Traditional Chinese medicine composition as well as preparation and application thereof

Abstract

The invention belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition and a preparation and application thereof. A compatibility system of monarch, minister, assistant and guide is adopted, rhizoma atractylodis, semen coicis and cortex phellodendri are taken as monarch drugs, polygonum cuspidatum, centella asiatica and fructus kochiae are taken as minister drugs, prepared rheum officinale, radix achyranthis bidentatae and caulis spatholobi are taken as guide drugs, gynostemma pentaphyllum, radix paeoniae alba and rhizoma polygonati are taken as adjuvant drugs, the medicinal materials are compounded according to a specific mass ratio, and the mass ratio of the monarch drugs to the minister drugs to the adjuvant drugs to the guide drugs is (50-80): (50-80): (30-55): (35-70). The traditional Chinese medicine composition provided by the invention can remarkably reduce the levels of blood uric acid, serum creatinine and urea nitrogen, reduce urine protein excretion and improve inflammation, a hypercoagulation state and lipid metabolism disorder, the total effective rate reaches 90%, the adverse reaction is slight, and the recurrence rate is low.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine, specifically relating to a traditional Chinese medicine composition, its preparation and application. Background Technology

[0002] Chronic uric acid nephropathy is caused by excessive production or reduced excretion of uric acid in the blood, leading to urate deposition in the kidneys and causing damage. Middle-aged and elderly men are the most susceptible group. Modern medicine focuses on lowering blood uric acid levels as the core treatment, but commonly used drugs have significant adverse reactions, and some even exacerbate kidney damage, limiting clinical treatment options. Meanwhile, hyperuricemia, as a major contributing factor, although sometimes asymptomatic and considered "pre-disease," easily progresses to complications such as gout and kidney damage, requiring early intervention.

[0003] Traditional Chinese medicine (TCM) does not have a specific disease name for chronic uric acid nephropathy. Based on symptoms, it can be categorized under terms such as "heat strangury," "stone strangury," "lower back pain," and "asthenia." Its pathogenesis is mostly characterized by deficiency of the root and excess of the branch. The root deficiency is primarily due to insufficiency of the liver and kidneys, and deficiency of both qi and yin. The branch excess is mainly due to internal accumulation of damp-heat, internal obstruction of blood stasis, and obstruction of the collaterals by turbid toxins. In recent years, TCM has made progress in the prevention and treatment of this disease. For example, Jin Zhouhui's modified Si Miao Fang (Four Marvelous Formulas) has shown good efficacy in patients with damp-heat and turbid blood stasis, providing insights for the development of subsequent formulas.

[0004] Based on the theory of regulating the three jiaos to treat kidney deficiency, previous studies have found that kidney-tonifying and spleen-strengthening, dampness-resolving and turbidity-reducing formulas can lower blood uric acid, inhibit uric acid synthesis, reduce urinary protein excretion, and protect the kidneys in the prevention and treatment of hyperuricemia and uric acid nephropathy, with fewer adverse reactions. Modern medicine has clearly defined the core mechanism of hyperuricemia and uric acid nephropathy as uric acid metabolism imbalance and subsequent inflammation and oxidative stress-mediated kidney damage, providing modern medical evidence for the target of traditional Chinese medicine formulas. To further optimize the treatment plan, targeting the complex pathogenesis of "damp-heat constitution + chronic strain," a dampness-resolving and turbidity-reducing traditional Chinese medicine composition integrating heat-clearing and dampness-removing, blood-activating and collateral-dredging, and yin-nourishing and kidney-tonifying formulas has been developed to compensate for the shortcomings of existing treatments. Summary of the Invention

[0005] To address the aforementioned technical problems, the first aspect of this invention provides a traditional Chinese medicine composition comprising a principal drug, an assistant drug, a adjuvant drug, and a guiding drug.

[0006] As an feasible example, the principal herbs include Atractylodes lancea (Thunb.) DC., Coix lacryma-jobi L. var. ma-yuen (Roman.) Stapf., and Phellodendron chinense Schneid.

[0007] As an example of an implementable practice, the medicinal herbs mentioned include Polygonum cuspidatum (Reynoutria japonica Houtt.), Centella asiatica (L.) Urban, and Kochia scoparia (L.) Schrad.

[0008] As an example of an implementable approach, the adjuvants include prepared rhubarb (Rheum palmatum L.), achyranthes bidentata Blume (Achyranthes bidentata Blume), and Spatholobus suberectus Dunn.

[0009] As an example of an implementable practice, the medicinal ingredients include Gynostemma pentaphyllum (Thunb.) Makino, Paeonia lactiflora Pall., and Polygonatum sibiricum Delar. ex Redoute.

[0010] Atractylodes lancea: It is warm in nature and enters the spleen, stomach and liver meridians. It has the effects of drying dampness and strengthening the spleen, dispelling wind and cold, enhancing the digestive function of the spleen and stomach, reducing the internal generation of dampness and turbidity, and is a basic medicinal material for clearing damp heat.

[0011] Job's tears: It is cool in nature and enters the spleen, stomach and lung meridians. It has the effects of strengthening the spleen and removing dampness, promoting diuresis and reducing swelling. It can gently drain damp heat in the lower burner and relieve symptoms such as edema of the limbs and scanty urination.

[0012] Phellodendron bark: It is cold in nature and enters the kidney and bladder meridians. It has the effects of clearing heat and drying dampness, purging fire and detoxifying. It is good at clearing damp heat in the lower jiao and is effective for damp heat syndromes such as yellow and reddish urine and yellow and greasy tongue coating.

[0013] Polygonum cuspidatum: It is cold in nature and enters the liver, gallbladder and lung meridians. It has the effects of promoting diuresis and relieving jaundice, clearing heat and detoxifying, dispersing blood stasis and relieving pain. It can enhance the effects of clearing damp heat in the liver and gallbladder and removing blood stasis and toxins.

[0014] Centella asiatica: It is cold in nature and enters the liver, spleen and kidney meridians. It has the effects of clearing heat and dampness, detoxifying and reducing swelling. It can help clear damp toxins from the body and reduce kidney inflammation and damage.

[0015] Kochia scoparia: It is cold in nature and enters the kidney and bladder meridians. It has the effects of clearing heat and dampness, dispelling wind and relieving itching. It can clear damp heat and guide the medicine to the surface, while also taking into account skin-related symptoms.

[0016] Prepared rhubarb: It is cold in nature and enters the spleen, stomach, large intestine, liver and pericardium meridians. It has the effects of purging heat and relieving constipation, cooling blood and detoxifying, and removing blood stasis and promoting menstruation. It can relieve blood stasis and heat and allow turbid toxins to be excreted through the stool.

[0017] Achyranthes bidentata: It is neutral in nature and enters the liver and kidney meridians. It has the effects of removing blood stasis and promoting menstruation, tonifying the liver and kidneys, strengthening tendons and bones, and guiding blood downward. It can guide the medicinal power directly to the lower jiao and is suitable for lower limb diseases and kidney diseases.

[0018] Chicken blood vine: It is warm in nature and enters the liver and kidney meridians. It has the effects of promoting blood circulation and nourishing blood, regulating menstruation and relieving pain, and relaxing muscles and tendons. It can clear the stagnation of kidney meridians and improve the state of internal obstruction of blood stasis.

[0019] Gynostemma pentaphyllum: It is cool in nature and enters the spleen and lung meridians. It has the effects of invigorating qi and strengthening the spleen, resolving phlegm and relieving cough, and clearing heat and detoxifying. It can replenish qi and clear deficiency heat, and avoid damage to qi and yin by clearing and draining drugs.

[0020] White peony root: slightly cold in nature, enters the liver and spleen meridians, has the effects of nourishing blood and regulating menstruation, astringing yin and stopping sweating, softening the liver and relieving pain. It can nourish yin and soften the liver, and moderate the warm and dry nature of drying and dampness-reducing drugs.

[0021] Polygonatum: It is neutral in nature and enters the spleen, lung and kidney meridians. It has the effects of replenishing qi and nourishing yin, strengthening the spleen, moistening the lungs and benefiting the kidneys. It can replenish qi and nourish yin, and also take into account the underlying pathogenesis of liver and kidney deficiency.

[0022] As an implementable example, the mass ratio of the principal drug, assistant drug, adjuvant drug and guiding drug is (50-80):(50-80):(30-55):(35-70).

[0023] As an feasible example, the mass ratio of Atractylodes lancea, Coix lacryma-jobi and Phellodendron chinense is (10-20):(30-40):(10-20).

[0024] Furthermore, the mass ratio of Atractylodes lancea, Coix lacryma-jobi, and Phellodendron chinense is 12:30:12.

[0025] As an implementable example, the mass ratio of Polygonum cuspidatum, Centella asiatica and Kochia scoparia is (10-20):(10-20):(30-40).

[0026] Furthermore, the mass ratio of Polygonum cuspidatum, Centella asiatica, and Kochia scoparia is 15:15:30.

[0027] As an implementable example, the mass ratio of the prepared rhubarb, achyranthes bidentata and chicken blood vine is (10-20):(10-15):(10-20).

[0028] Furthermore, the mass ratio of the prepared rhubarb, achyranthes bidentata, and chicken blood vine is 15:12:15.

[0029] As an implementable example, the mass ratio of Gynostemma pentaphyllum, Paeonia lactiflora and Polygonatum sibiricum is (15-30):(10-20):(10-20).

[0030] Furthermore, the mass ratio of Gynostemma pentaphyllum, Paeonia lactiflora, and Polygonatum sibiricum is 20:15:15.

[0031] This application designates 15g of Polygonum cuspidatum, 15g of Centella asiatica, and 30g of Kochia scoparia as assistant herbs, primarily because this composition precisely matches the main pathogenesis of "dampness and turbidity obstruction," aligning with the role of assistant herbs in supporting the principal herb to strengthen the elimination of pathogenic factors. The principal herb, based on Atractylodes lancea, Coix lacryma-jobi, and Phellodendron chinense, forms the foundation of the "Three Marvelous Pill," specifically targeting damp-heat in the lower burner. Dampness and turbidity obstruction often coexist with other symptoms such as damp-heat in the liver and gallbladder, damp-toxin in the kidney meridians, and damp-heat in the skin. Polygonum cuspidatum, being cold in nature, can purge damp-heat in the liver and gallbladder, disperse blood stasis, and relieve pain; Centella asiatica, also cold in nature, can detoxify, promote diuresis, and protect the kidneys; and Kochia scoparia, being cold in nature, effectively clears damp-heat in the skin and guides the medicine to the exterior. These three herbs enhance the principal herb's ability to clear damp-heat and blood stasis from different dimensions, precisely targeting other symptoms such as abdominal distension and pain, dark yellow urine, kidney damage, and skin problems. In terms of dosage, 30g of Kochia scoparia ensures the ability to clear heat and reach the surface, while 15g each of Polygonum cuspidatum and Centella asiatica enhance the effect of clearing damp-heat and blood stasis. This is in line with the routine clinical dosage and forms a reasonable ratio with the principal drug to strengthen the synergistic effect of eliminating pathogens.

[0032] Meanwhile, this application designates 20g of Gynostemma pentaphyllum, 15g of Paeonia lactiflora, and 15g of Polygonatum sibiricum as adjuvant herbs, and 15g of Rheum palmatum, 12g of Achyranthes bidentata, and 15g of Spatholobus suberectus as guiding herbs. These two types of herbs together perfect the compatibility system of "combining attack and tonification, treating both the root cause and the symptoms." The adjuvant herbs address the shortcomings of the principal and assistant herbs, which are prone to drying and dampness, easily damaging Yin, and depleting Qi and Yin in prolonged illness. Paeonia lactiflora nourishes Yin and softens the liver to counteract dryness; Polygonatum sibiricum tonifies Qi and nourishes Yin to replenish liver and kidney deficiencies; and Gynostemma pentaphyllum tonifies Qi and clears deficiency heat to protect the body's vital energy. These three herbs form a "Yin-nourishing + Qi-tonifying + deficiency-heat-clearing" system to protect the body's vital energy, avoiding harm to the body's vital energy when expelling pathogens. The guiding herbs align with the pathogenesis of "blood stasis and heat accumulation, with the disease located in the lower body." Spatholobus suberectus invigorates blood and replenishes blood to clear stagnation; Rheum palmatum gently drains stagnant heat to guide turbid toxins out; and Achyranthes bidentata guides blood downwards to target the diseased area in the lower Jiao. These three herbs not only clear kidney meridian stagnation but also guide the medicinal power directly to the kidneys and lower limb lesions. In terms of dosage, 20g of Gynostemma pentaphyllum focuses on replenishing qi and clearing deficiency heat, while 15g each of Paeonia lactiflora and Polygonatum sibiricum balance yin and benefit the kidneys; 15g each of Rheum palmatum and Spatholobus suberectus ensure the efficacy of clearing stagnation and removing turbidity, and 12g of Achyranthes bidentata is suitable for guiding the medicine to the meridians. Each dosage takes into account both efficacy and safety, forming a hierarchical combination of "clearing and draining - supporting the body's resistance - clearing the meridians" with the principal and assistant herbs, which is precisely suitable for the complex pathogenesis of dampness and turbidity obstruction combined with liver and kidney deficiency.

[0033] A second aspect of the present invention provides a traditional Chinese medicine preparation, which is made from the above-mentioned traditional Chinese medicine composition.

[0034] As an feasible example, the dosage form of the traditional Chinese medicine preparation is one of the following: decoction, pill, tablet, powder, or ointment.

[0035] Furthermore, the dosage form of the aforementioned traditional Chinese medicine preparation is a decoction. The decoction is prepared by adding 400 mL of drinking water to the traditional Chinese medicine composition and decocting it down to 100 mL. The method of use for the decoction is to take it twice a day, 50 mL each time, in the morning and evening, while warm. One course of treatment is 14 days.

[0036] The third aspect of this invention provides an application of a traditional Chinese medicine composition in the preparation of a drug for treating uric acid.

[0037] Beneficial effects

[0038] (I) The traditional Chinese medicine composition in this application is based on "Sanmiao Pill" and integrates multiple methods such as clearing heat and dampness, promoting blood circulation and unblocking collaterals, nourishing yin and tonifying the kidneys to form a compatibility system of "combining attack and tonification, treating both the root cause and the symptoms". It precisely matches the core pathogenesis of dampness and turbidity obstruction and liver and kidney deficiency. It has a targeted therapeutic effect on gout, hyperuricemia and chronic uric acid nephropathy caused by dampness and turbidity obstruction. It can simultaneously improve multiple clinical symptoms such as dizziness and tinnitus, soreness of the waist and knees, edema of the limbs and swelling and pain of the feet and knees.

[0039] (II) Clinical data show that the traditional Chinese medicine composition of this application can significantly reduce the serum creatinine and blood urea nitrogen levels of patients, reduce the excretion of urinary microalbumin / urinary creatinine and urinary β2-microglobulin, and effectively delay the progression of chronic kidney disease by improving glomerular filtration function, reducing the deposition of urate in the renal tubules, and slowing down the damage to the renal tubules and interstitium. Compared with Western medicine treatment alone, it has more prominent advantages in protecting renal function.

[0040] (III) In addition to regulating uric acid and kidney function, the traditional Chinese medicine composition of this application can also significantly reduce the levels of C-reactive protein, D-dimer, fibrin degradation products and blood lipids. It can simultaneously improve inflammatory response, hypercoagulable state and lipid metabolism disorder, correct disease-related pathophysiological abnormalities from multiple targets, and achieve overall conditioning of the body.

[0041] (iv) In clinical application, the adverse reactions of the traditional Chinese medicine composition of this application are mainly mild symptoms such as diarrhea and skin itching, which can be relieved by adjusting the dosage of relevant drugs or by symptomatic treatment. No serious adverse reactions have occurred. Compared with some Western medicines that may aggravate the risk of kidney damage, this formula has better safety and is suitable for the long-term treatment needs of chronic diseases.

[0042] (V) Follow-up data showed that the recurrence rate of gout in patients taking the traditional Chinese medicine composition of this application was significantly lower than that in the control group, and there was no recurrence of urinary tract stones. Patients in the control group who switched to traditional Chinese medicine treatment also did not relapse. By improving the pathological basis and enhancing the body's resistance, it can effectively reduce the risk of disease recurrence and improve the stability and effectiveness of long-term treatment. Detailed Implementation

[0043] Example 1

[0044] This example provides a traditional Chinese medicine composition, which, by mass parts, consists of 54 parts of principal ingredient, 60 parts of assistant ingredient, 42 parts of adjuvant ingredient, and 50 parts of guiding ingredient.

[0045] The mass ratio of Atractylodes lancea, Coix lacryma-jobi, and Phellodendron chinense is 12:30:12; that is, 12g of Atractylodes lancea, 30g of Coix lacryma-jobi, and 12g of Phellodendron chinense.

[0046] The mass ratio of Polygonum cuspidatum, Centella asiatica and Kochia scoparia is 15:15:30; that is, 15g of Polygonum cuspidatum, 15g of Centella asiatica and 30g of Kochia scoparia.

[0047] The mass ratio of the prepared rhubarb, achyranthes bidentata, and chicken blood vine is 15:12:15; that is, 15g of prepared rhubarb, 12g of achyranthes bidentata, and 15g of chicken blood vine.

[0048] The mass ratio of Gynostemma pentaphyllum, Paeonia lactiflora and Polygonatum sibiricum is 20:15:15; that is, 20g of Gynostemma pentaphyllum, 15g of Paeonia lactiflora and 15g of Polygonatum sibiricum.

[0049] The second aspect of this invention provides a traditional Chinese medicine preparation, which is a decoction, also known as the Dampness-Clearing and Turbidity-Reducing Formula. The preparation method of the Dampness-Clearing and Turbidity-Reducing Formula decoction involves adding 400 mL of drinking water to the traditional Chinese medicine composition and decocting it down to 100 mL.

[0050] The method of using the decoction for dispelling dampness and reducing turbidity is to take it twice a day, 50mL each time in the morning and evening, warm. One course of treatment is 14 days.

[0051] The third aspect of this invention provides an application of a traditional Chinese medicine composition in the preparation of a drug for treating uric acid.

[0052] Performance Evaluation

[0053] 1. Medical record data

[0054] Medical record data is the primary source of clinical practice data. Currently, the vast majority of medical records are electronic, but some may still be in paper form. Generally, outpatient and emergency room medical records contain less information, with significant gaps in outpatient data, particularly regarding clinical outcome variables. These gaps directly impact the completeness of longitudinal data for individual cases, and the use of such data in clinical research should be approached with extreme caution.

[0055] Patient Information: Mr. Li, male, 55 years old. Initial consultation date: May 23, 2021. He has a history of hypertension for over 20 years, with regular use of antihypertensive medication and good control. He also has a history of hyperuricemia for 10 years, taking allopurinol 0.1g / day, with serum uric acid controlled at around 400μmol / L. Two months ago, the patient experienced a sudden onset of gout due to dietary indiscretion, with redness, swelling, and pain in the metatarsal joint of his left big toe. The symptoms were relieved after one week of benzbromarone treatment. Subsequent urinalysis revealed proteinuria (++), RBC (+++), and renal function tests showed a serum creatinine (Scr) of 155μmol / L, blood urea nitrogen (BUN) of 9.58 mmol / L, and urine output (UA) of 487 mmol / L. He also experienced morning facial edema, dizziness, headache, chest tightness, irritability, lower back pain, occasional nausea, loss of appetite, frequent urination at night, and constipation. His tongue was red with a thick, greasy white coating, and the veins under his tongue were tortuous. His pulse was soft and slippery. Blood routine examination showed: HB 95g / L; kidney ultrasound showed: left kidney 97mm×40mm, right kidney 100mm×43mm.

[0056] Western medical diagnosis: Chronic uric acid nephropathy (CKD stage 3), hypertension stage 3 (high-risk stage)

[0057] Traditional Chinese Medicine Diagnosis: Chronic renal failure (liver and kidney deficiency, internal accumulation of turbidity and blood stasis)

[0058] Prescription: Example 1, Dampness-Clearing and Turbidity-Reducing Formula.

[0059] After taking the dampness-resolving and turbidity-reducing formula for two weeks, the facial edema subsided, and the patient's symptoms of lower back pain, weakness, dizziness, and nausea improved. Bowel movements were 2-3 times per day. The tongue was pale red with a thin, greasy coating, and the veins under the tongue were tortuous. The pulse was deep and thready. A follow-up kidney function test showed: Scr 220 μmol / L, BUN 9.1 mmol / L.

[0060] Continue taking the above medication for two weeks to nourish the kidneys and spleen, and promote blood circulation.

[0061] After taking the above medication for 3 months, blood tests showed HB 106 g / L, Scr 106 μmol / L, BUN 7.8 mmol / L, and UA 387 mmol / L. Urinalysis showed protein (+). The patient complained of persistent lower back pain, occasional dizziness and headache, thin tongue coating, and a thready pulse; other symptoms were normal. The patient continued medication for 5 years, and renal function was satisfactorily controlled.

[0062] 2. Clinical trials

[0063] 2.1 Case Selection

[0064] Sixty patients with hyperuricemia and uric acid nephropathy who were treated at the outpatient and inpatient departments of the Department of Traditional Chinese Medicine (TCM) of our hospital (Pudong New Area People's Hospital) between July 2019 and December 2023 were selected. Western medicine diagnosis was based on the diagnostic criteria for hyperuricemia and uric acid nephropathy in *Nephrology* (4th edition). TCM syndrome differentiation criteria were based on the TCM syndrome differentiation criteria for liver and kidney deficiency with dampness and turbidity obstruction, as defined in *Diagnosis, Syndrome Differentiation and Efficacy Evaluation of Uric Acid Nephropathy*, formulated by the Nephrology Branch of the China Association of Traditional Chinese Medicine in 2008.

[0065] 1. Liver and kidney deficiency syndrome

[0066] Main symptoms of liver yin deficiency: dizziness, tinnitus, dry mouth and bitter taste;

[0067] The main symptoms of kidney qi deficiency are: lower back and knee pain, and edema of the limbs;

[0068] Secondary symptoms: fatigue, nausea and vomiting, joint swelling and pain, dry stools and throat.

[0069] Tongue and pulse characteristics: The tongue is red with a thin or little coating, and the pulse is deep, thready, or slippery.

[0070] 2. Dampness and turbidity syndrome

[0071] Main symptoms: nausea and vomiting, heaviness and fatigue.

[0072] Secondary symptoms: abdominal distension and sticky feeling in the mouth.

[0073] Tongue and pulse characteristics: The tongue coating is white and greasy or yellow and greasy (essential), and the pulse is soft and rapid.

[0074] 3. Blood stasis syndrome

[0075] Main symptoms: rough and dry skin, and dark purple lips.

[0076] Secondary symptoms: joint pain, chest tightness and abdominal distension.

[0077] Tongue and pulse characteristics: The tongue is red or has purple spots, the tongue body is swollen with teeth marks on the edges, the coating is white and greasy, and the pulse is thin and hesitant or wiry and tight.

[0078] Diagnostic suggestions: Dizziness and tinnitus, dry mouth and bitter taste, or dry stool and throat indicate liver yin deficiency syndrome; soreness and weakness in the lower back and knees, fatigue or edema of the limbs indicate kidney qi deficiency syndrome; nausea and vomiting, joint swelling and pain, greasy tongue coating and swollen tongue indicate damp-heat syndrome; dark tongue or ecchymosis indicates blood stasis syndrome.

[0079] A diagnosis can be made if two main symptoms are met, or one main symptom and two secondary symptoms are met.

[0080] 2.2 Inclusion Criteria

[0081] 1. Age 30-80 years old;

[0082] 2. It belongs to stage 2-4 of chronic kidney disease;

[0083] 3. According to traditional Chinese medicine syndrome differentiation, it belongs to the type of spleen and kidney deficiency with dampness and blood stasis.

[0084] 4. All patients signed informed consent forms;

[0085] 5. All patients were approved by our hospital's ethics committee and were monitored throughout the entire process.

[0086] 2.3 Exclusion Criteria

[0087] 1. Other secondary or primary kidney diseases, acute renal failure, ultrasound showing urinary tract obstruction, and late-stage joint stiffness and degeneration.

[0088] 3. Has received relevant treatment, which may affect the observation of the effect;

[0089] 3. Other physiological or pathological conditions that may affect the observation and judgment of effect indicators;

[0090] 4. Severe damage to the heart, liver, and kidneys can affect drug metabolism;

[0091] 5. Special populations: pregnant women, patients with mental illness, patients with critical illness, cancer patients, etc.

[0092] If a patient was receiving drug treatment before inclusion, and meets the inclusion criteria after the washout period, they will not be considered an excluded case.

[0093] 2.4 Exit Criteria

[0094] 1. Failure to take medication as prescribed makes it impossible to determine the efficacy of the treatment;

[0095] 2. Incomplete data makes it impossible to determine efficacy and safety;

[0096] 3. Severe adverse reactions, complications, or special physiological changes occur, making it difficult to continue treatment (those experiencing adverse reactions are included in the adverse reaction statistics);

[0097] 4. Use of drugs that affect efficacy. For cases that are withdrawn, the efficacy at the time of withdrawal will be included in the efficacy assessment.

[0098] 2.5 Treatment Methods

[0099] Patients were randomly assigned to a treatment group (n=30) and a control group (n=30) using a random number table. Both groups received a low-purine and low-salt diet, with a protein intake of 0.8–1.0 g / (kg·d), abstained from alcohol, and were given oral rhubarb sodium bicarbonate tablets to alkalize urine and maintain a urine pH of 6.0–6.5. The control group received febuxostat tablets 40 mg once daily until serum uric acid decreased to 360 μmol / L, at which point the dose was reduced to a maintenance dose of 20 mg once daily. The treatment group received the treatment formula, one dose daily, decocted in water and taken twice daily (morning and evening), for a course of 3 months for both groups.

[0100] 2.6. Observation Indicators

[0101] Both groups of patients underwent pretreatment and posttreatment testing for urinary β2-microglobulin (Uβ2MG), urinary microalbumin, urinary microalbumin / creatinine ratio (UACR), serum uric acid (UA), serum blood urea nitrogen (BUN), serum creatinine (Scr), CRP, and blood lipids such as cholesterol (TG), triglycerides (TG), and low-density lipoprotein (LDL). Serum D-dimer (DD) and fibrin degradation products (FDP) levels were measured using chemiluminescence immunoassay.

[0102] 2.7 Efficacy Criteria

[0103] According to the standard of the literature "Diagnosis, Syndrome Differentiation and Efficacy Evaluation of Uric Acid Nephropathy" (Trial Scheme), it is divided into clinical control, significant effect, effective and ineffective.

[0104] Clinical control: clinical symptoms and signs disappear, UA returns to normal, and renal function recovers or remains normal; urine tests show negative protein levels, or the red blood cell count in urine sediment is normal.

[0105] Significant effect: Clinical symptoms and signs are significantly improved; UA decreases by >20% compared to before; Scr and BUN remain normal or decrease by more than 50% compared to before; 24-hour urine protein quantification decreases by ≥40%, or urine sediment red blood cells decrease by ≥40%.

[0106] Effective: Clinical symptoms and signs have improved, UA has decreased by >10% and <20% compared to before, Scr and BUN remain normal or have decreased by >20% and <50% compared to before, 24-hour urine protein quantification has decreased by ≥40%, or urine sediment red blood cell count has decreased by <40%.

[0107] Ineffective: Those whose symptoms and signs do not improve significantly or worsen, whose UA is abnormal, whose Scr and BUN levels are unchanged or worsen, and whose urine tests show no change.

[0108] Overall effective rate = (number of clinically controlled cases + number of cases with significant effect + number of cases with effect) / total number of cases × 100%.

[0109] ② The clinical symptom scoring criteria are based on the Stanghellini scale, which is divided into 4 levels according to the severity of symptoms.

[0110] Asymptomatic cases score 0 points;

[0111] Symptoms are present but not obvious and do not affect daily work and life; this is considered mild and is scored as 1 point.

[0112] Symptoms are relatively common; mild impact on daily life is rated as moderate (2 points).

[0113] Severe symptoms, frequent occurrences, and impact on work and daily life are classified as severe (3 points).

[0114] 2.8 Statistical Methods

[0115] SPSS 18.0 software was used for statistical analysis. Quantitative data were expressed as mean ± standard deviation (x̄ ± s). For normally distributed data, independent samples t-tests or paired t-tests were used; for non-normally distributed data, rank-sum tests were used. Ridit analysis was used to compare rates between two groups. All data were two-tailed tests, and p < 0.05 was considered statistically significant.

[0116] Experimental Results Section

[0117] 2.9 General Information

[0118] The dampness-resolving and turbidity-reducing formula group consisted of 30 patients (22 males and 8 females), with an average age of (54.87±14.29) years and a disease duration of (4.77±3.62) years. The control group consisted of 30 patients (24 males and 6 females), with an average age of (49.30±12.91) years and a disease duration of (5.26±2.18) years. There were no statistically significant differences in baseline data (age, sex, disease duration, serum creatinine (Scr), acute ulceration (UA), and ulcer-reducing urinary tract infection (UACR)) between the two groups (P>0.05), making them comparable. Detailed experimental results are shown in Table 1.

[0119] Table 1 Comparison of the two sets of baseline data

[0120]

[0121] Among them, P>0.05.

[0122] 2.10 Comparison of changes before and after treatment

[0123] A comparison of clinical symptom changes before and after treatment showed that, in the group treated with the dampness-resolving and turbidity-reducing formula, the scores for dizziness and tinnitus, dry mouth and bitter taste, lower back and knee pain, fatigue, nausea and vomiting, abdominal distension, joint swelling and pain, and purplish tongue were significantly improved compared to before treatment (P<0.01). In the control group, there were statistically significant differences in lower back and knee pain, nausea and vomiting, abdominal distension, joint swelling and pain, and purplish tongue before and after treatment (P<0.05), while other symptoms showed no statistically significant differences compared to before treatment (P>0.05). The symptoms in both groups showed significant improvement compared to the control group (P<0.05 or P<0.01). Detailed experimental results are shown in Table 2.

[0124] Table 2 Comparison of changes in TCM syndrome scores before and after treatment in the two groups

[0125]

[0126] Note: Comparison before and after treatment: * P<0.05, ** P<0.01; Intergroup comparison: # P<0.05, ## P<0.01, the same applies below.

[0127] 2.11 Comparison of renal function indicators before and after treatment

[0128] After treatment, the levels of BUN, Scr, and UA in the Huashi Jiangzhuo formula group decreased compared to before treatment, and the differences were statistically significant (P<0.05 or P<0.01). In the control group, Scr and UA decreased compared to before treatment, and the differences were statistically significant (P<0.05). After treatment, compared with the control group, the Scr level in the Huashi Jiangzhuo formula group decreased significantly, and the difference was statistically significant (P<0.05). The experimental results are detailed in Table 3.

[0129] Table 3 Comparison of renal function before and after treatment in the two groups of patients.

[0130]

[0131] 2.12 Comparison of TCH, TG, and CRP levels before and after treatment in the two groups of patients.

[0132] Comparison of total cholesterol (TCH), triglycerides (TG), and C-reactive protein (CRP) levels before and after treatment in both groups. After treatment, TCH, TG, and CRP levels in both groups decreased compared to before treatment, with statistically significant differences (P<0.05, P<0.01). After treatment, the TCH, TG, and CRP levels in the Huashi Jiangzhuo formula group were significantly different from those in the control group (P<0.05, P<0.01). Detailed experimental results are shown in Table 4.

[0133] Table 4 Comparison of TCH, TG, and CRP levels before and after treatment in the two groups of patients.

[0134]

[0135] 2.13 Comparison of urinary microalbumin / urinary creatinine (UACR) and urinary β2-microglobulin between the two groups of patients

[0136] After treatment, the UACR and Uβ2-MG levels in the Huashi Jiangzhuo formula group improved compared to before treatment, with statistically significant differences (P<0.05 or P<0.01). Compared with the control group, the improvement was significant, with statistically significant differences (P<0.01). In the control group, UACR improved compared to before treatment, with statistically significant differences (P<0.01), while there was no statistically significant difference in Uβ2-MG compared to before treatment (P>0.05). Detailed experimental results are shown in Table 5.

[0137] Table 5 Comparison of UACR and U-β2-MG before and after treatment in the two groups

[0138]

[0139] 2.14 Comparison of D-dimer (DD) and fibrin degradation products (FDP) before and after treatment in both groups: DD and FDP levels in both groups decreased significantly after treatment compared to before treatment, with statistically significant differences (P<0.01). After treatment, the DD and FDP levels in the Huashi Jiangzhuo formula group were significantly different from those in the control group (P<0.05). Detailed experimental results are shown in Table 6.

[0140] Table 6 Comparison of DD and FDP before and after treatment in the two groups

[0141]

[0142] 2.15 Comparison of Clinical Efficacy

[0143] In the group treated with the dampness-resolving and turbidity-reducing formula, 5 out of 30 patients achieved clinical control, 15 showed significant improvement, 7 showed improvement, and 3 showed no improvement, with a total effective rate of 90%. In the control group, 8 patients showed significant improvement, 14 showed improvement, and 8 showed no improvement, with a total effective rate of 73.33%. Ridit analysis showed a statistically significant difference between the two groups (P<0.05). Detailed experimental results are shown in Table 7.

[0144] Table 7 Comparison of clinical efficacy before and after treatment in the two groups of patients (%)

[0145]

[0146] Ridit analysis: * P is less than 0.05.

[0147] 2.16 Adverse Reactions and Follow-up

[0148] All patients were followed up for 12 months after the observation period. In the group treated with the dampness-resolving and turbidity-reducing formula, two patients frequently experienced mild diarrhea, and one patient experienced skin itching. The mild diarrhea was relieved after adjusting the dosage of rhubarb sodium bicarbonate to one tablet per day, and the skin allergy improved after adding antihistamines. During the one-year follow-up, a total of 16 patients experienced gout recurrence, including 4 in the treatment group (13.33%) and 12 in the control group (40%). Two patients in the control group experienced more than two recurrences within one year, and five patients in the control group did not experience recurrence after switching to traditional Chinese medicine treatment. There were 3 cases of urinary tract stone recurrence, all of whom were patients in the control group. Two patients in the control group were switched to hemodialysis after their serum creatinine (Scr) levels exceeded 707 μmol / L.

[0149] Conclusion: Chronic uric acid nephropathy is caused by abnormal purine metabolism leading to increased uric acid production or impaired uric acid excretion, resulting in elevated blood uric acid levels and urate deposition in the kidneys, thereby damaging the normal structure and function of the kidneys. Western medicine treatment mainly involves inhibiting uric acid production with drugs such as allopurinol, but due to numerous adverse reactions, long-term use is difficult. Therefore, a combination of traditional Chinese and Western medicine is currently recommended. In traditional Chinese medicine, chronic uric acid nephropathy can be classified under the categories of "edema," "lower back pain," and "arthralgia." Its etiology is complex, its course is long, and its condition is prone to recurrence. Clinical diagnosis often presents with both deficiency and excess patterns, with deficiency patterns mainly indicating liver and kidney insufficiency, and excess patterns mainly indicating turbidity, blood stasis, and damp-heat. When the liver fails to regulate the flow of Qi, the ascending and descending functions become disordered, leading to dysfunction of the internal organs. This results in the failure to transform food and water into essential substances, forming dampness and turbidity. Prolonged dampness and turbidity can transform into heat, obstructing the meridians, hindering the flow of Qi and blood, and causing internal blood stasis. Where there is obstruction, there is pain, leading to gout. Over time, dampness and turbidity can further obstruct the kidney meridians, causing disharmony of the meridian Qi, kidney Qi deficiency, and impaired Qi transformation. This leads to turbidity and stasis accumulating in the lower back, potentially manifesting as urinary stones or cloudy urine. Undigested dampness and stagnant fluids can cause edema, urinary obstruction, and other complications; or dampness can congeal into blood stasis, and the combination of blood stasis and turbidity can lead to gouty tophi. Treatment should address both the root cause and the symptoms. Clinical treatment should adhere to the principles of soothing the liver, promoting diuresis, and eliminating turbidity (heat). When liver Qi flows smoothly and the ascending and descending functions of Qi are normal, the source of internal dampness and turbidity can be eliminated. Promoting diuresis and eliminating turbidity, and clearing the orifices (both urinary and fecal orifices), allows existing dampness and turbidity to be expelled through urination and defecation, providing an outlet for the pathogenic factors. Once dampness is eliminated, heat will naturally dissipate, and blood stasis will have no place to arise. Clinically, patients with gout and hyperuricemia often have a fondness for rich and fatty foods or are obese. They often exhibit symptoms of internal damp-heat or liver overactivity that suppresses the spleen and stomach, accompanied by damp-heat. During acute attacks, the affected joints are accompanied by redness, swelling, heat, and pain. According to the principle of "treating the symptoms in acute cases" in traditional Chinese medicine, the treatment focuses on clearing heat, promoting diuresis, and eliminating turbidity, supplemented by soothing the liver and strengthening the spleen.

[0150] The formula for resolving dampness and reducing turbidity provided by this invention, consisting of Atractylodes lancea, Coix lacryma-jobi, and Phellodendron chinense, primarily targets pathogenic factors and has the effects of clearing heat and promoting diuresis. Atractylodes lancea dries dampness and strengthens the spleen, Coix lacryma-jobi promotes diuresis and eliminates dampness, and Phellodendron chinense clears heat and dries dampness. These three herbs form the basis of the "Three Marvelous Pills," specifically targeting damp-heat in the lower burner and serving as the principal herbs. Polygonum cuspidatum drains damp-heat from the liver and gallbladder, Centella asiatica detoxifies and promotes diuresis, and Kochia scoparia clears damp-heat from the skin. The combination of these three herbs enhances the clearing power of the principal herbs against damp-heat and blood stasis. Paeonia lactiflora softens the liver and relieves pain, Polygonatum sibiricum tonifies qi and nourishes yin, and Gynostemma pentaphyllum tonifies qi and clears deficiency heat. These three herbs prevent the drying herbs from damaging yin and are suitable for those with long-term damp-heat depletion of qi and yin, serving as the adjuvant herbs. Spatholobus suberectus invigorates blood and nourishes blood, Achyranthes bidentata guides blood downward and strengthens tendons and bones, and Rheum palmatum gently drains blood stasis and heat. These three herbs target joint pain and constipation caused by the mutual binding of blood stasis and heat, and have the effect of clearing stagnation. The entire formula works synergistically to clear heat and promote diuresis, soothe the liver, strengthen the spleen and kidneys, invigorate blood and eliminate turbidity. Modern pharmacological studies show that Atractylodes lancea, Phellodendron chinense, Coix lacryma-jobi, and Achyranthes bidentata have antioxidant, free radical scavenging, cell metabolism-promoting, and diuretic effects, thereby regulating lipid and glucose metabolism disorders in glomerular diseases. Polygonum cuspidatum and Paeonia lactiflora have anti-inflammatory and antioxidant effects; Polygonatum sibiricum and Gynostemma pentaphyllum have effects such as reducing urinary albumin excretion, promoting liver albumin synthesis, lowering lipids, regulating immunity, and lowering blood pressure. Centella asiatica and processed rhubarb can significantly reduce Scr anhydride concentration and increase glomerular filtration rate, thereby accelerating the clearance of drugs primarily eliminated through renal excretion. Spatholobus suberectus has the effects of scavenging oxygen free radicals in tissues, inhibiting the migration of circulating neutrophils, and protecting renal vascular endothelial cells, thereby weakening the activation of immune molecules in renal tissue.

[0151] The above experimental results showed a statistically significant difference in the total effective rate between the treatment group and the control group (P<0.05). The treatment group was superior to the control group in improving CRP, serum uric acid, serum creatinine (Scr), and blood urea nitrogen (BUN), as well as reducing UACR and Uβ2-MG (P<0.05). Furthermore, the Huashi Jiangzhuo formula group was superior to the control group in regulating blood lipids and improving DD and FDP (P<0.05 or P<0.01). This suggests that the Huashi Jiangzhuo formula is effective in treating hyperuricemia and chronic uric acid nephropathy. It is speculated that this may be achieved by improving glomerular filtration, reducing urate deposition in the renal tubules, improving hypercoagulability and inflammation, and slowing down tubulointerstitial damage, thereby delaying the progression of chronic kidney disease.

Claims

1. A traditional Chinese medicine composition, characterized in that, This includes principal drugs, assistant drugs, adjuvant drugs, and guiding drugs; The principal herbs mentioned include Atractylodes lancea, Coix lacryma-jobi, and Phellodendron chinense; The medicinal ingredients mentioned include Polygonum cuspidatum, Centella asiatica, and Kochia scoparia. The adjuvant herbs mentioned include prepared rhubarb, achyranthes bidentata, and chicken blood vine; The medicinal ingredients include Gynostemma pentaphyllum, Paeonia lactiflora, and Polygonatum sibiricum.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The mass ratio of the principal drug, assistant drug, adjuvant drug and guiding drug is (50-80): (50-80): (30-55): (35-70).

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The mass ratio of Atractylodes lancea, Coix lacryma-jobi and Phellodendron chinense is (10-20):(30-40):(10-20).

4. The traditional Chinese medicine composition according to claim 1, characterized in that, The mass ratio of Polygonum cuspidatum, Centella asiatica and Kochia scoparia is (10-20):(10-20):(30-40).

5. The traditional Chinese medicine composition according to claim 1, characterized in that, The mass ratio of the prepared rhubarb, achyranthes bidentata and chicken blood vine is (10-20):(10-15):(10-20).

6. The traditional Chinese medicine composition according to claim 1, characterized in that, The mass ratio of Gynostemma pentaphyllum, Paeonia lactiflora and Polygonatum sibiricum is (15-30):(10-20):(10-20).

7. The traditional Chinese medicine composition according to claim 3, characterized in that, The mass ratio of Atractylodes lancea, Coix lacryma-jobi, and Phellodendron chinense is 12:30:

12.

8. The traditional Chinese medicine composition according to claim 4, characterized in that, The mass ratio of Polygonum cuspidatum, Centella asiatica and Kochia scoparia is 15:15:

30.

9. A traditional Chinese medicine preparation, characterized in that, Made from the traditional Chinese medicine composition as described in any one of claims 1 to 8.

10. An application of the traditional Chinese medicine composition according to any one of claims 1 to 8, characterized in that, It is used in the preparation of drugs for treating uric acid.

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