were found.

[0120] In summary, the clinical research results of this project show that the treatment group has achieved significant results in improving the symptoms of brain degenerative diseases and kidney deficiency and blood stasis, with good effectiveness, safety and tolerability. The Chinese medicine composition provided by the embodiment of the present invention is of great significance in improving the quality of life of elderly patients and preventing the risk of falls.

[0121] Second, the rationality of the medicinal ingredients of the traditional Chinese medicine composition prepared in the embodiment of the present invention is studied and explained as follows:

[0122] 1. Subjects A total of 30 elderly patients with brain degeneration in outpatient clinics from January 2014 to January 2015 were selected and divided into a treatment group and a control group according to a random number table. Inclusion criteria: ① Meet the diagnostic criteria: diagnosed with brain degeneration by a medical institution, and meet any of the following diagnoses: Alzheimer's disease (AD) according to DSM-5 or NINCDS-ADRDA criteria; mild cognitive impairment (MCI) and at risk of developing Alzheimer's disease; amyotrophic lateral sclerosis (ALS). ② Age: ≥45 years old and in the elderly (patients aged 65 and above are preferred). ③ Disease course restrictions: The disease course is between 6 months and 5 years, ensuring that the patient is in the early or middle stage of the disease in order to evaluate the intervention effect. ④ Cognitive function assessment: The score of the Mini Mental State Examination (MMSE) is between 10-24 points, meeting the criteria for mild to moderate cognitive impairment. ⑤ Concomitant symptoms: Mild depression or anxiety symptoms are allowed, but the score using the relevant scale (such as HAMD or HAMA) must not exceed the mild degree. ⑥ Assessment of living ability: Daily living activities ability (such as Barthel Scale score) ≥ 40 points, and able to carry out basic daily living care.

[0123] 2. Intervention method: Both groups of patients continued the basic western medicine treatment plan before enrollment, and the dosage, method and type of western medicine taken during the first 3 months of treatment remained unchanged.

[0124] Control group: on the basis of basic treatment, the patients were given Chinese medicine for comparison (15 parts of Cistanche deserticola, 18 parts of Cornus officinalis, 15 parts of Chuanxiong, 15 parts of Polygala tenuifolia, 12 parts of Acorus calamus, 6 parts of Hirudo, 22 parts of Salvia miltiorrhiza, 3 parts of Panax notoginseng, 20 parts of Anemarrhena asphodeloides, the preparation method is the same as that in Example 1), orally, 1 bag / time, 2 times / day. The observation period is 2 months.

[0125] Treatment group: The control group was given the Chinese medicine composition prepared in Example 1 of the present invention orally, 1 bag / time, 2 times / day. The observation period was 2 months.

[0126] 3. Observation indicators: ① PDQ-39 scale; ② DA level; ③ Traditional Chinese Medicine Syndrome Scale score.

[0127] 4. Statistical methods: SPSS 26.0 statistical software was used for statistical analysis. Measurement data were expressed as x ± s. Independent sample t test was used for inter-group comparison, and paired sample t test was used for intra-group comparison. In case of non-normal distribution, independent sample Mann-Whitney U test was used for inter-group comparison, and paired sample Wilcoxon signed rank test was used for intra-group comparison. Count data were analyzed using X-test. 2 test.

[0128] 5. Results: (1) Analysis of the PDQ-39 scale before and after treatment showed that there was no significant difference in the scores of cognitive function, motor function, daily living activities, emotional state, social activities, pain and discomfort between the two groups before treatment (P>0.05), which was comparable. After treatment, the scores of cognitive function, motor function, emotional state, social activities, etc. in the treatment group and the control group were improved compared with those before treatment, and the differences were statistically significant (P<0.05); inter-group comparison showed that the scores of cognitive function, motor function, emotional state, social activities, and emotional fatigue in the treatment group were significantly improved compared with those in the control group after treatment, which was statistically significant (P<0.05), as follows:

[0129] ① Motor function (items 1-10): There were significant differences between different time periods before and after treatment (F=6.479 P=0.003); there was an interaction between the time factor and the treatment factor (F=19.008 P=0.000), as shown in Table 8.

[0130] Table 8 Changes in motor scores in PDQ-39 between the two groups before and after treatment (points, )

[0131]

[0132] Daily activities (items 11-16): There was no difference between the different time periods before and after treatment (F=2.635 P=0.077); there was an interaction between the time factor and the treatment factor (F=11.182 P=0.000), as shown in Table 9.

[0133] Table 9 Changes in the scores of daily activities in the PDQ-39 between the two groups before and after treatment (points, )

[0134]

[0135] Emotion (items 17-22): There were significant differences between different times before and after treatment (F=5.864 P=0.002); there was an interaction between the time factor and the treatment factor (F=25.455 P=0.000), as shown in Table 10.

[0136] Table 10 Changes in emotion scores in PDQ-39 between the two groups before and after treatment (points, )

[0137]

[0138] Stigma (items 23-26): There were significant differences between different time periods before and after treatment (F=9.314 P=0.000); there was an interaction between time factor and treatment factor (F=9.324 P=0.000), as shown in Table 11.

[0139] Table 11 Changes in stigma scores in the PDQ-39 between the two groups before and after treatment (points, )

[0140]

[0141] Social support (items 27-29): There were significant differences between different times before and after treatment (F=6.498 P=0.001); there was no interaction between the time factor and the treatment factor (F=0.560 P=0.611), as shown in Table 12.

[0142] Table 12 Changes in social support scores in PDQ-39 between the two groups before and after treatment (points, )

[0143]

[0144] Cognitive ability (30-33 items): There were significant differences between different times before and after treatment (F=5.416 P=0.003); there was an interaction between the time factor and the treatment factor (F=22.109 P=0.000), as shown in Table 13.

[0145] Table 13 Changes in cognitive ability scores in PDQ-39 between the two groups before and after treatment (points, )

[0146]

[0147] Communication (items 34-36): There was no difference between different time periods before and after treatment (F=1.850 P=0.137); there was an interaction between time factor and treatment factor (F=5.279 P=0.001), as shown in Table 14.

[0148] Table 14 Changes in the PDQ-39 communication scores of the two groups before and after treatment (points, )

[0149]

[0150] Physical discomfort (items 37-39): There were differences between different time periods before and after treatment (F=3.519 P=0.027); there was an interaction between the time factor and the treatment factor (F=21.862 P=0.000), as shown in Table 15.

[0151] Table 15 Changes in physical discomfort scores in PDQ-39 between the two groups before and after treatment (points, )

[0152]

[0153] (2) Analysis of DA before and after treatment in the two groups showed that there was no significant difference in DA levels between the two groups before treatment (P>0.05), which was comparable. After treatment, DA levels in both the treatment and control groups improved compared with those before treatment, and the differences were statistically significant (P<0.05); inter-group comparison showed that DA levels in the treatment group after treatment were significantly improved compared with those in the control group, which was statistically significant (P<0.05), as shown in Table 16:

[0154] Table 16 DA levels of the two groups of patients before and after treatment ( )

[0155]

[0156] (3) Analysis of TCM symptoms before and after treatment: There was no significant difference in TCM symptoms between the two groups before treatment (P>0.05), which was comparable. After treatment, the TCM symptom scores of the treatment group and the control group were improved compared with those before treatment, and the differences were statistically significant (P<0.05); compared between the two groups, there was no significant difference in muscle tremor, forgetfulness, limb cramps, soreness of waist and knees, insomnia, and constipation between the control group and the treatment group, while the scores of mental depression, clumsy activities, less limb movement, pain, and frequent urination in the treatment group were significantly different from those in the control group, which was statistically significant (P<0.05), as shown in Table 17.

[0157] Table 17 Changes in TCM syndrome scores in the two groups before and after treatment (points, )

[0158]

[0159] (4) Adverse reaction monitoring: The safety indicators of liver and kidney function of the two groups of subjects were within the clinical normal range before treatment, 1 month after treatment, and 6 months after treatment. However, some patients in the control group experienced stomach discomfort during treatment, especially those with more underlying diseases and taking more oral medications. Anemarrhena asphodeloides is cold in nature, which can damage the stomach, so many elderly people cannot tolerate it.

[0160] In summary, the clinical research results of this project show that the treatment group has achieved significant results in improving the PDQ-39 scale scores, DA levels and TCM syndrome scores of patients with brain degenerative diseases, with better safety and tolerance. The control group containing Anemarrhena asphodeloides and Panax notoginseng had no significant difference from the treatment group in relieving muscle tremor, forgetfulness, limb cramps, soreness of waist and knees, insomnia and dreaminess, and constipation, while the treatment group had significant differences in mental depression, clumsy activities, less limb movement, pain, and frequent nocturia, and had higher safety. What is more noteworthy is that the PDQ-39 scale scores and DA levels of the treatment group were significantly different from those of the control group, achieving unpredictable technical effects, with outstanding substantive characteristics and significant progress.

[0161] The rationality of the medicinal taste ratio of the present invention is explained as follows:

[0162] 1. Grasping the proportion of kidney-tonifying drugs: The ancients said that men "at the age of 58, kidney qi declines, hair falls and teeth become dry; at the age of 68, yang qi declines from above, the face becomes burnt, and hair and temples become gray; at the age of 78, liver qi declines, tendons cannot move, and at the age of 88, the essence is exhausted, the kidneys decline, and the body is in a state of extreme; then the teeth and hair fall. The kidney governs water, receives the essence of the five internal organs and six bowels and stores it, so the five internal organs are strong and can be discharged. Now the five internal organs are all declining, tendons and bones are loose and falling, and the essence is exhausted. Therefore, the hair and temples become gray, the body becomes heavy, the steps are not straight, and there is no child". Therefore, brain degenerative diseases are mainly caused by kidney deficiency. The present invention focuses on tonifying the kidney, with processed Polygonum multiflorum, Cistanche deserticola, and Cornus officinalis as the main ingredients, and the ratio is 5:5:6. Cornus officinalis is mainly used to nourish kidney yin, nourish blood and calm the mind. The kidney governs the storage of essence, and the brain is the sea of ​​marrow. The fullness of kidney essence helps to benefit the brain and has a certain help in improving the function of the nervous system, especially for brain symptoms caused by kidney yin deficiency. Prepared Polygonum multiflorum has the functions of nourishing liver and kidney, nourishing blood and calming the mind, blackening hair and prolonging life, anti-aging, improving blood circulation and promoting metabolism. It can enhance the nutritional supply of brain cells, promote anti-aging, and promote the functional recovery of the nervous system. Cistanche can nourish the kidney and strengthen yang, nourish qi and blood, increase the vitality of the body, improve blood circulation, help the brain with oxygen supply, and have the potential to promote nerve regeneration. The three medicines are in a ratio of 5:5:6 for two main purposes: synergistic tonic. This ratio makes the tonic effects of the three medicinal materials complement each other, and can more comprehensively support the supplementation of kidney essence, liver blood and qi and blood, and better play the role of nourishing the kidney, benefiting the brain and adding essence, which is crucial to the maintenance and repair of brain function. Balanced regulation. The nourishing yin effect of Cornus officinalis balances the aphrodisiac effect of Cistanche, while prepared Polygonum multiflorum promotes the coordinated operation of various organs by nourishing blood and improving blood circulation, forming a state of dynamic balance. Clinical observation of kidney deficiency in the elderly, increasing the ratio of Cistanche deserticola (processed Polygonum multiflorum, Cistanche deserticola, Cornus officinalis = 5:8:5), some elderly patients developed dry mouth, hot flashes, night sweats, and irritability after long-term use, and 3 patients had elevated blood pressure. Considering that the yin and yang balance of elderly patients is relatively fragile, long-term excessive yang supplementation will cause imbalance of yin and yang, thereby causing the rise of virtual fire, manifested as dry mouth, hot flashes, night sweats, irritability and other symptoms, while stimulating the sympathetic nerves, negatively affecting cardiovascular health, and leading to elevated blood pressure. Therefore, brain degenerative diseases are more common in the elderly, and elderly patients are weak and cannot be supplemented, so the proportion of tonic drugs should be used more cautiously. Through the reasonable compatibility of processed Polygonum multiflorum, Cistanche deserticola, and Cornus officinalis, the replenishment of kidney essence, liver blood, and qi and blood is guaranteed, and the dynamic balance of nourishing kidney yang, kidney yin, and kidney qi is balanced to better play the role of nourishing the kidney, benefiting the brain, and replenishing essence.

[0163] 2. Grasp the proportion of kidney-tonifying and blood-activating drugs: The ratio of kidney-tonifying drugs (processed Polygonum multiflorum, Cistanche deserticola, and Cornus officinalis): blood-activating drugs (leech + Salvia miltiorrhiza) in the formula is greater than 2:1. Processed Polygonum multiflorum, Cistanche deserticola, and Cornus officinalis are all kidney-tonifying drugs, which have the effects of nourishing yin and kidney, benefiting the brain and producing marrow. They can effectively enhance the function of the kidneys and support the nutritional supply of the brain. Especially in the face of brain degenerative diseases, it is very important to replenish kidney qi and kidney essence and provide the brain with necessary nutrients. The combination of these three drugs ensures sufficient nourishment and can improve the patient's overall energy and physical condition.

[0164] Leeches and salvia miltiorrhiza, as blood-activating drugs, not only have the effect of promoting blood circulation and removing blood stasis, but also can promote blood circulation, improve brain perfusion, and slow down the progress of degenerative diseases. By setting a ratio of 16:7, it emphasizes that nourishing is the main and promoting blood circulation is the auxiliary, so that the essence and marrow can be replenished to achieve the effect of protecting brain nerves. At the same time, while improving circulation, blood-activating drugs avoid the phenomenon of weakness that may be caused by excessive blood circulation. Especially for elderly patients, if the dosage of blood-activating drugs is too large, it may cause fatigue, weakness and collapse. A reasonable ratio ensures that qi and blood flow smoothly without excessive blood circulation. It can be seen that if the dosage ratio of drugs is changed arbitrarily, it will inevitably affect the clinical efficacy. For example, if the ratio of kidney-tonifying drugs to blood-activating drugs is ≤2:1, clinical observations show that some elderly patients have bleeding gastrointestinal discomfort, and some patients (especially those who need to take anticoagulants due to underlying diseases) have blood in their stools. In particular, when the ratio of kidney-tonifying drugs to blood-activating drugs is ≤1:1, the bleeding is aggravated, and the treatment effects of sore waist and knees, limb tremors, etc. are also poor. From the perspective of the compatibility of the above compound prescription, its mechanism is complex, and the components complement each other and work synergistically, which directly affects the clinical effect. The clever combination of the dosage of the whole prescription leads to a unique therapeutic effect, which is just right and indispensable. It can be seen that even if the drugs are the same, due to the different relationships between the monarch, minister, assistant and envoy, the dosage and ratio are different, the efficacy is also different, even opposite, and the safety is also poor. Therefore, how can we only view the drugs in isolation? It is better to regard them as a whole and discuss the effects of the types, dosages and ratios of the drugs on the efficacy.

[0165] 3. The network pharmacology prediction and verification mechanism of the traditional Chinese medicine composition provided by the embodiment of the present invention is as follows:

[0166] 1. Query on the targets of the effective ingredients of the invention and the targets related to brain aging: the main active ingredients of the prescription are Polygala tenuifolia III (CAS No. 162857-78-5), echinacoside (CAS No. 82854-37-3), sodium danshensu (CAS No. 67920-52-9), tanshinone B (CAS No. 121521-90-2), 3,6-dicansinoylsucrose, β-asarone (Beta-asarone CAS No.: 5273-86-9), tetramethylpyrazine, and hirudin (CAS No. 113274-56-9). The SMILES ID of each compound was obtained through the pubchem database (https: / / pubchem.ncbi.nlm.nih.gov / ), and the SMILES ID was imported into the Swisstargets database (http: / / www.swisstargetprediction.ch / ) to obtain the corresponding compound targets. All targets were corrected by the uniprot database (https: / / www.uniprot.org / ) to remove non-human targets. Using "brain aging" as the keyword, human gene searches were performed in the GeneCards database (https: / / www.genecards.org / ), the NCBI gene database (https: / / www.ncbi.nlm.nih.gov / ), and the OMIM database (https: / / www.omim.org / ). After the search, 470 related targets were obtained in the GeneCards database; 831 related targets were obtained in the NCBI database; and 148 related targets were obtained in the OMIM database. After merging and deleting the genes in these three databases, 1,339 disease-related genes were obtained.

[0167] 2. Venn diagram: Input the selected drug targets and disease targets into the Venn diagram making software Venny 2.1, and obtain 61 common targets, which are used as the predicted targets of drugs acting on diseases for the following pathway enrichment analysis, such as Figure 2 .

[0168] 3. Establishment and topological analysis of protein interaction network: The Chinese medicine composition and disease common targets provided by the embodiment of the present invention are input into the String database (https: / / string-db.org / cgi / input.pl) to construct the PPI network, and the biological species is set to "Homo sapiens" with a credibility of > 0.4 to obtain the PPI network. The network has 61 nodes, 487 edges, and an average degree of 16. Figure 3 As shown, Figure 3The color and size of the nodes in the graph are adjusted according to the degree value. The larger the degree value, the redder the color. The larger the degree value, the thickness of the line, from thick to thin, represents the edge betweenness from large to small.

[0169] 4. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway function enrichment analysis: The core targets of the main active ingredients of the traditional Chinese medicine composition provided by the embodiment of the present invention for treating brain degenerative diseases were subjected to KEGG pathway enrichment analysis, and the items with a corrected P value of <0.05 were screened, and a total of 129 signal pathways were enriched. Using R 4.1.2, after installing and citing the clusterProfiler package, a bar graph was drawn, see Figure 4 As shown in the figure, after deleting signaling pathways that are not related to sarcopenia, such as pertussis and hepatitis B, the main active ingredients of the prescription are likely to play a therapeutic role in brain degenerative diseases through the relaxin signaling pathway, IL-17 signaling pathway, and TNF signaling pathway.

[0170] 5. Prescription active ingredients - brain degenerative diseases - signal pathways - core targets network construction: Based on the active ingredients of the Chinese medicine composition provided in the embodiment of the present invention, sarcopenia, the signal pathways and core targets of the effect, a component-disease-pathway-target network diagram was constructed, and the network diagram was drawn and visualized in Cytoscape 3.8.0, as shown in Figure 5. Figure 5 Through network pharmacology research, it was found that the main active ingredients of the Chinese medicine compound prescription of the present invention can play a therapeutic effect on treating brain degenerative diseases through AKT1, IL1B, ESR1 and other multi-target regulation of relaxin signaling pathway, TNF signaling pathway, interleukin 17 signaling pathway and other signaling pathways, which explains the potential molecular mechanism of action of the Chinese medicine composition provided by the present invention in treating brain degenerative diseases.

[0171] The drug compatibility mechanism of the Chinese medicine composition provided by the embodiment of the present invention is as follows:

[0172] Cistanche deserticola and leech medicine pair: Cistanche deserticola, known as the "desert ginseng", is sweet, salty and warm in nature, and belongs to the kidney and large intestine meridians. It is rich in a variety of bioactive ingredients, such as polysaccharides, amino acids and trace elements, and has the effects of nourishing the kidney and essence, moistening the intestines and relieving constipation. In the treatment of brain degenerative diseases, Cistanche deserticola can warm the kidney yang and enhance the body's vitality, thereby improving the patient's symptoms such as back pain, weak legs, and slow movement caused by insufficient kidney qi. At the same time, its role in nourishing essence and blood helps to promote blood circulation in the brain, provide nutritional support for damaged nerve cells, and indirectly improve memory and language expression ability. Leeches, which are flat in nature, salty and bitter in taste, belong to the liver meridian, but have excellent therapeutic effects in promoting blood circulation, removing blood stasis, and promoting menstruation and breaking stagnation. Brain degenerative diseases are often accompanied by poor blood circulation, especially the obstruction of brain microcirculation, which directly leads to brain hypoxia and insufficient nutrient supply. Leeches, with their powerful ability to break blood and remove blood stasis, can penetrate into the subtle parts, remove blood stasis and sediments in blood vessels, restore blood vessel patency, increase blood flow to the brain, and thus relieve symptoms such as dull expression and slurred speech caused by insufficient blood supply. The clever combination of Cistanche deserticola and leeches can not only fundamentally replenish kidney qi and nourish essence and blood, but also directly act on the blood circulation system, improve brain microcirculation, and achieve the effect of treating both the symptoms and the root causes.

[0173] Compatibility of Cistanche and Acorus calamus: Cistanche is a medicinal material that nourishes kidney yang and benefits essence and blood. It can enhance kidney function and promote the production of essence and blood, thereby improving the supply of qi and blood to the brain and relieving the symptoms of brain degenerative diseases. Acorus calamus has the effects of resolving phlegm, opening the orifices, refreshing the mind and improving intelligence. It can clear the phlegm and blood stasis in the brain and make the brain qi and blood flow more smoothly. The compatibility of Cistanche and Acorus calamus can not only relieve the symptoms of brain degenerative diseases, but also fundamentally improve the patient's physique. By nourishing the kidney and filling the essence, Cistanche can help patients strengthen their physique and improve their quality of life. The phlegm-resolving and orifice-opening effect of Acorus calamus can help improve patients' cognitive function, memory and thinking ability. The active ingredients in Cistanche can enhance the effect of Acorus calamus in resolving phlegm and opening the orifices, while Acorus calamus can promote the effect of Cistanche in nourishing the kidney and filling the essence, thereby achieving better therapeutic effects.

[0174] Acorus calamus and processed Polygonum multiflorum: Acorus calamus has the effect of opening the mind and removing phlegm, and can remove phlegm and dampness, while processed Polygonum multiflorum has the effect of nourishing the liver and kidney and benefiting the essence and blood. Acorus calamus and processed Polygonum multiflorum are compatible. On the one hand, they combine opening the mind and nourishing. Acorus calamus can open the mind and wake up the mind, improve consciousness and cognition, while Polygonum multiflorum can nourish the liver and kidney and enhance the basic ability of the body. The two medicines can improve the brain function of elderly patients. On the other hand, the pharmacological effects of the two jointly promote blood circulation in the brain, which is beneficial to the nutrition and metabolism of neurons. The most important thing is that the combination of the two strengthens anti-oxidation and nerve protection. The antioxidant properties of Acorus calamus and the anti-aging properties of Polygonum multiflorum work synergistically to protect nerve cells, thereby slowing down the process of brain aging and degenerative diseases.

[0175] The brain is the sea of ​​marrow. Cistanche deserticola and processed Polygonum multiflorum are used together. Both of them have the effect of nourishing the liver and kidney, thus strengthening the function of nourishing the kidney, replenishing essence and nourishing the marrow, helping to improve brain blood circulation and nerve cell metabolism and repair, reducing oxidative stress, and protecting brain cells from damage. At the same time, the combination of the two medicines can help improve cognitive functions such as memory and attention.

[0176] In summary, there is currently no effective intervention drug for brain degeneration in the clinic. The inventor has innovatively discovered that the fundamental pathogenesis of brain degeneration is kidney deficiency and blood stasis based on many major topics in many years of clinical experience, and has created an effective treatment method for brain degeneration, which can significantly improve symptoms such as memory loss, difficulty in concentration, and language disorders, as well as complications such as soreness of waist and knees, forgetfulness, frequent urination, constipation, and tremor in elderly patients, and improve the quality of life of elderly patients. The present invention fills the gap of effective intervention in brain degeneration, and the prescription has high safety, small adverse reactions, no obvious adverse reactions in clinical practice, and can have a long-term health care effect. The present invention is clear in the medical theory of "brain degeneration", and the syndrome differentiation is very detailed. The prescription provided, each component is not a dispensable fabrication, the taste of the medicine is simple and refined, the duties of the monarch, minister, assistant and envoy are clear, and the combination of various medicines is closely linked and indispensable. The symptoms match, the medicine and the syndrome are mutually beneficial, and the compatibility is rigorous and appropriate. The clinical trials have been sufficient to verify the efficacy of the drug, and the research on network pharmacology also provides novel technological support for the rationality of the drug.

[0177] Based on the above-mentioned ideal embodiments of the present invention, the relevant staff can make various changes and modifications without departing from the technical concept of the present invention through the above-mentioned description. The technical scope of the present invention is not limited to the contents of the specification.

Claims

1. A Chinese medicine composition for slowing down brain degenerative diseases, characterized in that: The invention is prepared from the following raw materials in parts by weight: 15-20 parts of processed Polygonum multiflorum, 15-20 parts of Cistanche deserticola, 10-20 parts of Cornus officinalis, 10-18 parts of Ligusticum chuanxiong, 15-22 parts of Polygala tenuifolia, 10-20 parts of Acorus calamus, 2-6 parts of Leech, 15-22 parts of Salvia miltiorrhiza and 2-6 parts of ginger.

2. The Chinese medicine composition for slowing down brain degenerative diseases according to claim 1, characterized in that: The invention is prepared from the following raw materials in parts by weight: 15-18 parts of processed Polygonum multiflorum, 15-18 parts of Cistanche deserticola, 15-20 parts of Cornus officinalis, 14-16 parts of Chuanxiong, 15-18 parts of Polygala tenuifolia, 10-15 parts of Acorus calamus, 4-6 parts of Leech, 20-22 parts of Salvia miltiorrhiza and 2-4 parts of ginger.

3. The Chinese medicine composition for slowing down brain degenerative diseases according to claim 2, characterized in that: The invention is prepared from the following raw materials in parts by weight: 15 parts of processed Polygonum multiflorum, 15 parts of Cistanche deserticola, 18 parts of Cornus officinalis, 15 parts of Chuanxiong, 15 parts of Polygala tenuifolia, 12 parts of Acorus calamus, 6 parts of Leech, 22 parts of Salvia miltiorrhiza and 2 parts of ginger.

4. A method for preparing a Chinese medicine composition for slowing down brain degenerative diseases as claimed in any one of claims 1 to 3, characterized in that: The following steps are involved: According to the weight proportions of the above components, take processed Polygonum multiflorum, Cistanche deserticola, Cornus officinalis, Ligusticum chuanxiong, Polygala tenuifolia, Acorus calamus, Leech, Salvia miltiorrhiza, and ginger; Grind Acorus calamus and Rhizoma Chuanxiong, soak them in water, and use a volatile oil extractor to collect volatile oil to obtain a pale yellow oily volatile oil; Soak Cistanche deserticola, Cornus officinalis, Polygala tenuifolia, Leech, Salvia miltiorrhiza and ginger in water, boil them for several times, filter and discard the residue to obtain a decoction; The decoction is mixed with the volatile oil and processed Polygonum multiflorum, concentrated under reduced pressure to a thick paste, and then dried under reduced pressure to obtain a dry paste; The dry paste is mixed with an appropriate amount of additives to obtain the traditional Chinese medicine composition.

5. The method for preparing the Chinese medicine composition for slowing down brain degenerative diseases according to claim 4, characterized in that: The temperature of reduced pressure concentration is 50-60°C; the relative density of the thick paste is 1.25-1.

4.

6. The method for preparing the Chinese medicine composition for slowing down brain degenerative diseases according to claim 4, characterized in that: The temperature of the reduced pressure drying is 60-80°C.

7. The method for preparing the Chinese medicine composition for slowing down brain degenerative diseases according to claim 4, characterized in that: The additives include dextrin and sucralose.

8. The method for preparing the Chinese medicine composition for slowing down brain degenerative diseases according to claim 7, characterized in that: The added amount of the dextrin is 0.1%-1% of the mass of the dry paste; the added amount of the sucralose is 0.01%-0.03% of the mass of the dry paste.

9. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for treating or slowing down brain degenerative diseases.

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