Use of a traditional Chinese medicine composition in the preparation of a drug for preventing and / or treating heart failure with cognitive impairment

Abstract

The application discloses application of a traditional Chinese medicine composition in preparation of a medicine for preventing and / or treating heart failure with cognitive impairment, and components of the traditional Chinese medicine composition include radix isatidis, gypsium, rhizoma phragmitis, radix rehmanniae, anemarrhena asphodeloides, alpinia officinarum, pachystachys lutea, forsythia suspensa and curcuma zedoary. The traditional Chinese medicine composition has a good treatment effect on heart failure with cognitive impairment, and a large amount of test data proves that: the traditional Chinese medicine composition can effectively relieve symptoms of heart failure with cognitive impairment from multiple aspects and block the progress of the disease course through reasonable compounding of various traditional Chinese medicine components, and is safe and reliable, has no toxic and side effects on human bodies.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of drug application, in particular to application of a traditional Chinese medicine composition in preparation of a drug for preventing and / or treating heart failure with cognitive impairment. BACKGROUND

[0002] Chronic heart failure (CHF) is the terminal stage of various cardiovascular diseases and the most important cause of death, and has become one of the most important diseases endangering the survival of the global middle-aged and elderly population. Studies have shown that CHF is closely related to cognitive impairment, and the quality of life of patients with CHF with cognitive impairment is significantly decreased, the mortality is increased, the nursing difficulty and cost are increased, and the medical cost is also greatly increased. Current studies believe that the mechanism of CHF with cognitive impairment may be related to factors such as cerebral hypoperfusion, ischemia and hypoxia leading to neuron apoptosis, neuroendocrine regulation disorder, cell inflammatory factor stimulation, thrombosis, apoE 4 genotype, elevated blood lipids, anxiety and depression. Studies have shown that about 50% of hospitalized patients with chronic heart failure have different degrees of cognitive impairment, and a considerable part of them develop into dementia, and the prognosis of these patients is poor. Foreign research data show that about 30-80% of CHF patients have different degrees of cognitive impairment. These pathogenic factors promote the further aggravation of CHF with cognitive impairment, and are important factors for the poor prognosis. The mechanism of chronic heart failure with cognitive impairment is relatively complex, and is the result of the interaction of complex pathophysiological processes such as insufficient blood supply, oxidative stress, inflammation and apoptosis. Therefore, the efficacy of a single drug is limited.

[0003] In the theory of heart in traditional Chinese medicine, the function of heart is more profound compared with the function of heart in modern western medicine. In traditional Chinese medicine, heart not only contains the blood and endocrine functions of heart in western medicine anatomy, but also discusses the physiological functions of heart from the theory of yin and yang: heart governs blood vessels and heart governs spirit. The function of heart governing blood vessels in traditional Chinese medicine is consistent with the pumping function of heart. In the study of the relationship between heart and brain, some scholars have proposed the theory of "heart dementia". Although the mechanism of the theory of heart governing spirit in traditional Chinese medicine is still unclear, a large number of scientific researches have shown that the function of heart is closely related to the spirit, emotion, thinking consciousness and emotion of brain. At present, some traditional Chinese medicine compositions often have single efficacy, complex composition or poor safety, and lack strict and systematic pharmacological experiments meeting the requirements of modern pharmacology, so it is difficult to carry out strict quality control and standardized production. Therefore, with the aid of modern technology, the function of heart governing spirit should be fully understood and utilized, and traditional Chinese medicine compounds can play a good therapeutic effect by targeting multiple links of chronic heart failure with cognitive impairment.

[0004] The clinical differentiation and treatment should distinguish between the symptoms and the root cause, strengthen the combination of systemic and local differentiation, and pay attention to the balance between supporting the healthy and eliminating the pathogenic. Sometimes the systemic manifestations and the local symptoms of the affected foot are not uniform, although the systemic manifestations are a virtual image, the local manifestations may be a real case, and the priority should be determined according to the severity of the healthy and the pathogenic. The use of traditional Chinese medicine compound can play a role in multiple aspects of heart failure with cognitive impairment, and has a good therapeutic effect.

[0005] Traditional Chinese medicine is widely used in the treatment of heart failure with cognitive impairment. Heat toxin plays an important role in the development of heart failure. The deficiency of heart qi and the dysfunction of viscera lead to the internal generation of heat toxin. Heat toxin damages the heart and the heart, consumes qi and yin, forces blood to run, and refines blood into stasis. The mutual entanglement of qi deficiency, heat toxin and blood stasis forms qi deficiency, heat toxin and blood stasis. Clearing heat and resolving toxin can eliminate the pathogenic factors. According to the different properties and positions of heat toxin, different treatment methods are used. For heat toxin on the upper and surface, use honeysuckle, forsythia and other light, clear and penetrating products to disperse heat toxin. For heat toxin in the lower and internal, use Huanglian, Dahuang and other bitter cold purgative drugs to make heat toxin from the two excretory organs. Clearing heat and resolving toxin can reduce the damage of heat toxin to the body and save yin fluid to reduce the internal generation of blood stasis. Clearing heat and resolving toxin is an indispensable strategy for the treatment of heart failure with cognitive impairment, and has important clinical significance. However, these drug compositions often have single effect or complex composition or poor safety, and lack strict and systematic pharmacological experiments in line with modern pharmaceutical requirements, which is difficult to control the quality and standardize the production. SUMMARY

[0006] The present application aims to solve at least one of the above-mentioned technical problems in the prior art. To this end, the purpose of the present application is to provide an application of a traditional Chinese medicine composition in the preparation of a medicine for preventing and / or treating heart failure with cognitive impairment.

[0007] In order to achieve the above-mentioned purpose, the technical solution adopted by the present application is:

[0008] The present application provides an application of a traditional Chinese medicine composition in the preparation of a medicine for preventing and / or treating heart failure with cognitive impairment, wherein the components of the traditional Chinese medicine composition include: Banlangen, Shigao, Lugen, Dihuang, Zhimu, Shichangpu, Guanghuoxiang, Lianqiao and Yujin.

[0009] In the present application, the traditional Chinese medicine composition includes Radix Isatidis for clearing heat and detoxifying, and for cooling blood and generating fluid, as the monarch drug. Gypsum Fibrosum and Rhizoma Anemarrhenae clear heat and purge fire, and clear heat in the lung and stomach; Radix Rehmanniae nourish Yin and clear heat in the lung, and cool blood and detoxify; Forsythia clear heat and detoxify, and dissipate wind and evil, and all are the minister drugs. The monarch and minister drugs are matched, and the clearing heat and detoxifying effect is enhanced, and the traditional Chinese medicine composition can also nourish Yin, moisten dryness, cool blood and detoxify, and prevent heat evil from damaging Yin and the bitter cold of the drugs from damaging Yin. With Atractylodes, Agastache and Turmeric for aromatherapy to open the orifices, regulate Qi and transform dampness; the Rhizoma Phragmitis is used as a guide, and can also clear heat in the lung and stomach, and generate fluid to stop thirst, and is the assistant drug. The drugs are matched, and heat is removed and dampness is cleared, and the traditional Chinese medicine composition can clear heat and expel dampness, cool blood and detoxify.

[0010] In some embodiments of the present application, the components of the traditional Chinese medicine composition include Radix Isatidis 170-285 parts, Gypsum Fibrosum 65-305 parts, Rhizoma Phragmitis 30-318 parts, Radix Rehmanniae 15-85 parts, Turmeric 35-100 parts, Rhizoma Anemarrhenae 10-65 parts, Atractylodes 17-65 parts, Agastache 25-70 parts, and Forsythia 5-45 parts by weight.

[0011] In some embodiments of the present application, the components of the traditional Chinese medicine composition include Radix Isatidis 170-260 parts, Gypsum Fibrosum 65-200 parts, Rhizoma Phragmitis 30-150 parts, Radix Rehmanniae 15-50 parts, Turmeric 35-80 parts, Rhizoma Anemarrhenae 10-55 parts, Atractylodes 17-50 parts, Agastache 25-60 parts, and Forsythia 5-30 parts by weight.

[0012] In some embodiments of the present application, the components of the traditional Chinese medicine composition include Radix Isatidis 173-177 parts, Gypsum Fibrosum 83-87 parts, Rhizoma Phragmitis 50-54 parts, Radix Rehmanniae 16-20 parts, Turmeric 38-42 parts, Rhizoma Anemarrhenae 23-27 parts, Atractylodes 25-30 parts, Agastache 28-33 parts, and Forsythia 8-12 parts by weight.

[0013] In some embodiments of the present application, the Rhizoma Anemarrhenae includes in vitro cultured Rhizoma Anemarrhenae.

[0014] In some embodiments of the present application, the Radix Rehmanniae includes artificial Radix Rehmanniae.

[0015] In some embodiments of the present application, the traditional Chinese medicine composition further includes a pharmaceutically acceptable excipient.

[0016] In some embodiments of the present application, the pharmaceutically acceptable excipient includes at least one of a filler, a disintegrant, a diluent, a lubricant, a binder, a humectant, a flavoring agent, a suspending agent, a solvent, a sustained release agent, an emulsifying agent, a vegetable oil, an absorption enhancer, a surfactant, or a preservative.

[0017] In some embodiments of the present application, the filler is selected from starch, sucrose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose or glucose, etc.; the binder is selected from cellulose derivatives, alginates, starch, water, dextrin, gelatin, hydroxypropyl cellulose, methyl cellulose or polyvinyl pyrrolidone, etc.; the diluent is selected from at least one of lactose, sucrose, mannitol, corn starch, potato starch, calcium phosphate, calcium citrate and crystalline cellulose; the disintegrant is selected from at least one of corn starch, potato starch, microcrystalline cellulose, sodium carboxymethyl starch, cross-linked polyvinyl pyrrolidone, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch, carboxymethyl cellulose, cross-linked sodium carboxymethyl cellulose, calcium carboxymethyl cellulose and alginic acid; the lubricant is selected from at least one of stearic acid, polyethylene glycol, calcium carbonate, sodium bicarbonate, microfine silica, talc, anhydrous silica gel and magnesium stearate; the suspending agent is selected from at least one of microfine silica, beeswax, cellulose, sodium carboxymethyl cellulose and solid polyethylene glycol; the wetting agent is selected from at least one of glycerol, Tween-80, oxyhydrogenated castor oil, sodium dodecyl sulfate and lecithin; the solvent is selected from at least one of water, ethanol, liquid polyethylene glycol, isopropyl alcohol, Tween-80, glycerol, propylene glycol and vegetable oil, the vegetable oil being selected from rapeseed oil, beeswax, soybean oil, castor oil, peanut oil, blended oil, etc.; the surfactant is selected from at least one of sodium dodecylbenzenesulfonate, stearic acid, polyoxyethylene-polyoxypropylene copolymer, sorbitan fatty acid ester and polysorbate; the flavoring agent is selected from at least one of aspartame, sucralose, essence, stevioside, acesulfame potassium, citric acid and sodium saccharin; and the preservative is selected from at least one of methyl or propyl paraben.

[0018] In some embodiments of the present application, the traditional Chinese medicine composition can be prepared by conventional methods in the art. The traditional Chinese medicine composition of the present application is a composition prepared by mixing the raw materials of the components after being pulverized; and / or an extract obtained by mixing the raw materials of the components after being extracted; and / or an extract obtained by mixing the raw materials of the components after being extracted separately. Optionally, the extract is further refined and purified. The extraction method includes decoction extraction, reflux extraction, immersion extraction, ultrasonic extraction, percolation extraction, microwave extraction, etc.; and the purification method includes water extraction and alcohol precipitation, alkali dissolution and acid precipitation, and / or various column chromatography purification methods, such as macroporous resin column, silica gel column, gel column, reverse phase column, etc.

[0019] In some embodiments of the present application, the dosage form of the traditional Chinese medicine composition includes any one of decoction, tablet, capsule, granule, pill, oral liquid, powder or ointment.

[0020] In some embodiments of the present application, the traditional Chinese medicine composition is prepared into the corresponding decoction, tablet, capsule, granule, pill, oral liquid, powder or ointment by the conventional preparation process of the required dosage form.

[0021] In some embodiments of the present application, the dosage form of the traditional Chinese medicine composition comprises soft capsules and hard capsules. Compared with oral liquid preparations, soft capsules are more stable in the preservation of low-boiling, volatile and other substances; after ingestion, the contents are rapidly released, with high bioavailability and high absorption rate. Therefore, when the traditional Chinese medicine composition of the present application is a soft capsule, the soft capsule preparation of traditional Chinese medicine heat-clearing and dampness-dissipating, blood-cooling and detoxifying drugs is used to improve the cardiac function, and / or cognitive function, and / or TCM symptoms of patients with heart failure combined with cognitive impairment.

[0022] In some embodiments of the present application, when the traditional Chinese medicine composition is a capsule, the preparation method of the traditional Chinese medicine composition comprises the following steps:

[0023] S1: After grinding and soaking in water, the patchouli and forsythia are filtered, the filter residue is extracted by supercritical extraction method, the volatile oil is collected and included, and the volatile oil inclusion compound is obtained; the filtrate and the extracted filter residue are added with acorus gramineus, gypsum and anemarrhena asphodeloides, and then extracted by heating and precipitated with ethanol, and the ethanol is recovered and concentrated into a first clear paste;

[0024] S2: After soaking in water and heating extraction, the isatis root, rehmannia, curcuma and phragmites communis are collected, ethanol is added, centrifuged, the centrifugal liquid is recovered and concentrated into a second clear paste under reduced pressure;

[0025] S3: The first clear paste and the second clear paste are combined and dried and crushed into dry paste powder, which is then mixed with the volatile oil inclusion compound to obtain the content, which is pressed with rubber to obtain the capsule of the traditional Chinese medicine composition.

[0026] In some embodiments of the present application, the volatile oil inclusion compound comprises β-cyclodextrin inclusion volatile oil.

[0027] In some embodiments of the present application, the content further comprises at least one of a dispersing agent and a suspending agent.

[0028] In some embodiments of the present application, the rubber comprises grape seed oil, tween, gelatin and beeswax.

[0029] In some embodiments of the present application, the rubber comprises grape seed oil, tween, gelatin, beeswax, sunscreen and preservative.

[0030] In some embodiments of the present application, when the traditional Chinese medicine composition is a soft capsule, the preparation method of the traditional Chinese medicine composition comprises the following steps:

[0031] S1: after grinding the patchouli, forsythia, soak in water for 1-10h, filter, filter residue is extracted by supercritical extraction, collect the volatile oil and use 3-10 times the mass of β-cyclodextrin inclusion, get the volatile oil inclusion; the filtrate and the extracted filtrate are added to the pinellia ternata, gypsum, zhimu, continue to heat extraction after ethanol precipitation, recover ethanol and concentrate into the first clear paste;

[0032] S2: take the isatis root, rehmannia, yujin, and soak in water for 3-10 times the mass of water, heat for 0.5-3h, extract, collect the extract, add ethanol, centrifuge, recover ethanol and concentrate into the second clear paste under reduced pressure;

[0033] S3: combine the first clear paste and the second clear paste and dry and crush into dry paste powder, then mix with the volatile oil inclusion, get the content, use rubber to press, get the soft capsules of the traditional Chinese medicine composition.

[0034] The beneficial effects of the present application are:

[0035] The present inventors have surprisingly found that the traditional Chinese medicine composition has good therapeutic effect on heart failure with cognitive impairment, and a large amount of test data recorded in the present application proves that: the traditional Chinese medicine composition can effectively relieve the symptoms of heart failure with cognitive impairment from multiple angles by reasonable matching of each traditional Chinese medicine component, and block the progression of the disease: and it is safe and reliable, and has no toxic and side effects on human body.

[0036] The composition provided by the present application is quality controllable, convenient for standardized production: and safe and reliable, and has no toxic and side effects on human body. DETAILED DESCRIPTION

[0037] The content of the present application is further described in detail through specific examples. Unless otherwise specified, the raw materials, reagents or devices used in the examples and comparative examples can be obtained from conventional commercial channels, or can be obtained by existing technical methods. Unless otherwise specified, the test or test method is a conventional method in the art.

[0038] EXAMPLE

[0039] This embodiment prepares an A, the specific process is:

[0040] Prescription one: isatis root 175 parts, gypsum 85 parts, reed 52 parts, rehmannia 18 parts, yujin 40 parts, zhimu 25 parts, pinellia ternata 27 parts, patchouli 31 parts, forsythia 10 parts.

[0041] Prescription two: isatis root 205 parts, gypsum 105 parts, reed 100 parts, rehmannia 45 parts, yujin 45 parts, zhimu 25 parts, pinellia ternata 27 parts, patchouli 31 parts, forsythia 20 parts.

[0042] Prescription three: Banlangen 260 parts, Shigao 105 parts, Lugen 100 parts, Dihuang 30 parts, Yujin 70 parts, Zhimu 35 parts, Shichangpu 27 parts, Guanghuoxiang 38 parts, Lianqiao 20 parts.

[0043] Process preparation:

[0044] (1) Take Guanghuoxiang and Lianqiao, crush them, soak them in water for 6 hours, filter, use supercritical extraction method to extract volatile oil from the filter residue, collect the volatile oil, and use 6 times the mass of β-cyclodextrin to package the volatile oil; soak the water solution and add Shichangpu, Shigao and Zhimu to the filter residue, heat and decoct to extract, filter, use ethanol to precipitate the filtrate, recover the ethanol, and concentrate into a clear paste for standby;

[0045] (2) Take Banlangen, Dihuang, Yujin and Lugen, soak them in 6 times the mass of water of raw medicinal materials, heat and decoct for 1.5 hours to extract, filter, add ethanol to the filtrate, stand still, centrifugalize, recover the ethanol, and concentrate into a clear paste under reduced pressure for standby;

[0046] (3) Heat and melt Shigao, Zhimu, Guanghuoxiang and Lianqiao into a glue solution according to the weight ratio of 0.5:1.0:1.5:0.5, add light-shielding agent and preservative, degas, and prepare into a glue skin for standby;

[0047] (4) Combine the clear pastes obtained in the above (1) and (2), dry and crush them into dry paste powder; mix the dry paste powder and the volatile oil package obtained in the above (1), add dispersant and suspending agent, stir well to obtain a capsule solution, and press the capsule solution and the glue skin prepared in the above (3) to obtain the soft capsules.

[0048] The soft capsules prepared by using the prescription one are used for the following clinical test:

[0049] Clinical test

[0050] 1 Patient data

[0051] 1.1 General data: 70 patients with heart failure and cognitive impairment were randomly divided into two groups according to whether they had diabetes, and were respectively the example group (test group) and the control group, 35 patients in each group. Among the patients in the example group, there were 18 males and 17 females; the age was 61-85 years old, with an average of 70.28 years old; the average education years were 8.9 years. Among the patients in the control group, there were 19 males and 16 females; the age was 62-87 years old, with an average of 71.83 years old; the average education years were 8.2 years. Through statistics, there was no statistically significant difference in age, gender composition ratio, diabetes, hypertension, BMI index, disease duration, symptoms and the like between the test group and the control group.

[0052] 1.2 Inclusion criteria:

[0053] (1) Refer to the diagnostic criteria for chronic heart failure in the "Chinese Heart Failure Diagnosis and Treatment Guidelines" (2018 edition);

[0054] (2) Age 18-85 years and willing to take Chinese medicine;

[0055] (3) Meet the diagnostic criteria for coronary heart disease: coronary angiography > 50% or echocardiography shows phase wall motion abnormalities;

[0056] (4) The New York Heart Association (NYHA) standard for classification of cardiac function was used, and all cases were classified as cardiac function II-IV;

[0057] (5) According to the "Chinese Dementia Diagnosis and Treatment Guidelines" (2017 edition), the neuropsychological scale (MMSE or MoCA scale shows mild to moderate cognitive dysfunction;

[0058] (6) No similar efficacy of Chinese medicine preparation within 3 months;

[0059] (7) Sign the informed consent form.

[0060] 1.3 Exclusion criteria:

[0061] (1) Not meeting the inclusion criteria;

[0062] (2) Severe dyspnea; such as COPD combined with encephalopathy, upper gastrointestinal bleeding, etc. Chronic with obvious hypoxemia and hemodynamic instability;

[0063] (3) Combined with heart valve disease, severe liver and kidney function damage, blood disease, autoimmune disease, malignant tumor and other diseases;

[0064] (4) Various serious infectious diseases;

[0065] (5) Pregnant or lactating women, patients with mental illness, allergic constitution and allergic to multiple drugs;

[0066] (6) Stroke or cardiac arrest or history of alcohol, drug abuse / dependence within the past two years;

[0067] (7) MRI shows signs of brain tumor or cortical stroke;

[0068] (8) Unable to communicate in written / verbal Chinese.

[0069] 1.4 Exclusion criteria

[0070] (1) Cases that do not meet the inclusion criteria and cases that meet the inclusion criteria but have been taken for <2 weeks after inclusion;

[0071] (2) Adverse reactions affect normal life or endanger life. For patients with adverse reactions, the reasons should be analyzed as much as possible, whether they are related to drug treatment, and safety analysis can be done according to the needs of the study.

[0072] 1.5 Dropout criteria

[0073] (1) The subject's condition continues to deteriorate during the trial, and it is judged that the trial should be stopped. The clinical trial of this case is terminated;

[0074] (2) The subject fails to complete the treatment observation as required due to various reasons, such as not completing a course of treatment, incomplete efficacy observation records, not taking medication as required, inability to judge efficacy or incomplete data affecting efficacy or safety judgment;

[0075] (3) The observer naturally drops out or loses contact;

[0076] (4) The subject has poor sex, severe adverse reactions, complications, and is not suitable for further trial. The safety analysis of the dropout patients is done as much as possible under the condition.

[0077] 1.6 Treatment of trial-related adverse events and adverse reactions

[0078] (1) This study stratifies all subjects according to the presence or absence of diabetes and randomly divides them into two groups, each with a 50% chance of being assigned to the trial group or the implementation case group. During medication, all patients will be regularly monitored for blood routine, liver and kidney function, electrocardiogram, echocardiogram, etc;

[0079] (2) If there are adverse reactions such as acute exacerbation of heart failure, acute myocardial infarction, sudden death, etc., the drug should be stopped immediately and the trial terminated;

[0080] (3) If the implementation case has drug-related adverse reactions, it should be stopped immediately, and medical personnel will treat the symptoms according to the bleeding situation, and decide whether to terminate the clinical trial according to the condition;

[0081] (4) All adverse events should be investigated and the treatment process and results should be recorded in detail until the problem is resolved or the condition is stable. The follow-up methods can be selected according to the severity of the adverse reactions, such as hospitalization, outpatient service, home visit, telephone, communication, etc;

[0082] (5) All terminated cases need to do safety analysis, report to the hospital drug adverse reaction monitoring center according to the drug adverse report system, and report to the national drug adverse reaction monitoring center by the drug adverse reaction monitoring center.

[0083] 2. Research methods

[0084] 2.1 Study design:

[0085] Seventy patients who met the diagnostic criteria for chronic heart failure with cognitive impairment were selected. According to whether they had diabetes, they were randomly divided into a control group and a test group using a random number table. Each group had 35 patients. The control group was given basic treatment. The test group was given the drug composition of the embodiment (2 capsules at a time, 3 times a day) on the basis of the basic treatment. The control group and the test group were compared, and the clinical efficacy was observed. The treatment course was 8 weeks. No other traditional Chinese medicine preparations were used during the medication period. If the acute exacerbation of chronic heart failure or the life-threatening condition occurred, the test should be stopped immediately and rescue should be actively performed. The changes in the diagnostic scale and the experimental value index of the patients in the two groups before and after treatment were observed. After the treatment course, all the data were statistically analyzed and processed using statistical software SPSS 25.0 to compare the differences between the test group and the control group before and after treatment and between the two groups.

[0086] 2.2 Treatment method

[0087] 2.2.1 Basic treatment:

[0088] (1) Both groups of patients were given diabetes education and were advised to quit smoking and drinking and to have a reasonable diet. (2) Blood glucose control: Insulin intensive therapy was used for hypoglycemic treatment to make the random blood glucose ≤10 mmol / L. (3) Anti-infection: Based on the results of bacterial culture and drug sensitivity test, appropriate antibiotics were selected for anti-infection. (4) Improve circulation: For patients with lower limb ischemia (ABI <0.9), alprostadil injection was used for intravenous infusion. (5) Nutritional nerve: For patients with neuropathy, mecobalamin tablets were given orally. (6) Symptomatic treatment and supportive therapy: Based on the blood pressure and albumin of the patients, antihypertensive and albumin supplement were given for symptomatic treatment. (7) Local debridement and dressing change: The necrotic tissue of the foot ulcer was removed.

[0089] 2.2.2 Group treatment:

[0090] (1) Test group:

[0091] On the basis of the basic treatment, the drug composition soft capsule preparation of the embodiment was taken.

[0092] (2) Control group:

[0093] On the basis of the basic treatment, the antiviral oral liquid was taken.

[0094] The observation time of the test group and the control group was 8 weeks, and then regular follow-up was conducted to understand the improvement of the subjective symptoms and the laboratory examination of the patients before and after treatment and to record the adverse reactions.

[0095] 2.3 Observation index

[0096] Efficacy index

[0097] Western medicine related indicators of chronic heart failure:

[0098] 2.3.1 Western medicine efficacy indicators:

[0099] (1) Comparison of NT-proBNP level changes before and after treatment in the two groups

[0100] (2) Comparison of color Doppler echocardiography results before and after treatment in the two groups: LVEF, FS values (measured according to the standard recommended by the American Ultrasound Society, all patients were measured by the same operator to ensure consistency).

[0101] (3) According to the Minnesota Heart Failure Quality of Life Survey (University of Minnesota, 1986), the TCM symptomatology scale, the quality of life of patients before and after treatment was evaluated

[0102] (4) Cognitive function evaluation: MMSE and MCA cognitive function evaluation scales were used for evaluation.

[0103] Cognitive function evaluation criteria:

[0104] MMSE: Dementia classification criteria: illiterate <17 points, primary school degree <20 points, secondary school degree and above (including technical secondary school) <24 points.

[0105] MoCA: Add 1 point if the education years are ≤12 years, the maximum score is 30 points, <26 points is abnormal.

[0106] 2.3.2 TCM symptom efficacy indicators:

[0107] According to the "Guiding Principles for Clinical Research of New Drugs of Traditional Chinese Medicine" (2002 version) "Guiding Principles for Clinical Research of New Drugs of Traditional Chinese Medicine for the Treatment of CHF", diagnostic criteria and the standard proposed by the consensus of clinical experts in recent years: the changes of the body symptoms of the subjects in the two groups before and after treatment are observed (main symptoms: palpitation, shortness of breath, fatigue, mass under the ribs, edema; secondary symptoms: shortness of breath, self-sweating, aversion to cold, abdominal distension and stool, poor appetite, color of lips and nails, skin ecchymosis, purple tongue, purple ecchymosis, tortuous sublingual collaterals, pulse is rough or fine and weak, etc., 4 main symptoms or 2 main symptoms and 2 or more symptoms of other symptoms) are observed. The specific scoring is as follows: (1) no chest pain, 0 points: no chest pain, 3 points: chest pain relieved after rest and does not affect daily life, 6 points: chest pain requires drug treatment and can continue normal activities after relief, 9 points: frequent chest pain affecting daily life, (2) no chest tightness, 0 points: occasional chest tightness, 3 points: chest tightness occurs frequently but does not affect normal life and work, 6 points: chest tightness lasts and affects life and work, 9 points, (3) collaterals obstruction: according to the number of lips, gums, nail purple, sublingual collaterals thick and tortuous, local skin ecchymosis and other sites, no collaterals obstruction, 0 points: 1 site with a small amount of collaterals obstruction, 3 points: 2 or more sites with collaterals obstruction, 6 points: 3 or more sites or severe collaterals obstruction at the end of the limb, 9 points, (4) no shortness of breath, 0 points: shortness of breath after general activity, 2 points: shortness of breath after slight activity, 4 points: shortness of breath even without activity, 6 points, (5) no fatigue, 0 points: fatigue after general activity, 2 points: fatigue after slight activity, 4 points: fatigue even without activity, 6 points, (6) no palpitation, 0 points: occasional mild palpitation, 1 point: palpitation occurs occasionally, lasts for a long time and the discomfort is obvious, 2 points: palpitation occurs frequently and even palpitation is difficult to calm down, 3 points, (7) no dry mouth, 0 points: dry mouth in the morning, 1 point: dry mouth and loss of appetite, 2 points: dry mouth and bitter, 3 points, (8) no irritability, 0 points: occasional irritability, 1 point: irritability occurs occasionally and the discomfort is obvious, 2 points: irritability occurs frequently and cannot be controlled, 3 points, (9) tongue appearance: according to tongue redness, purple, ecchymosis, thick and greasy fur, 0 points for no above tongue appearance, 1 point for mild, 2 points for severe, (10) pulse appearance: according to pulse weakness, smoothness, and fineness, 0 points for no above pulse appearance, 1 point for presence.

[0108] 2.4 Statistical analysis

[0109] An Excel database was established, and SPSS25.0 statistical software was used for data analysis. The data conformed to normal distribution, and the measurement data were described by mean and standard deviation (X±S). The t test was used for homogeneity of variance, and the approximate t test was used for non-homogeneity of variance. The count data were described by rate (%) and the chi-square (χ 2Test: Rank-sum test was used for nonparametric data and median, interquartile range was used for data not in normal distribution. All statistical methods were double-sided test, and the difference was statistically significant when P<0.05.

[0110] 3. Results and analysis

[0111] 3.1 Therapeutic effect

[0112] 3.1.1 NT-proBNP comparison

[0113] The results are shown in Table 1. Before treatment, the NT-proBNP scores of the control group and the case group were compared, and the difference was not statistically significant (P>0.05). The scores before and after treatment in each group were significantly different (P<0.01), indicating that the treatment plan in each group can reduce the score. After treatment, the scores of the two groups (control group and test group) were significantly different (P<0.05), indicating that the syndrome score of the case group decreased better than the control group.

[0114] Table 1 Symptom score before and after treatment in each group

[0115] Group n (person) Before treatment After treatment P Control group 35 3582.36±859.36 2552.22±459.36 * Example group 35 3728.35±1052.61 1642.36±511.78 ** / #

[0116] Note: *, compared with before treatment, P<0.01; **, compared with before treatment, P<0.01; #, compared with the control group after treatment, P<0.05.

[0117] 3.1.2 LVEF value comparison

[0118] The results are shown in Table 2. The LVEF values of the two groups (control group and test group) were compared before and after treatment, and the t test showed that there was no significant difference in the LVEF values of the two groups before treatment (P>0.05), but there was a significant difference in the LVEF values of the two groups after treatment (P<0.05), and the comparison of LVEF values after treatment had statistical significance.

[0119] Table 2 Comparison of LVEF values

[0120] Group n (person) Before treatment After treatment P Control group 35 0.452±0.081 0.501±0.056 * Example group 35 0.447±0.102 0.558±0.045 * / #

[0121] Note: *, compared with before treatment, P<0.05; #, compared with the control group after treatment, P<0.05.

[0122] 3.2.3 Left ventricular short axis shortening rate FS% comparison

[0123] FS% of the two groups before treatment, P> 0.05, the difference was not statistically significant. The two groups were compared before and after treatment, P<0.05, the difference was significant, indicating that the two treatment regimens can improve FS%; after treatment, the scores of the two groups were compared, P<0.05, the difference was significant, indicating that the improvement of FS% in the test group was better than that in the control group.

[0124] Table 3 Comparison of left ventricular fractional shortening (FS%)

[0125] Group n (person) Before treatment After treatment P Control group 35 0.2659±0.057 0.3196±0.036 * Example 4 group 35 0.2578±0.0.061 0.3496±0.039 * / #

[0126] Note: *, compared with before treatment, P<0.05; #, compared with the control group after treatment, P<0.05.

[0127] 3.2.4 Comparison of MoCA and MMSE scores

[0128] Before treatment, MoCA and MMSE of the two groups were compared, P> 0.05, the difference was not statistically significant. The two groups were compared before and after treatment, P<0.05, the difference was significant, indicating that the two treatment regimens can improve MoCA and MMSE; after treatment, the scores of the two groups were compared, P<0.05, the difference was significant, indicating that the improvement of MoCA and MMSE in the test group was better than that in the control group.

[0129] Table 4 Comparison of MoCA and MMSE scores

[0130]

[0131] Note: *, compared with before treatment, P<0.05; #, compared with the control group after treatment, P<0.05.

[0132] 3.2.4 Comparison of clinical symptom efficacy

[0133] After treatment, the total effective rate of the implementation case group was 90.91%, and the total effective rate of the control group was 69.70%. The implementation case group was compared with the control group, and the non-parametric test was used for one-way ordinal contingency table data, P<0.05, the difference was statistically significant.

[0134] Table 5 Clinical symptom efficacy

[0135] Group n (person) Effective Effective Ineffective Total effective rate % P Control group 35 10 15 10 71.42 Example group 35 21 9 3 91.42 P<0.05

[0136] 3.2.5 Comparison of Minnesota Heart Failure Scale scores

[0137] The Minnesota Heart Failure Scale scores of the two groups of patients before treatment were compared, P>0.05, and the difference was not statistically significant. The Minnesota Heart Failure Scale scores of the two groups before and after treatment were compared, P<0.05, and the difference was significant, indicating that the treatment regimens of the two groups can reduce the Minnesota Heart Failure Scale scores; the scores of the two groups after treatment were compared, P<0.05, and the difference was significant, indicating that the increase of FS% of the test group is better than that of the control group.

[0138] Table 6 Comparison of Minnesota Heart Failure Scale scores before and after treatment

[0139] Group n (person) Before treatment After treatment P Control group 35 57.28±5.62 54.25±4.89 * Example group 35 58.49±4.98 51.36±3.62 * / #

[0140] Note: *, compared with before treatment, P<0.05; #, compared with the control group after treatment, P<0.05.

[0141] 3.2.6 Comparison of TCM syndrome efficacy

[0142] The results are shown in Table 7. After treatment, the TCM syndrome scores of the patients in the control group and the case group were reduced, P<0.05; compared with the control group, the improvement in the case group was more obvious, which was better than that in the control group, P<0.05.

[0143] Table 7 Comparison of TCM syndrome scores

[0144]

[0145] Note: *, compared with before treatment, P<0.05; **, compared with before treatment, P<0.01; #, compared with the control group after treatment, P<0.05.

[0146] From the TCM syndrome efficacy indicators of the patients in each group, as shown in Table 8, the significant efficiency (%) and total efficiency (%) of the case group were significantly higher than those of the control group (there was a significant difference between the two groups (P<0.5)); the significant efficiency of the TCM syndrome efficacy of the case was 51.42%, and the total efficiency was 94.28%, which was significantly better than 22.86% (8 / 35) and 57.14% of the control group. This indicates that starting from the TCM diagnostic criteria, the efficacy of the drug composition provided in the embodiment on heart failure combined with cognitive impairment is better than that of single basic treatment.

[0147] Table 8 Comparison of TCM syndrome efficacy

[0148] Group n (person) Effective Effective Ineffective Total effective rate % P Control group 35 8 12 15 57.14 Example group 35 18 15 2 94.28 P<0.05

[0149] 3.3 Safety evaluation

[0150] No drug-related discomfort symptoms and adverse reaction events occurred in the patients in each group during the treatment, and the safety was good, and the safety evaluation was grade 1.

[0151] From the above, the statistical results of Tables 1-7 can be seen that before treatment, the NT-proBNP, LVEF, left ventricular short axis shortening rate FS%, LVEF, MoCA and MMSE scores, Minnesota Heart Failure Scale score, syndrome score of the case group and the control group had no significant difference; after treatment, the NT-proBNP, LVEF, left ventricular short axis shortening rate FS%, LVEF, MoCA and MMSE scores, Minnesota Heart Failure Scale score, syndrome score of the case group and the control group were significantly improved (P<0.05). Further comparison can be obtained that the comparison difference of NT-proBNP, LVEF, left ventricular short axis shortening rate FS%, LVEF, MoCA and MMSE scores, Minnesota Heart Failure Scale score, syndrome score of the case group before and after treatment is greater than that of the control group, and the results are more significant (P<0.05); and the total effective rate is higher (P<0.05). Therefore, starting from the western medicine diagnostic criteria, the curative effect of the drug composition of the application for treating heart failure combined with cognitive impairment is stronger than that of single standard treatment.

[0152] It has been verified that the treatment effect of the traditional Chinese medicine composition of prescription two and prescription three is similar to that of prescription one.

[0153] The above embodiments are the preferred embodiments of the present application, but the embodiments of the present application are not limited by the above embodiments, and any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present application should be equivalent replacement methods, and are all included in the protection scope of the present application.

Claims

1. The use of a traditional Chinese medicine composition in the preparation of a drug for the prevention and / or treatment of heart failure with cognitive impairment, characterized in that: The traditional Chinese medicine composition consists of the following active components in parts by weight: Banlangen 170-285 parts, Shigao 65-305 parts, Lugen 30-318 parts, Dihuang 15-85 parts, Yujin 35-100 parts, Zhimu 10-65 parts, Shichangpu 17-65 parts, Guanghuoxiang 25-70 parts, Lianqiao 5-45 parts.

2. Use according to claim 1, characterized in that: The Zhimu includes in-vitro cultivated Zhimu.

3. Use according to claim 1, characterized in that: The Dihuang includes artificial Dihuang.

4. Use according to claim 1, characterized in that: The traditional Chinese medicine composition further includes a pharmaceutically acceptable excipient.

5. Use according to claim 4, characterized in that: The pharmaceutically acceptable excipient includes at least one of a filler, a disintegrant, a diluent, a lubricant, a binder, a humectant, a flavoring agent, a suspending agent, a solvent, a sustained-release agent, an emulsifying agent, a vegetable oil, an absorption enhancer, a surfactant, or a preservative.

6. Use according to claim 1, characterized in that: The dosage form of the traditional Chinese medicine composition includes any one of a decoction, a tablet, a capsule, a granule, a pill, an oral liquid, a powder, or a paste.

7. The use according to claim 1, characterized in that: The dosage form of the traditional Chinese medicine composition includes a soft capsule and a hard capsule.

8. The use according to claim 1, characterized in that: The traditional Chinese medicine composition is a composition of raw materials of each component after being crushed and mixed; and / or an extract obtained by mixing raw materials of each component after being extracted; and / or an extract obtained by mixing raw materials of each component after being extracted separately.

9. The use according to claim 1, characterized in that: When the traditional Chinese medicine composition is a capsule, the preparation method of the traditional Chinese medicine composition includes the following steps: S1: crushing Guanghuoxiang and Lianqiao, soaking in water, filtering, extracting the filter residue by supercritical extraction, collecting the volatile oil and inclusion, obtaining a volatile oil inclusion; adding Shichangpu, Shigao, and Zhimu to the filtrate and the extracted filter residue, continuing to extract by heating, precipitating with ethanol, recovering ethanol, and concentrating into a first clear paste; S2: soaking Banlangen, Dihuang, Yujin, and Lugen in water, heating to extract, adding ethanol to the extract, centrifuging, recovering ethanol from the centrifugal liquid, and concentrating under reduced pressure into a second clear paste; S3: combining the first clear paste and the second clear paste, drying and crushing into a dry paste powder, mixing with the volatile oil inclusion, obtaining the content, pressing with rubber, and obtaining the capsule of the traditional Chinese medicine composition.

Images