A traditional Chinese medicine composition for improving cognitive impairment combined with insomnia and application thereof

Abstract

This invention relates to a traditional Chinese medicine composition for improving cognitive impairment combined with insomnia and its application, which can effectively solve the medication problem of cognitive impairment combined with insomnia. The technical solution is that the traditional Chinese medicine is made from the following raw materials by weight: 16-24 parts tortoise shell, 24-36 parts dragon bone, 8-12 parts polygala tenuifolia, 8-12 parts acorus tatarinowii, 12-18 parts stir-fried jujube seed, 12-18 parts poria cocos, 8-12 parts ginseng, 10-14 parts ophiopogon japonicus, 5-7 parts schisandra chinensis, 12-18 parts prepared rehmannia glutinosa, 12-18 parts cornus officinalis, 12-18 parts lycium barbarum, 24-36 parts raw yam, 12-18 parts prepared he shou wu, and 10-14 parts tangerine peel. The formulation of this invention is scientific, the combination is reasonable, the raw materials are readily available, and the whole formula has the effects of tonifying the kidney and marrow, nourishing yin and blood, and calming the mind and soothing the nerves. It is an innovation in medication for improving cognitive impairment combined with insomnia.

Description

Technical Field

[0001] This invention relates to the field of medicine, and in particular to a traditional Chinese medicine composition for improving cognitive impairment combined with insomnia and its application. Background Technology

[0002] With the arrival of an aging society, the prevalence of cognitive impairment in the elderly is rising year by year, making its prevention and treatment a focal point of social concern. Clinically, in addition to cognitive decline, patients often experience a variety of non-cognitive psychobehavioral symptoms, among which insomnia is the most common comorbidity. Insomnia not only exacerbates the condition of patients with cognitive impairment and the burden on caregivers, but long-term chronic insomnia is also a significant cause of cognitive decline. Cognitive impairment and insomnia influence each other, exhibiting a comorbid mechanism.

[0003] The incidence of sleep disorders is significantly higher in patients with cognitive impairment than in those without. A study comparing patients with and without Alzheimer's disease found that patients with Alzheimer's had significantly higher rates of difficulty falling asleep, fragmented sleep, nocturnal restlessness, sleep-wake rhythm disturbances, and obstructive sleep apnea syndrome. Furthermore, different types of cognitive impairment are accompanied by different types of sleep disorders. For example, patients with mild cognitive impairment mainly experience long sleep latency, short total sleep time, and low sleep efficiency; Alzheimer's disease patients mainly experience circadian rhythm disturbances and altered sleep structure; Lewy body dementia patients mainly experience REM sleep behavior disorder and excessive daytime sleepiness; vascular dementia most commonly presents with sleep-disordered breathing; and frontotemporal dementia patients often exhibit insomnia, fragmented sleep, and excessive daytime sleepiness.

[0004] Sleep, as the most important periodic physiological activity of the human body, is an essential physiological process for maintaining bodily health and the normal function of the central nervous system. Sleep promotes metabolism, growth, and memory, protects the central nervous system, restores physical strength, and enhances immune function. Persistent insomnia can have many adverse effects. [5-7] Insomnia not only affects an individual's normal life and work, but it is also a contributing factor to, aggravating, and persisting in various cardiovascular and cerebrovascular diseases, mental illnesses such as anxiety and depression, endocrine disorders, and even tumors. Long-term chronic insomnia can cause brain dysfunction, leading to reduced work efficiency, decreased attention, and memory loss. A meta-analysis published in the journal *Sleep Medicine* in 2017 included 27 studies analyzing 69,216 individuals with and without sleep disorders. The results showed that individuals with sleep problems had a 1.68 times higher risk of developing cognitive impairment and / or Alzheimer's disease than those without sleep disorders, and approximately 15% of Alzheimer's disease cases in the population may be attributable to sleep problems, confirming the significant impact of insomnia on cognitive function.

[0005] Currently, Western medicine lacks effective drugs for treating the comorbidities of this disease. The pathogenesis of cognitive impairment in Western medicine is highly complex, and effective treatments are still lacking. Commonly used drugs include cholinesterase inhibitors, glutamate receptor antagonists, and drugs that improve brain metabolism. These drugs are symptomatic treatments, primarily improving cognitive and memory impairments, but they cannot stop or slow the progression of cognitive impairment, and all have varying degrees of side effects. Western medicine primarily treats insomnia with sedatives, anti-anxiety and antidepressant drugs, and melatonin receptor agonists, but long-term use can lead to adverse reactions such as daytime dysfunction, drug intolerance, drug dependence, and addiction.

[0006] Traditional Chinese medicine (TCM) believes that cognitive impairment originates in the brain, while insomnia originates in the heart, but both are closely related to the heart and kidneys. Human intellectual activity depends on the coordinated function of the heart and kidneys; only through their interaction and the balance of water and fire can normal thinking and emotional activity be maintained. Chen Shiduo stated, "Kidney water nourishes the heart, thus wisdom is continuously generated; heart fire nourishes the kidneys, thus wisdom is also infinitely generated." The pathogenesis of insomnia is generally attributed to an excess of Yang and a deficiency of Yin, a disharmony between Yin and Yang, primarily due to the disharmony between the heart and kidneys. Therefore, the common pathogenesis of cognitive impairment and insomnia is deficiency of the heart and kidneys, leading to disharmony between them. Firstly, kidney essence deficiency leads to malnourishment of the brain marrow, resulting in symptoms such as dullness, forgetfulness, and mental impairment. Kidney Yin deficiency cannot restrain heart Yang, leading to excessive heart fire, disturbing the mind, and causing insomnia. Simultaneously, the generation of kidney essence also depends on the warming effect of heart Yang. Secondly, the brain is the residence of the primordial spirit; the kidneys store essence and generate marrow to nourish the brain, while the heart governs blood and stores the spirit. Essence transforms into Qi and generates spirit, serving as the source of Qi and spirit; spirit governs essence and directs Qi, serving as the master of essence and Qi. Qi and blood originate from the essence and Qi in the kidneys. Kidney deficiency leads to insufficient sources of Qi and blood production, resulting in insufficient heart blood and causing the heart spirit to be malnourished, making it difficult to fall asleep. There is a close connection between the heart and kidneys, where spirit and essence mutually interact and transform into each other. Therefore, when heart and kidney function is imbalanced, clinical manifestations may include forgetfulness, lethargy, mental confusion, difficulty falling asleep, frequent awakenings after falling asleep, difficulty falling back asleep, early awakenings, intermittent sleep, vivid dreams, dizziness, palpitations, fatigue, tinnitus, lower back and knee weakness, a pale red tongue, and a deep, thready pulse.

[0007] Currently, there are relevant studies and prescriptions in Traditional Chinese Medicine (TCM) for treating cognitive impairment and insomnia, but research on their comorbid mechanisms and effective prescriptions that can achieve the goal of treating different diseases with the same method are lacking. Therefore, it is imperative to develop therapeutic drugs targeting the comorbid mechanisms of cognitive impairment combined with insomnia. Summary of the Invention

[0008] In view of the above situation and to overcome the shortcomings of the prior art, the purpose of this invention is to provide a traditional Chinese medicine composition and its application that can improve cognitive impairment combined with insomnia, and can effectively solve the medication problem of cognitive impairment combined with insomnia.

[0009] Traditional Chinese medicine (TCM) treatment of cognitive impairment combined with insomnia focuses on regulating the heart and kidneys, with the principle of tonifying the kidneys and marrow, nourishing the heart and calming the mind. TCM possesses the advantage of a holistic approach to diagnosis and treatment, and its compound herbal formulas exhibit the therapeutic characteristics of synergistic effects from multiple components, pathways, and targets, enabling the treatment of different diseases with the same method, demonstrating significant advantages. Therefore, the technical solution provided by this invention is that the herbal formula is made from the following raw materials by weight: 16-24 parts tortoise shell, 24-36 parts dragon bone, 8-12 parts polygala tenuifolia, 8-12 parts acorus tatarinowii, 12-18 parts stir-fried jujube seed, 12-18 parts poria cocos, 8-12 parts ginseng, 10-14 parts ophiopogon japonicus, 5-7 parts schisandra chinensis, 12-18 parts prepared rehmannia glutinosa, 12-18 parts cornus officinalis, 12-18 parts wolfberry, 24-36 parts raw yam, 12-18 parts prepared he shou wu, and 10-14 parts tangerine peel.

[0010] Because this disease is more common in middle-aged and elderly people, the *Neijing* states, "At forty, yin qi is halved," therefore the pathogenesis of this disease is insufficient yin and blood in the heart and kidneys. In middle-aged and elderly people, kidney yin deficiency is the root cause. This may be due to kidney essence deficiency, resulting in malnourishment of the brain marrow, excessive heart fire, and disharmony between the heart and kidneys, leading to yang failing to enter yin and insomnia; or it may be due to the mutual transformation of heart and kidney essence and blood, with kidney essence deficiency affecting blood production, resulting in insufficient heart blood, malnourishment of the heart spirit, and restlessness of the spirit, leading to insomnia. Therefore, the formula uses tortoise shell, prepared rehmannia root, ginseng, and dragon bone as the chief ingredients. Among them, tortoise shell and dragon bone are the most potent yin and yang substances, using their yin and yang properties to supplement the body's yin and yang, and their spiritual energy to assist the body's spiritual energy. Prepared rehmannia root greatly replenishes yin and blood, benefits essence and fills marrow; ginseng tonifies heart qi, calms the mind and stabilizes the will. The four herbs together enter the heart meridian to calm the mind and the kidney meridian to improve intelligence, guiding yang into yin and promoting the interaction of yin and yang. With Polygala tenuifolia and Acorus tatarinowii as assistant herbs, the combined use of these two herbs can promote the upward flow of kidney qi to the heart, connecting the heart and brain, clearing away phlegm, dampness, and impurities from the heart and brain orifices, thus restoring mental clarity. Fried Ziziphus jujuba seeds, Poria cocos, Ophiopogon japonicus, Schisandra chinensis, Cornus officinalis, Lycium barbarum, raw Dioscorea opposita, processed Polygonum multiflorum, and Citrus reticulata peel are adjuvant herbs. Among them, fried Ziziphus jujuba seeds, Poria cocos, Ophiopogon japonicus, and Schisandra chinensis primarily enter the heart meridian to enhance the effects of invigorating qi and nourishing blood, calming the mind and spirit, and tonifying the heart to invigorate the kidneys; Cornus officinalis, Lycium barbarum, raw Dioscorea opposita, and processed Polygonum multiflorum enter the kidney meridian, possessing the functions of nourishing yin and blood, replenishing essence and marrow, assisting the tortoise shell in nourishing yin and blood, tonifying the kidneys and replenishing marrow, and tonifying the kidneys to invigorate the heart. Citrus reticulata peel, which regulates qi, strengthens the spleen, and resolves phlegm, also serves as an adjuvant herb, making the tonics nourishing without being cloying, and preventing the tonics from hindering the spleen. The formula has the combined effects of nourishing the heart and kidneys, calming the mind and improving intelligence. Clinical application has proven that this traditional Chinese medicine can simultaneously improve patients' cognitive function and insomnia, with good efficacy and no adverse reactions have been found during use.

[0011] The traditional Chinese medicine of this invention can be prepared into various dosage forms such as decoctions, powders (granules), tablets, granules, pills, and capsules according to the actual clinical needs and conventional preparation methods. The decoction prepared by conventional methods is as follows: First, mix tortoise shell, dragon bone, prepared rehmannia root, ginseng, polygala root, acorus tatarinowii rhizome, stir-fried jujube seed, poria cocos, ophiopogon japonicus, schisandra chinensis fruit, cornus officinalis fruit, wolfberry fruit, raw yam, prepared he shou wu, and tangerine peel together, put them in a medicine pot, add water to cover them, soak for 30-60 minutes, bring to a boil over high heat, then simmer over low heat for 20-30 minutes, filter to obtain filtrate, add water to cover the residue again, bring to a boil over high heat, then simmer over low heat for 20-30 minutes, filter to obtain filtrate, combine the two filtrates, mix well and it is ready.

[0012] This invention features a scientifically formulated and rationally combined prescription, with readily available raw materials. The entire formula works to nourish the kidneys and marrow, replenish yin and blood, and calm the mind and soothe the nerves. It is an innovation in medications for improving cognitive impairment combined with insomnia. Deficiency of the heart and kidneys is a comorbid mechanism of cognitive impairment combined with insomnia. This invention adopts the principle of tonifying the heart and kidneys, calming the mind and improving intelligence. The principal herbs are tortoise shell, prepared rehmannia root, ginseng, and dragon bone, which can not only nourish the marrow and improve brain function, but also harmonize yin and yang to help people fall asleep peacefully. Polygala root and acorus tatarinowii are the assistant herbs, which can open the orifices, awaken the mind, and harmonize the heart and kidneys to assist the principal herbs. The adjuvant herbs are stir-fried jujube seed, poria cocos, ophiopogon japonicus, schisandra chinensis, cornus officinalis, wolfberry, raw yam, prepared he shou wu, and tangerine peel, which can exert the effects of tonifying the heart and calming the mind, and tonifying the kidneys and nourishing the marrow. The whole formula has the effects of tonifying the kidneys and nourishing the marrow, nourishing yin and blood, and calming the mind. It is effective for patients with cognitive impairment combined with insomnia of the type of deficiency of heart and kidney yin and blood. It can give full play to the therapeutic characteristics of the multi-component, multi-pathway, and multi-target synergistic effect of traditional Chinese medicine, and can achieve the same treatment for different diseases. It has significant advantages, can improve patients' sleep and cognitive function, and has good promotion and application value. Detailed Implementation

[0013] The specific embodiments of the present invention will be further described in detail below with reference to examples.

[0014] Example 1 In specific implementation, this invention can be made from the following raw materials by weight: 17 parts tortoise shell, 25 parts dragon bone, 9 parts polygala root, 9 parts acorus tatarinowii rhizome, 13 parts stir-fried jujube seed, 13 parts poria cocos, 9 parts ginseng, 11 parts ophiopogon japonicus root, 5 parts schisandra chinensis fruit, 13 parts prepared rehmannia root, 13 parts cornus officinalis fruit, 13 parts wolfberry fruit, 25 parts raw yam, 13 parts prepared he shou wu (Polygonum multiflorum root), and 11 parts tangerine peel.

[0015] Example 2 In specific implementation, this invention can also be made from the following raw materials by weight: 20 parts tortoise shell, 30 parts dragon bone, 10 parts polygala root, 10 parts acorus tatarinowii rhizome, 15 parts stir-fried jujube seed, 15 parts poria cocos, 10 parts ginseng, 12 parts ophiopogon japonicus root, 6 parts schisandra chinensis fruit, 15 parts prepared rehmannia root, 15 parts cornus officinalis fruit, 15 parts wolfberry fruit, 30 parts raw yam, 15 parts prepared he shou wu (Polygonum multiflorum root), and 12 parts tangerine peel.

[0016] Example 3 In specific implementation, this invention can be made from the following raw materials by weight: 23 parts tortoise shell, 35 parts dragon bone, 11 parts polygala root, 11 parts acorus tatarinowii rhizome, 17 parts stir-fried jujube seed, 17 parts poria cocos, 11 parts ginseng, 13 parts ophiopogon japonicus root, 7 parts schisandra chinensis fruit, 17 parts prepared rehmannia root, 17 parts cornus officinalis fruit, 17 parts wolfberry fruit, 35 parts raw yam, 17 parts prepared he shou wu (Polygonum multiflorum root), and 13 parts tangerine peel.

[0017] The relevant experimental data are as follows: 1. Case selection criteria (1) Meets the diagnostic criteria for cognitive impairment: Refer to the relevant diagnostic criteria in the 2018 edition of the Chinese Guidelines for the Diagnosis and Treatment of Dementia and Cognitive Impairment, and screen for objective evidence of impairment in one or more cognitive domains through cognitive assessment scales. The Montreal Cognitive Assessment (MoCA) score is ≤26 points and the Mini-Mental State Examination (MMSE) score is ≤24 points.

[0018] (2) Meets the diagnostic criteria for insomnia disorder: Refer to the diagnostic criteria for “insomnia” in the Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM-5) published by the American Psychiatric Association in 2013 and the International Classification of Sleep Disorders, Third Edition (ICSD-3) published by the American Academy of Sleep Medicine in 2014. (1) Chief complaint (meeting at least one of the following): a. Difficulty falling asleep; b. Difficulty maintaining sleep; c. Early awakening; (2) Daytime dysfunction (meeting at least one of the following): a. Feeling tired; b. Difficulty concentrating; c. Decreased communication or work skills; d. Easily experiencing mood swings; e. Easily feeling sleepy during the day; f. Lack of motor vitality; g. Easily stressed and experiencing headaches; h. Easily making mistakes or causing accidents; i. Experiencing anxiety about sleep; (3) The frequency of sleep disturbances and daytime dysfunction is ≥3 times / week; (4) Exclude those whose chief complaint is insomnia due to unsatisfactory sleep conditions (environment and schedule).

[0019] (3) Meets the diagnostic criteria for cognitive impairment combined with insomnia due to deficiency of heart and kidney yin and blood in traditional Chinese medicine: formulated with reference to the "Guidelines for Diagnosis and Treatment of Common Diseases in Internal Medicine of Traditional Chinese Medicine" published by the China Association of Traditional Chinese Medicine, the 2017 edition of the "Guidelines for Diagnosis and Treatment of Dementia in China", and the "Standards for Diagnosis and Efficacy of Diseases in Traditional Chinese Medicine" published by the State Administration of Traditional Chinese Medicine in 2017. Main symptoms: forgetfulness, dullness, mental confusion, difficulty falling asleep, or waking up easily after falling asleep and having difficulty falling asleep again after waking up, or waking up early, or having intermittent sleep; Secondary symptoms: dreaminess, dizziness, palpitations, fatigue, tinnitus, soreness and weakness of the waist and knees, pale red tongue, and deep and thready pulse.

[0020] Cases that simultaneously meet the Western medical diagnostic criteria for cognitive impairment and insomnia, and also meet the syndrome diagnostic criteria for heart and kidney deficiency, are selected as cases.

[0021] Inclusion criteria (1) Meets the relevant diagnostic criteria for both cognitive impairment and insomnia; (2) The TCM diagnosis is consistent with the syndrome of deficiency of heart and kidney; (3) Age between 50 and 80 years old, gender not limited; (4) When selected, 7 points ≤ PSQI ≤ 15 points; (5) Those who have not taken any Western medicine, Chinese patent medicine or decoction for treating insomnia in the past week; (6) Voluntarily cooperate with clinical trials and sign informed consent forms.

[0022] Only those who meet all of the above conditions can be selected.

[0023] Exclusion criteria (1) Patients who must regularly take sleep aids or health supplements; (2) Other medical history that affects sleep: hypersomnia, circadian rhythm sleep disorder, sleepwalking, sleep-related breathing disorder, obstructive or central sleep apnea syndrome, restless legs syndrome, etc.; (3) Having a serious mental illness or emotional disorder (such as anxiety, depression, suicidal tendencies or history of suicide) within the past year, or having long-term use of central nervous system depressants or stimulants; (4) At the time of enrollment screening, the Hamilton Anxiety Rating Scale score is ≥ 14 points, or the Hamilton Depression Rating Scale score is ≥ 17 points; (5) Other causes of insomnia in the past month, such as pain, fever, cough, surgery, external environmental disturbances or stressful life events; (6) Patients with serious diseases of the cardiovascular, cerebrovascular, lung, liver, kidney and hematopoietic systems, or tumors; (7) Individuals allergic to any known component of the medication used; (8) Patients who are pregnant or breastfeeding; (9) Individuals who are alcoholics, drug abusers, or dependent on psychotropic drugs; (10) Has participated in other drug clinical trials within the past month; If any one of the above criteria is met, the application will be excluded.

[0024] Treatment plan Control group: Cognitive impairment and insomnia were treated in accordance with the 2018 edition of the "Guidelines for the Diagnosis and Treatment of Dementia and Cognitive Impairment in China" and the "Guidelines for the Diagnosis and Treatment of Insomnia in Adults in China".

[0025] Treatment group: In addition to the treatment plan of the control group, the patients took the traditional Chinese medicine decoction prepared in Example 2 of this invention, 200-250ml twice a day, once in the morning and once in the evening, for 12 weeks as one course of treatment. The efficacy was evaluated after one course of treatment.

[0026] Observation indicators (1) Pittsburgh Sleep Quality Index (PSQI) score: used to assess sleep quality. This rating scale has 7 factors: sleep quality, sleep onset time, sleep duration, sleep efficiency, sleep disorders, hypnotics, and daytime functioning. Each scoring item is scored from 3 levels: "good", "poor", and "very poor". The scores of the 7 factors are added together to obtain the total PSQI score. The lowest score is 0 and the highest score is 21. The higher the score, the worse the sleep quality. 0-5 is considered normal, 6-10 is mild, 11-15 is moderate, and 16-21 is severe. The higher the score, the more severe the sleep disorder.

[0027] (2) Montreal Cognitive Assessment (MoCA) score: used to assess cognitive impairment, including 11 items in 8 cognitive domains such as attention and concentration, executive function, memory, language, visual-structural skills, abstract thinking, calculation, and orientation. The total score is 30 points, and a score of ≥26 is normal. A score of 18-26 indicates mild cognitive impairment, a score of 10-17 indicates moderate cognitive impairment, and a score of less than 10 indicates severe cognitive impairment.

[0028] (3) TCM syndrome scoring scale: The TCM syndrome scoring scale was developed with reference to the "Guiding Principles for Clinical Research of New Chinese Medicine". The main symptoms were scored as 0, 2, 4 and 6 points respectively according to their severity, and the secondary symptoms were scored as 0, 1, 2 and 3 points respectively according to their severity. The TCM syndrome scores before and after treatment were compared to determine the changes.

[0029] Statistical processing All experimental data were analyzed using SPSS 22.0 statistical software. Categorical data were analyzed using the nonparametric rank-sum test or chi-square test; continuous data were analyzed using (` x ± s This indicates that a t-test is used for those following a normal distribution, while a non-parametric rank-sum test is used for those following a non-normal distribution. P <0.05 indicates a statistically significant difference.

[0030] result 7.1 Baseline Data Comparison This invention included 80 outpatients and inpatients who visited the First Affiliated Hospital of Henan University of Traditional Chinese Medicine. Patients meeting the inclusion criteria were randomly divided into a treatment group and a control group using a random number table, with 40 patients in each group. The treatment group consisted of 22 males and 18 females, with a mean age of (64.3±11.74) years; the control group consisted of 21 males and 19 females, with a mean age of (65.28±9.66) years. There were no statistically significant differences in gender or age between the two groups. P (>0.05), making them comparable.

[0031] Comparison of PSQI scores before and after treatment in the two groups Before treatment, there was no statistically significant difference in PSQI scores between the treatment group and the control group. P >0.05), indicating comparability; after treatment, compared with the control group, the PSQI score in the treatment group decreased significantly, and the difference was statistically significant. P <0.05). See Table 1. This indicates that the traditional Chinese medicine decoction prepared using Example 2 of this invention can significantly improve patients' sleep quality.

[0032] Table 1 Comparison of PSQI scores between the two groups Group Number of examples Treatment time Total Score Treatment group 40 Before treatment <![CDATA[13.98±2.28 ＊ ]]> After treatment <![CDATA[7.63±3.77 # ]]> control group 40 Before treatment 13.76±2.61 After treatment 8.43±3.67 Note: Compared with the control group before treatment. ＊ P >0.05; compared with the control group after treatment, # P <0.05.

[0033] Comparison of MoCA scores before and after treatment in the two groups Before treatment, there was no statistically significant difference in MoCA scale scores between the treatment group and the control group. P >0.05), indicating comparability; after treatment, compared with the control group, the MoCA scale score of the treatment group was significantly improved, and the difference was statistically significant. P <0.05). See Table 2. This suggests that the traditional Chinese medicine decoction prepared using Example 2 of this invention can significantly improve the cognitive function of patients.

[0034] Table 2 Comparison of MoCA scale scores between the two groups Group Number of examples Treatment time Total Score Treatment group 40 Before treatment <![CDATA[21.48±1.81 ＊ ]]> After treatment <![CDATA[24.78±2.28 # ]]> control group 40 Before treatment 21.45±1.92 After treatment 23.13±2.62 Note: Compared with the control group before treatment. ＊ P >0.05; compared with the control group after treatment, # P <0.05.

[0035] Comparison of TCM syndrome scale scores before and after treatment in the two groups Before treatment, there was no statistically significant difference in the TCM syndrome scale scores between the treatment group and the control group. P >0.05), indicating comparability; after treatment, compared with the control group, the TCM syndrome scale score in the treatment group decreased significantly, and the difference was statistically significant. P <0.05). See Table 3. This indicates that the traditional Chinese medicine decoction prepared using Example 2 of this invention can significantly improve the TCM symptoms of heart and kidney deficiency in patients.

[0036] Table 3 Comparison of scores on the two groups of TCM syndrome scales Group Number of examples Treatment time Total Score Treatment group 40 Before treatment <![CDATA[36.67±2.75 ＊ ]]> After treatment <![CDATA[24.35±1.86 # ]]> control group 40 Before treatment 36.23±2.81 After treatment 27.37±2.29 Note: Compared with the control group before treatment. ＊ P >0.05; compared with the control group after treatment, # P <0.05.

[0037] Safety assessment No allergic reactions or adverse reactions were observed in either group of patients during the treatment period; no significant changes were found in routine blood, urine, and stool tests, liver and kidney function tests, and electrocardiograms before and after treatment, indicating that the study protocol had no obvious toxic side effects and was safe and reliable.

[0038] To illustrate the therapeutic effects of this invention in more detail, the following typical cases are provided: Case 1: Ms. Wu, female, 65 years old, from Zhengzhou, Henan Province. Initial consultation date: January 9, 2022. Chief complaint: Memory loss and slow reaction time for more than half a year Present Illness: The patient has experienced memory decline and forgetfulness for the past six months. He often forgets where he puts things at home, repeatedly forgets instructions given to family members, and forgets what he wanted to buy when shopping. He has not yet experienced getting lost or failing to recognize relatives. He used to exercise regularly in the community, but recently he dislikes going out, is reluctant to communicate with others, and feels unable to express himself clearly. He often feels fatigued, weak, and listless. He has not sought medical treatment during this period. His appetite is generally good, but he experiences abdominal bloating after meals, dry mouth with a thirst, but no bitter taste in his mouth. He occasionally experiences dizziness and light sleep, and has poor sleep quality, difficulty falling asleep, and frequent awakenings. Bowel movements and urination are normal.

[0039] Past medical history: 10-year history of hypertension, with blood pressure typically fluctuating between 130-150 / 70-80 mmHg. 1-year history of cerebral infarction, initially presenting with weakness in the left upper limb, which improved after treatment without residual limb dysfunction. Currently taking enteric-coated aspirin, atorvastatin calcium tablets, and amlodipine tablets regularly.

[0040] Physical signs: chronic illness appearance, apathetic expression, pale red tongue with thin white coating, and deep, thready pulse.

[0041] Laboratory findings: MoCA score 25, PSQI score 13.

[0042] Western medical diagnosis: 1. Mild cognitive impairment; 2. Insomnia; 3. Hypertension; 4. Post-stroke sequelae. Traditional Chinese Medicine (TCM) Diagnosis: 1. Dementia; 2. Insomnia. TCM Pattern: Heart and Kidney Yin Deficiency. Pathogenesis Analysis: The *Neijing* (Inner Canon of Medicine) records that after the age of 49, a woman's kidney essence becomes insufficient, the Ren meridian weakens, and her *tiankui* (menstrual blood) depletes. This patient is an elderly woman with kidney essence deficiency, leading to malnourishment of the brain marrow and the gradual appearance of symptoms such as forgetfulness, poor memory, and slow reaction. The *Lvshantang Leibian* (Classified Treatise on Smallpox) states, "The kidney is the water organ, responsible for storing essence and transforming it into blood." Due to kidney essence deficiency, the production of qi and blood is insufficient, and blood deficiency leads to malnourishment of the mind and spirit, resulting in restlessness, difficulty falling asleep, and frequent awakenings. Treatment should focus on tonifying the kidney and replenishing the marrow, nourishing blood and calming the mind. The prescription from Example 2 of this invention was administered for treatment.

[0043] Second visit: January 23, 2022. The patient reported improved sleep after taking the medication. Before taking the medication, it took 1-2 hours to fall asleep, but now it takes less than 1 hour. The number of awakenings at night has also significantly improved. The patient feels more energetic than before, and the symptoms of fatigue and lethargy have significantly improved. The abdominal distension has disappeared. Continue taking the same 14 doses as before, using the same method of administration.

[0044] The patient subsequently returned for several follow-up visits, and the prescription was adjusted according to the symptoms, and the patient continued to take the medication for three months. A follow-up visit on April 27th revealed that the patient reported significant improvement in memory, felt energetic, enjoyed outdoor activities, no longer resisted communicating with others, and that sleep had largely returned to normal, with occasional difficulty falling asleep, but no more than twice a week.

[0045] Case 2: Mr. Li, male, 68 years old, from Zhengzhou, Henan Province. First visit: September 22, 2021.

[0046] Chief complaint: Poor sleep for over 20 years, worsening and accompanied by slowed reaction time for over 1 year. Present Illness: The patient has suffered from poor sleep for nearly 20 years, experiencing difficulty falling asleep, vivid dreams, and frequent awakenings, with inability to fall back asleep after waking. He has intermittently taken tranquilizers and traditional Chinese medicine, with symptoms fluctuating in severity. In the past year, his symptoms have worsened, requiring nightly tranquilizers to fall asleep. He has also experienced sluggishness, difficulty performing tasks, such as taking significantly longer to cook the same meals (previously a regular occurrence), forgetting where he has placed items (though he can recall them after being reminded), difficulty with accounting, decision-making, and repeatedly asking the same questions. Tasks he previously handled independently now require the assistance of family members. He generally has a good appetite, but experiences lower back pain, irritability, dry and sticky mouth, normal urination, and constipation (bowel movements every 3-4 days).

[0047] Previous history: None.

[0048] Physical signs: Chronic illness appearance, haggard face, pale and dark tongue with white coating, deep and thready pulse, and tortuous sublingual veins.

[0049] Test results: PSQI score 16, MoCA score 26.

[0050] Western medical diagnosis: 1. Insomnia disorder, 2. Subjective cognitive impairment Traditional Chinese Medicine diagnosis: 1. Insomnia, 2. Dementia Traditional Chinese Medicine Syndrome: Deficiency of Heart and Kidneys with Blood Stasis Pathogenesis Analysis: The patient suffers from long-term insomnia, leading to depletion of heart blood and insufficient blood supply to nourish kidney essence. Kidney essence deficiency results in malnourishment of the brain marrow and impaired mental function, manifesting as sluggishness and forgetfulness. Due to blood deficiency and impaired blood circulation, coupled with prolonged illness leading to blood stasis, the flow of Qi is obstructed, and liver Qi stagnation causes irritability. Blood deficiency also leads to intestinal fluid depletion and constipation. Therefore, treatment should focus on nourishing blood and calming the mind, tonifying the kidneys and replenishing marrow, as described in Example 1 of this invention.

[0051] Second visit: October 8, 2021. The patient reported slight improvement in poor sleep and slow reaction after taking the medication, but significant constipation and irritability had lessened. The same prescription was continued for 14 doses, decocted in water and taken once daily, twice a day, morning and evening.

[0052] Third visit: October 22, 2021. The patient's sleep improved compared to before, with shorter sleep onset time, fewer dreams, improved mental state, significant improvement in lower back pain, and stable mood. Continue taking the prescribed medication. Subsequently, the patient's symptoms gradually improved.

[0053] On January 19, 2022, during a follow-up visit, the patient reported significant improvement in sleep after taking the medication. The time to fall asleep was shortened to 30-60 minutes, and the nightly sleep duration increased from 3-4 hours to 5-6 hours. The previously taken tranquilizers had been discontinued. The patient's sluggishness had significantly improved, and their daily living abilities had now basically returned to normal.

[0054] 9 Conclusions The drug formulation of this invention is scientifically sound and has significant clinical efficacy. It is safe and reliable, without side effects such as drug dependence or addiction, and has a strong synergistic effect. It targets the root cause of the disease and can not only improve patients' cognitive functions such as memory, attention, and reaction time, but also effectively shorten the time it takes for patients to fall asleep, reduce the number of awakenings, and improve the quality of their sleep.

Claims

1. A traditional Chinese medicine composition for improving cognitive impairment combined with insomnia, characterized in that, It is made from the following raw materials by weight: 20 parts tortoise shell, 30 parts dragon bone, 10 parts polygala, 10 parts acorus, 15 parts stir-fried jujube seed, 15 parts poria, 10 parts ginseng, 12 parts ophiopogon, 6 parts schisandra, 15 parts prepared rehmannia, 15 parts cornus, 15 parts wolfberry, 30 parts raw yam, 15 parts prepared he shou wu, and 12 parts tangerine peel.

2. The use of the traditional Chinese medicine composition of claim 1, which improves cognitive impairment combined with insomnia, in the preparation of a medicament for treating cognitive impairment combined with insomnia.