Traditional Chinese medicine composition for treating vascular cognitive impairment as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention provides a traditional Chinese medicine composition for treating vascular cognitive impairment. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 24-36 parts of prepared rehmannia root, 12-18 parts of rhizoma polygonati, 4.8-7.2 parts of prepared fleece flower root, 12-18 parts of ligusticum wallichii, 8-12 parts of polygala tenuifolia, 12-18 parts of herba epimedii, 25 parts of dendrobe, 12-18 parts of poria cocos, 12-18 parts of thunberg fritillary bulb, 12-18 parts of rhizoma acori graminei, 10 parts of radix ophiopogonis, 20 parts of radix curcumae, 8-12 parts of cinnamon, 4.8-7.2 parts of black prepared aconite root and 0.24-0.36 part of borneol. The invention provides a preparation method and application of the traditional Chinese medicine composition. The medicine disclosed by the invention is used for treating the vascular cognitive impairment, especially for treating the vascular cognitive impairment with the syndrome of kidney deficiency and phlegm stasis, and the medicine effect is definite.

Description

Technical Field

[0001] This invention relates to a traditional Chinese medicine composition for treating vascular cognitive impairment, belonging to the field of traditional Chinese medicine. Background Technology

[0002] Vascular cognitive impairment (VCI) is a decline in cognitive function caused by cerebrovascular disease or related risk factors (such as hypertension and diabetes). It manifests as memory loss, decreased attention, or impaired executive function and is the second most common type of dementia after Alzheimer's disease.

[0003] CN202111585113.9, entitled "Pharmaceutical Composition for Improving Cerebral Ischemia and Its Application," discloses a pharmaceutical composition for improving cerebral ischemia and its application. The pharmaceutical composition comprises the following components in parts by weight: ginseng 1-30 parts, prepared rehmannia root 0-30 parts, angelica root 1-30 parts, chuanxiong rhizome 1-30 parts, white peony root 1-30 parts, acorus root 0-30 parts, and polygala root 0-45 parts. This pharmaceutical composition can improve the decline in learning and memory abilities caused by cerebral ischemia, promote cortical angiogenesis in vascular cognitive impairment caused by cerebral ischemia, and improve cortical blood flow in vascular cognitive impairment caused by cerebral ischemia. This prescription is mainly used for vascular cognitive impairment of the qi deficiency and blood stasis type.

[0004] Vascular cognitive impairment falls under the categories of "dementia" or "mental illness" in Traditional Chinese Medicine (TCM). Its basic pathogenesis involves depletion of marrow and brain function, leading to impaired mental function. The disease is located in the brain and is closely related to the dysfunction of the five internal organs. It is characterized by deficiency of the root and excess of the branch, with the root cause being deficiency of the internal organs and insufficient qi and blood, and the branch causes being phlegm, blood stasis, and heat toxins. Modern clinical and syndrome studies have summarized vascular cognitive impairment into the following main syndrome types: kidney deficiency with phlegm and blood stasis syndrome, blood stasis obstructing the collaterals syndrome, phlegm and blood stasis intertwined syndrome, mixed deficiency and excess syndrome, and qi deficiency with blood stasis syndrome, etc. TCM diagnosis is complex. Its core lies in "deficiency of the root and excess of the branch," with kidney essence deficiency and spleen dysfunction as the root cause, and phlegm, blood stasis, and turbid toxins obstructing the brain collaterals as the branch causes. Kidney deficiency with phlegm and blood stasis syndrome is its main syndrome type. Due to the complexity of the pathogenesis of vascular cognitive impairment, the mixed deficiency and excess, and the difficulty in addressing both simultaneously, the efficacy of treatment drugs is limited, long-term efficacy is difficult to maintain, patient compliance is poor, there are many complications, and many interfering factors in treatment. Currently, there are no reported effective drugs for treating vascular cognitive impairment with kidney deficiency and phlegm and blood stasis syndrome. Summary of the Invention

[0005] This invention presents a traditional Chinese medicine composition for treating vascular cognitive impairment based on the principles of "tonifying the kidney and replenishing marrow, resolving blood stasis and eliminating phlegm." It provides a traditional Chinese medicine composition for treating vascular cognitive impairment, its preparation method, and its uses.

[0006] This invention provides a traditional Chinese medicine composition for treating vascular cognitive impairment, which is prepared from the following raw materials in the indicated weight ratios:

[0007] Prepared Rehmannia Root 24-36 parts, Polygonatum Rhizome 12-18 parts, Prepared Polygonum Multiflorum Root 4.8-7.2 parts, Ligusticum Rhizome 12-18 parts, Polygala Root 8-12 parts, Epimedium Root 12-18 parts, Dendrobium Root 20-30 parts, Poria Cocos 12-18 parts, Fritillaria Bulb 12-18 parts, Acorus Root 12-18 parts, Ophiopogon Root 8-12 parts, Curcuma Root 16-24 parts, Cinnamon Bark 8-12 parts, Prepared Aconite Root 4.8-7.2 parts, Borneol 0.24-0.36 parts.

[0008] Preferably, it is prepared from the following raw materials in the indicated weight ratios:

[0009] Prepared Rehmannia Root 30 parts, Polygonatum Rhizome 15 parts, Prepared Polygonum Multiflorum Root 6 parts, Ligusticum Rhizome 15 parts, Polygala Root 10 parts, Epimedium Rhizome 15 parts, Dendrobium Root 25 parts, Poria Cocos 15 parts, Fritillaria Bulb 15 parts, Acorus Root 15 parts, Ophiopogon Root 10 parts, Curcuma Rhizome 20 parts, Cinnamon Bark 10 parts, Prepared Aconite Root 6 parts, Borneol 0.3 parts.

[0010] The traditional Chinese medicine composition of the present invention is prepared into a commonly used pharmaceutical formulation by adding pharmaceutically acceptable excipients or auxiliary ingredients, with the active ingredient being the raw drug powder, water or organic solvent extract.

[0011] The preparations mentioned above are tablets, capsules, granules, pills, and oral liquids.

[0012] This invention provides a method for preparing the traditional Chinese medicine composition for treating vascular cognitive impairment, comprising the following steps:

[0013] a. Weigh the raw materials according to the specified weight ratio;

[0014] b. First, boil the black aconite slices in water, then add the raw materials other than borneol, boil in water, filter, concentrate, add borneol to the concentrate, and then add pharmaceutically acceptable excipients or auxiliary ingredients to prepare a commonly used pharmaceutical preparation.

[0015] This invention provides the use of the aforementioned traditional Chinese medicine composition in the preparation of a medicament for treating vascular cognitive impairment.

[0016] The use of the aforementioned traditional Chinese medicine composition in the preparation of a drug for treating vascular dementia.

[0017] In this invention, the traditional Chinese medicine composition uses Rehmannia glutinosa (processed) to nourish kidney yin, Polygonum multiflorum (processed) to replenish the deficiency of liver and kidney essence and blood, Polygonatum sibiricum (processed) to replenish the lung, spleen and kidney, and has the effect of replenishing both qi and yin, and Epimedium brevicornu (processed) to warm and strengthen kidney yang. These four herbs together serve as the principal herbs, working synergistically to nourish yin and assist yang, and replenish essence and marrow. Aconitum carmichaelii (processed) and Cinnamomum cassia (processed) are added, taking advantage of their pungent, hot and warm properties, which can both assist yang and transform qi to warm and nourish the lower body, and also contain floating yang and guide fire back to its origin. Dendrobium nobile and Ophiopogon japonicus (processed) nourish the yin of the lung and kidney, taking the meaning of "metal and water generating each other", strengthening the water element to control the yang element, and are all assistant herbs. Borneol and Fritillaria thunbergii enhance the ability to resolve phlegm and open the orifices, Curcuma longa and Ligusticum chuanxiong are used to resolve blood stasis, nourish blood, relieve depression and open the orifices, and Acorus tatarinowii, Polygala tenuifolia and Poria cocos resolve phlegm, open the orifices, calm the mind and improve intelligence, and are adjuvant herbs. When used together, these medicines address both the symptoms and the root cause, resolving phlegm and turbidity, removing blood stasis, clearing the brain orifices, and nourishing the mind.

[0018] This invention relates to a drug for treating vascular cognitive impairment, particularly vascular cognitive impairment due to kidney deficiency and phlegm stasis syndrome, with a clearly defined efficacy. This formula has been used clinically for many years, and two clinical trials have verified the clinical efficacy, safety, and predisposing syndromes of this traditional Chinese medicine composition. Furthermore, the mechanism of action of this traditional Chinese medicine composition has been demonstrated at the cellular and animal levels. Attached Figure Description

[0019] Figure 1 Escape latency test trajectory diagrams of rats in each group (A. Sham-operated group; B. Model group; C. JWDHYZ-L group; D. JWDHYZ-M group; E. JWDHYZ-H group; F. Positive drug group);

[0020] Figure 2 Comparison of the number of times rats crossed the platform at different time points in each group;

[0021] Figure 3 Pathological morphological changes in the CA1 region of the hippocampus of rats in each group (200×) (A. Sham-operated group; B. Model group; C. JWDHYZ-L group; D. JWDHYZ-M group; E. JWDHYZ-H group; F. Positive drug group);

[0022] Figure 4 Immunohistochemical detection of angiogenesis in rat brain tissue (40×) (A. Sham-operated group; B. Model group; C. JWDHYZ-L group; D. JWDHYZ-M group; E. JWDHYZ-H group; F. Positive drug group; G. Statistical analysis of angiogenesis in rat brain tissue of each group);

[0023] Figure 5 Comparison of serum SOD, MDA, Hcy, VEGF, and bFGF levels in rats of different groups (A. Changes in SOD level; B. Changes in MDA level; C. Changes in Hcy level; D. Changes in VEGF level; E. Changes in bFGF level);

[0024] Figure 6 Movement trajectory diagrams of different treatment groups during the escape latency test. Detailed Implementation

[0025] Example 1: Preparation of the traditional Chinese medicine composition granules of the present invention

[0026] Prepared Rehmannia Root 30g, Polygonatum Rhizome 15g, Prepared Polygonum Multiflorum Root 6g, Ligusticum Rhizome 15g, Polygala Root 10g, Epimedium Rhizome 15g, Dendrobium Root 25g, Poria Cocos 15g, Fritillaria Bulb 15g, Acorus Root 15g, Ophiopogon Root 10g, Curcuma Rhizome 20g, Cinnamon Bark 10g, Prepared Aconite Root 6g, Borneol 0.3g.

[0027] The herbs are first decocted, then other herbs except borneol are added and decocted, filtered, concentrated, and borneol and starch are added to the concentrated liquid. The mixture is then granulated and sized to prepare granules.

[0028] Example 2: Preparation of tablets based on the traditional Chinese medicine composition of the present invention

[0029] Prepared Rehmannia glutinosa 24g, Polygonatum sibiricum 12g, prepared Polygonum multiflorum 4.8g, Ligusticum chuanxiong 12g, Polygala tenuifolia 8g, Epimedium brevicornu 12g, Dendrobium nobile 20 parts, Poria cocos 12g, Fritillaria thunbergii 12g, Acorus tatarinowii 12g, Ophiopogon japonicus 8g, Curcuma longa 16g, Cinnamomum cassia 8g, Aconitum carmichaelii 4.8g, Borneol 0.24g. The raw materials were extracted according to the method of Example 1, and borneol and starch were added. The mixture was prepared, granulated, and compressed into tablets to obtain tablets.

[0030] Example 3: Preparation of the oral liquid of the traditional Chinese medicine composition of the present invention

[0031] Prepared Rehmannia glutinosa 36g, Polygonatum sibiricum 18g, Polygonum multiflorum 7.2g, Ligusticum chuanxiong 18g, Polygala tenuifolia 12g, Epimedium brevicornu 18g, Dendrobium nobile 30g, Poria cocos 18g, Fritillaria thunbergii 18g, Acorus tatarinowii 18g, Ophiopogon japonicus 12g, Curcuma longa 24g, Cinnamomum cassia 12g, Aconitum carmichaelii 7.2g, Borneol 0.36g, add borneol to the concentrated solution prepared according to Example 1 to prepare an oral liquid.

[0032] The following demonstrates the beneficial effects of the present invention through pharmacological efficacy or clinical trials.

[0033] Example 1: Clinical trial of the traditional Chinese medicine composition of the present invention in vascular cognitive impairment.

[0034] This invention explores the efficacy and safety of the traditional Chinese medicine composition of this invention in treating patients with vascular cognitive impairment through human clinical trials.

[0035] 1. Subject inclusion and exclusion criteria

[0036] Inclusion criteria: ① Meets the diagnostic criteria for vascular cognitive impairment and related TCM syndromes, with a disease course of more than 3 months; ② Age of patients with vascular cognitive impairment ≤ 45 years ≤ 85 years, gender not limited; ③ Education level of 6 years or more (including 6 years); ④ Hachinski Ischemic Index (HIS) total score ≥ 7; ⑤ TCM syndrome of kidney deficiency and phlegm stasis, with a syndrome score ≥ 7; ⑥ Patients with mild to moderate disease, Mini-Mental State Examination (MMSE) score 10 ≤ MMSE ≤ 26, Clinical Dementia Rating Scale (CDR) score 1 ≤ CDR ≤ 2; ⑦ Participants voluntarily participate in the clinical trial, and the participants and their representatives sign informed consent forms before the trial.

[0037] Exclusion criteria: ① Brain diseases other than vascular cognitive impairment, such as Parkinson's disease, central nervous system demyelinating diseases, tumors, hydrocephalus, trauma, central nervous system infections such as syphilis, AIDS, Creutzfeldt-Jakob disease, etc.; ② Severe neurological deficits preventing completion of the examination, such as visual and auditory impairments; ③ Severe circulatory, respiratory, urinary, and hematopoietic system diseases, such as uncontrolled asthma; ④ Severe mental illnesses, such as schizophrenia and epilepsy; ⑤ Alcohol and drug abuse; ⑥ Allergy to any of the drug components used in the study; ⑦ Use of drugs affecting cognitive function within one month prior to the start of this study, such as cholinesterase inhibitors, memantine, cholinergic drugs, antipsychotics, anxiety-inducing drugs, hypnotics, and cognitive-enhancing drugs (including traditional Chinese medicines and pills, such as Cistanche deserticola capsules and Jiannaoan); ⑧ Use of kidney-tonifying and phlegm-resolving decoctions or granules within two weeks prior to enrollment; ⑨ Allergy to the granules of the herbal composition of this invention; ⑩ Severe bleeding tendency and liver dysfunction (transaminase levels exceeding three times the upper limit of normal). Pregnant and breastfeeding women; Those who participated in other interventional clinical studies within 3 months prior to enrollment; Those who cannot undergo MRI cranial imaging; Those who are unwilling to accept research measures or are unable to cooperate for other reasons; Patients with other diseases that affect limb function, such as rheumatoid arthritis, gouty arthritis, etc., which cause limb function impairment; Complications that affect drug evaluation include post-vascular dementia depression and anxiety-induced epilepsy. There are cases where researchers believe the trial will cause significant harm to patients, or where researchers believe the patient is unsuitable to participate in this clinical trial.

[0038] 2. Drug intervention

[0039] Treatment group: Take the granules prepared in Example 1, 12g / bag (equivalent to 55g of raw medicinal material), 3 bags at a time, 3 times a day, taken with warm water, for 3 months.

[0040] Control group: No additional medication was given, and patients were required not to take other traditional Chinese medicines or health products with similar effects on their own.

[0041] Patients in both groups with underlying medical conditions (such as hypertension, lipoproteinemia, and diabetes) can take targeted medications under the guidance of a doctor. During treatment, both groups were instructed to follow a low-sodium, low-fat diet, engage in moderate exercise, and abstain from smoking and alcohol.

[0042] 3. Clinical trial results

[0043] The clinical study of this invention included 60 subjects, who were randomly divided into an experimental group and a control group, with 30 cases in each group. After 3 months of treatment, a total of 56 subjects completed the trial, including 28 cases in the experimental group (2 dropouts) and 28 cases in the control group (2 dropouts).

[0044] 3.1 General Information of Subjects

[0045] Table 1 shows the gender, age, disease duration, disease severity, education level, and comorbidities of the two groups of subjects before enrollment. There were no significant differences between the experimental and control groups (P > 0.05), indicating that the subjects had consistent baseline characteristics at enrollment and were comparable.

[0046] Table 1 General information of subjects in the clinical study of this invention

[0047]

[0048] 3.2 Main therapeutic indicators

[0049] After treatment, the efficacy of the two groups of patients was assessed. The TCM syndrome score of the experimental group decreased compared with that before treatment, and the difference was statistically significant (P<0.01). Compared with the control group, the TCM syndrome score of the experimental patients decreased after treatment, and the difference was statistically significant (P<0.05), indicating that the experimental group can effectively reduce the TCM syndrome score of VD patients. The results are shown in Table 2.

[0050] Table 2. Main efficacy indicators in clinical studies of this invention

[0051]

[0052] After treatment, the efficacy of the two groups of patients was evaluated. In the control group, the clinical efficacy was: 0 cases with significant effect, 2 cases with effect, and 28 cases with no effect, with a total effective rate of 6.67%. In the experimental group, the clinical efficacy was: 3 cases with significant effect, 22 cases with effect, and 5 cases with no effect, with a total effective rate of 83.33%. Compared with the control group, the clinical efficacy of the experimental group was significantly improved, and the difference between the two groups was statistically significant (P<0.05), indicating that the herbal composition granules of this invention can significantly improve the TCM symptoms of patients. The results are shown in Table 3.

[0053] Table 3 Clinical efficacy of the present invention

[0054]

[0055] 3.3 Secondary efficacy indicators

[0056] The results of the secondary efficacy indicators in the clinical study of this invention are shown in Table 4. After treatment, the MMSE scores of patients in the experimental group improved compared to before treatment, with a statistically significant difference (P<0.01); indicating that the traditional Chinese medicine composition of this invention can effectively improve the MMSE scores of patients with vascular cognitive impairment and improve their cognitive function. After treatment, the ADL scores of patients in the experimental group increased compared to before treatment, with a statistically significant difference (P<0.01); indicating that the traditional Chinese medicine composition of this invention can effectively improve ADL scores, and the daily living abilities of patients in the experimental group improved compared to before treatment.

[0057] Table 4 Secondary efficacy indicators in clinical studies of this invention

[0058]

[0059]

[0060] 4) Safety indicators

[0061] A total of 4 cases dropped out during the entire trial, 2 in the experimental group and 2 in the control group. One case in the experimental group dropped out due to failure to take the medication as prescribed, and the other was lost to follow-up; both cases in the control group were lost to follow-up.

[0062] All patients in this study underwent routine blood and urine tests, liver and kidney function tests, and electrocardiograms before and after treatment. Results showed no abnormalities in these indicators in either group. Among the patients who completed the trial, two patients in the control group experienced dizziness and headache, respectively; both symptoms resolved spontaneously without specific treatment. One patient in the experimental group experienced gastrointestinal reactions (nausea and stomach discomfort) after taking the medication; after being instructed to wait at least half an hour after eating before taking the medication, the symptoms resolved spontaneously without specific treatment. The incidence of adverse reactions was 6.7% in the control group and 3.3% in the experimental group; the difference between the two groups was not statistically significant (P>0.05).

[0063] Example 2: Clinical trial of the traditional Chinese medicine composition of the present invention for the treatment of vascular cognitive impairment.

[0064] This study was a second clinical trial, with inclusion and exclusion criteria, observation indicators, and treatment methods consistent with the first clinical trial. Seventy-eight patients with vitamin D deficiency (VD) who visited the outpatient clinics of the Affiliated Hospital and the Second Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine between August 2022 and August 2023 were included. They were randomly assigned to a control group and an experimental group, with 39 patients in each group. After three months of treatment, 75 subjects completed the trial: 38 in the experimental group (1 dropout) and 37 in the control group (2 dropouts).

[0065] 1. General information of the subjects

[0066] Table 5 shows the gender, age, disease duration, disease severity, education level, and comorbidities of the two groups of subjects before enrollment. There were no significant differences between the experimental and control groups (P>0.05), indicating that the subjects had consistent baseline characteristics at enrollment and were comparable.

[0067] Table 5 General information of subjects in the clinical study of this invention

[0068]

[0069] 2. Main therapeutic indicators

[0070] After treatment, the efficacy of the two groups of patients was assessed. The TCM syndrome score of the experimental group decreased compared with that before treatment, and the difference was statistically significant (P<0.01). Compared with the control group, the TCM syndrome score of the experimental patients decreased after treatment, and the difference was statistically significant (P<0.05), indicating that the experimental group can effectively reduce the TCM syndrome score of VD patients. The results are shown in Table 6.

[0071] Table 6. Main efficacy indicators in clinical studies of this invention

[0072]

[0073] After treatment, the efficacy of the two groups of patients was evaluated. In the control group, the clinical efficacy was: 0 cases with significant effect, 6 cases with effect, and 31 cases with no effect, with a total effective rate of 16%. In the experimental group, the clinical efficacy was: 0 cases with significant effect, 22 cases with effect, and 16 cases with no effect, with a total effective rate of 58%. Compared with the control group, the clinical efficacy of the experimental group was significantly improved, and the difference between the two groups was statistically significant (P<0.05), indicating that the herbal composition granules of this invention can significantly improve the TCM symptoms of patients. The results are shown in Table 7.

[0074] Table 7 Clinical efficacy of the present invention

[0075]

[0076] 3. Secondary therapeutic indicators

[0077] The results of the secondary efficacy indicators in the clinical study of this invention are shown in Table 8. After treatment, the MMSE scores of patients in the experimental group improved compared to before treatment, with a statistically significant difference (P<0.01); indicating that the traditional Chinese medicine composition of this invention can effectively improve the MMSE scores of patients with vascular cognitive impairment and improve their cognitive function. After treatment, the ADL scores of patients in the experimental group increased compared to before treatment, with a statistically significant difference (P<0.01); indicating that the traditional Chinese medicine composition of this invention can effectively improve ADL scores, and the daily living abilities of patients in the experimental group improved compared to before treatment.

[0078] Table 8 Secondary efficacy indicators in clinical studies of this invention

[0079]

[0080] 4. Safety indicators

[0081] A total of 4 cases dropped out during the entire trial, 2 in the experimental group and 2 in the control group. One case in the experimental group dropped out due to failure to take the medication as prescribed, and the other was lost to follow-up; both cases in the control group were lost to follow-up.

[0082] All patients in this invention underwent routine blood and urine tests, liver and kidney function tests, and electrocardiograms before and after treatment. Results showed no abnormalities in these indicators in either group. Among the patients completing the trial, two patients in the control group experienced dizziness and headache, respectively; both symptoms resolved spontaneously without specific treatment. Three patients in the experimental group experienced gastrointestinal reactions (nausea and stomach discomfort) after taking the medication; they were instructed to wait at least half an hour after eating before taking the medication, and their symptoms disappeared spontaneously without special treatment. The incidence of adverse reactions was 5% in the control group and 7% in the experimental group; the difference between the two groups was not statistically significant (P>0.05).

[0083] Experimental Example 3: Animal Experiments of the Traditional Chinese Medicine Composition of the Present Invention

[0084] 1. Animal model construction

[0085] The pathogenesis of vascular cognitive impairment (VD) is closely related to chronic cerebral hypoperfusion and localized hippocampal ischemia. Currently, the bilateral common carotid artery permanent ligation method is the most widely used experimental model for VD. This model highly matches the pathogenesis characteristics of human VD; after bilateral common carotid artery ligation, rats experience reduced cerebral blood flow, leading to learning and memory impairments. This model not only has a low mortality rate and is easy to operate, but also results in rapid postoperative recovery. Sixty male SD rats were acclimatized for 7 days before the VD animal model was established using the bilateral common carotid artery ligation method. The rats were fasted for 12 hours prior to surgery but allowed free access to water. The weight of each rat was measured electronically to control the anesthetic dosage, and intraperitoneal anesthesia was administered. A sterile environment was maintained during the surgery. After successful anesthesia, the anesthetized rats were placed supine and fixed on the operating table, with rubber bands securing their limbs and teeth to prevent escape. The surgical area was prepared to expose the pink skin, and the neck skin was gently wiped with an alcohol swab for disinfection. A longitudinal incision of about 1 cm was made along the midline of the neck, and the subcutaneous tissue and muscle groups of the neck were bluntly dissected until the common carotid artery on one side was fully exposed. The white nerve and blood vessel on the common carotid artery were carefully separated. Surgical ligation was performed on both the proximal and distal ends of one common carotid artery using surgical sutures. After both ligations were completed, the middle part was cut. There was no blood leakage. The other common carotid artery was treated in the same way. After both sides were ligated, they were immediately sutured layer by layer. The suture sites were disinfected with iodine swabs and penicillin powder was applied to prevent infection. The animals were then returned to their cages and kept warm. In the sham surgery group, only the bilateral common carotid arteries and nerves were separated without ligation. Disinfection was carried out in the same way as before, and then the skin was sutured.

[0086] 2. Group administration

[0087] Ten days after modeling, most rats were in good condition, while 10 rats died due to modeling injuries. The remaining model rats were randomly divided into 5 groups: the model group, the low-dose group of the traditional Chinese medicine composition of this invention (hereinafter referred to as JWDHYZ), the medium-dose group of the traditional Chinese medicine composition of this invention, the high-dose group of the traditional Chinese medicine composition of this invention, and the positive control group (donepezil hydrochloride), with 8 rats in each group. The low-dose group of the traditional Chinese medicine composition of this invention was administered at a dose of 10.5 g / kg. -1 For administration, the dosage group of the traditional Chinese medicine composition of the present invention is 21 g·kg. -1 The high-dose group of the traditional Chinese medicine composition of this invention was administered at 42 g / kg. -1 The donepezil hydrochloride group was administered at a dose of 0.55 mg / kg. -1 The sham-operated group and the model group were given the same volume of distilled water. The medication was administered once daily for 28 consecutive days at the same time each day.

[0088] 3. Treatment efficacy

[0089] As shown in Table 9, with the 5-day Morris water maze navigation experiment training, the escape latency of rats in all groups decreased with the increase of training days. Compared with the sham-operated group, the escape latency of the model group was prolonged from day 1 to day 5, with significant differences (p<0.01). After drug treatment, the escape latency of rats in the low, medium, and high dose groups of the herbal composition of this invention and the positive drug group was significantly shortened. However, the inter-group comparison showed that the low dose group on day 1 and day 2 showed a significant reduction in escape latency compared with the model group (p<0.01); the medium dose group and the positive drug group on day 1 and day 2 showed a significant reduction in escape latency compared with the model group (p<0.01); after day 5 of training, the escape latency of rats in each drug treatment group was significantly higher than that of the model group (p<0.01). Figure 1 The movement trajectories of rats during the escape latency test are shown in the diagrams.

[0090] Table 9 Comparison of escape latency during 5 days of water maze training in different groups of rats

[0091]

[0092] Compared with the sham surgery group, # p < 0.05 ## p < 0.01; compared with the model group, * p < 0.05 ** p < 0.01

[0093] Statistical analysis was performed on the spatial exploration test results of each group of rats. Compared with the sham-operated group, the model group showed a significant difference in the number of times rats crossed the platform (p<0.01). After drug intervention, the number of times rats crossed the platform in each group increased significantly (p<0.05); among them, the medium-dose group showed a significant increase (p<0.01), as shown in Table 10. Figure 2 As shown.

[0094] Table 10 Comparison of the number of times rats crossed the platform in each group at different time periods.

[0095]

[0096] Compared with the sham surgery group, # p<0.05, ## p < 0.01; compared with the model group, * p<0.05, ** p<0.01

[0097] After HE staining, the results showed that the CA1 region of the hippocampus in the sham-operated group was neatly and uniformly arranged and tightly packed. The number of cells was high and the nucleoli were clearly visible. Compared with the sham-operated group, the model group showed pathological damage, with disordered and sparse structural arrangement, increased intercellular spaces, reduced cell number, and unclear nucleoli morphology, which were condensed into irregular shapes. Compared with the model group, the pathological morphology of the CA1 region of the hippocampus in all groups of rats treated with the herbal composition of this invention and donepezil hydrochloride was improved, with a more neat structural arrangement, reduced sparse areas, and cell nucleus morphology tending towards normal, especially in the medium-dose treatment group. The results are as follows... Figure 3 As shown.

[0098] The immunohistochemical results of CD31 are as follows: Figure 4 As shown, newly formed blood vessels in cerebral cortex cells are marked in brown. Compared with the sham-operated group, the CD31 positivity rate in the model group was significantly increased. Compared with the model group, the CD31 positivity rate in the medium- and high-dose groups and the positive control group of the herbal composition of this invention was significantly increased. These results preliminarily indicate that the herbal composition granules of this invention have a certain promoting effect on cerebral angiogenesis in rats.

[0099] The results of serum SOD, MDA, Hcy, VEGF, and bFGF levels in each group of rats are as follows: Figure 5 As shown in the figure. Compared with the sham-operated group, the model group showed a significant decrease in SOD (p<0.01) and a significant increase in MDA, Hcy, VEGF, and bFGF levels (p<0.01). Compared with the model group, the low-, medium-, and high-dose groups and the positive control group significantly increased the levels of SOD, VEGF, and bFGF in rats (p<0.01), while significantly decreasing the levels of MDA and Hcy (p<0.01). Among them, the medium-dose group showed the most significant therapeutic effect on VD (p<0.01).

[0100] Experimental Example 4: Pharmacological Test of the Traditional Chinese Medicine Composition of the Present Invention

[0101] Comparative Example 1: Preparation of granules of the principal herb component in a traditional Chinese medicine composition

[0102] Prepared Rehmannia glutinosa 30g, Polygonatum sibiricum 15g, Polygonum multiflorum 6g, Epimedium brevicornu 15g; decoct the medicinal materials, filter, concentrate, starch, granulate, and shape to prepare granules.

[0103] Comparative Example 2: Preparation of granules containing the principal herb and assistant herb in a traditional Chinese medicine composition.

[0104] Prepared Rehmannia Root 30g, Polygonatum Rhizome 15g, Prepared Polygonum Multiflorum Root 6g, Epimedium Root 15g, Dendrobium Root 25g, Ophiopogon Root 10g, Cinnamon Bark 10g, Prepared Aconite Root 6g.

[0105] (1) Animal model construction

[0106] The model construction method is the same as that in Experiment 3.

[0107] (2) Experimental grouping and drug administration

[0108] Ten days post-surgery, 35 rats with successful endothelial cell line formation were randomly divided into four groups: a model group (M group), a group receiving the complete traditional Chinese medicine formula (Q group), a group receiving the principal drug (J group), a group receiving both principal and assistant drugs (JC group), and a positive control group (donepezil hydrochloride, Y group), with seven rats in each group. Except for the model and positive control groups, all other groups received the medication at a dose of 21.2 g / kg / day, while the positive control group received the medication at a dose of 0.45 g / kg / day. The sham-operated group (C group, seven rats) and the model group received the same amount of distilled liquid via gavage. Gavage was administered once daily for 30 consecutive days at the same time each day.

[0109] (3) Treatment effect

[0110] After 5 days of water maze training, the escape latency of rats in all groups gradually decreased (P < 0.05). Compared with the sham-operated group, the escape latency of the model group was significantly prolonged from day 1 to day 5 (P < 0.01); after drug treatment, the escape latency of rats in all drug treatment groups and the positive drug group was significantly shortened. However, the inter-group comparison showed that the total formula group had a significantly lower escape latency, indicating that the total formula group was more effective than the principal drug group and the principal drug + assistant drug group (see Table 11). Figure 6 ).

[0111] Table 11 Comparison of escape latency in rats of different groups

[0112]

[0113] Note: Compared to the model group # P < 0.05 ## P < 0.05, compared with the full-strength group, * P < 0.05

[0114] ** P < 0.05

[0115] Statistical analysis was performed on the results of spatial exploration tests of rats in each group. Compared with the sham-operated group, the number of times rats in the model group crossed the platform was significantly reduced (P<0.01). After drug intervention, the number of times rats in each group crossed the platform was significantly increased (P<0.05). The total prescription group and the positive drug group showed a significant increase (P<0.01). The total prescription group was more effective than the principal drug group and the principal drug + assistant drug group, as shown in Table 12.

[0116] Table 12 Comparison of the number of times rats crossed the platform in each group at different time periods

[0117]

[0118] Note: Compared to the model group # P < 0.05 ## P < 0.05, compared with the full-strength group,* P < 0.05

[0119] ** P < 0.05

[0120] Animal experiments have demonstrated that the formulation of the traditional Chinese medicine composition of this invention conforms to the dialectical theory of traditional Chinese medicine. The combination of the drug of this invention with a single principal drug group or a principal and assistant drug group, at the same dosage, is significantly superior to the split formulation.

Claims

1. A traditional Chinese medicine composition for treating vascular cognitive impairment, characterized in that: It is prepared from the following raw materials in the indicated weight ratios: Prepared Rehmannia Root 24-36 parts, Polygonatum Rhizome 12-18 parts, Prepared Polygonum Multiflorum Root 4.8-7.2 parts, Ligusticum Rhizome 12-18 parts, Polygala Root 8-12 parts, Epimedium Root 12-18 parts, Dendrobium Root 20-30 parts, Poria Cocos 12-18 parts, Fritillaria Bulb 12-18 parts, Acorus Root 12-18 parts, Ophiopogon Root 8-12 parts, Curcuma Root 16-24 parts, Cinnamon Bark 8-12 parts, Prepared Aconite Root 4.8-7.2 parts, Borneol 0.24-0.36 parts.

2. The traditional Chinese medicine composition for treating vascular cognitive impairment according to claim 1, characterized in that: It is prepared from the following raw materials in the indicated weight ratios: Prepared Rehmannia Root 30 parts, Polygonatum Rhizome 15 parts, Prepared Polygonum Multiflorum Root 6 parts, Ligusticum Rhizome 15 parts, Polygala Root 10 parts, Epimedium Rhizome 15 parts, Dendrobium Root 25 parts, Poria Cocos 15 parts, Fritillaria Bulb 15 parts, Acorus Root 15 parts, Ophiopogon Root 10 parts, Curcuma Rhizome 20 parts, Cinnamon Bark 10 parts, Prepared Aconite Root 6 parts, Borneol 0.3 parts.

3. The traditional Chinese medicine composition for treating vascular cognitive impairment according to claim 1 or 2, characterized in that: It is a pharmaceutically commonly used formulation prepared by adding pharmaceutically acceptable excipients or auxiliary ingredients to the active ingredient, which is the original drug powder, water or organic solvent extract of the active pharmaceutical ingredient.

4. The traditional Chinese medicine composition for treating vascular cognitive impairment according to claim 3, characterized in that: The preparations mentioned are tablets, capsules, granules, pills, and oral liquids.

5. A method for preparing the traditional Chinese medicine composition for treating vascular cognitive impairment according to any one of claims 1-4, comprising the following steps: a. Weigh the raw materials according to the specified weight ratio; b. First, boil the black aconite slices in water, then add the raw materials other than borneol, boil in water, filter, concentrate, add borneol to the concentrate, and then add pharmaceutically acceptable excipients or auxiliary ingredients to prepare a commonly used pharmaceutical preparation.

6. Use of the traditional Chinese medicine composition according to any one of claims 1-4 in the preparation of a medicament for treating vascular cognitive impairment.

7. Use of the traditional Chinese medicine composition according to any one of claims 1-4 in the preparation of a medicament for treating vascular dementia.

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