A kidney-nourishing and phlegm-dissolving traditional Chinese medicine compound, a preparation method thereof and an anti-atherosclerosis application thereof

Abstract

This invention belongs to the field of traditional Chinese medicine technology, and discloses a kidney-tonifying and turbidity-resolving traditional Chinese medicine compound, its preparation method, and its anti-atherosclerotic application. The effective components of the kidney-tonifying and turbidity-resolving traditional Chinese medicine compound, by mass, consist of 15 parts Rehmannia glutinosa (processed), 15 parts Astragalus membranaceus (raw), 9 parts Cistanche deserticola, 10 parts Nelumbo nucifera (lotus leaf), 20 parts Gynostemma pentaphyllum, 12 parts Crataegus pinnatifida, and 6 parts Citrus reticulata (dried tangerine peel). The preparation method of the kidney-tonifying and turbidity-resolving traditional Chinese medicine compound is simple, without any additives, and has strong pharmacological compatibility. The anti-atherosclerotic application of the kidney-tonifying and turbidity-resolving traditional Chinese medicine compound includes: including observation cases, grouping, measuring the CIMT value and plaque area of ​​the included cases, data processing, and result analysis. This invention's kidney-tonifying and turbidity-resolving traditional Chinese medicine intervention can reduce the CIMT value and carotid plaque area in patients with atherosclerosis, and has a significant anti-atherosclerotic effect.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, and particularly relates to a kidney-tonifying and turbidity-resolving traditional Chinese medicine compound, its preparation method, and its anti-atherosclerotic application. Background Technology

[0002] Currently, atherosclerosis (AS), the main pathological basis for the occurrence and progression of cardiovascular and cerebrovascular diseases, is a chronic proliferative disease characterized by thickening and hardening of the vessel wall, plaque formation, and luminal narrowing. It is caused by endothelial lipid deposition, mononuclear cell infiltration, foam cell and fatty streak formation, fibrous tissue proliferation, accompanied by medial degeneration and calcification. Cerebrovascular disease (CVD), with AS as its pathological basis, is the leading cause of death among urban and rural residents, accounting for 45.01% in rural areas and 42.61% in urban areas. Furthermore, the prevalence and mortality rates are still rising, seriously impacting people's living standards and quality of life. Therefore, the prevention and treatment of AS is urgently needed.

[0003] Traditional Chinese medicine (TCM) does not have a specific disease name for "atherosclerosis." Previously, it was often classified based on clinical symptoms into conditions such as "chest pain," "dizziness," and "pulse pain." "Pain" refers to obstruction, where the blood vessels are blocked. AS is located in the blood vessels, which are the reservoir of blood and involve many internal organs. Its onset is related to old age and physical decline, improper diet, internal emotional disturbances, and external pathogenic factors. Our research group's previous studies suggest a close relationship between aging and the development of AS, with the pathogenesis being a deficiency of the root and an excess of the branch, with kidney essence deficiency as the root and phlegm and blood stasis as the branch. Since AS is more common in the elderly, it suggests that it is a degenerative disease related to aging. Cohort studies have found a close correlation between AS and aging, but not a significant relationship with hypertension or diabetes. Chen Mingquan et al., through cluster analysis, concluded that the most common syndrome type of carotid atherosclerosis is kidney deficiency and essence depletion.

[0004] The kidneys store essence, forming the foundation of innate constitution. The *Suwen* (Plain Questions) states, "At forty, the yin energy is halved." In old age, kidney essence is deficient, failing to transform into qi; kidney yang declines, hindering the warming and vaporizing of body fluids, leading to phlegm and turbidity. Poor circulation of qi and blood results in the accumulation of phlegm and blood stasis, obstructing the blood vessels and eventually affecting the normal function of blood vessel walls. Combined with clinical findings that ankylosing spondylitis (AS) is most common after age 40, the age when kidney qi begins to decline, this indicates that the pathogenic factors of AS are related to aging. Related animal experiments and clinical studies have shown that the herbal formula for tonifying the kidneys and resolving turbidity can exert anti-AS effects through multiple pathways and targets, with few adverse reactions. Its mechanisms are related to anti-oxidative stress, regulation of lipid metabolism, inhibition of vascular smooth muscle proliferation, anti-inflammation, and stabilization of AS plaques, revealing the importance of this herbal formula in the prevention and treatment of AS. Simultaneously, the kidneys govern bone marrow production and store essence. Research confirms that pluripotent hematopoietic stem cells originating from the bone marrow participate in immune responses, thus highlighting the close relationship between the kidneys and immunity. Kidney deficiency and aging can lead to immune system disorders. Traditional Chinese medicine compound formulas that benefit the kidneys and eliminate turbidity have the effects of regulating immune function and anti-aging.

[0005] Ruanmai Decoction is mainly composed of Rehmannia glutinosa (processed), Astragalus membranaceus (raw), Cistanche deserticola, Nelumbo nucifera leaf, Gynostemma pentaphyllum, Crataegus pinnatifida, and Citrus reticulata peel. Rehmannia glutinosa is the principal ingredient, described in the *Compendium of Materia Medica* as "replenishing deficiencies in the five internal organs, clearing blood vessels, filling bone marrow, building muscle, and generating essence and blood." Astragalus membranaceus and Cistanche deserticola are the assistant ingredients, replenishing qi and essence. The *Compendium of Materia Medica* describes Astragalus membranaceus as "the chief of tonics," and together with Cistanche deserticola and Rehmannia glutinosa, they enhance the effects of replenishing vital energy and nourishing essence and blood. Gynostemma pentaphyllum and Nelumbo nucifera leaf are added to replenish qi, promote diuresis, and resolve turbidity. Crataegus pinnatifida promotes qi circulation and removes blood stasis, while Citrus reticulata peel regulates qi and resolves phlegm, inhibiting the nourishing and cloying properties of Rehmannia glutinosa and Astragalus membranaceus. This compound formula, with its balanced approach and harmonious balance of yin and yang, can replenish kidney essence, nourish qi and blood, and resolve phlegm and blood stasis.

[0006] Based on the above analysis, the problems and shortcomings of the existing technology are as follows:

[0007] (1) In related technologies, there are reports of using intraoperative extracts to prevent restenosis. However, this requires the combination of multiple compounds in a specific ratio from the extract, and it relies on vascular stents to allow the drug to enter the human circulation directly through the blood to achieve the desired effect. If gastrointestinal administration is used, it may not be effective in preventing restenosis because it requires an absorption process compared to blood administration.

[0008] (2) In routine treatment, mixed lipid-lowering drugs and aspirin are often used to prevent thrombosis. However, due to their side effects such as liver damage, rhabdomyolysis, and gastrointestinal bleeding, especially since the risk of muscle toxicity in Chinese patients is nearly 10 times that of European patients, their clinical use is limited. In addition, the routine use of mixed drugs can only prevent 30% to 40% of cardiovascular events, and the clinical efficacy is not significant.

[0009] (3) Current TCM treatments for atherosclerosis often focus on "phlegm and blood stasis," but we believe that while phlegm and blood stasis are symptoms, deficiency of vital energy is the root cause. Aging leads to a decline in the function of the internal organs, causing the pathological stagnation of normally functioning body fluids and blood, resulting in phlegm and blood stasis. Atherosclerosis is a type of vascular aging, related to aging. Therefore, starting with anti-aging, tonifying the kidney is the most direct and effective method. Ruanmai Decoction is a formula developed by reducing the original formula based on previous research on tonifying the kidney and treating atherosclerosis, and adding phlegm-resolving drugs. Clinical and experimental studies have confirmed its anti-atherosclerotic effect. It embodies the TCM idea of ​​"treating the root cause of the disease," and Ruanmai Decoction is a small compound formula with most of its ingredients being both medicinal and edible, suitable for long-term use, meeting the needs of long-term treatment for atherosclerosis.

[0010] The difficulty in addressing the above problems and shortcomings lies in the fact that the progression of AS is closely related to factors such as advanced age, obesity, abnormal lipid metabolism, hypertension, diabetes, and hyperuricemia, and is also linked to living environment and unhealthy lifestyle habits. Large-scale and long-term evidence-based research is still needed for TCM treatment.

[0011] The significance of addressing the above problems and shortcomings is as follows: Ruanmai Decoction is a proprietary formula within our hospital. In this formula, Rehmannia glutinosa (Shu Di Huang) is the principal herb, nourishing the kidneys and replenishing essence; Cistanche deserticola (Huang Qi) is the assistant herb, tonifying kidney yang and replenishing essence and blood; Gynostemma pentaphyllum (Jiao Gu Lan) and Nelumbo nucifera (He Ye) are the adjuvant herbs, invigorating qi, promoting diuresis, and resolving turbidity; Crataegus pinnatifida (Shan Zha) is the adjuvant herb, resolving blood stasis and promoting qi circulation; and Citrus reticulata (Chen Pi) is the guiding herb, regulating qi and resolving phlegm. The entire formula combines active and passive ingredients to ensure that tonification is not stagnant, tonifying the kidneys and replenishing qi, harmonizing yin and yang, and achieving the effect of simultaneously tonifying essence and qi. Our team has confirmed through RCTs and cohort studies that Ruanmai Decoction has anti-atherosclerotic effects, with significant clinical efficacy. Larger-scale evidence-based studies will be conducted in the future. Summary of the Invention

[0012] The purpose of this invention is to address the problems existing in the prior art by providing a traditional Chinese medicine compound for tonifying the kidney and clearing turbidity, its preparation method, and its application in anti-atherosclerosis.

[0013] The above-mentioned technical objective of the present invention is achieved through the following technical solution: the kidney-tonifying and turbidity-resolving traditional Chinese medicine compound comprises the following components, by mass parts: 15-20 parts of Rehmannia glutinosa, 15-20 parts of Astragalus membranaceus, 9-15 parts of Cistanche deserticola, 10-20 parts of Nelumbo nucifera leaf, 20-30 parts of Gynostemma pentaphyllum, 12-20 parts of Crataegus pinnatifida, and 6-12 parts of Citrus reticulata peel.

[0014] Preferably, the herbal compound for tonifying the kidney and dispelling turbidity comprises the following components, in parts by weight: 15-18 parts of Rehmannia glutinosa, 15-18 parts of Astragalus membranaceus, 9-12 parts of Cistanche deserticola, 10-15 parts of Nelumbo nucifera leaf, 20-25 parts of Gynostemma pentaphyllum, 12-18 parts of Crataegus pinnatifida, and 6-10 parts of Citrus reticulata peel.

[0015] Preferably, the herbal compound for tonifying the kidneys and dispelling turbidity comprises the following components, in parts by weight: 15 parts Rehmannia glutinosa, 15 parts Astragalus membranaceus, 9 parts Cistanche deserticola, 10 parts Nelumbo nucifera, 20 parts Gynostemma pentaphyllum, 12 parts Crataegus pinnatifida, and 6 parts Citrus reticulata.

[0016] This invention also provides a method for preparing a traditional Chinese medicine compound for tonifying the kidney and resolving turbidity, the method comprising the following steps:

[0017] (1) Weigh out the proportions of Rehmannia glutinosa, Astragalus membranaceus, Cistanche deserticola, Nelumbo nucifera leaf, Gynostemma pentaphyllum, Crataegus pinnatifida, and Citrus reticulata peel;

[0018] (2) Add water to submerge the herbs and soak for 2 hours. Then heat over high heat until boiling and simmer over low heat for 30 minutes to extract the medicinal juice.

[0019] (3) Add water to the remaining dregs in step (2) until they are submerged, soak for 30 minutes, then heat over high heat until boiling, and simmer over low heat for 30 minutes to extract the medicinal juice.

[0020] (4) After mixing the medicinal juices prepared in steps (2) and (3), concentrate them over a low flame to 300-400 ml, store them in a refrigerator at 4°C for later use, and take them twice a day.

[0021] Another object of the present invention is to provide a traditional Chinese medicine compound for tonifying the kidney and resolving turbidity for anti-atherosclerosis application, wherein the anti-atherosclerosis application includes the following steps:

[0022] (1) Cases included in the study:

[0023] The study subjects were patients from the AS specialist outpatient clinic, geriatric outpatient clinic, and geriatric ward of Longhua Hospital. The observation period started in June 2018 and ended in December 2019. Patients who met the TCM diagnosis of kidney essence deficiency and the Western medicine CAS criteria were selected. The observational study was conducted with the informed consent of the patients. The follow-up time of the included cases was analyzed. There were 53 cases in the no-medication group with a median follow-up time of 195.5 days, 68 cases in the TCM group with a median follow-up time of 201 days, 97 cases in the Western medicine group with a median follow-up time of 185.5 days, and 62 cases in the integrated TCM and Western medicine group with a median follow-up time of 182 days. There was no statistically significant difference between the groups (P>0.05).

[0024] 1) Diagnostic criteria for kidney essence deficiency in Traditional Chinese Medicine:

[0025] Based on the "Guiding Principles for Clinical Research of Traditional Chinese Medicine (New Drugs)" published by the Ministry of Health of the People's Republic of China in 2002, and in conjunction with the fifth edition of the textbook "Traditional Chinese Medicine Diagnostics" for higher medical colleges.

[0026] Main symptoms: soreness and weakness of the lower back and knees, hair loss and loose teeth, forgetfulness, tinnitus, and deafness.

[0027] Secondary symptoms: lethargy, weakness in the legs.

[0028] Pulse diagnosis: Weak pulse

[0029] Two of the primary symptoms must be present, and one of the secondary symptoms must be present. Combined with pulse diagnosis, a diagnosis can be made.

[0030] 2) CAS diagnostic criteria:

[0031] 1) Referring to the definition in the 2003 European Heart Association guidelines for the treatment of hypertension, a carotid intima-media thickness (CIMT) ≥ 0.9 mm is considered a CAS.

[0032] 3) Inclusion criteria:

[0033] ① Age ≥ 50 years old;

[0034] ② Meets the diagnostic criteria for kidney essence deficiency in Traditional Chinese Medicine;

[0035] ③ Meets the diagnostic criteria for carotid atherosclerosis;

[0036] ④ Able to understand the contents of the questionnaire and participate voluntarily.

[0037] 4) Exclusion criteria:

[0038] ① Patients who have participated in other clinical studies;

[0039] ② Patients with severe primary diseases affecting other systems and impacting their daily lives;

[0040] ③Those who have undergone surgery or suffered trauma within the past 4 weeks;

[0041] ④ Individuals infected with tuberculosis and other infectious diseases;

[0042] ⑤ Meets the inclusion criteria but used traditional Chinese medicine other than the kidney-tonifying and turbidity-resolving method.

[0043] 5) Exclusion criteria:

[0044] ① Cases that were mistakenly included because the case selection did not meet the inclusion criteria;

[0045] ② Those whose carotid artery ultrasound data is incomplete and cannot be completed according to the research plan;

[0046] ③Loss to follow-up.

[0047] (2) Grouping:

[0048] Based on whether patients received traditional Chinese medicine intervention using the kidney-tonifying and turbidity-resolving method as an exposure factor, patients were divided into four groups: no medication group, traditional Chinese medicine group, Western medicine group, and integrated traditional Chinese and Western medicine group. Patients in the no medication group served as a blank control. Patients in the traditional Chinese medicine group received a traditional Chinese medicine treatment regimen with the kidney-tonifying and turbidity-resolving method as the main treatment principle. Patients in the Western medicine group received a statin medication regimen. Patients in the integrated traditional Chinese and Western medicine group received both the kidney-tonifying and turbidity-resolving traditional Chinese medicine intervention regimen and statin medication.

[0049] (3) Measurement of CIMT values ​​and plaque areas in included cases:

[0050] CIMT values ​​and plaque areas were measured at the time of enrollment and every 180 days after enrollment.

[0051] Measurements were performed using a color Doppler ultrasound system from Esaote, Italy, with a probe frequency of 5.0-10.0 MHz. The procedure was performed by designated professional operators in the hospital's ultrasound department.

[0052] 1) The patient lies supine with their head turned to the opposite side. Bilateral CIMT and internal carotid artery blood flow velocity are measured. Measurements are taken starting from the point where the arterial structure is clearest on the imaging. The distance between the intima-media interface and the media-adventitia interface of the arterial lumen is marked. Three measurements are taken, and the average of the three measurements is the final result, which is the CIMT. Measurements are taken on both sides equally, avoiding plaques.

[0053] 2) If plaques have formed on the patient's neck, observe them using color Doppler blood flow imaging to measure the nature, location, and size of the plaques.

[0054] 3) Patch area calculation: The patch area is determined by multiplying the transverse diameter and longitudinal diameter of the patch.

[0055] (5) Data processing: The measured data were analyzed using Foxtable and SPSS 20.0 statistical software. If the data followed a normal distribution and had homogeneous variance, the statistical description was expressed as (x±s); if the data did not follow a normal distribution, the statistical description was expressed as the median M, the minimum value (min) and the maximum value (max).

[0056] (6) Results analysis: A total of 237 patients were included in the CIMT statistics. There were no statistically significant differences in baseline values ​​among the groups, making them comparable. Within-group comparisons, the CIMT value of the untreated group increased (P<0.05), while the CIMT values ​​of the Western medicine group, traditional Chinese medicine group, and integrated traditional Chinese and Western medicine group decreased after treatment (P<0.05).

[0057] Intergroup comparisons showed that, compared with the untreated group, the CIMT values ​​of the traditional Chinese medicine group, the Western medicine group, and the integrated traditional Chinese and Western medicine group were all reduced (P < 0.05). Compared with the Western medicine group, there were no statistically significant differences in CIMT values ​​between the traditional Chinese medicine group and the integrated traditional Chinese and Western medicine group (P > 0.05).

[0058] A total of 237 patients were included in the study, and the baseline differences among the groups were not statistically significant, making them comparable. Within-group comparisons, there were statistically significant differences among the no-medication group, the traditional Chinese medicine group, and the integrated traditional Chinese and Western medicine group (P < 0.05). Specifically, the plaque area increased in the no-medication group, while the plaque area decreased in the traditional Chinese medicine group and the integrated traditional Chinese and Western medicine group. There was no statistically significant change in plaque area before and after medication in the Western medicine group (P > 0.05).

[0059] Intergroup comparisons showed that, compared with the no-treatment group, the plaque area was smaller in the traditional Chinese medicine group and the integrated traditional Chinese and Western medicine group (P < 0.05), while there was no statistically significant difference in plaque area change in the Western medicine group (P > 0.05). Compared with the Western medicine group, the plaque area was smaller in the traditional Chinese medicine group and the integrated traditional Chinese and Western medicine group (P < 0.05).

[0060] Conclusion: Comparing the CIMT values ​​of CAS patients with kidney essence deficiency before and after medication, the CIMT values ​​of the proposed kidney-tonifying and turbidity-resolving traditional Chinese medicine decreased after treatment compared with those before treatment and with the untreated group, showing a statistically significant difference in efficacy; however, there was no statistically significant difference compared with the Western medicine group.

[0061] Comparing the plaque area before and after medication in patients with CAS of kidney essence deficiency, the plaque area decreased after treatment with the proposed kidney-tonifying and turbidity-resolving traditional Chinese medicine compared with the pre-treatment group and the untreated group, with statistically significant differences in efficacy; compared with the Western medicine group, the plaque area in the traditional Chinese medicine group decreased with statistically significant differences.

[0062] Analysis shows that traditional Chinese medicine intervention using the kidney-tonifying and turbidity-resolving method can significantly reduce CIMT values ​​and carotid plaque area. Western medicine intervention, however, can only reduce CIMT values ​​and has no significant improvement in plaque area reduction. The mechanisms of atherosclerosis are multifaceted, and current views largely suggest that atherosclerosis is related to inflammation, immunity, and blood lipids. Statins only act on some mechanisms, while traditional Chinese medicine compound formulas have the advantage of multi-target regulation. Therefore, although lipid regulation (especially the regulation of low-density lipoprotein) may not be superior to statins, its effect on slowing the progression of atherosclerosis and stabilizing plaques is no less than that of statins, and may even be superior. This result has also been confirmed in our previous RCT studies.

[0063] Combining all the above technical solutions, the advantages and positive effects of this invention are as follows:

[0064] CIMT values ​​before and after medication in CAS patients with kidney essence deficiency were found to be lower after treatment with the declared kidney-tonifying and turbidity-resolving traditional Chinese medicine compared to before treatment and the untreated group.

[0065] Traditional Chinese medicine intervention using the kidney-tonifying and turbidity-resolving method can significantly reduce CIMT values ​​and carotid plaque area; the compound Chinese medicine has the advantage of multi-target regulation. Although its lipid regulation (especially the regulation of low-density lipoprotein) may not be superior to statins, its effect of slowing down the process of atherosclerosis and stabilizing plaques is no less than that of statins, and may even be better.

[0066] Professor Gu Yun has over thirty years of clinical experience treating geriatric diseases and studied under several nationally renowned traditional Chinese medicine experts, including Lin Shuimiao. In the prevention and treatment of ankylosing spondylitis (AS), while inheriting and developing Professor Lin's theory of "deficiency of essence and blood," he also emphasizes individualized treatment based on syndrome differentiation. Through a long-term follow-up study of 679 patients with carotid atherosclerosis (unpublished), Professor Gu Yun used factor and cluster analysis and other analytical methods to summarize six common syndrome types. All of these showed deficiency of kidney essence and qi, with mixed deficiency and excess patterns frequently observed, further confirming the "deficiency of essence and blood" theory of AS. The Ruanmai Decoction is a compound formula determined based on Professor Lin's principle of "returning essence," derived from the decomposition of kidney-tonifying formulas. Its efficacy in treating AS is significantly superior to the phlegm-resolving and blood-activating compound formula used in the control group during the same period.

[0067] The Ruanmai Decoction, composed of Rehmannia glutinosa, Astragalus membranaceus, and Cistanche deserticola, balances the effects of both mild and strong herbs, harmonizing Yin and Yang. It can replenish kidney essence and benefit kidney Qi, achieving a good therapeutic effect on AS. Rehmannia glutinosa is the chief herb, replenishing essence and marrow, nourishing blood and Yin. The Compendium of Materia Medica states that it "replenishes deficiencies in the five internal organs, unblocks blood vessels, replenishes bone marrow, strengthens muscles, and generates essence and blood." Astragalus membranaceus is the assistant herb, replenishing Qi and benefiting essence. The Compendium of Materia Medica states that it is "the leader of tonics." Together with Cistanche deserticola, it enhances the replenishment of vital Qi and benefits essence and blood. Gynostemma pentaphyllum and lotus leaf are added to benefit Qi, promote diuresis, and resolve turbidity, while hawthorn removes blood stasis and promotes Qi circulation. Tangerine peel is used to regulate Qi and resolve phlegm, inhibiting the nourishing and cloying nature of Rehmannia glutinosa and Astragalus membranaceus. Attached Figure Description

[0068] Figure 1 This invention provides a comparison of CIMT values ​​in different treatment groups before and after medication for patients with kidney essence deficiency type CAS.

[0069] Figure 2 This is a comparison of plaque area before and after medication in CAS patients with kidney essence deficiency. Detailed Implementation

[0070] To enable those skilled in the art to better understand the present invention, the technical solution of the present invention will be further described below in conjunction with the accompanying drawings and embodiments. It should be noted that all directional indications (such as up, down, left, right, front, back, etc.) in the embodiments of the present invention are only used to explain the relative positional relationship and movement of the components in a certain specific posture (as shown in the accompanying drawings). If the specific posture changes, the directional indication will also change accordingly.

[0071] Furthermore, the use of terms such as "first" and "second" in this invention is for descriptive purposes only and should not be construed as indicating or implying their relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined with "first" or "second" may explicitly or implicitly include at least one of that feature. Additionally, the technical solutions of the various embodiments can be combined with each other, but only on the basis of being achievable by those skilled in the art. When the combination of technical solutions is contradictory or impossible to implement, such a combination of technical solutions should be considered non-existent and not within the scope of protection claimed by this invention.

[0072] Example:

[0073] like Figure 1-2 As shown, a traditional Chinese medicine compound for tonifying the kidneys and clearing turbidity consists of 15 parts Rehmannia glutinosa (processed), 15 parts Astragalus membranaceus (raw), 9 parts Cistanche deserticola, 10 parts Nelumbo nucifera (lotus leaf), 20 parts Gynostemma pentaphyllum, 12 parts Crataegus pinnatifida, and 6 parts Citrus reticulata (dried tang

[0074] (1) Weigh out the proportions of Rehmannia glutinosa, Astragalus membranaceus, Cistanche deserticola, Nelumbo nucifera leaf, Gynostemma pentaphyllum, Crataegus pinnatifida, and Citrus reticulata peel;

[0075] (2) Add water to submerge the herbs and soak for 2 hours. Then heat over high heat until boiling and simmer over low heat for 30 minutes to extract the medicinal juice.

[0076] (3) Add water to the remaining dregs in step (2) until they are submerged, soak for 30 minutes, then heat over high heat until boiling, and simmer over low heat for 30 minutes to extract the medicinal juice.

[0077] (4) After mixing the medicinal juices prepared in steps (2) and (3), concentrate them over a low flame to 300-400 ml, store them in a refrigerator at 4°C for later use, and take them twice a day.

[0078] The anti-atherosclerotic application includes the following steps:

[0079] (1) Cases included in the study:

[0080] The study subjects were patients from the AS specialist outpatient clinic, geriatric outpatient clinic, and geriatric ward of Longhua Hospital. The observation period started in June 2018 and ended in December 2019. Patients who met the TCM diagnosis of kidney essence deficiency and the Western medicine CAS criteria were selected. The observational study was conducted with the informed consent of the patients. The follow-up time of the included cases was analyzed. There were 53 cases in the no-medication group with a median follow-up time of 195.5 days, 68 cases in the TCM group with a median follow-up time of 201 days, 97 cases in the Western medicine group with a median follow-up time of 185.5 days, and 62 cases in the integrated TCM and Western medicine group with a median follow-up time of 182 days. There was no statistically significant difference between the groups (P>0.05).

[0081] 1) Diagnostic criteria for kidney essence deficiency in Traditional Chinese Medicine:

[0082] Based on the "Guiding Principles for Clinical Research of Traditional Chinese Medicine (New Drugs)" published by the Ministry of Health of the People's Republic of China in 2002, and in conjunction with the fifth edition of the textbook "Traditional Chinese Medicine Diagnostics" for higher medical colleges.

[0083] Main symptoms: soreness and weakness of the lower back and knees, hair loss and loose teeth, forgetfulness, tinnitus, and deafness.

[0084] Secondary symptoms: lethargy, weakness in the legs.

[0085] Pulse diagnosis: Weak pulse

[0086] Two of the primary symptoms must be present, and one of the secondary symptoms must be present. Combined with pulse diagnosis, a diagnosis can be made.

[0087] 2) CAS diagnostic criteria:

[0088] 1) Referring to the definition in the 2003 European Heart Association guidelines for the treatment of hypertension, a carotid intima-media thickness (CIMT) ≥ 0.9 mm is considered a CAS.

[0089] 3) Inclusion criteria:

[0090] ① Age ≥ 50 years old;

[0091] ② Meets the diagnostic criteria for kidney essence deficiency in Traditional Chinese Medicine;

[0092] ③ Meets the diagnostic criteria for carotid atherosclerosis;

[0093] ④ Able to understand the contents of the questionnaire and participate voluntarily.

[0094] 4) Exclusion criteria:

[0095] ① Patients who have participated in other clinical studies;

[0096] ② Patients with severe primary diseases affecting other systems and impacting their daily lives;

[0097] ③Those who have undergone surgery or suffered trauma within the past 4 weeks;

[0098] ④ Individuals infected with tuberculosis and other infectious diseases;

[0099] ⑤ Meets the inclusion criteria but used traditional Chinese medicine other than the kidney-tonifying and turbidity-resolving method.

[0100] 5) Exclusion criteria:

[0101] ① Cases that were mistakenly included because the case selection did not meet the inclusion criteria;

[0102] ② Those whose carotid artery ultrasound data is incomplete and cannot be completed according to the research plan;

[0103] ③Loss to follow-up.

[0104] (2) Grouping:

[0105] Based on whether patients received traditional Chinese medicine intervention using the kidney-tonifying and turbidity-resolving method as an exposure factor, patients were divided into four groups: no medication group, traditional Chinese medicine group, Western medicine group, and integrated traditional Chinese and Western medicine group. Patients in the no medication group served as a blank control. Patients in the traditional Chinese medicine group received a traditional Chinese medicine treatment regimen with the kidney-tonifying and turbidity-resolving method as the main treatment principle. Patients in the Western medicine group received a statin medication regimen. Patients in the integrated traditional Chinese and Western medicine group received both the kidney-tonifying and turbidity-resolving traditional Chinese medicine intervention regimen and statin medication.

[0106] (3) Measurement of CIMT values ​​and plaque areas in included cases:

[0107] CIMT values ​​and plaque areas were measured at the time of enrollment and every 180 days after enrollment.

[0108] Measurements were performed using a color Doppler ultrasound system from Esaote, Italy, with a probe frequency of 5.0-10.0 MHz. The procedure was performed by designated professional operators in the hospital's ultrasound department.

[0109] 1) The patient lies supine with their head turned to the opposite side. Bilateral CIMT and internal carotid artery blood flow velocity are measured. Measurements are taken starting from the point where the arterial structure is clearest on the imaging. The distance between the intima-media interface and the media-adventitia interface of the arterial lumen is marked. Three measurements are taken, and the average of the three measurements is the final result, which is the CIMT. Measurements are taken on both sides equally, avoiding plaques.

[0110] 2) If plaques have formed on the patient's neck, observe them using color Doppler blood flow imaging to measure the nature, location, and size of the plaques.

[0111] 3) Patch area calculation: The patch area is determined by multiplying the transverse diameter and longitudinal diameter of the patch.

[0112] (5) Data processing: The measured data were analyzed using Foxtable and SPSS 20.0 statistical software. If the data followed a normal distribution and had homogeneous variance, the statistical description was expressed as (x±s); if the data did not follow a normal distribution, the statistical description was expressed as the median M, the minimum value (min) and the maximum value (max).

[0113] (6) Results analysis: A total of 237 patients were included in the CIMT statistics. There were no statistically significant differences in baseline values ​​among the groups, making them comparable. Within-group comparisons, the CIMT value of the untreated group increased (P<0.05), while the CIMT values ​​of the Western medicine group, traditional Chinese medicine group, and integrated traditional Chinese and Western medicine group decreased after treatment (P<0.05).

[0114] Intergroup comparisons showed that, compared with the untreated group, the CIMT values ​​of the traditional Chinese medicine group, the Western medicine group, and the integrated traditional Chinese and Western medicine group were all reduced (P < 0.05). Compared with the Western medicine group, there were no statistically significant differences in CIMT values ​​between the traditional Chinese medicine group and the integrated traditional Chinese and Western medicine group (P > 0.05).

[0115] A total of 237 patients were included in the study, and the baseline differences among the groups were not statistically significant, making them comparable. Within-group comparisons, there were statistically significant differences among the no-medication group, the traditional Chinese medicine group, and the integrated traditional Chinese and Western medicine group (P < 0.05). Specifically, the plaque area increased in the no-medication group, while the plaque area decreased in the traditional Chinese medicine group and the integrated traditional Chinese and Western medicine group. There was no statistically significant change in plaque area before and after medication in the Western medicine group (P > 0.05).

[0116] Intergroup comparisons showed that, compared with the no-treatment group, the plaque area was smaller in the traditional Chinese medicine group and the integrated traditional Chinese and Western medicine group (P < 0.05), while there was no statistically significant difference in plaque area change in the Western medicine group (P > 0.05). Compared with the Western medicine group, the plaque area was smaller in the traditional Chinese medicine group and the integrated traditional Chinese and Western medicine group (P < 0.05).

[0117] (7) Conclusion: Comparing the CIMT values ​​of CAS patients with kidney essence deficiency before and after medication, the CIMT values ​​of the Chinese herbal medicine for tonifying the kidney and eliminating turbidity decreased after treatment compared with those before treatment and compared with the untreated group, and the efficacy was statistically different; compared with the Western medicine group, there was no statistical significance.

[0118] Comparing the plaque area before and after medication in patients with CAS of kidney essence deficiency, the plaque area decreased after treatment with the proposed kidney-tonifying and turbidity-resolving traditional Chinese medicine compared with the pre-treatment group and the untreated group, with statistically significant differences in efficacy; compared with the Western medicine group, the plaque area in the traditional Chinese medicine group decreased with statistically significant differences.

[0119] The advantage of this embodiment is that the traditional Chinese medicine intervention of tonifying the kidney and resolving turbidity can significantly reduce CIMT values ​​and carotid plaque area. In contrast, Western medicine intervention can only reduce CIMT values, without significantly improving plaque area reduction. The mechanisms of atherosclerosis are multifaceted. Currently, many believe that atherosclerosis is related to inflammation, immunity, and blood lipids. Statins only act on some mechanisms, while traditional Chinese medicine compound formulas have the advantage of multi-target regulation. Therefore, although lipid regulation (especially the regulation of low-density lipoprotein) may not be superior to statins, its effect in slowing the progression of atherosclerosis and stabilizing plaques is no less than, and may even be superior to, statins. This result has also been confirmed in our previous RCT studies.

[0120] The above descriptions are merely embodiments of the present invention. Commonly known structures and characteristics of the solutions are not described in detail here. Those skilled in the art are aware of all common technical knowledge in the field prior to the application date or priority date, are aware of all existing technologies in that field, and have the ability to apply conventional experimental methods prior to that date. Those skilled in the art can, under the guidance of this application, improve and implement this solution in combination with their own capabilities. Some typical known structures or methods should not be obstacles for those skilled in the art to implement this application. It should be noted that those skilled in the art can make several modifications and improvements without departing from the structure of the present invention. These should also be considered within the scope of protection of the present invention, and will not affect the effectiveness of the implementation of the present invention or the practicality of the patent.

Claims

1. A traditional Chinese medicine compound for tonifying the kidneys and clearing turbidity, characterized in that, The kidney-tonifying and turbidity-resolving traditional Chinese medicine compound is composed of the following raw material components, by mass parts: 15-20 parts of Rehmannia glutinosa, 15-20 parts of Astragalus membranaceus, 9-15 parts of Cistanche deserticola, 10-20 parts of Nelumbo nucifera leaf, 20-30 parts of Gynostemma pentaphyllum, 12-20 parts of Crataegus pinnatifida, and 6-12 parts of Citrus reticulata peel.

2. The kidney-tonifying and turbidity-resolving traditional Chinese medicine compound according to claim 1, characterized in that, The kidney-tonifying and turbidity-clearing traditional Chinese medicine compound is composed of the following raw material components, by mass parts: 15-18 parts of Rehmannia glutinosa, 15-18 parts of Astragalus membranaceus, 9-12 parts of Cistanche deserticola, 10-15 parts of Nelumbo nucifera leaf, 20-25 parts of Gynostemma pentaphyllum, 12-18 parts of Crataegus pinnatifida, and 6-10 parts of Citrus reticulata peel.

3. The traditional Chinese medicine compound for tonifying the kidney and resolving turbidity according to claim 1, characterized in that, The herbal compound for tonifying the kidneys and dispelling turbidity is characterized in that it is composed of the following raw material components, in parts by weight: 15 parts Rehmannia glutinosa, 15 parts Astragalus membranaceus, 9 parts Cistanche deserticola, 10 parts Nelumbo nucifera, 20 parts Gynostemma pentaphyllum, 12 parts Crataegus pinnatifida, and 6 parts Citrus reticulata.

4. A method for preparing a kidney-tonifying and turbidity-resolving traditional Chinese medicine compound according to any one of claims 1 to 3, characterized in that, The preparation method of the kidney-tonifying and turbidity-resolving traditional Chinese medicine compound includes the following steps: (1) Weigh out the proportions of Rehmannia glutinosa, Astragalus membranaceus, Cistanche deserticola, Nelumbo nucifera leaf, Gynostemma pentaphyllum, Crataegus pinnatifida, and Citrus reticulata peel; (2) Add water to submerge the herbs, soak for 2 hours, then heat over high heat to a boil, simmer over low heat for 30 minutes to extract the medicinal juice; (3) Add water to the remaining dregs from step (2) until they are submerged, soak for 30 minutes, then heat over high heat until boiling, and simmer over low heat for 30 minutes to extract the medicinal juice. (4) After mixing the medicinal juices prepared in steps (2) and (3), concentrate them over a low flame to 300-400 ml, store them in a refrigerator at 4°C for later use, and take them twice a day.

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