Traditional Chinese medicine composition for treating cerebral arterial thrombosis sequelae

Abstract

The invention provides a traditional Chinese medicine composition for treating cerebral arterial thrombosis sequelae. The traditional Chinese medicine composition is prepared from the following components in parts by weight: 5-7 parts of turtle shells, 2-5 parts of vinegar tortoise shells, 6-8 parts of oysters, 2-5 parts of angelica sinensis, 5-7 parts of radix paeoniae alba, 2-5 parts of ligusticum wallichii, 2-5 parts of rhizoma acori graminei, 2-5 parts of radix curcumae, 2-5 parts of wine-treated rhubarb, 2-5 parts of peach kernels, 5-7 parts of fried earthworms, 5-7 parts of radix puerariae, 5-7 parts of radix gentianae macrophyllae, 5-7 parts of caulis spatholobi and 15-20 parts of auxiliary materials. The invention also provides a preparation method of the traditional Chinese medicine composition. The traditional Chinese medicine composition for treating ischemic cerebral apoplexy sequelae provided by the invention has the effects of nourishing yin and suppressing yang, and promoting blood circulation to remove meridian obstruction, can realize the protection effect on cerebral ischemia, and has the effect of improving blood viscosity so as to influence hemorheology.

Description

Technical Field

[0001] The invention belongs to the field of traditional Chinese medicine and relates to a traditional Chinese medicine composition for treating sequelae of ischemic cerebral apoplexy (stroke). Background Art

[0002] Cerebral stroke, also known as "stroke" or "cerebrovascular accident," is a group of diseases characterized by impaired cerebral blood circulation and functional or structural damage to brain tissue caused by sudden rupture and bleeding of a brain blood vessel or ischemic stroke due to vascular obstruction. Stroke can be divided into hemorrhagic stroke (cerebral hemorrhage or subarachnoid hemorrhage) and ischemic stroke (cerebral infarction or cerebral thrombosis). Cerebral infarction is the most common, accounting for approximately 70% to 80% of all cerebrovascular diseases. This disease is characterized by high morbidity, disability, recurrence, mortality, and complications. The most common clinical symptoms are sudden weakness on one side of the face, arm, or leg, sudden fainting, and unconsciousness. Other symptoms include sudden numbness on one side of the face, arm, or leg, sudden facial paralysis, hemiplegia, confusion, difficulty speaking or understanding, difficulty seeing in one or both eyes, difficulty walking, dizziness, loss of balance or coordination, severe, unexplained headaches, and fainting. After the acute phase of stroke, patients may still have hemiplegia of limbs, facial paralysis, tongue stiffness and slurred speech, difficulty swallowing, abnormal emotions, numbness and heaviness in hands and feet, and difficulty defecating, which are the sequelae of stroke.

[0003] Currently, Western medicine treatments for stroke primarily include early thrombolysis, antiplatelet aggregation, anticoagulation, surgical intervention, rehabilitation, and symptomatic treatment (such as blood pressure and blood sugar control, nutritional support, and anti-infection). While these treatments offer the advantages of rapid disease relief and targeted action, they are also associated with certain toxic side effects, such as liver damage. Studies have shown that Traditional Chinese Medicine (TCM) has achieved significant results in the prevention and treatment of stroke.

[0004] "Stroke" falls under the categories of "hemips" (traumatic atrophy), "wind rash," and "weak syncope" in Traditional Chinese Medicine. The Yellow Emperor's Classic of Internal Medicine is widely recognized as the earliest medical text to record this topic. For example, in "Suwen: Wind Theory," it states: "A stroke caused by drinking alcohol is called leaking wind. A stroke caused by sweating during sex is called internal wind. A stroke caused by a recent bath is called head wind." "Lingshu: Cijie Zhenxie" states: "When a weak evil invades one side of the body, it penetrates deeply and lodges in the blood and defense systems. When the blood and defense systems weaken, the true qi disappears, leaving only the evil qi, causing hemiplegia."

[0005] The Yellow Emperor's Classic of Internal Medicine proposed the theory that "external wind" causes stroke. After the Jin and Yuan dynasties, the possibility of "internal wind" as a contributing factor to illness began to be considered. The development of "external wind" into "internal wind" was particularly closely linked to liver wind. The term "internal wind" first appeared in the Suwen (Suwen) Treatise on Wind: "... if one suffers from a stroke after sexual intercourse and sweats, it is internal wind." The term "stroke" here is not used as a disease name, but rather as a causative factor, meaning "infected by wind." Wang Bing commented: "This depletes the essence internally, opens the pores externally, and allows the internal wind to attack, hence the term internal wind." The pathogenesis of wind infection due to physical weakness is called "internal wind." Zhang Zhicong's Huangdi Neijing (Suwen) Annotated Treatise on Wind, Chapter 42, further states: "Sexual intercourse depletes Yin essence internally, and sweating displaces Yang energy externally. Therefore, a stroke is caused by the intrusion of wind energy into the body, resulting in internal wind." Excessive sexual intercourse and excessive sexual exertion can damage the tendons and essence. Essence is stored in the kidneys, while tendons are governed by the liver. The liver and kidneys share a common origin. Damage to kidney essence leads to water deficiency. Less water cannot nourish wood, and less wood nourishes it, leading to internal changes in liver qi, with yang movement transforming into wind. Furthermore, the Yellow Emperor's Classic of Internal Medicine notes that liver yang imbalance and disordered qi flow can manifest as symptoms of internal liver wind. "Suwen: The Great Treatise on the Five Movements" states: "Wind harms the liver, and dryness overcomes wind." "Suwen: The Great Treatise on the Essential Truth" states: "When wind and wood are affected by evil, liver disease arises. ... All wind-induced dizziness and vertigo are attributed to the liver." "Suwen: The Treatise on the Vital Energy of Life" states: "Extreme anger weakens yang qi, causing fainting. ... Sweat and fatigue can lead to partial exhaustion." This suggests that the liver is most susceptible to invasion by wind evil, leading to the common symptoms of "wind prevailing, causing movement," such as dizziness and trembling, being classified as liver diseases. This laid the foundation for the later theory of liver yang transforming into wind. Among them, Miao Xiyong proposed the theory of internal deficiency and hidden wind, and pointed out in Xianxingzhai Medical Notes: "Internal deficiency and hidden wind are indeed due to deficiency of both yin and yang, and yin deficiency is more common, which is different from external wind evil." Ye Tianshi further elaborated on the content of "internal wind" on this basis and proposed the concept of "yang transforming into internal wind". In the Clinical Guide Medical Cases: Stroke, he said: "It is the change of yang energy in the body. The liver is the wind organ. Due to the depletion of essence and blood, water cannot contain wood, and wood is less nourishing. Therefore, liver yang is hyperactive and internal wind arises from time to time." Later doctors Inspired by Ye's theory of "yin deficiency and yang hyperactivity" as the pathogenesis of stroke, scholars have further explored the pathogenesis of stroke, incorporating modern medical knowledge. Zhang Bolong proposed in his "Lei Zhong Mi Zhi" that "water deficiency cannot contain wood, leading to liver wind becoming active... The treatment principle is to suppress yang, nourish and descend, and calm the liver and kidneys." Zhang Shanlei's "Zhong Feng Ke Quan" states that "in the event of a sudden stroke, in addition to suppressing yang, expectorants are particularly essential." Zhang Xichun also believed that stroke is caused by "liver yang transforming into wind, causing qi to rise upward." "Yi Men Fa Lu·Zhong Feng Men" explains the pathogenesis of stroke: "Stroke is caused by weak rongwei qi, leading to the coagulation of body fluids and blood stasis. Coagulation of body fluids becomes phlegm, and blood stasis becomes stasis." "Yu Yi Sui Bi·Bi San" states: "Blood is like a boat, and body fluids are water." "When body fluids are burned and depleted by fire, blood circulation becomes more stagnant." "Yin deficiency leads to blood stasis." This shows that when yin and body fluids are deficient, the blood vessels become incomplete and blood circulation is impaired, which in turn leads to blood stasis and obstruction of the cerebral arteries.In addition, blood stasis will hinder the Qi movement over time, and stagnant Qi will hinder the liver's function of dispersing and damaging the liver. The liver is Yin and uses Yang, so the liver is injured and the liver Yin is damaged. Yin deficiency and Yang hyperactivity will cause wind, which will cause stroke.

[0006] Traditional Chinese Medicine (TCM) believes that the sequelae of stroke are located in the heart and brain, and are closely related to the liver and kidneys. The liver is the organ of wind and wood, governing the tendons. The liver stores blood, while the kidneys store essence. Essence generates blood, and blood transforms into essence. Liver wood relies on the nourishment of kidney water. If kidney water is insufficient, water cannot nourish wood, leading to insufficient liver yin, inability of yin to control yang, and hyperactivity of yang causing wind. The liver and kidneys share a common origin, and prolonged illness affecting the kidneys ultimately leads to deficiency of liver and kidney yin, which in turn causes liver yang to rise. Combined with improper rest, qi and blood rush upward to the brain, obstructing the spiritual orifices, resulting in sudden collapse and hemiplegia. After the acute phase of stroke, the main pathological factors are wind, phlegm, and blood stasis. The pathological nature is often characterized by underlying deficiency and superficial excess, with deficiency being the underlying cause. The pathogenesis is mostly due to deficiency of yin and blood, excess of yang and fire, easy burning of wind and fire, or old age and physical weakness, liver and kidney yin deficiency, and hyperactivity of liver yang; and it is triggered by improper work and rest, emotional frustration, drinking and overeating, or invasion of external evils, resulting in yin deficiency and yang hyperactivity, violent expansion of liver yang, swirling internal wind, accompanied by phlegm and fire, running across the meridians, obscuring the mind, and thus causing hemiplegia.

[0007] Therefore, it is necessary to develop a Chinese medicine composition that can treat the sequelae of ischemic stroke with liver and kidney yin deficiency and meridian stasis syndrome. Summary of the Invention

[0008] In order to solve the above problems, the purpose of the present invention is to provide a traditional Chinese medicine composition for treating the sequelae of ischemic stroke, which has the effect of "nourishing yin and suppressing yang, promoting blood circulation and unblocking meridians", can achieve a protective effect on cerebral ischemia, improve blood viscosity, and thus affect blood rheology.

[0009] Another object of the present invention is to provide a method for preparing a traditional Chinese medicine composition for treating sequelae of ischemic stroke.

[0010] In order to achieve the above object, the present invention provides a traditional Chinese medicine composition for treating sequelae of ischemic stroke, comprising 5-7 parts by weight of turtle shell, 2-5 parts by weight of vinegar-soaked turtle shell, 6-8 parts by weight of oyster, 2-5 parts by weight of angelica, 5-7 parts by weight of white peony root, 2-5 parts by weight of Chuanxiong, 2-5 parts by weight of Acorus calamus, 2-5 parts by weight of Curcuma aromatica, 2-5 parts by weight of wine-soaked rhubarb, 2-5 parts by weight of peach kernel, 5-7 parts by weight of stir-fried earthworm, 5-7 parts by weight of Pueraria root, 5-7 parts by weight of Gentiana macrophylla, 5-7 parts by weight of Millettia reticulata, and 15-20 parts by weight of auxiliary materials.

[0011] Furthermore, the auxiliary material is maltodextrin.

[0012] The present invention also provides a method for preparing the above-mentioned Chinese medicine composition for treating sequelae of ischemic stroke, comprising the following steps:

[0013] The turtle shell, vinegar turtle shell and peach kernel are crushed into coarse powder respectively, and extracted twice with water together with oyster, angelica, white peony root, Chuanxiong, Acorus gramineus, Curcuma aromatica, wine rhubarb, stir-fried earthworm, Pueraria root, Gentiana macrophylla and Millettia reticulata. The first time, 8 times the weight of the medicinal materials are added with water to extract for 2 hours, and the second time, 6 times the weight of the medicinal materials are added with water to extract for 1.5 hours. The filtrates are combined and concentrated under reduced pressure to a clear paste with a relative density of 1.05 at 60°C. The paste is spray-dried, auxiliary materials are added, mixed, granulated, granulated into granules, and packaged at 10 g / bag.

[0014] The present invention is formulated in accordance with the theory of traditional Chinese medicine. Among them, turtle shell, tortoise shell and oyster are products of blood and flesh, with salty and cold taste, and can nourish the lower part of the body. They imitate the idea of ​​Sanjia Fumai Decoction in "Treatise on Warm Diseases", and can nourish the liver and kidney, benefit essence and blood, nourish yin and suppress yang. The three are monarch drugs. In the prescription, angelica sinensis nourishes blood and invigorates blood circulation, and its texture is moist and greasy, and it has the power to invigorate blood circulation while nourishing blood; white peony root is bitter and sour, and its function is to restrain yin and soften the liver, and when combined with angelica sinensis, the function of nourishing blood and nourishing yin is more pronounced; Chuanxiong is pungent, warm and dry, and it is partial to promoting qi and invigorating blood circulation, and is good at removing blood stasis. The three are mutually dependent and mutually useful, and are all blood medicines, forming a tripod shape, with nourishing and promoting circulation, promoting circulation and astringing, nourishing blood without stagnation, and promoting blood circulation without injury. They are particularly suitable for the blood deficiency and blood stasis syndrome of sequelae of cerebral stroke. The three medicines are minister drugs. In this formula, Acorus calamus is pungent, warm, aromatic, and dispersing, effectively opening the orifices and resolving phlegm, refreshing the mind and strengthening the brain. Curcuma zedoaria activates blood circulation, relieves pain, promotes qi circulation, relieves depression, and clears the heart and cools the blood. The Compendium of Materia Medica states, "Curcuma zedoaria clears qi, resolves illness, and dissipates blood stasis... It regulates the flow of qi upwards and downwards to the lower parts of the body." Both herbs enter the heart and liver meridians, opening the orifices and relieving depression. Their combination is effective for treating symptoms such as confusion and emotional distress caused by turbid evil obscuring the clear orifices after a stroke. Rhubarb clears heat and fire, dispels blood stasis, and promotes menstruation with a powerful downward force. Peach kernel activates blood circulation, dispels blood stasis, moistens the intestines, and promotes laxative effects, effectively relieving blood stasis and possessing a strong stasis-removing effect. This combination of two herbs, taken from the Didang-type formula in the Treatise on Febrile Diseases, is effective for treating various blood stasis conditions. Because stasis often persists in the post-stroke period, the insect-based Chinese herb Earthworm is added to enhance its wind-clearing and meridian-opening properties. These herbs, when used together, effectively remove blood stasis, promote menstruation, clear heat, and eliminate accumulation, while also providing a way out for the pathogenic factors. In the formula, Pueraria root is used to relax muscles, increase fluid and soothe tendons; Gentiana macrophylla dispels rheumatism, dredges meridians and relieves pain, and is a moisturizing agent among wind-clearing herbs, treating tendon and vein stiffness, regardless of whether it is new or long-standing; Millettia reticulata promotes blood circulation, replenishes blood, relaxes tendons and activates collaterals. Together, these three herbs treat numbness in the hands and feet, and paralysis of the limbs caused by blocked meridians and disharmony of the collaterals. Together, they serve as adjuvants in the formula.

[0015] The beneficial effects of the present invention are:

[0016] The present invention provides a traditional Chinese medicine composition for treating sequelae of ischemic stroke. The traditional Chinese medicine composition has the effects of "nourishing yin and suppressing yang, promoting blood circulation and unblocking meridians", can achieve a protective effect on cerebral ischemia, and has the effects of improving blood viscosity and further affecting blood rheology. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 These are photos of the rat cerebral ischemia model after successful establishment.

[0018] Figures 2A to 2G These are photos showing the pathological changes in brain tissue of a rat model of middle cerebral artery infarction induced by the Chinese medicine composition. DETAILED DESCRIPTION

[0019] The embodiments of the present invention will be described in detail and comprehensively below so that the advantages and features of the present invention can be more easily understood by those skilled in the art, thereby making a clearer and more precise definition of the protection scope of the present invention.

[0020] Example 1

[0021] The traditional Chinese medicine composition is composed of the following ingredients: 5 parts by weight of turtle shell, 3.3 parts by weight of vinegar turtle shell, 6.7 parts by weight of oyster, 2 parts by weight of angelica, 5 parts by weight of white peony root, 3 parts by weight of Chuanxiong, 3 parts by weight of Acorus calamus, 3.3 parts by weight of Curcuma, 3 parts by weight of wine-soaked rhubarb, 3 parts by weight of peach kernel, 5 parts by weight of stir-fried earthworm, 5 parts by weight of Pueraria root, 5 parts by weight of Gentiana macrophylla, 5 parts by weight of Millettia reticulata, and 17.4 parts by weight of maltodextrin.

[0022] The preparation method is as follows: turtle shell, vinegar tortoise shell and peach kernel are crushed into coarse powder respectively, and extracted twice with oyster, angelica, white peony root, Chuanxiong, Acorus gramineus, Curcuma aromatica, wine rhubarb, stir-fried earthworm, Pueraria root, Gentiana macrophylla and Millettia reticulata with water, the first time adding 8 times the weight of the medicinal materials for 2 hours, the second time adding 6 times the weight of the medicinal materials for 1.5 hours, combining the filtrates, concentrating under reduced pressure to a clear paste with a relative density of 1.05 at 60°C, spray drying, adding maltodextrin, mixing evenly, granulating, whole-granulating, making granules, and packaging according to 10g / bag to obtain the product.

[0023] Example 2 Effect of Chinese medicine composition on rat middle cerebral artery embolism ischemia model

[0024] A total of 180 male SPF rats with a body weight of 245.2 to 316.8 g that passed quarantine were selected and divided into two groups for the experiment. Ten rats were selected from each group as the sham operation group. Except for the sham operation group, the rats in the other groups were treated with a modified suture embolization method to establish a permanent cerebral ischemia model in rats. The operation steps were as follows: the rats were anesthetized with isoflurane and fixed in the supine position. The neck skin was disinfected with iodine and alcohol. Then the midline of the neck was incised and the tissue was separated layer by layer to expose the right common carotid artery ( The CCA), external carotid artery (ECA), and internal carotid artery (ICA) were permanently ligated at the proximal end of the CCA. The distal end of the CCA was temporarily clamped with a micro-arteriolar clamp. An oblique incision was made at the distal end of the CCA ligation site. A suture with a smooth spherical tip was inserted through this incision. The suture passed through the internal carotid artery at the CCA bifurcation and entered the skull to the beginning of the anterior cerebral artery (ACA). The suture was inserted to a depth of 20 mm. The distal end of the CCA was ligated to fix the nylon thread and prevent bleeding. The suture was performed layer by layer. Penicillin was injected intramuscularly to prevent infection after surgery. The sham operation group did not insert the thread, and the rest of the steps were the same as the model control group. Figure 1As shown, A shows flexion of the left forelimb; B shows left lateral tilting and turning. Both A and B performances indicate successful modeling. The neck incision was sutured, and after waking up, the surviving rats were selected. Referring to the Longa scoring method, model rats with a score of 2 or above were randomly divided into a model control group, a butylphthalide soft capsule group (0.108 g / kg), a nasal shuantong capsule group (0.324 g / kg), and a low-, medium-, and high-dose group of the Chinese medicine composition (5.16, 10.32, 20.64 g crude drug / kg). The animals in each group were gavaged with the drug. The sham operation group and the model control group were given distilled water, and the other groups were gavaged with the corresponding drug solution. The dosage volume was 10 mL / kg, once a day, for 28 consecutive days. During this period, the animals were scored for neurological function, and the grip strength and bipedal balance tests were performed at the last dose. The results are shown in Tables 1 to 4. The rat brain tissue was weighed and histopathological examination was performed. The results are shown in Tables 5 to 6 and Figures 2A to 2G shown. Figures 2A to 2G middle Figure 2A sham operation group; Figure 2B The model control group; Figure 2C Butylphthalide soft capsule group; Figure 2D Naoshuantong capsule group; Figure 2E This is a low-dose group of the Chinese medicine composition; Figure 2F This is a medium dose group of the Chinese medicine composition; Figure 2G This is a high-dose group of the Chinese medicine composition.

[0025] Among them, the positive control drug, butylphthalide soft capsules, is a drug for treating cerebrovascular diseases. It has a significant effect on improving central nervous system damage in patients with acute ischemic stroke, promoting functional recovery in patients, and is clinically used to treat mild to moderate acute ischemic stroke. The positive control drug, Naoshuantong capsules, is a traditional Chinese medicine that has the effects of promoting blood circulation and unblocking meridians, dispelling wind and resolving phlegm. Clinically, it is mainly used to treat Qi deficiency and blood stasis in the meridian recovery phase of ischemic stroke, with symptoms such as hemiplegia, facial paralysis, hemiplegia, and speech impairment. In addition, it is also used to treat the acute and recovery phases of cerebral infarction.

[0026] Table 1 Effects of Chinese medicine composition on rat body weight ( n=12~20)

[0027]

[0028]

[0029] Note: Compared with the sham operation group, ++ P≤0.01.

[0030] Table 2 Effects of Chinese medicine composition on rat neurological function scores ( n=12~20)

[0031]

[0032] Note: Compared with the sham operation group, ++ P≤0.01; compared with the model control group, * P≤0.05, ** P≤0.01.

[0033] Table 3 Effects of Chinese herbal composition on grip strength in rats with middle cerebral artery infarction model

[0034]

[0035] Note: Compared with the sham operation group, ++ P≤0.01; compared with the model control group, ** P≤0.01.

[0036] Table 4 Effects of Chinese medicine composition on bipedal balance in rat middle cerebral artery infarction model

[0037]

[0038] Note: Compared with the sham operation group, ++ P≤0.01; compared with the model control group, * P≤0.05, ** P≤0.01.

[0039] Table 5 Effects of Chinese medicine composition on brain tissue organ coefficients in rat middle cerebral artery infarction model

[0040]

[0041] Note: Compared with the sham operation group, ++ P≤0.01; compared with the model control group, * P≤0.05.

[0042] Table 6 Effects of Chinese medicine composition on brain tissue pathological changes in rat middle cerebral artery infarction model

[0043]

[0044] From Table 1 to Table 6 and Figures 2A to 2G As can be seen, low, medium, and high doses of the Chinese herbal composition had no significant effect on body weight in rats modeling middle cerebral artery embolism and ischemia. Medium and high doses significantly reduced neurological deficit scores in rats 14 and 28 days after administration. Low, medium, and high doses significantly increased grip strength in rats. Medium and high doses significantly increased the pressure difference between the hind limbs of rats, significantly reduced the organ coefficient of brain tissue in rats, and significantly reduced interstitial edema and inflammatory cell infiltration in brain tissue.

[0045] Example 3 Effect of Chinese medicine composition on rat blood stasis model

[0046] Sixty SPF-grade SD rats that passed quarantine were selected, half of which were male and half were female, weighing 202.5-274.2 g. The animals were randomly divided into 6 groups according to their body weight, namely normal control group, model control group, aspirin tablet group (9 mg / kg), low-dose, medium-dose and high-dose groups of Chinese medicine composition (5.16, 10.32 and 20.64 g crude drug / kg), half of which were male and half were female, with 10 rats in each group.

[0047] Among them, the positive control drug aspirin tablets are non-steroidal anti-inflammatory drugs with antipyretic, analgesic, and platelet aggregation inhibitory effects. They are clinically used to prevent and treat transient ischemic attacks, myocardial infarction, or thrombosis after other surgeries.

[0048] The rats in the normal control group and the model control group were orally gavaged with pure water; the rats in the other groups were gavaged with the corresponding drug solution at a volume of 10 mL / kg, once a day for 7 consecutive days. After the drug was administered on the 6th day, the rats in the other groups, except the normal control group, were subcutaneously injected with 0.08 mg / kg of epinephrine hydrochloride. Two hours later, the animals were immersed in 4°C ice water for 5 minutes, taken out, and injected with the same dose of epinephrine again 2 hours later to establish the rat cold coagulation and blood stasis model. The rats in each group were fasted for 16 hours but not water. Thirty minutes after the drug was administered the next day, they were anesthetized with isoflurane, and blood was collected from the abdominal aorta. The hemorheological indicators of the rats in each group were tested. The results are shown in Table 7.

[0049] Table 7 Effects of Chinese medicine composition on hemorheology in rat blood stasis model ( n=10)

[0050]

[0051] Note: Compared with the normal control group, ++ P≤0.01; compared with the model control group, * P≤0.05, ** P≤0.01.

[0052] As can be seen from Table 7, the high dose of the Chinese medicine composition can significantly reduce the shear rate of rat whole blood and plasma viscosity.

[0053] It can be seen from Examples 2 and 3 that the Chinese medicine composition can significantly improve neurological function damage and behavioral disorders after cerebral infarction, has a significant protective effect on brain tissue, and has the effect of improving blood viscosity.

[0054] Example 4 Single-dose toxicity test

[0055] Forty ICR mice, half male and half female, weighing 18.0-21.2g, were randomly divided into two groups based on sex and weight: a blank control group and a Chinese herbal medicine composition group, with 20 mice in each group. The Chinese herbal medicine composition group was given 0.65g of dry extract powder / mL of Chinese herbal medicine composition solution at a dose of 40mL / kg via oral gavage twice daily (with at least 6 hours between doses), for a cumulative dose of 236.60g of crude drug / kg. The blank control group was given purified water in the same manner, but fasted for approximately 13 hours before dosing. Within 0-4 hours after dosing, the signs and characteristics of poisoning, the onset and recovery time of toxic reactions, and deaths in each group were carefully observed and recorded. Observations continued the following day, once in the morning and once in the afternoon, for 14 consecutive days. Animals were weighed on the day of dosing (Day 1 for the Provantis system), before dosing, and on Days 4, 7, 10, and 14 (Days 5, 8, 11, and 15 for the Provantis system) after dosing, and weight changes were recorded. After the study, all animals were anesthetized with a 2.0 mL / kg injection of propofol (10.0 mg / kg) via the tail vein. The animals were euthanized by exsanguination of the abdominal aorta, and gross anatomical examinations were performed. The location, size, color, and adhesions of the skin and organs at the dosing site were visually observed. The texture of the organ surface and cross-sections were also examined. The results are shown in Table 8.

[0056] Table 8 Experimental dosage and group design

[0057]

[0058] Note: (1) Adult body weight is 60 kg, (2) Each 1g of dry extract powder is equivalent to 4.55g of crude drug.

[0059] As can be seen from Table 8, under the experimental conditions, ICR mice were orally gavaged with the Chinese medicine composition solution at 40 mL / kg twice a day, with a cumulative dose of 236.60 g crude drug / kg. No relevant acute toxic reactions or deaths were observed, indicating that its maximum tolerated dose (MTD) was ≥236.60 g crude drug / kg, which is approximately 246 times the intended clinical dose for adults (0.96 g crude drug / kg) (based on kilograms of body weight) and 32 times the equivalent dose for mice (7.45 g crude drug / kg) (based on body surface area).

[0060] Example 5 Repeated dose toxicity test

[0061] 160 SD rats that passed quarantine, weighing 180.1-218.2g, half male and half female, were randomly divided into four groups based on sex and weight, with 40 rats in each group, half male and half female, to form a blank control group, a low-dose group, a medium-dose group, and a high-dose group (17.1, 30.7, and 44.4g crude drug / kg) of the Chinese medicine composition. Each group received a 15mL / kg dose once daily for 6 consecutive months (26 weeks), followed by a 4-week drug-free recovery period. At the mid-dose (week 13th week), the end of the dosing period (week 26th week), and the end of the recovery period (week 30th week), 40 SD rats (10 / group), 80 (20 / group), and 40 (10 / group), half male and half female, were dissected as planned. The examination items included: general clinical observation; measurement of body weight and food intake; urine routine, hematology, serum biochemistry, coagulation and electrolyte examination, ophthalmological examination, bone marrow smear; measurement of organ coefficient and visceral brain coefficient; histopathological examination. The results are shown in Table 9.

[0062] Table 9 Dosage and group design for repeated dose toxicity test in rats

[0063]

[0064] Note: (1) Adult body weight is 60 kg, (2) Each 1g of dry extract powder is equivalent to 4.55g of crude drug.

[0065] As shown in Table 9, under the experimental conditions, SD rats were given low, medium, and high doses (17.1, 30.7, and 44.4 g crude drug / kg) of the Chinese herbal medicine composition by oral gavage for 6 consecutive months (26 weeks). The adverse reactions observed in the animals were primarily related to the pharmacological effects of the test substance (extramedullary hematopoiesis in the spleen and its compensatory response) and nonspecific effects of the test substance (satiety and weight loss after high-dose gavage). No obvious toxic effects related to the test substance itself were observed. Furthermore, the animals exhibited mild compensatory reactions (increased organ weights and abnormal urine routine results) after high-dose administration, but no further functional changes (no abnormalities in liver and kidney function) or organic changes (no abnormalities in tissue morphology) were observed in the metabolic and excretory organs (liver and kidney). The no-observed-adverse-effect level (NOAEL) was 44.4 g crude drug / kg, approximately 9 times (calculated by body surface area) and 46 times (by kilogram) the proposed clinical dose.

[0066] It can be seen from the above examples that the Chinese medicine composition for treating the sequelae of ischemic stroke provided by the present invention can significantly increase the pressure difference between the bilateral hind limbs of rats, significantly reduce the organ coefficient of the brain tissue of rats, and significantly reduce interstitial edema and inflammatory cell infiltration of brain tissue, and can significantly improve neurological function damage and behavioral disorders after cerebral infarction. It can be seen that it has a significant protective effect on brain tissue, especially brain tissue in a state of cerebral ischemia, and has the effect of improving blood viscosity and thus affecting blood rheology; and it can be seen from the toxicity test that no obvious organic changes were caused to rats.

[0067] The above-described embodiments merely illustrate several implementations of the present invention, and while their descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that a person skilled in the art would be able to make numerous variations and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the present invention shall be determined by the appended claims.

Claims

1. A Chinese medicine composition for treating sequelae of ischemic stroke, characterized in that: The invention is composed of the following ingredients: 5-7 parts by weight of turtle shell, 2-5 parts by weight of vinegar turtle shell, 6-8 parts by weight of oyster, 2-5 parts by weight of angelica, 5-7 parts by weight of white peony root, 2-5 parts by weight of ligusticum, 2-5 parts by weight of calamus, 2-5 parts by weight of turmeric, 2-5 parts by weight of wine-soaked rhubarb, 2-5 parts by weight of peach kernel, 5-7 parts by weight of stir-fried earthworm, 5-7 parts by weight of kudzu root, 5-7 parts by weight of gentiana macrophylla, 5-7 parts by weight of millettia reticulata, and 15-20 parts by weight of auxiliary materials.

2. The Chinese medicine composition for treating sequelae of ischemic stroke according to claim 1, wherein The auxiliary material is maltodextrin.

3. The method for preparing the Chinese medicine composition for treating sequelae of ischemic stroke according to claim 1 or 2, wherein: The steps include: The turtle shell, vinegar turtle shell and peach kernel are crushed into coarse powder respectively, and extracted twice with water together with oyster, angelica, white peony root, Chuanxiong, Acorus gramineus, Curcuma aromatica, wine-made rhubarb, stir-fried earthworm, kudzu root, gentiana macrophylla and Millettia reticulata. The first time, 8 times the weight of the medicinal materials are added with water for 2 hours, and the second time, 6 times the weight of the medicinal materials are added with water for 1.5 hours. The filtrates are combined and concentrated under reduced pressure to a clear paste with a relative density of 1.05 at 60°C. The paste is spray-dried, auxiliary materials are added, mixed, granulated, granulated into granules, and packaged at 10 g / bag.

Images