Traditional Chinese medicine composition and application thereof in preparation of medicine for treating cerebral small vascular diseases

Abstract

The invention provides application of a traditional Chinese medicine composition in preparation of medicines for treating cerebral small vascular diseases, and is characterized in that the traditional Chinese medicine composition comprises the following components in parts by weight: 10-100 parts of acanthopanax, 10-100 parts of cornu cervi degelatinatum, 5-50 parts of morinda officinalis, 5-50 parts of fructus broussonetiae, 5-50 parts of fructus lycii, 2-30 parts of leech, 5-50 parts of gastrodia elata, 5-50 parts of amethyst and 5-50 parts of polygala tenuifolia. The formula provided by the invention can effectively improve the cognitive function, anxiety, depression and other symptoms of patients with cerebral small vascular diseases.

Description

Technical Field

[0001] The present invention relates to a Chinese medicine composition and a preparation method thereof, in particular to a Chinese medicine composition for treating or improving cerebral small vessel disease and a preparation method thereof Background Art

[0002] Cerebral small vessel disease (CSVD) is a serious, systemic, global brain disease that accounts for 20% of cerebrovascular diseases, 40% of dementia cases, and 25% of strokes. CSVD increases the risk of developing vascular dementia by 73%. Over time, this complex disease complex of vascular damage, cognitive impairment, and affective disorders develops, severely impacting patients' quality of life and placing a significant economic burden on society.

[0003] The pathogenesis of CSVD is extremely complex. Modern medical research indicates that multiple processes and aspects are involved, including endothelial damage, blood-brain barrier leakage, neuroinflammation, oxidative stress, and β-amyloid (β-AP) aggregation. Furthermore, there are no specific and effective medications for the symptoms of memory and mild cognitive impairment caused by CSVD.

[0004] Modern medicine often uses secondary prevention comprehensive treatment (blood pressure reduction, antiplatelet, glucose and lipid lowering, etc.) to treat this disease, with blood pressure control as the main treatment. Clinical treatment often targets cognitive impairment and depression symptomatic treatment, and there is a lack of targeted treatment options. For patients with cognitive impairment, the main drugs currently used on the market to improve AD are cholinesterase inhibitors, such as donepezil. However, in an RCT targeting elderly patients with depression and comorbid cognitive impairment, donepezil was found to have no advantage in the conversion rate to dementia and had more adverse reactions. For patients with depression, selective serotonin reuptake inhibitors (SSRIs) are currently used, but studies have shown that long-term use of SSRIs can lead to cognitive impairment in patients, with a significantly increased incidence of memory impairment (OR = 7.25, P < 0.001). The above studies indicate that for this patient population, current clinical treatments may have certain limitations.

[0005] Leveraging the advantages of Traditional Chinese Medicine (TCM), which boasts multiple components and targets, we are actively seeking or developing single or combined TCM formulas for the treatment of CSVD. These formulas hold promise as an ideal means of delaying the progression of CSVD to dementia. Numerous studies have demonstrated that TCM mechanisms of action include alleviating neuroinflammation, promoting synaptic formation, regulating autophagy, inhibiting apoptosis and pyroptosis, improving neurotransmitter release, reducing toxic protein accumulation, combating oxidative stress and calcium overload, inhibiting platelet aggregation, and modulating the brain-gut axis.

[0006] In summary, current treatments for CSVD primarily rely on traditional secondary prevention of vascular risk factors and symptomatic treatment, but these approaches have proven ineffective clinically, and clinical trials of specific interventions are limited. To address this challenging situation, the present invention aims to explore and develop an innovative technical solution using a traditional Chinese medicine compound to delay or reverse cognitive decline and psychiatric symptoms associated with CSVD. Summary of the Invention

[0007] In view of the above problems, the present application provides a Chinese medicine composition for treating cerebral small vessel disease, improving memory and mild cognitive impairment, so as to overcome the above problems or at least partially solve the above problems.

[0008] A first aspect of the present invention provides a use of a traditional Chinese medicine composition for the preparation of a composition for treating cerebral small vessel disease. The traditional Chinese medicine composition comprises the following components in parts by weight: 10-100 parts of Acanthopanax senticosus, 10-100 parts of Deer Antler Powder, 5-50 parts of Morinda officinalis, 5-50 parts of Cuscuta australis, 5-50 parts of Lycium barbarum, 2-30 parts of Hirudo, 5-50 parts of Gastrodia elata, 5-50 parts of Amethyst, and 5-50 parts of Polygala tenuifolia.

[0009] In an optional embodiment, the traditional Chinese medicine composition includes the following components in parts by weight: 30g of Acanthopanax senticosus, 30g of Deer Antler Powder, 15g of Morinda officinalis, 10g of Cuscuta australis, 10g of Lycium barbarum, 6g of Hirudo, 15g of Gastrodia elata, 15g of Amethyst, and 10g of Polygala tenuifolia.

[0010] A second aspect of the present invention provides a use of a traditional Chinese medicine composition in the preparation of a composition for treating cerebral small vessel disease, wherein the traditional Chinese medicine composition comprises the following components in parts by weight: 10-100 parts of Acanthopanax senticosus, 10-100 parts of Deer Antler Cream, 2-30 parts of Hirudo, and 5-50 parts of Amethyst.

[0011] A third aspect of the present invention provides a method for preparing a traditional Chinese medicine composition, comprising the following steps: taking processed Acanthopanax senticosus, Deer Antler Powder, Morinda Officinalis, Cuscuta australis, Lycium barbarum, Hirudo, Gastrodia elata, Amethyst, and Polygala tenuifolia according to the weight portions of the components of the traditional Chinese medicine composition, decocting with water for 30-60 minutes, filtering, and collecting the filtrate; further adding water to the filter residue and decocting for 20-40 minutes, filtering, and collecting the filtrate; concentrating at 60-70° C. to a relative density of 1.05-1.15, allowing to stand, taking the supernatant, and concentrating at 60-70° C. to a relative density of 1.25-1.30 to obtain a decoction.

[0012] The fourth aspect of the present invention provides a method for preparing a traditional Chinese medicine composition, comprising the following steps: mixing the components of the traditional Chinese medicine composition according to parts by weight:

[0013] Preparation of Chinese medicine: Calcined antler frost to remove impurities, stir-fried leech talc powder, calcined and quenched amethyst, and the remaining components were cleaned and cut into sections or crushed.

[0014] Extraction and Purification: Soak each component in water for 1 hour. First, decoct the purple quartz, followed by the gastrodia elata. Decoction is repeated twice (1.5 hours each time), and the decoctions are combined. Soak the polygala root in liquorice water, remove the core, and reduce mucus. The extract is centrifuged and filtered, then purified by precipitation with 70% ethanol. Allow to stand for 12 hours. The supernatant is collected, ethanol is recovered, and vacuum concentrated to a thick paste with a relative density of 1.25 (60°C).

[0015] Drying and granulation: vacuum drying is used to obtain dry extract, which is then crushed and mixed with the combined excipients. 75% ethanol is used as a wetting agent to prepare a soft material, which is then extruded into granules and then dried and sized to obtain granules.

[0016] A fifth aspect of the present invention provides a method for preparing a traditional Chinese medicine composition, comprising the following steps: mixing the components of the traditional Chinese medicine composition in parts by weight:

[0017] Preparation of Chinese medicine: Calcined antler frost to remove impurities, stir-fried leech talc powder, calcined and quenched amethyst, and the remaining components were cleaned and cut into sections or crushed.

[0018] Extraction and Purification: Soak each component in water for 1 hour. First, decoct the purple quartz, followed by the gastrodia elata. Decoction is repeated twice (1.5 hours each time), and the decoctions are combined. Soak the polygala root in liquorice water, remove the core, and reduce mucus. The extract is centrifuged and filtered, then purified by precipitation with 70% ethanol. Allow to stand for 12 hours. The supernatant is collected, ethanol is recovered, and vacuum concentrated to a thick paste with a relative density of 1.25 (60°C).

[0019] Drying and granulation: The thick paste is vacuum dried to make a dry extract, which is then crushed into fine powder. 10% microcrystalline cellulose, 5% sodium starch glycolate, and 0.5% magnesium stearate are added and mixed evenly. The mixture is then softened with 85% ethanol and sieved through a 14-mesh sieve for granulation. The mixture is then dried at 60°C and sieved through a 10-mesh sieve for final granulation.

[0020] Tablet pressing: Place the granules in the tablet press and adjust the pressure to 3-5kg / cm 2 , pressed into tablets with a diameter of 5-8 mm.

[0021] A sixth aspect of the present invention provides a method for preparing a traditional Chinese medicine composition, comprising the following steps: mixing the components of the traditional Chinese medicine composition in parts by weight:

[0022] Preparation of Chinese medicine: Calcined antler frost to remove impurities, stir-fried leech talc powder, calcined and quenched amethyst, and the remaining components were cleaned and cut into sections or crushed.

[0023] Extraction and Purification: Soak each component in water for 1 hour. First, decoct the purple quartz, followed by the gastrodia elata. Decoction is repeated twice (1.5 hours each time), and the decoctions are combined. Soak the polygala root in liquorice water, remove the core, and reduce mucus. The extract is centrifuged and filtered, then purified by precipitation with 70% ethanol. Allow to stand for 12 hours. The supernatant is collected, ethanol is recovered, and vacuum concentrated to a thick paste with a relative density of 1.25 (60°C).

[0024] Use a capsule filling machine to fill the mixed powder into No. 0 or No. 1 hollow capsules, and adjust the filling amount so that each capsule contains 0.3-0.4g of extract powder.

[0025] The seventh aspect of the present invention provides a traditional Chinese medicine preparation comprising the above-mentioned traditional Chinese medicine composition as an active ingredient and in combination with a pharmaceutically acceptable carrier, diluent or excipient.

[0026] The eighth aspect of the present invention provides a method for preparing a Chinese medicine composition, comprising mixing the Chinese medicine composition with a diluent and / or other additives or adjuvants.

[0027] The ninth aspect of the present invention provides a traditional Chinese medicine composition for treating cerebral small vessel disease, which comprises the following components in parts by weight: 10-100 parts of Acanthopanax senticosus, 10-100 parts of Deer Antler Cream, 5-50 parts of Morinda officinalis, 5-50 parts of Cuscuta australis, 5-50 parts of Lycium barbarum, 2-30 parts of Hirudo, 5-50 parts of Gastrodia elata, 5-50 parts of Amethyst, and 5-50 parts of Polygala tenuifolia.

[0028] Compared with the existing technology, the present invention has achieved comprehensive and innovative technical effects:

[0029] The medicinal preparation of the present invention has fewer medicinal flavors, but has all the main, secondary, auxiliary and guiding ingredients, and has definite therapeutic effect.

[0030] The present invention can effectively improve the cognitive function and symptoms such as anxiety and depression in patients with cerebral small vessel disease by using a combination of Acanthopanax senticosus, Deer Horn Powder, Morinda officinalis, Cuscuta australis, Lycium barbarum, Hirudo, Gastrodia elata, Amethyst, and Polygala tenuifolia. The principle of the prescription of the Chinese medicine composition of the present invention is that the core pathogenesis of cerebral small vessel disease is "deficiency of essence and marrow, obstruction of collaterals, and sluggishness of spirit", and the treatment should be based on "tonifying the kidney and marrow, activating blood circulation and unblocking collaterals, and invigorating spirit". The main drugs of this prescription are Acanthopanax senticosus and Deer Horn Powder. Acanthopanax senticosus is pungent and warm in nature, and enters the kidney, heart, and spleen meridians. It has the effects of tonifying the kidney and calming the mind, activating blood circulation and unblocking collaterals; its slightly bitter taste can dry out dampness, and its warm nature can help yang, and it can directly tonify kidney yang without being dry; its pungent taste can disperse, dredge qi and blood, activate blood circulation and unblock collaterals, so as to dredge the obstruction of small blood vessels and collaterals; it can also regulate spirit, nourish the heart and calm the mind, and improve the damage of spirit. This medicine is the core drug for treatment. Deer antler frost, with its warm nature and salty, astringent flavor, warms the kidneys and boosts yang, while also astringing and stopping bleeding. Small blood vessel disorders are primarily caused by deficiency of essence and marrow, and blood stasis in the collaterals. Deer antler frost, a product of the essence of flesh and blood, is the residue left after deer antlers are boiled to make deer antler glue. Compared to velvet antler, it has milder properties, nourishing without drying, making it suitable for warming and tonifying kidney yang. Furthermore, its combined tonifying and purifying properties, while warming and tonifying kidney yang, can also dredge the blood vessels, making it suitable for kidney yang deficiency and blood stasis. These two herbs together constitute the monarch drug. The assistant drugs are Morinda officinalis, Hirudo, and Amethyst. Morinda officinalis, with its slightly warm nature and pungent and sweet flavor, enters the kidney and liver meridians, making it the primary assistant drug, tonifying kidney yang, strengthening bones and muscles, and dispelling rheumatism. Its pungent and warm properties complement the monarch drugs, Acanthopanax senticosus, and deer antler frost in warming and tonifying kidney yang. Its sweetness provides a gentle nourishing effect, while its slightly warming properties are not drying. Together, they complement the deer antler frost, enhancing its yang-warming properties without causing dryness. Leeches are neutral in nature, salty and bitter in flavor, and enter the Liver Meridian. This insect-based herb is known for its ability to dispel blood stasis and dredge the meridians, breaking up long-standing stasis. Its salty properties soften and dissipate lumps, while its bitter properties promote downward flow. They specifically target blood stasis in the collaterals, particularly those affecting small vessels. This complements the main herb, Acanthopanax senticosus, which promotes blood circulation and dredges. The former utilizes herbal properties to invigorate Qi and blood circulation, while the latter, with its potent insect properties, dissolves stasis and resolves symptoms, achieving a combined effect of dispelling blood stasis and unblocking the meridians. Amethyst, sweet in flavor and warm in nature, enters the Heart, Liver, and Kidney Meridians. This mineral-based herb, heavy and sinking, warms the kidneys and uterus, calms the heart, and soothes the mind. On the one hand, it aids the main herb in tonifying kidney yang and warming the lower burner, while on the other hand, its calming properties calm the rising of deficient yang, synergizing with Acanthopanax senticosus to harmonize the brain. These three herbs serve together as the auxiliary herb. Adjuvant herbs include Cuscuta australis, Lycium barbarum, Gastrodia elata, and Polygala tenuifolia. Cuscuta australis and wolfberry fruit both nourish yin and replenish essence, counteracting the warming and drying properties of the principal and auxiliary herbs to prevent damage to yin. Cuscuta australis, with its sweet and cold properties, nourishes the kidneys and clears the liver, improving eyesight and promoting diuresis; wolfberry fruit, with its neutral tonic properties, nourishes the liver and kidneys, improving essence and improving eyesight. These two herbs, combined with the "blood and flesh" nourishing properties of antler frost, balance yin and yang, filling the foundation for "essence and marrow deficiency." Gastrodia elata, sweet and neutral in nature, enters the liver meridian and is a key herb for calming the liver and calming wind. Its sweet, moist, and non-drying properties assist the principal and auxiliary herbs in harmonizing liver qi, alleviating damage to the collaterals caused by kidney deficiency and hyperactivity of the liver, preventing the transformation of wind into blood stasis and collateral damage. This aligns with the pathogenesis of "impaired spiritual function," synergizing with Acanthopanax senticosus to stabilize consciousness. Polygala tenuifolia, bitter and pungent in nature, enters the heart, kidney, and lung meridians, connecting the heart and kidneys, resolving phlegm, and calming the mind. Its pungent and warm properties boost yang, combining with the warming and nourishing power of the main medicine. Its bitter properties can relieve depression, dissolve stagnation and enhance the calming effect of the whole prescription.The formula's compatibility has three key characteristics. First, it focuses on warming and nourishing the kidney essence. Deer antler frost and Morinda officinalis warm the yang, while Cuscuta australis and Lycium barbarum nourish the yin, harmonizing the kidney's yin and yang and strengthening the foundation. Second, it emphasizes calming the mind. Acanthopanax senticosus, purple quartz, Polygala tenuifolia, and Gastrodia elata work synergistically to soothe the mind by tonifying the kidney, calming the liver, and resolving phlegm. Finally, it promotes blood circulation and unblocking the meridians: tonifying the kidney and activating blood circulation treats the root cause, while insect-based herbs resolve blood stasis and unclog the meridians, while Gastrodia elata calms the wind and soothes the mind, addressing the complex pathogenesis of "essence deficiency and marrow deficiency, and blocked meridians." BRIEF DESCRIPTION OF THE DRAWINGS

[0031] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments recorded in the embodiments of the present application. For ordinary technicians in this field, other drawings can also be obtained based on these drawings.

[0032] Figure 1 is a schematic diagram of the water maze for rats in each group;

[0033] Figure 2 is the number of times the platform is crossed;

[0034] Figure 3 is the effective area stop distance;

[0035] Figure 4 is the effective area residence time;

[0036] Figure 5 is the DTI value of the corpus callosum region of rats in each group;

[0037] Figure 6 is the myelin sheath damage of the corpus callosum of rats in each group under transmission electron microscope;

[0038] Figure 7 is the total clinical effectiveness rate;

[0039] Figure 8 It is the MOCA scale score;

[0040] Figure 9 is the HAMD scale score;

[0041] Figure 10 is the HAMA scale score;

[0042] Figure 11 is the Tinetti scale score;

[0043] Figure 12 It is the ADL scale score. DETAILED DESCRIPTION

[0044] In order to enable those skilled in the art to better understand the technical solutions in the embodiments of the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the embodiments of the present application, all other embodiments obtained by ordinary technicians in this field should fall within the scope of protection of the embodiments of the present application.

[0045] The present invention is further described below by way of specific examples, but the present invention is not limited to the following examples. Within the scope of the present invention or without departing from the content, spirit and scope of the present invention, changes, combinations or substitutions of the present invention will be obvious to those skilled in the art and are included within the scope of the present invention.

[0046] In one embodiment of the present application, a traditional Chinese medicine composition for use in the preparation of a composition for treating cerebral small vessel disease comprises the following components in parts by weight: 10-100 parts of Acanthopanax senticosus, 10-100 parts of Deer Antler Cream, 5-50 parts of Morinda officinalis, 5-50 parts of Cuscuta australis, 5-50 parts of Lycium barbarum, 2-30 parts of Hirudo, 5-50 parts of Gastrodia elata, 5-50 parts of Amethyst, and 5-50 parts of Polygala tenuifolia.

[0047] In an optional embodiment, the traditional Chinese medicine composition includes the following components in parts by weight: 30g of Acanthopanax senticosus, 30g of Deer Antler Powder, 15g of Morinda officinalis, 10g of Cuscuta australis, 10g of Lycium barbarum, 6g of Hirudo, 15g of Gastrodia elata, 15g of Amethyst, and 10g of Polygala tenuifolia.

[0048] A second aspect of the present invention provides a use of a traditional Chinese medicine composition for treating cerebral small vessel disease, the composition comprising the following components, measured in parts by weight: 10-100 parts of Acanthopanax senticosus, 10-100 parts of Deer Antler Powder, 2-30 parts of Hirudo, and 5-50 parts of Amethyst. In an alternative embodiment, the composition may further comprise 5-50 parts of Morinda officinalis, 5-50 parts of Cuscuta australis, 5-50 parts of Lycium barbarum, 5-50 parts of Gastrodia elata, and 5-50 parts of Polygala tenuifolia.

[0049] Another aspect of the present invention provides a traditional Chinese medicine preparation comprising the above-mentioned traditional Chinese medicine composition as an active ingredient and combined with a pharmaceutically acceptable carrier, diluent or excipient.

[0050] Another aspect of the present invention provides a method for preparing a Chinese medicine composition, comprising mixing the Chinese medicine composition with a diluent and / or other additives or adjuvants.

[0051] Another aspect of the present invention provides a traditional Chinese medicine composition for treating cerebral small vessel disease, which comprises the following components in parts by weight: 10-100 parts of Acanthopanax senticosus, 10-100 parts of Deer Antler Powder, 5-50 parts of Morinda officinalis, 5-50 parts of Cuscuta australis, 5-50 parts of Lycium barbarum, 2-30 parts of Hirudo, 5-50 parts of Gastrodia elata, 5-50 parts of Amethyst, and 5-50 parts of Polygala tenuifolia.

[0052] The following is a method for preparing the Chinese medicine composition:

[0053] Preparation method of the decoction: according to the weight parts of each component of the above-mentioned traditional Chinese medicine composition, take each medicinal material, decoct with water for 30-60 minutes, filter, and collect the filtrate; continue to add water to the filter residue and decoct for 20-40 minutes, filter, and collect the filtrate; concentrate at 60-70°C to a relative density of 1.05-1.15, let it stand, take the supernatant, and concentrate at 60-70°C to a relative density of 1.25-1.30 to obtain a decoction.

[0054] Granule preparation method: Weigh each medicinal ingredient according to the formula. Traditional Chinese medicine preparation: Calcined antler frost to remove impurities, stir-fried leech talc, calcined and quenched amethyst, and the remaining ingredients were cleaned and then cut into sections or crushed. Extraction and purification: Extraction is performed by decoction. Soak the medicinal ingredients in water for 1 hour. First, decoct the amethyst, then add the gastrodia elata. Decoction is repeated twice (1.5 hours each time), and the decoctions are combined. Soak the polygala root in liquorice water, remove the core, and reduce mucus. The extract is centrifuged and filtered, then purified by precipitation with 70% ethanol. The extract is allowed to stand for 12 hours. The supernatant is collected, the ethanol is recovered, and the extract is concentrated under reduced pressure to a thick paste with a relative density of 1.25 (60°C). Drying and granulation: A dry extract is obtained by vacuum drying. After pulverization, the dry extract powder is mixed with a combination of excipients (dextrin + mannitol) and 75% ethanol as a wetting agent to prepare a soft material. Granulation is performed by extrusion through a No. 2 sieve. The extract is then dried and granulated to obtain granules with uniform particle size and good solubility.

[0055] Preparation method of tablets: The preparation, extraction and purification of traditional Chinese medicine are the same as those of granules. Drying and granulation: The thick paste is vacuum dried (50°C, vacuum degree 0.07MPa) to make a dry extract, crushed into fine powder, and then 10% microcrystalline cellulose, 5% sodium starch glycolate, and 0.5% magnesium stearate are added. After mixing evenly, 85% ethanol is used to make a soft material, and granulated through a 14-mesh sieve. After drying at 60°C, the granules are sieved through a 10-mesh sieve; Tableting: The granules are placed in a tablet press and the pressure is adjusted to an appropriate range (usually 3-5kg / cm 2 ), pressed into tablets with a diameter of 5-8 mm, each tablet containing 0.3-0.5 g of extract powder.

[0056] Preparation of capsules: The Chinese medicine preparation, extraction and purification, drying and granulation are the same as for granules. Using a fully automatic capsule filling machine, fill the mixed powder into size 0 or size 1 hollow capsules, adjusting the filling volume so that each capsule contains 0.3-0.4g of extract powder. After filling, discard any defective capsules, such as those with leaking powder or deflated capsules.

[0057] Example

[0058] Example 1

[0059] Prescription: Acanthopanax senticosus 30g, Deer Antler Powder 30g, Morinda officinalis 15g, Cuscuta australis 10g, Lycium barbarum 10g, Hirudo 6g, Gastrodia elata 15g, Amethyst 15g, Polygala tenuifolia 10g.

[0060] Preparation method: take the above components, decoct with water for 90 minutes, filter, collect the filtrate to obtain filtrate; continue to add water to the filter residue and decoct for 45 minutes, filter, collect two filtrates, concentrate at 60-70°C to a relative density of 1.10, let it stand, take the supernatant, and concentrate at 60-70°C to a relative density of 1.25 to obtain a decoction.

[0061] Example 2

[0062] Prescription: Acanthopanax senticosus 10g, Deer Antler Powder 10g, Morinda officinalis 5g, Cuscuta australis 5g, Lycium barbarum 5g, Hirudo 2g, Gastrodia elata 5g, Amethyst 5g, Polygala tenuifolia 5g.

[0063] Preparation method: take the above components, decoct with water for 45 minutes, filter, collect the filtrate to obtain filtrate; continue to add water to the filter residue and decoct for 30 minutes, filter, collect two filtrates, concentrate at 60-70°C to a relative density of 1.15, let it stand, take the supernatant, and concentrate at 60-70°C to a relative density of 1.3 to obtain a decoction.

[0064] Example 3

[0065] Prescription: Acanthopanax senticosus 100g, Deer Antler Frost 100g, Morinda officinalis 50g, Cuscuta australis 50g, Lycium barbarum 50g, Hirudo 30g, Gastrodia elata 50g, Amethyst 50g, Polygala tenuifolia 50g.

[0066] Preparation method: take the above components, decoct with water for 120 minutes, filter, collect the filtrate to obtain filtrate; continue to add water to the filter residue and decoct for 90 minutes, filter, collect two filtrates, concentrate at 60-70°C to a relative density of 1.05, let it stand, take the supernatant, and concentrate at 60-70°C to a relative density of 1.25 to obtain a decoction.

[0067] Example 4

[0068] Prescription: Acanthopanax senticosus 30g, Deer Antler Powder 30g, Morinda officinalis 15g, Cuscuta australis 10g, Lycium barbarum 10g, Hirudo 6g, Gastrodia elata 15g, Amethyst 15g, Polygala tenuifolia 10g.

[0069] Preparation method: Take the above components and prepare them in traditional Chinese medicine: calcine antler frost to remove impurities, stir-fry leech talc, calcine quench and crush the amethyst, and clean the remaining ingredients before cutting into sections or crushing. Extraction and purification: Extract by decoction: Soak the medicinal materials in water for 1 hour. First, decoct the amethyst, then add the gastrodia elata. Decoction is repeated twice (1.5 hours each time), and the decoctions are combined. Soak the polygala root in liquorice water, remove the core, and reduce the mucilage. The extract is centrifuged and filtered, then purified by precipitation with 70% ethanol. The extract is allowed to stand for 12 hours. The supernatant is collected to recover the ethanol and concentrated under reduced pressure to a thick paste with a relative density of 1.25 (60°C). Drying and granulation: A dry extract is obtained by vacuum drying. After pulverization, the dry extract powder is mixed with a combination of excipients (dextrin + mannitol), and 75% ethanol is used as a wetting agent to prepare a soft material. Granulate the extract by extrusion through a No. 2 sieve, then dry and granulate to obtain granules with uniform particle size and good solubility.

[0070] Example 5

[0071] Prescription: Acanthopanax senticosus 30g, Deer Antler Powder 30g, Morinda officinalis 15g, Cuscuta australis 10g, Lycium barbarum 10g, Hirudo 6g, Gastrodia elata 15g, Amethyst 15g, Polygala tenuifolia 10g.

[0072] Preparation method: The preparation, extraction and purification of Chinese medicine are the same as those for granules. Drying and granulation: The thick paste is vacuum dried (50°C, vacuum degree 0.07MPa) to make a dry extract, crushed into fine powder, and then 10% microcrystalline cellulose, 5% sodium starch glycolate, and 0.5% magnesium stearate are added. After mixing evenly, 85% ethanol is used to make a soft material, and granulated through a 14-mesh sieve. After drying at 60°C, the granules are sieved through a 10-mesh sieve. Tableting: The granules are placed in a tablet press and the pressure is adjusted to an appropriate range (usually 3-5kg / cm 2 ), pressed into tablets with a diameter of 5-8 mm, each tablet containing 0.3-0.5 g of extract powder.

[0073] Example 6

[0074] Prescription: Acanthopanax senticosus 30g, Deer Antler Powder 30g, Morinda officinalis 15g, Cuscuta australis 10g, Lycium barbarum 10g, Hirudo 6g, Gastrodia elata 15g, Amethyst 15g, Polygala tenuifolia 10g.

[0075] Preparation Method: The Chinese herbal medicine preparation, extraction, and purification are the same as those for granules. This step is consistent with the granule purification process to ensure the retention of active ingredients and the removal of impurities. Drying and Powdering: The resulting thick paste is vacuum dried to form a dry extract. The dry extract is then crushed and passed through a No. 8 sieve (according to the Chinese Pharmacopoeia standard) to obtain a fine and uniform dry extract powder. This particle size ensures the fluidity of the capsule contents and prevents delamination or clogging of the capsule shell during filling. Excipient Mixing: The dry extract powder is thoroughly mixed with the combined excipients of microcrystalline cellulose and magnesium stearate. Capsule Filling: Using a fully automatic capsule filling machine, the uniformly mixed powder is filled into size 0 hollow capsule shells, with the filling volume variation controlled within ±7.5% (in compliance with the requirements for capsules in the Chinese Pharmacopoeia). The filled capsules are polished by a capsule polisher, quality inspected, and packaged. The capsules are checked for filling volume variation and disintegration time. Approved capsules are then packaged in aluminum-plastic blisters or bottles.

[0076] Comparative Example 1

[0077] Prescription: 160g ginseng, 120g Gastrodia elata, 180g stir-fried Atractylodes macrocephala, 60g Morinda officinalis, 6.50g Acorus calamus, and 5.50g Coptis chinensis.

[0078] Preparation method: same as Example 1.

[0079] Comparative Example 2

[0080] Prescription: Processed Polygonum multiflorum 15g, Cistanche deserticola 15g, Cornus officinalis 18g, Chuanxiong 15g, Polygala tenuifolia 15g, Acorus calamus 12g, Hirudo 6g, Salvia miltiorrhiza 22g, and ginger 2g.

[0081] Preparation method: same as Example 1.

[0082] Comparative Example 3

[0083] Formula: Leech 30g, Chuanxiong 30g, Danshen 20g, Astragalus 20g

[0084] Preparation method: A: pulverize leeches into coarse powder, add water, and stir and extract at 37°C. After centrifugation, collect the supernatant, pre-filter and sterilize it through a filter membrane, and then concentrate it through ultrafiltration. The concentrate is freeze-dried and pulverized to obtain leech freeze-dried powder for later use. B: Chuanxiong, Danshen and Astragalus are refluxed and extracted with 85% ethanol. The reflux liquid is filtered and concentrated to obtain an alcohol concentrate. The residue is added with water 4 times the amount of the raw medicinal materials, decocted and extracted, filtered, and the filtrate is concentrated to obtain an aqueous concentrate. The alcohol concentrate and the aqueous concentrate are combined and spray-dried to obtain a mixed powder of Chuanxiong, Danshen and Astragalus. C: The leech freeze-dried powder obtained in step A and the mixed powder of Chuanxiong, Danshen and Astragalus obtained in step B are uniformly mixed and prepared into an oral pharmaceutical preparation directly or by adding a pharmaceutically acceptable excipient through conventional procedures.

[0085] Animal experiment on the effect of the medicinal decoction of the present invention on the memory ability of CSVD rats

[0086] 1. Materials and Experimental Animals

[0087] 1.1 Experimental Animals

[0088] 14-week-old specific pathogen-free (SPF) male spontaneously hypertensive rats (SHR, n=80) were selected.

[0089] and its homologous normotensive control strain (Wistar-Kyoto, WKY, n = 10). The experimental animal model was provided by Beijing Weitonglihua Laboratory Animal Technology Co., Ltd. (Animal Use License No.: SYXK (Beijing)

[0090] 2020-0033).

[0091] 1.2 Model preparation

[0092] Spontaneously hypertensive rats were treated with D-galactose 300 mg / kg / d subcutaneous injection.

[0093] Prepare CSVD rat model.

[0094] 1.3 Drugs and reagents

[0095] The modeling drug is D-galactose (D-Galactose, D-gal) (Sigma, USA, V900922); the decoction drugs of Drug Example 1 and Comparative Examples 1-3 of the present invention are provided by the Chinese Medicine Pharmacy of the Third Affiliated Hospital of Beijing University of Chinese Medicine, and the quality of the decoction pieces meets the standards of the Pharmacopoeia of the People's Republic of China; Amlodipine besylate tablets (Pfizer Pharmaceutical Co., Ltd., National Medicine Standard H10950224, specification 5 mg) are ground into powder before use, added with physiological saline to make a suspension, and mixed before gavage.

[0096] 1.4 Animal grouping and drug administration

[0097] Animals were randomly divided into 9 groups: a blank control group, a model group, a positive control group, as well as Examples 1-6, Comparative Examples 1, 2, and 3. Each group consisted of 10 mice, each caged and adaptively fed for 1 week. Administration was continued for 12 weeks prior to testing, with oral gavage once daily. The normal and model groups were gavaged with normal saline. The positive group was given amlodipine besylate tablets. After 12 weeks of gavage, the mice underwent water maze testing, animal imaging DTI analysis, and electron microscopy analysis of white matter damage.

[0098] 2. Observation indicators and methods

[0099] 2.1 Morris water maze test

[0100] On the first day after the end of drug administration, mice in each group began to undergo behavioral testing in the Morris water maze. Before the test, the mice were allowed to swim freely to familiarize themselves with the environment. The mice were placed in the pool facing the pool wall from three quadrants, and the time it took for the mice to find the platform within 60 seconds (escape latency) was recorded. If the platform was not found after 60 seconds, the experimenter would manually lead the platform and stay on the platform for 30 seconds. The escape latency was recorded as 60 seconds. This was repeated for 5 consecutive days. On the 6th day, the platform was removed and the mice were allowed to search for the remembered platform without the platform and swim for 60 seconds. The movement trajectory of the mice was recorded, the number of times the mice crossed the original platform position was observed, and the total time they stayed in the original platform quadrant was summarized.

[0101] 2.2 DTI imaging analysis

[0102] MRI examinations were completed at the Central Laboratory Imaging Center of Capital Medical University, with 5 rats randomly selected from each group. A 7.0-T small animal functional magnetic resonance imaging (FMRI) was used to collect T2 and DTI sequences of rat brain tissue. During the test, the rat was first placed in an anesthesia induction box and anesthetized with isoflurane (the induction dose was 5%, and 2%-3% during the scan). After the rat was anesthetized, it was taken out and placed in a prone position on the scanning table with its head in the center of the coil. An anesthesia mask was added and a respiratory and pulse monitoring device was placed to keep the rat in an anesthetized state during the scan. The rat's breathing and pulse were closely monitored, and the respiratory rate was maintained at 40-60 times / min. During the scan, a T1 coarse scan was performed first for positioning, and then a T2-weighted structural image was scanned to obtain an anatomical structural image. The coronal T2-weighted image was used as a template for a DTI sequence scan. The field was uniformed before each scan, and the data was saved in DICOM format after the scan. T2 scan parameters were as follows: repetition time (TR) = 4200 ms, echo time (TE) = 36 ms, flip angle (FA) = 180°, field of view (FOV) = 3.3 cm × 3.3 cm, acquisition matrix = 256 × 256, slice thickness = 0.70 mm, no gap, number of slices = 35, and scan time = 6 min 43 s 200 ms. DTI scan parameters were as follows: TR = 5000 ms, TE = 23 ms, FA = 90°, b-value = 1000 s / mm2, diffusion direction = 30, number of segments = 4, slice thickness = 1 mm, no gap, and FOV = 3.5 cm.

[0103] ×3.5 cm, matrix size = 128 × 128, number of slices = 20, and scanning time = 14 min 35 s.

[0104] 2.3 Transmission electron microscopy observation of changes in corpus callosum myelin tissue

[0105] Rat corpus callosum was cut into 1 mm thick tissue sections. The specimens were immersed in electron microscopy fixative overnight at 4°C, fixed in osmium phosphate for 2 hours, stained in 1% uranyl acetate for 1 hour, dehydrated through a graded series of ethanol, and then embedded in epoxy resin. The specimens were cut using an ultramicrotome, stained with uranyl acetate and lead citrate, and observed using a transmission electron microscope.

[0106] 3. Results

[0107] 3.1 Morris water maze test of rats in each group

[0108] Schematic diagram of the Morris water maze experiment in rats Figure 1 shown.

[0109] Table 1 shows that the escape latency of rats in the model group was significantly higher than that in the blank group (P<0.05); the escape latency of rats in the western medicine group was significantly lower than that in the model group (P<0.05); the drug decoctions of inventive examples 1-6 were significantly lower than those in the western medicine group (P<0.05); and the drug decoctions of inventive examples 1-6 were significantly lower than those in the comparative examples 1-3 (P<0.05).

[0110] Figure 2 As shown in the results of the experiment, the number of times the rats in the model group crossed the platform was significantly lower than that in the blank group (P<0.05); the number of times the rats in the western medicine group crossed the platform was significantly higher than that in the model group (P<0.05); the drug decoctions of Examples 1-6 of the invention were significantly higher than those of the western medicine group (P<0.05); in addition, the drug decoctions of Examples 1, 2, and 3 of the invention were significantly higher than those of Comparative Examples 1-3 (P<0.05).

[0111] Figure 3 As shown in the results of the study, the effective area residence distance of rats in the model group was significantly lower than that in the blank group (P<0.05); the effective area residence distance of rats in the western medicine group was significantly higher than that in the model group (P<0.05); the medicinal decoctions of Examples 1-6 of the invention were significantly higher than those of the western medicine group (P<0.05); in addition, the medicinal decoctions of Examples 1, 2, and 3 of the invention were significantly higher than those of Comparative Examples 1-3 (P<0.05).

[0112] Figure 4 As shown in the results of the study, the residence time in the effective area of ​​the rats in the model group was significantly lower than that in the blank group (P<0.05); the residence time in the effective area of ​​the rats in the western medicine group was significantly higher than that in the model group (P<0.05); the medicinal decoctions of Examples 1-6 of the invention were significantly higher than those of the western medicine group (P<0.05); in addition, the medicinal decoctions of Examples 1, 2, and 3 of the invention were significantly higher than those of Comparative Examples 1-3 (P<0.05).

[0113] Table 1 Escape latency of rats in each group on Day 1-5

[0114]

[0115]

[0116] Note: a) Compared with the blank group, P<0.05; b) Compared with the model group, P<0.05; c) Compared with the Western medicine group, P<0.05.

[0117] 3.2 Diffusion Tensor Imaging (DIT) Analysis

[0118] Figure 5 As shown in the corpus callosum DTI, the number of times the rats in the model group crossed the platform was significantly lower than that in the blank group (P<0.05); the number of times the rats in the western medicine group crossed the platform was significantly higher than that in the model group (P<0.05); the drug decoctions of Examples 1-6 of the invention were significantly higher than those of the western medicine group (P<0.05); in addition, the drug decoctions of Examples 1, 2, and 3 of the invention were significantly higher than those of Comparative Examples 1-3 (P<0.05).

[0119] 2.3 Transmission electron microscopy observation of changes in corpus callosum myelin tissue

[0120] like Figure 6 As shown, transmission electron microscopy observation showed that compared with the blank group, the myelin sheath of the corpus callosum of the rats in the model group was swollen, the lamellar structure was separated and loose, and there was intermittent loss; the myelin sheath structure of the corpus callosum of the rats in the western medicine group was relatively complete, with uniform thickness, regular edges, and concentric arrangement. The myelinated nerve fibers were neatly arranged, and the myelin lamellar structure was dense; the myelin sheath structure, thickness, myelinated nerve fiber arrangement, and myelin lamellar structure of the medicinal decoctions of Examples 1-6 of the invention were significantly better than those of the western medicine group (P<0.05); in addition, the medicinal decoctions of Examples 1-6 of the present invention were significantly better than those of Comparative Examples 1-3 (P<0.05).

[0121] 2. Clinical Trial of the Medicinal Decoction of the Present Invention on CSVD Patients

[0122] From December 2023 to December 2024, 66 patients with cerebral small vessel disease were observed in the outpatient clinic and ward of the Third Affiliated Hospital of Beijing University of Chinese Medicine. A randomized double-blind, parallel-controlled clinical design method was adopted. Patients with cerebral small vessel disease who met the inclusion criteria were randomly divided into a test group (the Chinese medicine composition group of the present invention, the Chinese medicine composition granules of the present invention, prepared according to the method of Example 4) and a control drug (Chinese medicine placebo granules). Both groups were given basic treatments such as antihypertensive and hypoglycemic treatments for 12 consecutive weeks. Outcome indicator observation: At the 0th and 12th weeks of treatment, the efficacy was evaluated using ① Montreal Cognitive Assessment Scale (MoCA), ② Hamilton Depression Rating Scale (HAMD-24), ③ Hamilton Anxiety Rating Scale (HAMA), ④ Tinetti Balance and Gait Scale (TinettiPOMA), and ⑤ Daily Living Ability Scale (ADL), and safety evaluation was performed during the same period.

[0123] 1. Research Plan

[0124] 1. Diagnostic criteria and basis for cerebral small vessel disease

[0125] This study was developed with reference to the "2021 Chinese Expert Consensus on the Diagnosis and Treatment of Cerebral Small Vessel Disease" and the "STRIVE-2 Neuroimaging Criteria for Cerebral Small Vessel Disease Research." Clinical manifestations are nonspecific, with cognitive decline, gait disturbances, and affective disturbances being common. The imaging diagnosis of CSVD is based on the presence of white matter hyperintensities on MRI, recent small subcortical infarcts, lacunes, cerebral microbleeds, enlarged perivascular spaces, cerebral atrophy, cortical microinfarcts, and cortical surface iron deposition. Overall imaging requirements are recommended to meet at least the following criteria: a Fazekas score ≥3; or a Fazekas score ≥2 with one lacunar.

[0126] 2 Inclusion criteria:

[0127] (1) Age 45 to 85 years old, regardless of gender;

[0128] (2) meeting the Western medical diagnostic criteria for CSVD;

[0129] (3) Underwent cranial MRI examination before the start of the study;

[0130] (4) Be able to cooperate with clinical physicians to complete the corresponding scale evaluation;

[0131] (5) Volunteer to participate in the trial and sign the informed consent form.

[0132] Exclusion criteria:

[0133] (1) Patients with severe stenosis of the internal carotid artery, vertebral basilar artery and its branches;

[0134] (2) Patients with leukoencephalopathy or cardiogenic cerebral infarction caused by non-vascular factors;

[0135] (3) Patients with other neurological diseases such as large-area cerebral hemorrhage or cerebral infarction, craniocerebral trauma, multiple sclerosis, encephalitis, etc.;

[0136] (4) Patients with severe medical diseases such as blood system diseases, liver and kidney dysfunction, cardiopulmonary insufficiency, and tumors;

[0137] (5) Patients with severe mental illness or a history of psychoactive drug abuse; patients with confirmed neurodegenerative or degenerative diseases such as Parkinson's disease, Alzheimer's disease, vascular dementia, etc.

[0138] (6) Patients with severe aphasia, agnosia, severe visual and auditory impairment, severe cognitive impairment and inability to communicate, and other factors that make them unable to cooperate with the scale assessment;

[0139] (7) Suffering from severe bone and joint diseases of the waist, knees, ankles, etc., and being unable to walk normally;

[0140] (8) Those who have contraindications to MRI examination or are unable to complete MRI examination.

[0141] (9) Poor compliance, such as no caregiver or the caregiver cannot help the subject use the trial drug correctly or cannot accurately feedback the changes in the condition to cooperate in completing the experiment;

[0142] (10) Those who are known to be allergic to any component of Chinese herbal granules.

[0143] Those who meet any of the above conditions will be excluded.

[0144] Rejection criteria:

[0145] ① After enrollment, it was found that the patients did not meet the inclusion criteria for cerebral small vessel disease and were mistakenly included;

[0146] ② Those who have not taken the trial drug once after enrollment;

[0147] ③ Those who seriously violate the experimental plan.

[0148] The reasons for excluding cases should be stated in the case report form.

[0149] Exit criteria:

[0150] ① If allergic reactions or serious adverse events occur, the clinical trial should be stopped according to the doctor's judgment, that is, the patient should withdraw from the clinical trial.

[0151] ② Those who withdraw informed consent.

[0152] ③ Those who develop other serious diseases during the trial.

[0153] ④ Subjects whose blinding was broken during the trial.

[0154] ⑤ Lost to follow-up.

[0155] ⑥ The subjects had poor compliance during medication, taking less than 80% of the prescribed amount or exceeding 120% of the prescribed amount.

[0156] ⑦ During the medication process, prohibited drugs or treatments specified in the plan were used.

[0157] ⑧ Patients who develop sudden cerebral macrovascular disease during the trial.

[0158] 3. Dosage Method

[0159] Weeks 1 to 12 (Days 0 to 84):

[0160] The Chinese medicine composition group of the present invention: taking the Chinese medicine composition granules of the present invention in the morning and evening respectively combined with basic treatment;

[0161] Control group: taking Chinese medicine granules placebo combined with basic treatment in the morning and evening;

[0162] The Chinese medicine composition granules are produced and packaged by Guangdong Yifang Pharmaceutical Company. The drug composition includes (Acanthopanax senticosus, Deer Antler Powder, Morinda officinalis, Cuscuta australis, Lycium barbarum, Hirudo, Polygala tenuifolia, Gastrodia elata, and Amethyst).

[0163] The Chinese medicine granule placebo was prepared by adding granule excipients to 10% of the Chinese medicine composition (prepared in Example 1).

[0164] 4 Observation content, efficacy evaluation indicators and detection methods

[0165] 4.1 Main efficacy indicators:

[0166] The Montreal Cognitive Assessment (MoCA) was used for assessment;

[0167] 4.2 Secondary efficacy indicators

[0168] (1) Depression and anxiety assessment: The Hamilton Depression Rating Scale (HAMD-24) and the Hamilton Anxiety Rating Scale (HAMA) were used to assess mental and emotional disorders;

[0169] (2) Gait disorder assessment: The Tinetti Balance and Gait Assessment (Tinetti POMA) was used to assess gait disorder.

[0170] (3) Quality of life: The Activities of daily living (ADL) scale was used to evaluate the patient's daily living ability.

[0171] 4.3 Criteria for determining efficacy

[0172] Clinical efficacy was assessed using the MoCA score as the reference standard. Statistical analysis was performed on the results at weeks 0 and 12 of treatment. The efficacy index (EI) was calculated using the formula: (post-treatment score - pre-treatment score) / pre-treatment score × 100%. This index determined the effectiveness of cognitive improvement. Marked efficacy: ≥20%; effective: 12%-20%; ineffective: <12%. Effectiveness: (number of markedly effective patients + number of effective patients) / total number of patients treated × 100%.

[0173] 5 Safety evaluation

[0174] Safety assessments include vital signs, physical examinations, TESS, blood count, urine count, blood biochemistry, and electrocardiogram (ECG). Adverse events and serious adverse events will be recorded as other safety and tolerability indicators.

[0175] 6 Statistical methods

[0176] Data were analyzed using SPSS 26.0 statistical software. The MOCA, HAMD-24, HAMA, Tinetti Balance and Gait Scale, and Barthel Index scores were measured. Normally distributed data were expressed as mean ± standard deviation (x ± s) and tested using the independent sample t test. Data that did not meet normal distribution were expressed as M (P<0.05, P<0.05) and tested using the nonparametric rank sum test. All statistical tests were two-sided, with P<0.05 considered statistically significant.

[0177] 2. Research Results

[0178] 1 General

[0179] A total of 66 subjects were enrolled in this study, of whom 4 dropped out and 2 were excluded. The reason for dropout was loss to follow-up, with no statistically significant difference between the two groups. Exclusion was due to the patient taking other medications on their own. A total of 60 subjects completed clinical observation, including 33 males and 27 females. Thirty subjects were assigned to the traditional Chinese medicine composition group and 30 subjects to the control group.

[0180] 2Clinical efficacy

[0181] Figure 7 The total effective rate of the Chinese medicine composition group at the 12th week of treatment was 76.7%, while that of the control group was 43.3%, with a significant difference between the two groups (P<0.05).

[0182] 3 Main outcome measures

[0183] 3.1 Improvement of cognitive impairment

[0184] Figure 8 : The MOCA scores of the two groups at week 0 of treatment were consistent at baseline, with no statistical difference. At week 12 of treatment, the MOCA scores of both groups increased, with the score of the Chinese medicine composition group being 24.51±2.28 and the score of the control group being 21.41±1.83, and the difference between the two groups was significant (P<0.05).

[0185] 4 secondary outcome indicators

[0186] 4.1 Improvement of depression

[0187] Figure 9 : The baseline HAMD-24 scores of the two groups at week 0 of treatment were consistent, with no statistical difference. At week 12 of treatment, the HAMD-24 scores of both groups increased, with the score of the Chinese medicine composition group being 16.87±3.21 and the score of the control group being 20.30±3.41, and the difference between the two groups was significant (P<0.05).

[0188] 4.2 Anxiety Improvement

[0189] Figure 10 : The baseline HAMA scores of the two groups at week 0 of treatment were consistent, with no statistical difference. At week 12 of treatment, the HAMA scores of both groups increased, with the score of the Chinese medicine composition group being 12.67±2.21 and the score of the control group being 20.57±2.61, and the difference between the two groups was significant (P<0.05).

[0190] 4.3 Improvement of gait disorders

[0191] Figure 11 : The baseline Tinetti balance and gait scale scores of the two groups at week 0 of treatment were consistent, with no statistical difference. At week 12 of treatment, the Tinetti balance and gait scale scores of the two groups of patients increased. The score of the Chinese medicine composition group was 24.17±1.55, and the score of the control group was 22.58±1.77. The difference between the two groups was significant (P<0.05).

[0192] 4.4 Improvement in daily living abilities

[0193] Figure 12 : The baseline ADL scale scores of the two groups at week 0 of treatment were consistent, with no statistical difference. At week 12 of treatment, the ADL scale scores of the two groups of patients increased, with the score of the Chinese medicine composition group being 88.00±2.00 and the score of the control group being 82.00±2.00, and the difference between the two groups was significant (P<0.05).

[0194] 4.5 Criteria for determining efficacy

[0195] The effective rate was calculated based on the difference between the MOCA scale scores before and after treatment and the baseline. The total effective rate was 76.7% in the experimental group and 43.3% in the control group. The difference between the two groups was significant (P<0.05).

[0196] 5. Safety and side effect evaluation

[0197] All patients enrolled in this study showed no abnormalities in blood routine tests or liver and kidney function tests before and after treatment. Some patients experienced loose stools and mild stomach discomfort, which resolved spontaneously with continued medication. This suggests that the Chinese herbal composition of the present invention is safe and reliable for treating cerebral small vessel disease, without significant side effects.

[0198] 3. Research Conclusions

[0199] The results of this study show that the Chinese medicine composition of the present invention has the following advantages:

[0200] (1) Multidimensional therapeutic effects: The Chinese medicine composition of the present invention has multiple clinical therapeutic effects and has significant therapeutic effects on CSVD-related cognitive impairment, depression, anxiety and gait disorders.

[0201] (2) Good efficacy: At the end of the trial, the total clinical efficacy of the Chinese medicine composition of the present invention reached 78.3%, and cognitive function, depression, anxiety, and gait disorders were all improved.

[0202] (3) Small side effects: Most psychiatric drugs for anxiety, depression, and cognitive improvement have side effects such as dizziness, nausea and vomiting, abdominal distension and constipation, and weight gain. The Chinese medicine composition group of the present invention did not produce the above symptoms.

[0203] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the embodiments of the present application, and not to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, ordinary technicians in this field should understand that they can still modify the technical solutions recorded in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. These modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. Use of a Chinese medicine composition for treating cerebral small vessel disease, characterized in that: The traditional Chinese medicine composition comprises the following components in parts by weight: 10-100 parts of Acanthopanax senticosus, 10-100 parts of Deer Antler Powder, 5-50 parts of Morinda officinalis, 5-50 parts of Cuscuta australis, 5-50 parts of Lycium barbarum, 2-30 parts of Hirudo, 5-50 parts of Gastrodia elata, 5-50 parts of Amethyst, and 5-50 parts of Polygala tenuifolia.

2. Use of the Chinese medicine composition according to claim 1 in the preparation of a composition for treating cerebral small vessel disease, characterized in that: The traditional Chinese medicine composition comprises the following components in parts by weight: 30g of Acanthopanax senticosus, 30g of Deer Horn Powder, 15g of Morinda officinalis, 10g of Cuscuta australis fruit, 10g of Lycium barbarum fruit, 6g of Hirudo, 15g of Gastrodia elata, 15g of Amethyst, and 10g of Polygala tenuifolia.

3. Use of a Chinese medicine composition for treating cerebral small vessel disease, characterized in that: The traditional Chinese medicine composition comprises the following components in parts by weight: 10-100 parts of Acanthopanax senticosus, 10-100 parts of Deer Horn Powder, 2-30 parts of Leech, and 5-50 parts of Amethyst.

4. A method for preparing a Chinese medicine composition, characterized in that: The method comprises the following steps: taking processed Acanthopanax senticosus, Deer Antler Powder, Morinda Officinalis, Cuscuta australis, Lycium barbarum, Hirudo, Gastrodia elata, Amethyst, and Polygala tenuifolia according to the weight portions of the components of the traditional Chinese medicine composition according to any one of claims 1 to 3, decocting with water for 30-60 minutes, filtering, and collecting the filtrate; adding water to the filter residue and decocting for 20-40 minutes, filtering, and collecting the filtrate; concentrating at 60-70°C to a relative density of 1.05-1.15, allowing to stand, taking the supernatant, and concentrating at 60-70°C to a relative density of 1.25-1.30 to obtain a decoction.

5. A method for preparing a Chinese medicine composition, characterized in that: The method comprises the following steps: according to the weight parts of each component of the traditional Chinese medicine composition according to any one of claims 1 to 3, Preparation of Chinese medicine: Calcined antler frost to remove impurities, stir-fried leech talc powder, calcined and quenched amethyst, and the remaining components were cleaned and cut into sections or crushed. Extraction and Purification: Soak each component in water for 1 hour. First, decoct the purple quartz, followed by the gastrodia elata. Decoction is repeated twice (1.5 hours each time), and the decoctions are combined. Soak the polygala root in liquorice water, remove the core, and reduce mucus. The extract is centrifuged and filtered, then purified by precipitation with 70% ethanol. Allow to stand for 12 hours. The supernatant is collected, ethanol is recovered, and vacuum concentrated to a thick paste with a relative density of 1.25 (60°C). Drying and granulation: vacuum drying is used to obtain dry extract, which is then crushed and mixed with the combined excipients. 75% ethanol is used as a wetting agent to prepare a soft material, which is then extruded into granules and then dried and sized to obtain granules.

6. A method for preparing a Chinese medicine composition, characterized in that: The method comprises the following steps: according to the weight parts of each component of the traditional Chinese medicine composition according to any one of claims 1 to 3, Preparation of Chinese medicine: Calcined antler frost to remove impurities, stir-fried leech talc powder, calcined and quenched amethyst, and the remaining components were cleaned and cut into sections or crushed. Extraction and Purification: Soak each component in water for 1 hour. First, decoct the purple quartz, followed by the gastrodia elata. Decoction is repeated twice (1.5 hours each time), and the decoctions are combined. Soak the polygala root in liquorice water, remove the core, and reduce mucus. The extract is centrifuged and filtered, then purified by precipitation with 70% ethanol. Allow to stand for 12 hours. The supernatant is collected, ethanol is recovered, and vacuum concentrated to a thick paste with a relative density of 1.25 (60°C). Drying and granulation: The thick paste is vacuum dried to make a dry extract, which is then crushed into fine powder. 10% microcrystalline cellulose, 5% sodium starch glycolate, and 0.5% magnesium stearate are added and mixed evenly. The mixture is then softened with 85% ethanol and sieved through a 14-mesh sieve for granulation. The mixture is then dried at 60°C and sieved through a 10-mesh sieve for final granulation. Tablet pressing: Place the granules in the tablet press and adjust the pressure to 3-5kg / cm 2 , pressed into tablets with a diameter of 5-8 mm.

7. A method for preparing a Chinese medicine composition, characterized in that: The method comprises the following steps: according to the weight parts of each component of the traditional Chinese medicine composition according to any one of claims 1 to 3, Preparation of Chinese medicine: Calcined antler frost to remove impurities, stir-fried leech talc powder, calcined and quenched amethyst, and the remaining components were cleaned and cut into sections or crushed. Extraction and Purification: Soak each component in water for 1 hour. First, decoct the purple quartz, followed by the gastrodia elata. Decoction is repeated twice (1.5 hours each time), and the decoctions are combined. Soak the polygala root in liquorice water, remove the core, and reduce mucus. The extract is centrifuged and filtered, then purified by precipitation with 70% ethanol. Allow to stand for 12 hours. The supernatant is collected, ethanol is recovered, and vacuum concentrated to a thick paste with a relative density of 1.25 (60°C). Use a capsule filling machine to fill the mixed powder into No. 0 or No. 1 hollow capsules, and adjust the filling amount so that each capsule contains 0.3-0.4g of extract powder.

8. A Chinese medicine preparation comprising the Chinese medicine composition according to claim 1 as an active ingredient and combined with a pharmaceutically acceptable carrier, diluent or excipient.

9. A method for preparing a Chinese medicine composition, characterized in that: The Chinese medicine composition according to any one of claims 1 to 3 is mixed with a diluent and / or other additives or adjuvants.

10. A Chinese medicine composition for treating cerebral small vessel disease, characterized in that: The traditional Chinese medicine composition comprises the following components in parts by weight: 10-100 parts of Acanthopanax senticosus, 10-100 parts of Deer Antler Powder, 5-50 parts of Morinda officinalis, 5-50 parts of Cuscuta australis, 5-50 parts of Lycium barbarum, 2-30 parts of Hirudo, 5-50 parts of Gastrodia elata, 5-50 parts of Amethyst, and 5-50 parts of Polygala tenuifolia.

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