Traditional Chinese medicine raw material composition and pharmaceutical composition for treating ischemic stroke

Abstract

Provided are a traditional Chinese medicine raw material composition and a pharmaceutical composition for treating ischemic stroke. The traditional Chinese medicine raw material composition comprises the following effective components by weight: 8-15 parts of Chuanxiong, 8-12 parts of Zhizi, 3-9 parts of Sanqi, 1-5 parts of Shuishuichong, 8-15 parts of Shichangpu, 6-12 parts of Yujin, and 8-15 parts of Gualou. In the traditional Chinese medicine raw material composition and the pharmaceutical composition according to the present application, the seven kinds of medicines are used in combination, and play a significant synergistic role, the drug efficacy is clear, and the quality is controllable, thereby providing a new choice of medicine for treating ischemic stroke. In addition, the traditional Chinese medicine raw material composition and the pharmaceutical composition according to the present application can effectively improve the clinical symptoms of patients and improve the quality of life, and no obvious adverse reactions occur.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, and more specifically, this invention relates to a traditional Chinese medicine raw material composition and a pharmaceutical composition for treating ischemic stroke. Background Technology

[0002] Ischemic stroke is a disease caused by thrombosis, embolism, or insufficient systemic perfusion, leading to local cerebral ischemia and resulting in acute neurological damage. Globally, ischemic stroke is the most common type of stroke, accounting for 68% of all strokes, while in my country it accounts for 69.6% to 70.8%. The prevalence of ischemic stroke in my country is 1762.77 per 100,000. Currently, stroke is the leading cause of death and disability among adults in my country, characterized by high incidence, high disability rate, high mortality rate, and high recurrence rate, placing a heavy burden on society and patients' families. The acute phase is the critical period for treatment, and early thrombolysis is considered the most effective method. However, due to time window limitations, the annual thrombolysis rate is less than 5%, and current prevention and treatment measures are still insufficient to achieve satisfactory results. Therefore, scholars at home and abroad are exploring the pathogenesis of acute ischemic stroke from multiple perspectives to find effective prevention and treatment measures.

[0003] Furthermore, according to the "China Cardiovascular Health and Disease Report 2021," the prevalence of cardiovascular and cerebrovascular diseases in my country is on the rise, with 13 million people currently suffering from stroke. Ischemic stroke is the most common and prevalent type of stroke, characterized by high incidence, disability, and mortality rates, seriously threatening the health and lives of residents. Modern medicine has achieved significant benefits in the treatment of ischemic stroke, and traditional Chinese medicine also has unique advantages in its prevention and treatment. Currently, the widely accepted syndrome elements for ischemic stroke are qi, blood, phlegm, blood stasis, wind, and deficiency, with syndrome combinations often including wind-phlegm entering the collaterals, wind-yang disturbing the upper body, yin deficiency and wind stirring, phlegm-heat accumulation in the internal organs, and qi deficiency and blood stasis. Medically, ischemic stroke falls under the category of "stroke," with a complex pathogenesis, and blood stasis plays a crucial role in its development. However, this disease often has a rapid onset and severe symptoms, and the single theory of blood stasis cannot explain the complex pathogenic factors and pathogenesis of this disease. Summary of the Invention

[0004] One object of the present invention is to provide a traditional Chinese medicine raw material composition and a pharmaceutical composition for treating ischemic stroke.

[0005] According to one aspect of the present invention, a traditional Chinese medicine raw material composition for treating ischemic stroke is provided, the traditional Chinese medicine raw material composition comprising the following active ingredients by weight: 8-15 parts of Ligusticum chuanxiong, 8-12 parts of Gardenia jasminoides, 3-9 parts of Panax notoginseng, 1-5 parts of Hirudo medicinalis, 8-15 parts of Acorus tatarinowii, 6-12 parts of Curcuma longa and 8-15 parts of Trichosanthes kirilowii.

[0006] According to an exemplary embodiment of the present invention, the traditional Chinese medicine raw material composition may include the following active ingredients by weight: 8-13 parts of Ligusticum chuanxiong, 8-11 parts of Gardenia jasminoides, 4-8 parts of Panax notoginseng, 3-5 parts of Hirudo medicinalis, 8-13 parts of Acorus tatarinowii, 8-11 parts of Curcuma longa, and 10-15 parts of Trichosanthes kirilowii.

[0007] According to an exemplary embodiment of the present invention, the traditional Chinese medicine raw material composition may include the following active ingredients by weight: 9-11 parts of Ligusticum chuanxiong, 9-11 parts of Gardenia jasminoides, 5-7 parts of Panax notoginseng, 4-5 parts of Hirudo medicinalis, 9-11 parts of Acorus tatarinowii, 9-11 parts of Curcuma longa, and 12-15 parts of Trichosanthes kirilowii.

[0008] According to exemplary embodiments of the present invention, the traditional Chinese medicine raw material composition may include the following effective ingredients by weight: 10 parts of Ligusticum chuanxiong, 10 parts of Gardenia jasminoides, 6 parts of Panax notoginseng, 5 parts of Hirudo medicinalis, 10 parts of Acorus tatarinowii, 10 parts of Curcuma longa, and 15 parts of Trichosanthes kirilowii; 8 parts of Ligusticum chuanxiong, 9 parts of Gardenia jasminoides, 3 parts of Panax notoginseng, 2 parts of Hirudo medicinalis, 8 parts of Acorus tatarinowii, 6 parts of Curcuma longa, and 9 parts of Trichosanthes kirilowii; 15 parts of Ligusticum chuanxiong, 12 parts of Gardenia jasminoides, 8 parts of Panax notoginseng, 4 parts of Hirudo medicinalis, 15 parts of Acorus tatarinowii, 11 parts of Curcuma longa, and 15 parts of Trichosanthes kirilowii; or 11 parts of Ligusticum chuanxiong, 11 parts of Gardenia jasminoides, 7 parts of Panax notoginseng, 5 parts of Hirudo medicinalis, 11 parts of Acorus tatarinowii, 11 parts of Curcuma longa, and 9 parts of Trichosanthes kirilowii.

[0009] According to an exemplary embodiment of the present invention, the traditional Chinese medicine raw material composition may be composed of the following effective ingredients by weight: 8-15 parts of Ligusticum chuanxiong, 8-12 parts of Gardenia jasminoides, 3-9 parts of Panax notoginseng, 1-5 parts of Hirudo medicinalis, 8-15 parts of Acorus tatarinowii, 6-12 parts of Curcuma longa and 8-15 parts of Trichosanthes kirilowii.

[0010] According to another aspect of the present invention, a pharmaceutical composition for treating ischemic stroke is provided, said pharmaceutical composition being made from the traditional Chinese medicine raw material composition described above.

[0011] According to exemplary embodiments of the present invention, the pharmaceutical composition may further include pharmaceutically acceptable excipients.

[0012] According to exemplary embodiments of the present invention, pharmaceutically acceptable excipients may include at least one of starch, maltose, sucrose, and honey.

[0013] According to an exemplary embodiment of the present invention, the pharmaceutical composition can be prepared by the following steps: placing 8-15 parts of Ligusticum chuanxiong, 8-12 parts of Gardenia jasminoides, 1-5 parts of Hirudo medicinalis, 8-15 parts of Acorus tatarinowii, 6-12 parts of Curcuma longa, and 8-15 parts of Trichosanthes kirilowii in their respective decoction containers, and adding water to the decoction containers; after decoction for a predetermined time, filtering and concentrating into a clear extract; adding pharmaceutically acceptable excipients to the clear extract, mixing well, and granulating to obtain granules. The pharmaceutical composition comprises: 3-9 parts of Panax notoginseng in the form of medicinal slices, pulverized, with pharmaceutically acceptable excipients added, mixed and granulated to obtain granulated Panax notoginseng; or 3-9 parts of Panax notoginseng in the form of medicinal slices pulverized to obtain granulated Panax notoginseng; and granulated chuanxiong, gardenia, Panax notoginseng, leech, acorus, turmeric and trichosanthes fruit are mixed to obtain the pharmaceutical composition as at least one of granules and capsules.

[0014] According to an exemplary embodiment of the present invention, the pharmaceutical composition can be prepared by the following steps: placing 8-15 parts of Ligusticum chuanxiong, 8-12 parts of Gardenia jasminoides, 1-5 parts of Hirudo medicinalis, 8-15 parts of Acorus tatarinowii, 6-12 parts of Curcuma longa, and 8-15 parts of Trichosanthes kirilowii in the form of medicinal slices into a decoction container, and adding water to the decoction container; after decocting for a predetermined time, filtering and concentrating into a clear extract; and mixing the clear extract, 3-9 parts of Panax notoginseng by weight of the medicinal slices, and pharmaceutically acceptable excipients, and making pills to obtain the pharmaceutical composition as pills.

[0015] According to an exemplary embodiment of the present invention, the pharmaceutical composition can be prepared by the following steps: placing 8-15 parts of Ligusticum chuanxiong, 8-12 parts of Gardenia jasminoides, 1-5 parts of Hirudo medicinalis, 8-15 parts of Acorus tatarinowii, 6-12 parts of Curcuma longa, and 8-15 parts of Trichosanthes kirilowii in the form of medicinal slices into a decoction container, and adding water to the decoction container; and after decocting for a predetermined time, filtering to remove the dregs to obtain a decoction; and mixing the decoction with 3-9 parts of Panax notoginseng by weight of the medicinal slices to obtain the pharmaceutical composition as a decoction.

[0016] In this application, an animal model of ischemic stroke with blood stasis and toxin accumulation, characterized by carrageenan combined with dried yeast and middle cerebral artery occlusion (MCAO), was used. Modern medical analytical methods were employed to observe the effects of the traditional Chinese medicine raw material composition and drug composition according to the present invention on ischemic stroke. Experiments demonstrated that the seven herbs in the traditional Chinese medicine raw material composition and drug composition according to the present invention exhibit a significant synergistic effect, with clear efficacy and controllable quality, providing a new drug option for the clinical treatment of ischemic stroke. Furthermore, the traditional Chinese medicine raw material composition and drug composition according to the present invention can effectively improve patients' clinical symptoms and enhance their quality of life, with no significant adverse reactions. Attached Figure Description

[0017] The above and other objects and advantages of this application will become clearer from the following description of embodiments in conjunction with the accompanying drawings.

[0018] Figure 1 This is a comparison diagram of the auricular venous structures of rats in the sham-operated group (labeled A) and the Ca+Y group (labeled D) in the animal model.

[0019] Figure 2 This is a comparison of the nail colors of rats in the sham-operated group (labeled A) and the Ca+Y group (labeled D) in the animal model.

[0020] Figure 3 This is a comparison image of black-tailed rats in the sham-operated group (labeled A) and the Ca+Y group (labeled D) in the animal model.

[0021] Figure 4 These are comparison images of the tongues of rats in the sham-operated group (labeled A) and the Ca+Y group (labeled D) in the animal model.

[0022] Figure 5 This is a comparison of tail blood perfusion in rats in the sham-operated group (labeled A) and the Ca+Y group (labeled D) in the animal model.

[0023] Figure 6 This is a comparison chart of the cerebral infarction area in rats in the sham-operated group (labeled A) and the Ca+Y group (labeled D) in the animal model.

[0024] Figure 7 This is a diagram showing the HE staining of rat brain tissue in the sham-operated group (labeled A) and the Ca+Y group (labeled D) in the animal model.

[0025] Figure 8 This is a comparison of the tail blood perfusion of rats in the sham-operated group and model group that did not receive the drug composition of the present invention, and in the low-dose group and high-dose group that received the drug composition of Example 1.

[0026] Figure 9 These are comparative images of the tongues of rats in the sham-operated group and model group that did not receive the pharmaceutical composition of the present invention, and in the low-dose group and high-dose group that received the pharmaceutical composition of Example 1.

[0027] Figure 10 The graph shows the pulse detection results of the sham surgery group and model group who did not take the pharmaceutical composition of the present invention, as well as the low-dose group and high-dose group who took the pharmaceutical composition of Example 1. Detailed Implementation

[0028] The present invention will now be described in detail as a traditional Chinese medicine raw material composition, a pharmaceutical composition, a method for preparing the pharmaceutical composition for treating ischemic stroke, and its application.

[0029] Based on previous research, the inventors of this invention have established a standardized system for the diagnosis of acute stroke with fire-toxin syndrome. By reviewing the historical evolution of stroke and considering that blood stasis is the fundamental pathogenesis of stroke, they believe that acute stroke is a pathological change resulting from the imbalance of blood, blood vessels, and their interrelationships under the influence of blood stasis and toxicity. "Toxin" possesses characteristics such as duality, severity, violence, foulness, transformation, multiple occurrences, and destructive effects, which are extremely similar to the pathogenic characteristics of stroke. This indicates that the series of cascading reactions following an acute stroke are closely related to the "toxic" pathogen in Traditional Chinese Medicine. Blood stasis is a central link in the development of stroke; its accumulation transforms into heat, generating toxic pathogens, or transforming into toxicity, leading to "intertwining of blood stasis and toxicity." Over time, external factors trigger the sudden release of accumulated toxicity, causing a sudden change in the condition. This is the main cause and key pathological mechanism of stroke disease progression. Therefore, "stasis" and "toxin" can more comprehensively explain the acute onset and malignant development of stroke, and the mutual binding of stasis and toxin is the key mechanism for the turning point of the acute phase of stroke.

[0030] The inventors of this invention conducted a systematic evaluation of the efficacy and safety of traditional Chinese medicine (TCM) in treating acute ischemic stroke through clinical research. The results showed that TCM has potential advantages in improving patient symptoms and quality of life, and no serious adverse reactions were observed. Simultaneously, a survey of the distribution patterns of TCM syndromes in acute ischemic stroke revealed that the main TCM syndromes are blood stasis, accumulation of toxins, mutual binding of blood stasis and toxins, and damage to the brain's collaterals. The treatment principle should be to invigorate blood circulation, remove blood stasis, detoxify, and unblock the collaterals. Therefore, combining literature and clinical research, and using patients with ischemic stroke as the research subjects, this invention innovatively proposes a TCM raw material composition and drug composition for treating ischemic stroke based on the theory of mutual binding of blood stasis and toxins.

[0031] The traditional Chinese medicine raw material composition for treating ischemic stroke according to the present invention comprises (or is composed of) the following active ingredients by weight: 8-15 parts of Ligusticum chuanxiong, 8-12 parts of Gardenia jasminoides, 3-9 parts of Panax notoginseng, 1-5 parts of Hirudo medicinalis, 8-15 parts of Acorus tatarinowii, 6-12 parts of Curcuma longa and 8-15 parts of Trichosanthes kirilowii.

[0032] Furthermore, in exemplary embodiments of the present invention, the traditional Chinese medicine raw material composition for treating ischemic stroke according to the present invention may also include pharmaceutically acceptable excipients, such as at least one of starch, maltose, sucrose, and honey; however, the present invention is not limited thereto. Specifically, the traditional Chinese medicine raw material composition for treating ischemic stroke according to the present invention may include 8-15 parts of Ligusticum chuanxiong, 8-12 parts of Gardenia jasminoides, 3-9 parts of Panax notoginseng, 1-5 parts of Hirudo medicinalis, 8-15 parts of Acorus tatarinowii, 6-12 parts of Curcuma longa, and 8-15 parts of Trichosanthes kirilowii as active ingredients, as well as pharmaceutically acceptable excipients; or it may consist of 8-15 parts of Ligusticum chuanxiong, 8-12 parts of Gardenia jasminoides, 3-9 parts of Panax notoginseng, 1-5 parts of Hirudo medicinalis, 8-15 parts of Acorus tatarinowii, 6-12 parts of Curcuma longa, and 8-15 parts of Trichosanthes kirilowii as active ingredients, as well as pharmaceutically acceptable excipients.

[0033] Chuanxiong (Latin name: CHUANXIONG RHIZOMA) is the dried rhizome of *Ligusticum chuanxiong* Hort., a plant in the Apiaceae family. The dosage of Chuanxiong is in the range of 8-15 parts, for example, 8-13 parts, 8-12 parts, or 9-11 parts, or any range specified above, such as 8-11 parts or 9-12 parts. Chuanxiong is warm in nature, pungent in taste, purely yang in nature, and non-toxic. It has the effects of promoting blood circulation, regulating qi, dispelling wind, and relieving pain. Chuanxiong enters the liver, gallbladder, and pericardium meridians. Ancient texts often record Chuanxiong as a "qi-regulating herb in the blood." Modern pharmacological studies have shown that Ligusticum chuanxiong is rich in effective components such as tetramethylpyrazine and sodium ferulate, which can dilate microarteries, increase blood flow, facilitate the release of vasoactive substances by vascular endothelial cells, inhibit platelet aggregation, reduce blood viscosity, improve the compliance of vascular smooth muscle, and reduce the migration of smooth muscle cells, thereby promoting angiogenesis.

[0034] Gardenia (Latin name: *Gardenia fructus*) is the dried, ripe fruit of *Gardenia jasminoides* Ellis, a plant in the Rubiaceae family. The dosage of gardenia is in the range of 8-12 parts, for example, 8-11 parts or 9-11 parts, or any range specified above, such as 8-9 parts. Gardenia is bitter and cold in nature, and enters the heart, lung, and triple burner meridians. It has the effects of purging fire and relieving irritability, clearing heat and promoting diuresis, cooling blood and detoxifying. The *Shennong Bencao Jing* states: "Gardenia treats evil qi in the five internal organs, heat in the stomach, red face, rosacea, chapped nose, white leprosy, red leprosy, and sores." Geniposide is a representative iridoid compound from the genus *Gardenia*. It possesses pharmacological effects including anti-inflammatory and analgesic properties, improvement of sleep and cognitive function, hepatoprotective effects, and protection against cardiovascular and cerebral ischemia-reperfusion injury. Its neuroprotective effect may be achieved by downregulating the expression of aquaporin 4 (AQP-4) and glial fibrillary acidic protein (GFAP), reducing astrocyte swelling and exudation, and increasing sodium levels in brain tissue. + -K + -ATPase, Ca 2+ -Mg 2+ - The activity of ATPase reduces intracellular calcium overload, thereby affecting the formation and resolution of cerebral edema after brain injury with ischemia and hypoxia, and playing a neuroprotective role.

[0035] Panax notoginseng (Latin name: NOTOGINSENG RADIX ET RHIZOMA) is the dried root and rhizome of Panax notoginseng (Burk.) FHChen, a plant belonging to the Araliaceae family. The dosage of Panax notoginseng ranges from 3 to 9 parts, for example, 4 to 8 parts or 5 to 7 parts, or any range specified above, such as 4 to 7 parts or 5 to 8 parts. Panax notoginseng is sweet, slightly bitter, and warm in nature, and enters the liver and stomach meridians. It has the effects of dispersing blood stasis, stopping bleeding, reducing swelling, and relieving pain. The *Yuqiu Yaojie* states that it "harmonizes the blood and stops bleeding, unblocks the meridians and disperses blood stasis, promoting the flow of stagnant blood while astringing new blood. It breaks up all blood stasis after childbirth, during menstruation, after falls, and in cases of carbuncles." Modern research indicates its pharmacological effects, including protecting neurons, protecting endothelial cells, promoting bone repair after injury, protecting against cerebral ischemia, and exhibiting anti-tumor and anti-fibrotic effects.

[0036] Scalded leeches are obtained by processing leeches. Leeches (Latin name: HIRUDO) can be the dried whole body of *Whitmania pigra* Whitman, *Hirudo nipponica* Whitman, or *Whitmania acranulata* Whitman, all belonging to the Hirudo family. The dosage of scalded leeches ranges from 1 to 5 parts, for example, 2-5 parts, 3-5 parts, 4-5 parts, or any range specified above, such as 2-4 parts. Scalded leeches are salty, bitter, and neutral in nature, slightly toxic, and enter the liver meridian. They have the effects of breaking up blood stasis and promoting menstruation, removing blood stasis and eliminating masses. They are used for amenorrhea due to blood stasis, abdominal masses, hemiplegia due to stroke, and injuries from falls. Scalded leeches contain macromolecular components such as proteins and polypeptides, as well as small molecule components such as pteridines, glycolipids, carboxylic acid esters, and free amino acids. They have significant pharmacological effects such as anticoagulation, antithrombosis, antiatherosclerosis, anti-inflammation, and antitumor.

[0037] Acorus tatarinowii (Latin name: *ACORI TAATARINOWII RHIZOMA*) is the dried rhizome of *Acorus tatarinowii* Schott, a plant in the Araceae family. The dosage of Acorus tatarinowii ranges from 8 to 15 parts, for example, 8 to 13 parts, 9 to 12 parts, or 9 to 11 parts, or any range specified above, such as 8 to 12 parts or 9 to 13 parts. Acorus tatarinowii is pungent, bitter, and warm in nature, and enters the Heart and Stomach meridians. It has the effects of opening the orifices and resolving phlegm, refreshing the mind and improving intelligence, resolving dampness and invigorating the stomach. It is used for coma, epilepsy, forgetfulness, insomnia, tinnitus, deafness, epigastric fullness and lack of appetite, and aphthous stomatitis and diarrhea. *Benjing Fengyuan* describes it as being able to "open the heart orifices, unblock the nine orifices, and improve hearing and vision." The main chemical components of Acorus calamus include volatile oils, sesquiterpenes, organic acids, flavonoids, lignin, and amino acids. Acorus calamus possesses pharmacological effects such as sedation, anticonvulsant, antidepressant, antiarrhythmic, antitumor, lipid-regulating, and antioxidant properties, and also has certain effects on central nervous system diseases.

[0038] Turmeric (Latin name: CURCUMAE RADIX) can be the dried tuberous root of *Curcuma wenyujin* Y.H.Chen et C.Ling, *Curcuma longa* L., *Curcuma kwangsiensis* SGLee et CFLiang, or *Curcuma phaeocaulis* Val. The dosage of turmeric ranges from 6 to 12 parts, for example, 7 to 11 parts, 8 to 10 parts, or 9 to 11 parts, or any range specified above, such as 7 to 10 parts. Turmeric is pungent, bitter, and cold in nature; it enters the liver, heart, and lung meridians. Its functions include promoting blood circulation and relieving pain, regulating qi and relieving depression, clearing heat from the heart and cooling the blood, and promoting bile secretion and reducing jaundice. Turmeric is used for stabbing pain in the chest and hypochondrium, chest pain, amenorrhea, dysmenorrhea, breast distension and pain, delirium due to febrile diseases, epilepsy, hematemesis due to blood heat, and jaundice with dark urine. Turmeric is rich in sesquiterpenes, β-sitosterol, baicalin and other active ingredients, and has liver-protective, hemostatic, anticoagulant and anti-inflammatory and analgesic effects.

[0039] Trichosanthes fruit (Latin name: Trichosanthes fructus) is the dried, mature fruit of Trichosanthes skirilowii Maxim. or Trichosanthes rosthornii Harms, both belonging to the Cucurbitaceae family. The dosage of Trichosanthes fruit ranges from 8 to 15 parts, for example, 9 to 15 parts, 10 to 15 parts, or 13 to 15 parts, or any range specified above, such as 8 to 10 parts or 9 to 13 parts. Trichosanthes kirilowii: sweet, slightly bitter, cold, enters the lung, stomach, and large intestine meridians. It has the effects of clearing heat and resolving phlegm, relieving chest congestion and dispersing nodules, moistening dryness and lubricating the intestines. It can treat lung heat cough, thick yellow phlegm, chest pain, chest tightness and fullness, mastitis, lung abscess, intestinal abscess and other diseases. The main chemical components of Trichosanthes kirilowii include triterpenoids, flavonoids, phytosterols, fatty acids, as well as amino acids, proteins, alkaloids, polysaccharides, etc. It has a protective effect on myocardial cells and vascular cells. At the same time, it can exert an antithrombotic effect by inhibiting platelet aggregation and inhibiting the activation of the coagulation system.

[0040] Based on academic thought and clinical experience in ischemic stroke, the inventors of this invention have made a series of breakthroughs in the research of traditional Chinese medicine for the prevention and treatment of ischemic stroke. They have innovated the understanding of the etiology and pathogenesis of ischemic stroke in traditional Chinese medicine. Based on previous research, they discovered that blood stasis is a fundamental link in the occurrence and development of ischemic stroke, and a basic pathological state in the stable phase. However, if blood stasis persists and transforms into heat, generating toxins, or even transforming into poison, it can lead to the mutual binding of blood stasis and toxins, obstructing the brain's collaterals, causing sudden changes in the condition, and resulting in acute ischemic stroke and other acute and critical illnesses. Therefore, based on the understanding of the theory of blood stasis and toxins mutually binding and damaging the vessels, collaterals, and orifices in ischemic stroke, they established a treatment method of activating blood circulation, detoxifying, and unblocking the vessels, collaterals, and orifices. That is, taking "blood stasis obstruction, accumulation of toxins, mutual binding of blood stasis and toxins, and damage to the brain's collaterals" as the core key pathogenesis of ischemic stroke, and "activating blood circulation, removing blood stasis, detoxifying, and unblocking collaterals" as the basic treatment method. From this, they proposed a combination of Chinese herbal raw materials and a drug composition for treating ischemic stroke with blood stasis and toxin binding syndrome.

[0041] Specifically, the formulation principle of the traditional Chinese medicine raw material composition of the present invention is as follows: Chuanxiong (Ligusticum striatum) invigorates blood and removes blood stasis. The *Compendium of Materia Medica* states that Chuanxiong "treats all qi and blood stasis, breaks up stagnant blood, and nourishes new blood." Gardenia (Gardenia jasminoides) clears heat and detoxifies. The *Essentials of Materia Medica* states that Gardenia "drains fire from the triple burner, relieves heat stagnation, and promotes the flow of stagnant qi." Chuanxiong and Gardenia together serve as the principal herbs, targeting the key pathogenesis of blood stasis and toxin accumulation to achieve the effects of invigorating blood, removing blood stasis, and detoxifying. Sanqi (Panax notoginseng) and hot leech have the effects of invigorating blood, removing blood stasis, and unblocking collaterals. Since blood stasis is a fundamental link in the development of ischemic stroke, the two together serve as assistant herbs to assist and enhance the blood-invigorating and blood-stasis-removing power of the principal herbs, improving the circulation of qi and blood in the brain collaterals. As the *Compendium of Materia Medica* states, Sanqi "stops bleeding, disperses blood stasis, and relieves pain," and the *Shennong's Classic of Materia Medica* states, leech "is mainly used to expel..." "It treats stagnant blood and blood clots, breaking up blood stasis and accumulations." Acorus tatarinowii, Curcuma longa, and Trichosanthes kirilowii are used as adjuvant herbs to improve symptoms such as speech impairment, dysarthria, cognitive impairment, and impaired consciousness after stroke caused by the mutual accumulation of blood stasis and toxins damaging the collaterals and obstructing the orifices. Because the mutual accumulation of blood stasis and toxins easily damages the brain orifices and obstructs the six viscera, it leads to imbalance of qi and blood, obstruction of turbid evil, and failure of clear yang to ascend, thus damaging the clear orifices, obstructing the brain orifices, and causing phlegm-heat accumulation in the viscera. Therefore, Acorus tatarinowii and Curcuma longa are used to resolve turbidity, regulate qi, invigorate blood, and open the orifices, while Trichosanthes kirilowii resolves phlegm, clears heat, and unblocks the viscera. As stated in *Ben Cao Jing Ji Zhu*, Acorus tatarinowii "opens the nine orifices, produces sound, and benefits the mind and intellect." *Shennong Ben Cao Jing Shu* states that Curcuma longa "has a light and rising nature, can open up stagnation, and is therefore an essential medicine for regulating rebellious qi and moving blood stasis." *Ben Cao Bian Du* states that Trichosanthes kirilowii "reduces phlegm and fire, promotes downward movement, eliminates blood stasis, and cleanses impurities."

[0042] In summary, the pharmaceutical composition of this invention is well-formulated, based on the theory of blood stasis and toxin accumulation, and its principles, methods, prescriptions, and medications are consistent, effectively improving the pathological state of blood stasis and toxin accumulation in acute ischemic stroke and comprehensively improving disease symptoms. Furthermore, using this pharmaceutical composition can effectively improve patients' clinical symptoms and enhance their quality of life, and preliminary clinical observations show significant efficacy with no obvious adverse reactions. Moreover, this invention has evaluated the efficacy and safety of the traditional Chinese medicine raw material composition and the pharmaceutical composition through clinical trials, thus demonstrating the therapeutic advantages of promoting blood circulation and detoxifying in treating ischemic stroke, providing a new method for the treatment of ischemic stroke.

[0043] Furthermore, in a preferred embodiment of the present invention, the herbal raw material composition may include the following active ingredients (or be composed of the following active ingredients) by weight: 8-13 parts of Ligusticum chuanxiong, 8-11 parts of Gardenia jasminoides, 4-8 parts of Panax notoginseng, 3-5 parts of Hirudo medicinalis, 8-13 parts of Acorus tatarinowii, 8-11 parts of Curcuma longa, and 10-15 parts of Trichosanthes kirilowii.

[0044] In another preferred embodiment of the present invention, the traditional Chinese medicine raw material composition may include the following active ingredients (or be composed of the following active ingredients) by weight: 9-11 parts of Ligusticum chuanxiong, 9-11 parts of Gardenia jasminoides, 5-7 parts of Panax notoginseng, 4-5 parts of Hirudo medicinalis, 9-11 parts of Acorus tatarinowii, 9-11 parts of Curcuma longa, and 12-15 parts of Trichosanthes kirilowii.

[0045] In another preferred embodiment of the present invention, the traditional Chinese medicine raw material composition may include the following effective ingredients (or be composed of the following effective ingredients) by weight: 10 parts of Ligusticum chuanxiong, 10 parts of Gardenia jasminoides, 6 parts of Panax notoginseng, 5 parts of Hirudo medicinalis, 10 parts of Acorus tatarinowii, 10 parts of Curcuma longa, and 15 parts of Trichosanthes kirilowii; 8 parts of Ligusticum chuanxiong, 9 parts of Gardenia jasminoides, 3 parts of Panax notoginseng, 2 parts of Hirudo medicinalis, 8 parts of Acorus tatarinowii, 6 parts of Curcuma longa, and 9 parts of Trichosanthes kirilowii; 15 parts of Ligusticum chuanxiong, 12 parts of Gardenia jasminoides, 8 parts of Panax notoginseng, 4 parts of Hirudo medicinalis, 15 parts of Acorus tatarinowii, 11 parts of Curcuma longa, and 15 parts of Trichosanthes kirilowii; or 11 parts of Ligusticum chuanxiong, 11 parts of Gardenia jasminoides, 7 parts of Panax notoginseng, 5 parts of Hirudo medicinalis, 11 parts of Acorus tatarinowii, 11 parts of Curcuma longa, and 9 parts of Trichosanthes kirilowii.

[0046] Furthermore, in embodiments of the present invention, the aforementioned Chinese medicinal materials can be used in the form of processed medicinal slices that have reached quality standards after preliminary processing or preparation. The aforementioned Chinese medicinal materials can also be used in the form of raw medicinal herbs. Furthermore, the aforementioned Chinese medicinal materials can be used in the form of both raw medicinal herbs and processed medicinal slices. In another embodiment of the present invention, the aforementioned Chinese medicinal materials can be used in granule form after extraction (or processing) and the addition of pharmaceutically acceptable excipients. In this case, the amount of the aforementioned Chinese medicinal materials corresponds to the amount of each processed medicinal slice; for example, 10g of Ligusticum chuanxiong is equivalent to (means) 10g of processed Ligusticum chuanxiong.

[0047] The pharmaceutical composition for treating ischemic stroke according to the present invention is made from the above-mentioned traditional Chinese medicine raw material composition.

[0048] The pharmaceutical composition of the present invention can be prepared using conventional methods for preparing traditional Chinese medicine.

[0049] In one embodiment of the present invention, a pharmaceutical composition comprising at least one of granules and capsules can be prepared by the following steps: preparing each traditional Chinese medicine raw material into formulation granules; and mixing the formulation granules.

[0050] In the step of preparing each Chinese herbal raw material into formula granules, the following ingredients are placed in decoction containers: Ligusticum chuanxiong, Gardenia jasminoides, Hirudo medicinalis, Acorus tatarinowii, Curcuma longa, and Trichosanthes kirilowii, which are in the form of medicinal slices. Water is added to the decoction containers. After decoction for a predetermined time, the mixture is filtered and concentrated into a clear paste. Pharmaceutically acceptable excipients (e.g., at least one of starch, maltose, sucrose, and honey) are added to the clear paste, and the mixture is mixed and granulated to obtain formula granules of Ligusticum chuanxiong, Gardenia jasminoides, Hirudo medicinalis, Acorus tatarinowii, Curcuma longa, and Trichosanthes kirilowii. Additionally, Panax notoginseng, which is in the form of medicinal slices, is pulverized, pharmaceutically acceptable excipients are added, and the mixture is mixed and granulated to obtain formula granules of Panax notoginseng, or Panax notoginseng, which is in the form of medicinal slices, is pulverized to obtain formula granules of Panax notoginseng.

[0051] In an exemplary embodiment of the present invention, in the step of decocting for a predetermined time, the decoction container can be brought to a boil over high heat and then simmered over low heat for about 30 minutes; however, the embodiments of the present invention are not limited thereto.

[0052] The following mainly describes exemplary methods for preparing various traditional Chinese medicine formula granules. However, the embodiments of the present invention are not limited thereto.

[0053] For Ligusticum chuanxiong, take 3000g of Ligusticum chuanxiong slices, add water to decoct and filter, concentrate the filtrate into a clear extract (dry extract yield is 19%-28%), add an appropriate amount of pharmaceutically acceptable excipients, dry (or dry and pulverize), add an appropriate amount of excipients again, mix well, and granulate to make 1000g of Ligusticum chuanxiong formula granules.

[0054] For gardenia, take 3000g of gardenia slices, add water to decoct and filter, concentrate the filtrate into a clear extract (dry extract yield is 20%-28%), add an appropriate amount of pharmaceutically acceptable excipients, dry (or dry and pulverize), add an appropriate amount of excipients, mix well, and granulate to make 1000g of gardenia formula granules.

[0055] For Panax notoginseng, take 667g of Panax notoginseng slices, crush them, add an appropriate amount of excipients, mix well, and granulate to make 1000g of Panax notoginseng formula granules. Alternatively, take 667g of Panax notoginseng slices, crush them, and make 667g of Panax notoginseng formula granules.

[0056] For scalded leeches, take 2857g of scalded leech slices, add water to decoct, filter, concentrate the filtrate into a clear extract (dry extract yield is 25%-30%), add an appropriate amount of pharmaceutically acceptable excipients, dry (or dry and pulverize), add an appropriate amount of excipients again, mix well, and granulate to make 1000g of scalded leech formula granules.

[0057] For Acorus tatarinowii, take 4348g of Acorus tatarinowii slices, add water to decoct, filter, concentrate the filtrate into a clear extract (dry extract yield is 9%-15%), add an appropriate amount of pharmaceutically acceptable excipients, dry (or dry and pulverize), add an appropriate amount of excipients again, mix well, and granulate to make 1000g of Acorus tatarinowii formula granules.

[0058] For turmeric, take 5556g of turmeric slices, add water to decoct and filter, concentrate the filtrate into a clear extract (dry extract yield is 12%-15%), add an appropriate amount of pharmaceutically acceptable excipients, dry (or dry and pulverize), add an appropriate amount of excipients, mix well, and granulate to make 1000g of turmeric formula granules.

[0059] For Trichosanthes kirilowii, take 1600g of Trichosanthes kirilowii slices, add water to decoct, filter, concentrate the filtrate into a clear extract (dry extract yield is 31%-41%), add an appropriate amount of pharmaceutically acceptable excipients, dry (or dry and pulverize), add an appropriate amount of excipients again, mix well, and granulate to make 1000g of Trichosanthes kirilowii formula granules.

[0060] After the traditional Chinese medicine formula granules are prepared, the formula granules are mixed to obtain a pharmaceutical composition that is at least one of granules and capsules.

[0061] When the pharmaceutical composition is used in at least one of granules and capsules, the pharmaceutical composition comprises the following active ingredients by weight: 8-15 parts of Ligusticum chuanxiong, 8-12 parts of Gardenia jasminoides, 3-9 parts of Panax notoginseng, 1-5 parts of Hirudo medicinalis, 8-15 parts of Acorus tatarinowii, 6-12 parts of Curcuma longa, and 8-15 parts of Trichosanthes kirilowii.

[0062] In another embodiment of the present invention, the pharmaceutical composition as a pill can be prepared by the following steps: placing the sliced ​​chuanxiong, gardenia, leech, acorus, turmeric, and trichosanthes in a decoction container, and adding water to the decoction container; after decocting for a predetermined time, filtering and concentrating into a clear extract; and mixing the clear extract, 3-9 parts by weight of notoginseng, and pharmaceutically acceptable excipients to form pills. When the pharmaceutical composition is used in the form of pills, the pharmaceutical composition comprises the following active ingredients by weight: 8-15 parts chuanxiong, 8-12 parts gardenia, 3-9 parts notoginseng, 1-5 parts leech, 8-15 parts acorus, 6-12 parts turmeric, and 8-15 parts trichosanthes.

[0063] In the process of preparing a pharmaceutical composition as a pill, Panax notoginseng in the form of medicinal slices can be pulverized, pharmaceutically acceptable excipients can be added, and the mixture can be mixed and granulated to obtain Panax notoginseng in a weight of 3 to 9 parts by weight of medicinal slices; or Panax notoginseng slices can be ground into powder to obtain Panax notoginseng in a weight of 3 to 9 parts by weight of medicinal slices; or Panax notoginseng granules prepared in other suitable ways can be used to obtain Panax notoginseng in a weight of 3 to 9 parts by weight of medicinal slices.

[0064] In another embodiment of the present invention, the pharmaceutical composition as a decoction can be prepared by the following steps: placing the sliced ​​chuanxiong, gardenia, leech, acorus, turmeric, and trichosanthes into a decoction container, and adding water to the decoction container; after decocting for a predetermined time, filtering to remove the dregs to obtain a decoction; and mixing the decoction with 3-9 parts by weight of notoginseng to obtain the pharmaceutical composition as a decoction. When the pharmaceutical composition is used in the form of a decoction, the pharmaceutical composition comprises the following active ingredients by weight: 8-15 parts chuanxiong, 8-12 parts gardenia, 3-9 parts notoginseng, 1-5 parts leech, 8-15 parts acorus, 6-12 parts turmeric, and 8-15 parts trichosanthes.

[0065] In the process of preparing a pharmaceutical composition as a decoction, Panax notoginseng in the form of medicinal slices can be pulverized, pharmaceutically acceptable excipients can be added, and the mixture can be mixed and granulated to obtain Panax notoginseng in a weight of 3 to 9 parts by weight of medicinal slices; or Panax notoginseng slices can be ground into powder to obtain Panax notoginseng in a weight of 3 to 9 parts by weight of medicinal slices; or Panax notoginseng granules prepared in other suitable ways can be used to obtain Panax notoginseng in a weight of 3 to 9 parts by weight of medicinal slices.

[0066] The pharmaceutical composition for treating ischemic stroke according to the present invention has the effects of promoting blood circulation, removing blood stasis, clearing blockages, and detoxifying. Furthermore, the pharmaceutical composition for treating ischemic stroke according to the present invention has no obvious toxic side effects, can effectively improve patients' clinical symptoms and improve their quality of life, and has no obvious adverse reactions.

[0067] According to another aspect of the present invention, there is an application of a pharmaceutical composition in the preparation of a medicament for treating ischemic stroke, the pharmaceutical composition comprising, by weight, the following active ingredients: 8-15 parts of Ligusticum chuanxiong, 8-12 parts of Gardenia jasminoides, 3-9 parts of Panax notoginseng, 1-5 parts of Hirudo medicinalis, 8-15 parts of Acorus tatarinowii, 6-12 parts of Curcuma longa, and 8-15 parts of Trichosanthes kirilowii.

[0068] Furthermore, the traditional Chinese medicine raw material composition and pharmaceutical composition according to embodiments of the present invention have significant effects in treating ischemic stroke.

[0069] The pharmaceutical composition for treating ischemic stroke and its preparation method of the present invention will be described below with reference to specific examples 1-4.

[0070] Preparation of various Chinese herbal medicine formula granules

[0071] Take 3000g of Ligusticum chuanxiong slices, decoct with water, filter, and concentrate the filtrate into a clear extract (dry extract yield 19%-28%). Add an appropriate amount of pharmaceutically acceptable excipients, dry (or dry and pulverize), add an appropriate amount of excipients again, mix well, and granulate to make 1000g of Ligusticum chuanxiong formula granules. Take 3000g of Gardenia jasminoides slices, decoct with water, filter, and concentrate the filtrate into a clear extract (dry extract yield 20%-28%). Add an appropriate amount of pharmaceutically acceptable excipients, dry (or dry and pulverize), add an appropriate amount of excipients again, mix well, and granulate to make 1000g of Gardenia jasminoides formula granules. Take 667g of Panax notoginseng slices, pulverize, add an appropriate amount of excipients, mix well, and granulate to make 1000g of Panax notoginseng formula granules. Take 2857g of scalded leech slices, decoct with water, filter, and concentrate the filtrate into a clear extract (dry extract yield 25%-30%). Add an appropriate amount of pharmaceutically acceptable excipients, dry (or dry and pulverize), add an appropriate amount of excipients again, mix well, and granulate to make 1000g of scalded leech formula granules. Take 4348g of Acorus tatarinowii slices, decoct with water, filter, and concentrate the filtrate into a clear extract (dry extract yield 9%-15%). Add an appropriate amount of pharmaceutically acceptable excipients, dry (or dry and pulverize), add an appropriate amount of excipients again, mix well, and granulate to make 1000g of Acorus tatarinowii formula granules. Take 5556g of turmeric slices, decoct with water, filter, and concentrate the filtrate into a clear extract (dry extract yield 12%-15%). Add an appropriate amount of pharmaceutically acceptable excipients, dry (or dry and pulverize), add an appropriate amount of excipients again, mix well, and granulate to make 1000g of turmeric formula granules. Take 1600g of trichosanthes slices, decoct with water, filter, and concentrate the filtrate into a clear extract (dry extract yield 31%-41%). Add an appropriate amount of pharmaceutically acceptable excipients, dry (or dry and pulverize), add an appropriate amount of excipients again, mix well, and granulate to make 1000g of trichosanthes formula granules.

[0072] Example 1:

[0073] The following formula granules are prepared by mixing 10 parts of Ligusticum chuanxiong slices, 10 parts of Gardenia jasminoides slices, 6 parts of Panax notoginseng slices, 5 parts of Hirudo medicinalis slices, 10 parts of Acorus tatarinowii slices, 10 parts of Curcuma longa slices, and 15 parts of Trichosanthes kirilowii slices to obtain the pharmaceutical composition of the present invention as granules. This pharmaceutical composition can be dissolved in water to obtain a decoction for later use.

[0074] Example 2:

[0075] The following formula granules are prepared by mixing 8 parts of Ligusticum chuanxiong slices, 9 parts of Gardenia jasminoides slices, 3 parts of Panax notoginseng slices, 2 parts of Hirudo medicinalis slices, 8 parts of Acorus tatarinowii slices, 6 parts of Curcuma longa slices, and 9 parts of Trichosanthes kirilowii slices to obtain the pharmaceutical composition of the present invention as granules. This pharmaceutical composition can be dissolved in water to obtain a decoction for later use.

[0076] Example 3:

[0077] The following formula granules are prepared by mixing 15 parts of Ligusticum chuanxiong slices, 12 parts of Gardenia jasminoides slices, 8 parts of Panax notoginseng slices, 4 parts of Hirudo medicinalis slices, 15 parts of Acorus tatarinowii slices, 11 parts of Curcuma longa slices, and 15 parts of Trichosanthes kirilowii slices to obtain the pharmaceutical composition of the present invention as granules. This pharmaceutical composition can be dissolved in water to obtain a decoction for later use.

[0078] Example 4:

[0079] The following formula granules are prepared by mixing 11 parts of Ligusticum chuanxiong slices, 11 parts of Gardenia jasminoides slices, 7 parts of Panax notoginseng slices, 5 parts of Hirudo medicinalis slices, 11 parts of Acorus tatarinowii slices, 11 parts of Curcuma longa slices, and 9 parts of Trichosanthes kirilowii slices to obtain the pharmaceutical composition of the present invention as granules. This pharmaceutical composition can be dissolved in water to obtain a decoction for later use.

[0080] Animal experiments and clinical efficacy observations of the pharmaceutical compositions of the present invention

[0081] Establishment and evaluation of an animal model of ischemic stroke with blood stasis and toxin accumulation.

[0082] To deeply explore the pathogenesis and therapeutic mechanism of traditional Chinese medicine in the syndrome of blood stasis and toxin accumulation in ischemic stroke, establishing a mature animal model combining disease and syndrome is essential. This invention explores the construction of an animal model of the syndrome of blood stasis and toxin accumulation in ischemic stroke from the perspective of combining disease and syndrome. The model is evaluated from the perspectives of macroscopic manifestations of TCM syndrome, microscopic indicators of modern medicine, and histopathological morphology. Animal models with high clinical fit and possessing the pathological characteristics and syndrome features of the syndrome of blood stasis and toxin accumulation in ischemic stroke are selected, thus promoting the enrichment and improvement of the scientific connotation of "blood stasis and toxin".

[0083] Modern medicine believes that from the blood stasis state of the body before the occurrence of ischemic stroke to the occurrence of a series of ischemic cascade reactions after the occurrence of ischemic stroke, the biological basis behind it involves abnormal hemorheology, imbalance of the coagulation and fibrinolysis system, abnormal platelet aggregation function, inflammatory response, excitatory amino acid neurotoxicity, etc. Previous studies have shown that substances such as carrageenan and dried yeast can induce changes in the above microscopic indicators and are often regarded as pathogenic factors such as "toxic pathogen" and "heat pathogen" in traditional Chinese medicine. Therefore, on the basis of this research, the above methods are adopted and combined with the middle cerebral artery occlusion model to construct and screen a stable animal model of the syndrome of mutual binding of blood stasis and toxin in ischemic stroke.

[0084] 1 Materials

[0085] 1.1 Experimental animals

[0086] 30 SPF-grade male SD rats, weighing (220 - 240) g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. Animal license number: SYXK(Beijing)2018 - 0018. The rats were placed in a constant temperature environment of 18 - 22 °C, and the humidity was controlled at 50% - 60%. They were allowed to eat and drink freely.

[0087] 1.2 Main reagents

[0088] Carrageenan (abbreviated as Ca, Shanghai Macklin Biochemical Co., Ltd., batch number: C14408398); Active dry yeast (abbreviated as Y, Angel Yeast Co., Ltd., batch number: HY2009R); Chloral hydrate (Shanghai Yuanye Bio-Technology Co., Ltd., batch number: Z16J10Y80098); Universal tissue fixative (Wuhan Sevier Biotechnology Co., Ltd., batch number: XS191501); 2,3,5-Triphenyltetrazolium chloride (Shanghai Yuanye Bio-Technology Co., Ltd., batch number: L09A10S83253); Hematoxylin and Eosin (HE) staining solution (Beijing Yili Fine Chemicals Co., Ltd., batch number: 20211223); Rat interleukin-6 (IL-6) enzyme-linked immunosorbent assay kit (Cohesion Biosciences, UK, batch number: CK6E19B); MCAO embolization wire (Hebei Tiannong Biotechnology Co., Ltd., batch number: 20,210,63,0).

[0089] 1.3 Main instruments

[0090] Mouse Ox type non-invasive pulse oximeter for small animals (Starr Life Science Inc., USA); PeriCam PSI perfusion speckle imager (PERIMED, Sweden); Nikon D90 digital SLR camera (Nikon, Japan); SA6600 fully automated blood rheology analyzer (Beijing Saikeshid Technology Co., Ltd.); PL-12 platelet aggregation analyzer (Jiangsu Innova Medical Technology Co., Ltd.); cryo-erecting device (Shanghai Jingxin Technology Co., Ltd.); ChemDoc™ XRS+ gel imaging system (Bio-Rad, USA); Olympus BX53 upright microscope (Olympus Ltd.).

[0091] 2 methods

[0092] 2.1 Drug Preparation

[0093] Carrageenan was prepared with physiological saline to a concentration of 1 g / L. -1 The solution should be prepared fresh and used immediately, at a dose of 10 mg / kg of rat body weight. -1 Dosage. The dried yeast was prepared into a 200 g / L solution using distilled water. -1 Prepare and use immediately, at a dose of 2 mg / kg of rat body weight. -1 Administer the medication.

[0094] 2.2 Animal handling

[0095] After 3 days of acclimatization feeding, the rats were randomly divided into two groups of 15 each using a random number table: the sham group and the carrageenan (Ca) combined with dried yeast (Yeast) MCAO group (Ca+Y group).

[0096] Middle cerebral artery occlusion (MCAO) surgery was performed on rats: After anesthesia with intraperitoneal injection of 4% chloral hydrate, the rats were fixed in a supine position on the operating table. An incision was made along the midline of the neck. Using forceps, the cervical glandular tissue and fascia were bluntly dissected to expose and separate the right common carotid artery, internal carotid artery, and external carotid artery. The root of the external carotid artery and the proximal end of the common carotid artery were ligated. A "V"-shaped incision was made on the common carotid artery. Before making the incision, the distal end of the common carotid artery was clamped with a micro-arterial clamp to prevent bleeding. A suture was inserted into the internal carotid artery through the "V"-shaped incision and advanced to occlude the middle cerebral artery. The moment the suture was inserted into the middle cerebral artery was designated as time 0. Postoperatively, the skin was sutured, leaving the suture tip exposed. The suture was removed 1.5 hours later to simulate cerebral ischemia-reperfusion.

[0097] Modeling method: On the first day of modeling, rats in the Ca+Y group were injected intraperitoneally with Ca 10 mg·kg -1The sham-operated group received an equal volume of saline intraperitoneally under the same conditions. The next day, the Ca+Y group rats underwent the same middle cerebral artery occlusion (MCAO) surgery to establish an MCAO cerebral ischemia-reperfusion model. The sham-operated group rats underwent the same surgical procedure except for the absence of a suture. Immediately after suture insertion into the middle cerebral artery, 2 mg / kg of dried yeast was subcutaneously injected into the rat's back. -1 .

[0098] 2.3 Detection Indicators and Methods

[0099] 24 hours after MCAO surgery, the following indicators were measured in rats:

[0100] 2.3.1 General conditions: Observe the rat's coat color, activity, diet and mental state, etc.

[0101] 2.3.2 Neurological function scoring: Neurological function was scored on rats, and the scoring criteria were established with reference to the Zea Longa method: 0 points: no neurological deficit symptoms; 1 point: unable to fully extend the left forepaw when the tail is lifted; 2 points: walks in circles to the left; 3 points: walks leaning to the left; 4 points: decreased level of consciousness, unable to walk spontaneously.

[0102] 2.3.3 Pulse Measurement: After neurological function scoring, rats were anesthetized with 2% isoflurane. The pulse amplitude was monitored using a Mouse Ox small animal non-invasive pulse oximeter for 30 seconds. Fifteen continuous and stable valid data points were selected and the average value was calculated. After pulse measurement, 10 mL / kg of 4% chloral hydrate was injected intraperitoneally. -1 Anesthetize rats and test the following indicators.

[0103] 2.3.4 Collection of Stasis and Toxin Characteristics: Rats were anesthetized by intraperitoneal injection of 4% chloral hydrate, and images of the rat's auricle, claws, and tail were collected under the same angle and lighting conditions.

[0104] 2.3.5 Tongue Image Acquisition: The rats were placed in a supine position. Under fixed light source, fixed shooting environment and fixed light intensity, the tip of the rat's tongue was gently pulled out with tweezers to expose the root of the tongue. A colorimetric card was placed next to the tongue, and the digital camera was fixed at a fixed focal length to photograph the rat's tongue image. After image acquisition, the image was processed using Photoshop image processing software. Three fixed points on the tongue surface were selected, and the R (red), G (green) and B (blue) component values ​​of the pixel area were read respectively, and the average value was taken. The color saturation analysis of the tongue image was performed according to the literature method (Li Lei, Xu Li, Li Zhen, et al. Effect of Qilong Capsules on Acute Myocardial Ischemia in Dogs [J]. World Journal of Traditional Chinese Medicine, 2018, 13(01):31-35+40; Chen Jincheng, Liu Jianxun, Ren Junguo, et al. Study on Syndrome Characteristics of Qi Deficiency Syndrome Based on Literature Mining Technology [J]. Chinese Materia Medica, 2018, 43(11):2184-2189.).

[0105] 2.3.6 Tail Perfusion: The blood perfusion of the rat tail was detected using a PeriCam PSI speckle imager. The cursor was focused 1 cm above the tip of the rat tail, and the blood perfusion was observed and recorded. Laser speckle images of blood perfusion were generated, and the mean blood perfusion of the rat tail was analyzed using the PeriCam PSI software PIM Soft.

[0106] 2.3.7 Blood rheology test: 5 mL of blood was collected from the abdominal aorta into a heparin anticoagulant tube, and the low, medium, and high shear whole blood viscosity and plasma viscosity were tested according to the SA6600 fully automated blood rheology analyzer.

[0107] 2.3.8 Platelet aggregation rate detection: 2 mL of blood was collected from the abdominal aorta of rats and placed in a 3.8% sodium citrate anticoagulant tube. The platelet aggregation rate of rats was detected according to the PL platelet function tester method.

[0108] 2.3.9 Determination of cerebral infarction area using 2,3,5-triphenyltetrazolium chloride (TTC) staining method: Seven rats were randomly selected, and their brains were rapidly removed via craniotomy and promptly longitudinally sectioned into six slices along the coronal axis. The brain slices were immediately immersed in 1.2% TTC staining solution at 37℃ for 5 minutes in the dark, and then fixed in paraformaldehyde fixative for 24 hours. Photographs showing the distribution of infarct foci were taken of the brain slices, and the infarct area of ​​each slice and the total brain slice area were calculated using Image Pro Plus software. The infarct area is the unstained area (appearing white). Cerebral infarction area = infarct area / total brain slice area × 100%.

[0109] 2.3.10 Detection of IL-6, an inflammatory factor in brain tissue: Brain tissue from the infarcted side of rats was collected, and tissue from the same side was collected from the sham-operated group. After adding an appropriate amount of lysis buffer, the tissue was ground using a cryo-grinder, allowed to settle, and then heated at 5000 r·min. -1 Centrifuge at 4℃ for 10 min, collect the supernatant, and then perform the ELISA kit according to the instructions to detect the expression level of IL-6 in rat brain tissue.

[0110] 2.3.11 Pathological morphology of rat brain tissue: Rat brain tissue was fixed with tissue fixative, dehydrated, embedded in paraffin, sectioned (4μm), stained with hematoxylin and eosin (HE), and the pathological changes of rat brain tissue were observed under an optical microscope.

[0111] 2.3.12 Statistical analysis was performed using GraphPad Prism 6.0 software. Experimental data for each group were expressed as mean ± standard deviation. This indicates that one-way ANOVA was used for comparisons among multiple groups, and P < 0.05 was considered statistically significant.

[0112] 3 Results

[0113] 3.1 General Case

[0114] No rats died in the sham-operated group, while two rats died in the Ca+Y group. Rats in the sham-operated group had normal appetite, moved freely, and were in good spirits, although their fur was slightly dry and rough. Rats in the Ca+Y group showed significantly reduced activity, decreased food intake, sparse and dull fur, decreased body weight, and lethargy. They exhibited marked listlessness, preferred to curl up in a corner, and their fur appeared "stirred." They resisted less when grasped.

[0115] 3.2 Neurological function scores of rats in each group

[0116] The neurological function scores of rats in the Ca+Y group were significantly higher than those in the sham-operated group (P < 0.01). The neurological deficits in the Ca+Y group were more severe. See Table 1.

[0117] Table 1 Comparison of neurological function scores in rats

[0118] Group n Neurological function score Sham surgery group 15 0 Ca+Y group 13 <![CDATA[2.83±0.68 2) ]]>

[0119] Note: Compared with the sham surgery group. 2) P < 0.01; (Same as Tables 2-8).

[0120] 3.3 Macroscopic observation of "blood stasis and toxin" in rats of each group

[0121] In the Ca+Y group, after modeling, rats exhibited obvious purplish-dark veins on the auricle, swollen and dark purple nails, and a "black tail" appearance. No significant changes were observed in the sham-operated group. (See...) Figures 1-3 .

[0122] 3.4 Comparison of pulse amplitude among different groups of rats

[0123] Compared with the sham-operated group, the pulse amplitude of rats in the Ca+Y group was significantly decreased (P<0.01). See Table 2.

[0124] Table 2 Comparison of pulse amplitude in rats

[0125] Group n Pulse amplitude (um) Sham surgery group 15 45.15±12.31 Ca+Y 13 <![CDATA[15.12±5.39 2) ]]>

[0126] 3.5 Comparison of tongue appearance of rats in different groups

[0127] RGB color model analysis of tongue images showed that, compared with the sham-operated group, the R, G, and B values ​​of the tongue image in the Ca+Y group were significantly decreased (P < 0.05). See [link / reference needed]. Figure 4 And Table 3.

[0128] Table 3 Comparison of RGB color mode analysis results of rat tongue images

[0129] Group n R (8 bits) G (8 bits) B (8 bits) Sham surgery group 15 149.33±11.69 93.50±10.24 95.17±11.64 Ca+Y group 13 <![CDATA[131.50±14.59 2) ]]> <![CDATA[76.33±5.79 2) ]]> <![CDATA[81.16±9.42 2) ]]>

[0130] 3.6 Comparison of tail blood perfusion in different groups of rats

[0131] In blood perfusion images, the number of warm-toned pixels is positively correlated with the abundance of blood flow per unit area. For example... Figure 5 As shown in Table 4, the sham-operated group had abundant blood perfusion at the tail end. However, the blood flow at the tail end in the Ca+Y group was significantly lower than that in the sham-operated group (Ca+Y: P<0.01).

[0132] Table 4 Comparison of blood perfusion at the tail end of rats

[0133] Group n Blood perfusion (PU) Sham surgery group 15 74.01±6.23 Ca+Y group 13 <![CDATA[19.19±9.26 2) ]]>

[0134] 3.7 Comparison of whole blood viscosity and plasma viscosity among different groups of rats

[0135] Compared with the sham-operated group, the Ca+Y group showed significantly higher whole blood viscosity at low shear rate (P < 0.05); the Ca+Y group also showed significantly higher whole blood viscosity at medium and high shear rates (Ca+Y: P < 0.01). Plasma viscosity in the Ca+Y group was also significantly higher than that in the sham-operated group (P < 0.01). See Table 5.

[0136] Table 5 Comparison of whole blood viscosity and plasma viscosity in rats

[0137]

[0138] 3.8 Comparison of platelet aggregation rates among different groups of rats

[0139] Compared with the sham-operated group, the Ca+Y group showed significantly higher maximum and average platelet aggregation rates (P < 0.01). See Table 6.

[0140] Table 6 Comparison of platelet aggregation rate in rats

[0141]

[0142] 3.9 Comparison of cerebral infarction area among different groups of rats

[0143] TTC staining results showed significant infarct foci in all Ca+Y groups (P < 0.01). See Table 7 and... Figure 6 .

[0144] Table 7 Comparison of cerebral infarction area in rats

[0145]

[0146] 3.10 IL-6 content in the brain tissue of rats in each group

[0147] Compared with the sham-operated group, the levels of the inflammatory factor IL-6 in the brain tissue of the Ca+Y group were significantly increased (Ca+Y: P<0.01). See Table 8.

[0148] Table 8 Comparison of IL-6 levels in rat brain tissue.

[0149] Group n IL-6 level (pg / ml) Sham surgery group 8 20.62±8.04 Ca+Y group 6 <![CDATA[267.66±44.92 2) ]]>

[0150] 3.11 Pathological morphology of rat brain tissue in each group

[0151] HE staining results showed that no obvious pathological changes were observed in the brain tissue of rats in the sham-operated group. Cells were arranged in an orderly manner, neurons had normal morphology, and no pathological changes such as degeneration or necrosis were observed. In contrast, rats in the Ca+Y group showed obvious pathological damage, disordered cell arrangement, loose structure, common neuronal degeneration and necrosis, nuclear pyknosis, glial cell proliferation, and multiple infarct foci. Numerous degenerated and necrotic neurons were also observed, indicating more severe pathological damage. (See...) Figure 7 .

[0152] Based on the above research results, the Ca+Y group animal model exhibits stable characteristics of ischemic stroke and the syndrome of blood stasis and toxin accumulation, and can be regarded as the preferred method for constructing an animal model of ischemic stroke with blood stasis and toxin accumulation.

[0153] The following will use the pharmaceutical compositions of Examples 1 to 4 to illustrate the effects of the pharmaceutical compositions of the present invention on the above. The effects of animal models

[0154] Method of administering medication

[0155] Sixty healthy male SPF-grade SD rats, weighing 220g-240g, were purchased from Beijing Vital River Co., Ltd. After a 3-day acclimatization period, experiments were conducted at room temperature of 22-26℃ and relative humidity of 50%-70%, with free access to water and food.

[0156] Sixty rats were randomly divided into three groups using a random number table: a sham-operated group, a model group, a low-dose group (referred to as the "low-dose group") receiving the drug compositions from Examples 1 to 4, and a high-dose group (referred to as the "high-dose group") receiving the drug compositions from Examples 1 to 4, with six rats in each group. The low-dose group and the high-dose group were administered the decoctions from Examples 1 to 4 by gavage at 1.25 g / (kg·d) and 5 g / (kg·d) of the total effective ingredient, respectively, at 10:00 AM daily. The low-dose group received the equivalent dose for a 70 kg adult, and the high-dose group received four times the low-dose dose. The sham-operated group and the model group were administered 2 mL of physiological saline by gavage. All groups were administered the decoctions once daily for seven consecutive days. Except for the sham-operated group, all other groups of rats were given carrageenan (Ca) 10 mg / kg intraperitoneally on the 6th day of gavage. One hour after gavage on the morning of the 7th day, a rat model of cerebral ischemia was established in each group of rats using the middle cerebral artery occlusion (MCAO) suture occlusion method. The sham-operated group of rats had the same surgical procedure except that no suture was inserted. Immediately after the suture was inserted into the middle cerebral artery, all other groups of rats except the sham-operated group were injected subcutaneously with 20% dry yeast suspension in their backs.

[0157] MCAO suture occlusion procedure: After anesthesia with 4% chloral hydrate via intraperitoneal injection, rats were fixed in a supine position on the operating table. An incision was made along the midline of the neck. Using forceps, the cervical glandular tissue and fascia were bluntly dissected to expose and separate the right common carotid artery, internal carotid artery, and external carotid artery. The root of the external carotid artery and the proximal end of the common carotid artery were ligated. A "V"-shaped incision was made on the common carotid artery. Before making the incision, the distal end of the common carotid artery was clamped with a micro-arterial clamp to prevent bleeding. The suture was inserted into the internal carotid artery through the "V"-shaped incision and advanced to occlude the middle cerebral artery. The moment the suture was inserted into the middle cerebral artery was designated as time 0. Postoperatively, the skin was sutured, leaving the suture tip exposed. The suture was removed 1.5 hours later to simulate cerebral ischemia-reperfusion.

[0158] Detection indicators and methods

[0159] (1) Platelet aggregation rate detection: 2 mL of blood was collected from the abdominal aorta of rats and placed in a 3.8% sodium citrate anticoagulant tube. The platelet aggregation rate of rats was detected according to the PL platelet function tester method.

[0160] (2) Blood rheology test: 5 mL of blood was collected from the abdominal aorta of rats and placed in a heparin anticoagulant tube. The low, medium and high shear viscosity values ​​of whole blood and plasma were tested according to the SA6600 fully automatic blood rheology tester.

[0161] (3) Tail blood perfusion: The blood perfusion of rats at the tail tip was detected using the PeriCam PSI speckle imager. The cursor was focused 1 cm above the tip of the rat tail to observe and record the blood perfusion at the tail tip, generating laser blood perfusion speckle images. The average blood perfusion at the tail tip of each group of rats was analyzed using the PeriCam PSI software PIM Soft.

[0162] (4) Tongue image collection: The rats were placed in a supine position. Under a fixed light source, fixed shooting environment and fixed light intensity, the tip of the rat's tongue was gently pulled out with tweezers to expose the root of the tongue. A colorimetric card was placed next to the tongue, and the digital camera was fixed at a fixed focal length to take pictures of the rat's tongue. After the images were collected, they were processed using Photoshop image processing software. Three fixed points were selected on the tongue surface, and the R (red), G (green) and B (blue) component values ​​of the pixel area were read respectively, and the average value was taken. The color saturation analysis of the tongue image was performed according to the literature method (Li Lei, Xu Li, Li Zhen, et al. Effect of Qilong capsule on acute myocardial ischemia in dogs [J]. World Journal of Traditional Chinese Medicine, 2018, 13(01):31-35+40; Chen Jincheng, Liu Jianxun, Ren Junguo, et al. Study on the syndrome feature spectrum of Qi deficiency syndrome based on literature mining technology [J]. Chinese Journal of Traditional Chinese Medicine, 2018, 43(11):2184-2189.).

[0163] (5) Pulse measurement: Rats were anesthetized with 2% isoflurane and the pulse amplitude of rats was monitored using a Mouse Ox small animal non-invasive pulse oximeter for 30 seconds. Fifteen continuous and stable valid data were selected and the average value was calculated.

[0164] (6) Neurological function score: The neurological function score of rats was established with reference to the Zea Longa method: 0 points: no neurological deficit symptoms; 1 point: unable to fully extend the left forepaw when the tail is lifted; 2 points: turns to the left when walking; 3 points: leans to the left when walking; 4 points: decreased level of consciousness, unable to walk spontaneously.

[0165] Results Comparison

[0166] Comparison of platelet aggregation rates among different groups of rats

[0167] As can be seen from Tables 9 to 12 below, the maximum and average platelet aggregation rates of the low-dose and high-dose groups of the pharmaceutical composition of the present invention were significantly lower than those of the model group.

[0168] Table 9 Comparison of platelet aggregation rate in rats

[0169]

[0170] Note: Compared with the sham surgery group.1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0171] Table 10 Comparison of platelet aggregation rates in rats

[0172]

[0173] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0174] Table 11 Comparison of platelet aggregation rate in rats

[0175]

[0176] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0177] Table 12 Comparison of platelet aggregation rate in rats

[0178]

[0179] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0180] Comparison of whole blood viscosity and plasma viscosity among different groups of rats

[0181] Compared with the model group, the whole blood viscosity at low, medium, and high shear rates and plasma viscosity in the low-dose and high-dose groups were significantly lower than those in the model group, as shown in Tables 13 to 16.

[0182] Table 13 Comparison of whole blood viscosity and plasma viscosity in rats

[0183]

[0184] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4)P < 0.01.

[0185] Table 14 Comparison of whole blood viscosity and plasma viscosity in rats

[0186]

[0187] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0188] Table 15 Comparison of whole blood viscosity and plasma viscosity in rats

[0189]

[0190] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0191] Table 16 Comparison of whole blood viscosity and plasma viscosity in rats

[0192]

[0193] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0194] Comparison of tail blood perfusion in different groups of rats

[0195] from Figure 8 As shown in Tables 17 to 20 below, the blood perfusion volume at the tail end of the model group was lower than that of the sham-operated group, indicating sluggish blood flow. However, the low-dose and high-dose groups that received the drug compositions from Examples 1 to 4 showed a trend towards increased blood perfusion volume at the tail end, indicating the therapeutic potential of the blood-activating and detoxifying method.

[0196] Table 17 Comparison of blood perfusion at the tail end of rats

[0197] Group n Blood perfusion (PU) Sham surgery group 6 48.59±12.65 Model group 4 <![CDATA[18.64±4.84 2) ]]> The low-dose group of Example 1 5 <![CDATA[29.09±8.18 2) ]]> High-dose group of Example 1 6 <![CDATA[31.06±5.66 2,3) ]]>

[0198] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0199] Table 18 Comparison of blood perfusion at the tail end of rats

[0200] Group n Blood perfusion (PU) Sham surgery group 6 48.59±12.65 Model group 4 <![CDATA[18.64±4.84 2) ]]> The low-dose group of Example 2 5 <![CDATA[29.52±7.39 2) ]]> High-dose group of Example 2 6 <![CDATA[31.15±11.36 2,3) ]]>

[0201] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0202] Table 19 Comparison of blood perfusion at the tail end of rats

[0203] Group n Blood perfusion (PU) Sham surgery group 6 48.59±12.65 Model group 4 <![CDATA[18.64±4.84 2) ]]> The low-dose group of Example 3 5 <![CDATA[28.99±11.21 2) ]]> High-dose group of Example 3 6 <![CDATA[30.46±9.15 2,3) ]]>

[0204] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0205] Table 20 Comparison of tail blood perfusion in rats

[0206] Group n Blood perfusion (PU) Sham surgery group 6 48.59±12.65 Model group 4 <![CDATA[18.64±4.84 2) ]]> The low-dose group of Example 4 5 <![CDATA[27.79±9.44 2) ]]> High-dose group of Example 4 6 <![CDATA[28.97±8.69 2,3) ]]>

[0207] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0208] Comparison of tongue appearance of rats in different groups

[0209] Reference Figure 9 Tables 21 to 24 show the results of RGB color model analysis of tongue images. The R, G, and B values ​​of the tongue image in the model group were significantly lower than those in the sham-operated group, indicating that the tongue of the rats in the model group was dull, consistent with signs of "blood stasis and toxin accumulation." Meanwhile, the R, G, and B values ​​of the tongue image in the low-dose and high-dose groups of the drug compositions from Examples 1 to 4 showed an increasing trend, reflecting to some extent the protective effect of the drug compositions of the present invention.

[0210] Table 21 Comparison of RGB color mode analysis results of rat tongue images in each group

[0211] Group n R (8 bits) G (8 bits) B (8 bits) Sham surgery group 6 150.23±11.77 92.17±9.24 94.33±11.21 Model group 4 <![CDATA[133.23±8.72 2) ]]> <![CDATA[83.76±9.65 2) ]]> <![CDATA[86.74±12.35 2) ]]> The low-dose group of Example 1 5 <![CDATA[137.65±12.36 2,3) ]]> <![CDATA[85.63±10.42 2,3) ]]> <![CDATA[87.93±10.11 2,3) ]]> High-dose group of Example 1 6 <![CDATA[139.67±9.21 2,3) ]]> <![CDATA[88.43±11.12 2,3) ]]> <![CDATA[90.55±8.11 2,3) ]]>

[0212] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3)P < 0.05 4) P < 0.01.

[0213] Table 22 Comparison of RGB color mode analysis results of tongue images of rats in each group

[0214]

[0215]

[0216] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0217] Table 23 Comparison of RGB color mode analysis results of rat tongue images in each group

[0218] Group n R (8 bits) G (8 bits) B (8 bits) Sham surgery group 6 150.23±11.77 92.17±9.24 94.33±11.21 Model group 4 <![CDATA[133.23±8.72 2) ]]> <![CDATA[83.76±9.65 2) ]]> <![CDATA[86.74±12.35 2) ]]> The low-dose group of Example 3 5 <![CDATA[135.56±11.76 2,3) ]]> <![CDATA[84.76±11.76 2,3) ]]> <![CDATA[87.17±12.41 2,3) ]]> High-dose group of Example 3 6 <![CDATA[137.52±12.46 2,3) ]]> <![CDATA[85.91±8.93 2,3) ]]> <![CDATA[88.36±10.42 2,3) ]]>

[0219] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0220] Table 24 Comparison of RGB color mode analysis results of rat tongue images in each group

[0221] Group n R (8 bits) G (8 bits) B (8 bits) Sham surgery group 6 150.23±11.77 92.17±9.24 94.33±11.21 Model group 4 <![CDATA[133.23±8.72 2) ]]> <![CDATA[83.76±9.65 2) ]]> <![CDATA[86.74±12.35 2) ]]> The low-dose group of Example 4 5 <![CDATA[135.34±11.98 2,3) ]]> <![CDATA[84.96±11.86 2,3) ]]> <![CDATA[89.17±12.68 2,3) ]]> High-dose group of Example 4 6 <![CDATA[136.52±12.46 2,3) ]]> <![CDATA[85.96±9.33 2,3) ]]> <![CDATA[88.98±10.88 2,3) ]]>

[0222] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0223] Comparison of pulse amplitude among different groups of rats

[0224] from Figure 10 As can be seen from the pulse detection results in Tables 25 to 28 below, the pulse amplitude in the model group was lower than that in the sham surgery group, indicating that blood stasis and toxin accumulation, deficiency of qi, blood, yin and yang, and slow and sluggish blood flow in the pulse channels. Furthermore, both the low-dose and high-dose groups that took the drug compositions of Examples 1 to 4 showed improved pulse amplitude, indicating that the drug compositions of the present invention have the therapeutic potential for promoting blood circulation and detoxification.

[0225] Table 25 Rats in each group Comparison of pulse amplitude

[0226] Group n Pulse amplitude (μm) Sham surgery group 6 45.28±9.93 Model group 4 <![CDATA[17.16±3.21 2) <!-- 19 -->]]> The low-dose group of Example 1 5 <![CDATA[23.10±6.48 2) ]]> High-dose group of Example 1 6 <![CDATA[26.09±4.48 2,3) ]]>

[0227] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0228] Table 26 Rats in each group Comparison of pulse amplitude

[0229] Group n Pulse amplitude (μm) Sham surgery group 6 45.28±9.93 Model group 4 <![CDATA[17.16±3.21 2) ]]> The low-dose group of Example 2 5 <![CDATA[24.10±5.48 2) ]]> High-dose group of Example 2 6 <![CDATA[27.09±5.48 2,3) ]]>

[0230] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0231] Table 27 Rats in each group Comparison of pulse amplitude

[0232] Group n Pulse amplitude (μm) Sham surgery group 6 45.28±9.93 Model group 4 <![CDATA[17.16±3.21 2) ]]> The low-dose group of Example 3 5 <![CDATA[24.10±3.18 2) ]]> High-dose group of Example 3 6 <![CDATA[26.89±4.28 2,3) ]]>

[0233] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0234] Table 28 Comparison of pulse amplitude in rats of different groups

[0235] Group n Pulse amplitude (μm) Sham surgery group 6 45.28±9.93 Model group 4 <![CDATA[17.16±3.21 2) ]]> The low-dose group of Example 4 5 <![CDATA[24.73±1.47 2) ]]> High-dose group of Example 4 6 <![CDATA[25.33±2.38 2,3) ]]>

[0236] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0237] Rats in each group Comparison of neurological function scores

[0238] As can be seen from the neurological function scores in Tables 29 to 32, the neurological function scores of the rats in the model group were significantly higher than those in the sham-operated group, indicating a severe neurological deficit in the model group. Both the low-dose and high-dose groups administered the drug compositions from Examples 1 to 4 showed improvement in the neurological deficit symptoms.

[0239] Table 29 Comparison of neurological function scores among different groups of rats

[0240] Group n Neurological function score Sham surgery group 6 0 Model group 4 <![CDATA[2.16±0.41 2) ]]> The low-dose group of Example 1 5 <![CDATA[1.85±0.23 2,3) ]]> High-dose group of Example 1 6 <![CDATA[1.53±0.30 2,4) ]]>

[0241] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0242] Table 30 Comparison of neurological function scores among different groups of rats

[0243] Group n Neurological function score Sham surgery group 6 0 Model group 4 <![CDATA[2.16±0.41 2) ]]> The low-dose group of Example 2 5 <![CDATA[1.86±0.13 2,3) ]]> High-dose group of Example 2 6 <![CDATA[1.60±0.22 2,4) ]]>

[0244] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0245] Table 31 Comparison of neurological function scores among different groups of rats

[0246] Group n Neurological function score Sham surgery group 6 0 Model group 4 <![CDATA[2.16±0.41 2) ]]> The low-dose group of Example 3 5 <![CDATA[1.81±0.15 2,3) ]]> High-dose group of Example 3 6 <![CDATA[1.75±0.12 2,4) ]]>

[0247] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0248] Table 32 Comparison of neurological function scores among different groups of rats

[0249] Group n Neurological function score Sham surgery group 6 0 Model group 4 <![CDATA[2.16±0.41 2) ]]> The low-dose group of Example 4 5 <![CDATA[1.77±0.33 2,3) ]]> High-dose group of Example 4 6 <![CDATA[1.51±0.28 2,4) ]]>

[0250] Note: Compared with the sham surgery group. 1) P < 0.05 2) P < 0.01; compared with the model group, 3) P < 0.05 4) P < 0.01.

[0251] The results above show that the low-dose and high-dose groups of the drug composition of the present invention showed significant improvements in platelet aggregation rate, blood rheology, tail blood perfusion, tongue RGB value, pulse, and nerve function compared to the model group.

[0252] In addition, the pharmaceutical composition of the present invention, which has the effects of promoting blood circulation and detoxifying, can effectively reduce the area of ​​cerebral infarction, increase the RGB value of the rat tongue image, reduce the level of the inflammatory factor IL-6 in brain tissue, and improve the pathological morphology of brain tissue.

[0253] In summary, the inventors of this invention, based on the distribution patterns of TCM syndromes in acute ischemic stroke, concluded that the TCM syndromes of acute ischemic stroke are mainly characterized by blood stasis, accumulation of toxins, mutual binding of blood stasis and toxins, and damage to the brain's collaterals. The treatment should focus on promoting blood circulation, removing blood stasis, detoxifying, and unblocking the collaterals. The drug composition of this invention can achieve the effects of promoting blood circulation, removing blood stasis, unblocking the collaterals, and clearing away toxins and turbidity.

[0254] Animal experiments have shown that the pharmaceutical composition of the present invention can improve platelet aggregation rate, blood rheology, and blood perfusion, and has a significant effect on the treatment of acute ischemic stroke. Furthermore, the pharmaceutical composition of the present invention can effectively reduce the infarct area, increase the RGB value of the rat tongue image, reduce the level of the inflammatory factor IL-6 in brain tissue, and improve the pathological morphology of brain tissue.

[0255] To evaluate the clinical efficacy and safety of the pharmaceutical composition of the present invention in treating acute ischemic stroke, and to demonstrate its therapeutic advantages in promoting blood circulation and detoxification, a multicenter, randomized, double-blind, placebo-controlled clinical trial was designed, and 64 patients have been enrolled so far. Furthermore, preliminary clinical observations of the pharmaceutical composition of the present invention in patients with acute ischemic stroke show significant efficacy, effectively improving patients' clinical symptoms and quality of life, with no significant adverse reactions observed.

[0256] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited to the specific details described above. Within the scope of the inventive concept, various modifications and combinations can be made to the technical solutions of the present invention, and all such modifications and combinations fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine raw material composition for treating ischemic stroke, characterized in that, The traditional Chinese medicine raw material composition consists of the following traditional Chinese medicine raw materials by weight: Chuanxiong (8-15 parts), Gardenia (8-12 parts), Panax notoginseng (3-9 parts), Hirudo medicinalis (1-5 parts), Acorus tatarinowii (8-15 parts), Curcuma longa (6-12 parts), and Trichosanthes kirilowii (8-15 parts).

2. The traditional Chinese medicine raw material composition according to claim 1, characterized in that, The herbal raw material composition consists of the following herbal raw materials by weight: 8-13 parts of Ligusticum chuanxiong, 8-11 parts of Gardenia jasminoides, 4-8 parts of Panax notoginseng, 3-5 parts of Hirudo medicinalis, 8-13 parts of Acorus tatarinowii, 8-11 parts of Curcuma longa, and 10-15 parts of Trichosanthes kirilowii.

3. The traditional Chinese medicine raw material composition according to claim 1, characterized in that, The herbal raw material composition consists of the following herbal raw materials by weight: 9-11 parts of Ligusticum chuanxiong, 9-11 parts of Gardenia jasminoides, 5-7 parts of Panax notoginseng, 4-5 parts of Hirudo medicinalis, 9-11 parts of Acorus tatarinowii, 9-11 parts of Curcuma longa, and 12-15 parts of Trichosanthes kirilowii.

4. The traditional Chinese medicine raw material composition according to claim 1, characterized in that, The traditional Chinese medicine raw material composition consists of the following traditional Chinese medicine raw materials by weight: 10 parts of Ligusticum chuanxiong, 10 parts of Gardenia jasminoides, 6 parts of Panax notoginseng, 5 parts of Hirudo medicinalis, 10 parts of Acorus tatarinowii, 10 parts of Curcuma longa, and 15 parts of Trichosanthes kirilowii; 8 parts of Ligusticum chuanxiong, 9 parts of Gardenia jasminoides, 3 parts of Panax notoginseng, 2 parts of Hirudo medicinalis, 8 parts of Acorus tatarinowii, 6 parts of Curcuma longa, and 9 parts of Trichosanthes kirilowii; 15 parts of Ligusticum chuanxiong, 12 parts of Gardenia jasminoides, 8 parts of Panax notoginseng, 4 parts of Hirudo medicinalis, 15 parts of Acorus tatarinowii, 11 parts of Curcuma longa, and 15 parts of Trichosanthes kirilowii; or 11 parts of Ligusticum chuanxiong, 11 parts of Gardenia jasminoides, 7 parts of Panax notoginseng, 5 parts of Hirudo medicinalis, 11 parts of Acorus tatarinowii, 11 parts of Curcuma longa, and 9 parts of Trichosanthes kirilowii.

5. A pharmaceutical composition for treating ischemic stroke, characterized in that, The pharmaceutical composition is made from the traditional Chinese medicine raw material composition according to claim 1.

6. The pharmaceutical composition according to claim 5, characterized in that, The pharmaceutical composition also includes pharmaceutically acceptable excipients.

7. The pharmaceutical composition according to claim 5, characterized in that, The pharmaceutical composition is prepared by the following steps: Place 8-15 parts of Chuanxiong (in the form of medicinal slices), 8-12 parts of Zhizi (Gardenia jasminoides), 1-5 parts of scalded leech, 8-15 parts of Shichangpu (Acorus tatarinowii), 6-12 parts of Yujin (Curcuma longa), and 8-15 parts of Gualou (Trichosanthes kirilowii) into a decoction container, and add water to the decoction container. After simmering for the predetermined time, filter and concentrate into a clear paste; Pharmaceutically acceptable excipients were added to the ointment, and the mixture was mixed and granulated to obtain granular chuanxiong, gardenia, leech, acorus, turmeric and trichosanthes. Three to nine parts of Panax notoginseng in the form of medicinal slices are pulverized, pharmaceutically acceptable excipients are added, and the mixture is stirred and granulated to obtain granulated Panax notoginseng; or three to nine parts of Panax notoginseng in the form of medicinal slices are pulverized to obtain granulated Panax notoginseng. as well as The granular forms of Ligusticum chuanxiong, Gardenia jasminoides, Panax notoginseng, Hirudo medicinalis, Acorus tatarinowii, Curcuma longa, and Trichosanthes kirilowii are mixed to obtain the pharmaceutical composition as at least one of granules and capsules.

8. The pharmaceutical composition according to claim 5, characterized in that, The pharmaceutical composition is prepared by the following steps: Place 8-15 parts of Chuanxiong (in the form of medicinal slices), 8-12 parts of Zhizi (Gardenia jasminoides), 1-5 parts of scalded leech, 8-15 parts of Shichangpu (Acorus tatarinowii), 6-12 parts of Yujin (Curcuma longa), and 8-15 parts of Gualou (Trichosanthes kirilowii) into a decoction container, and add water to the decoction container; After simmering for the predetermined time, filter and concentrate into a clear paste; Pulverize 3 to 9 parts of Panax notoginseng in the form of medicinal slices, add pharmaceutically acceptable excipients, mix well, and granulate to obtain granular Panax notoginseng, or grind 3 to 9 parts of Panax notoginseng in the form of medicinal slices to obtain powdered Panax notoginseng; as well as Granular or powdered Panax notoginseng is mixed with the extract and pharmaceutically acceptable excipients and made into pills to obtain the pharmaceutical composition as pills.

9. The pharmaceutical composition according to claim 5, characterized in that, The pharmaceutical composition is prepared by the following steps: Place 8-15 parts of Chuanxiong (in the form of medicinal slices), 8-12 parts of Zhizi (Gardenia jasminoides), 1-5 parts of scalded leech, 8-15 parts of Shichangpu (Acorus tatarinowii), 6-12 parts of Yujin (Curcuma longa), and 8-15 parts of Gualou (Trichosanthes kirilowii) into a decoction container, and add water to the decoction container; After decocting for the predetermined time, filter to remove the dregs and obtain the medicinal soup; Pulverize 3 to 9 parts of Panax notoginseng in the form of medicinal slices, add pharmaceutically acceptable excipients, mix well, and granulate to obtain granular Panax notoginseng, or grind 3 to 9 parts of Panax notoginseng in the form of medicinal slices to obtain powdered Panax notoginseng; as well as Granular or powdered Panax notoginseng is mixed with the decoction to obtain the drug composition as a decoction.

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