Traditional Chinese medicine composition for treating idiopathic membranous nephropathy and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating idiopathic membranous nephropathy and a preparation method thereof. The traditional Chinese medicine composition is prepared from the following raw materials in parts by mass: 12-45 parts of radix astragali (raw), 10-15 parts of radix stephaniae tetrandrae, 10-20 parts of angelica sinensis, 10-20 parts of radix paeoniae alba, 10-15 parts of ligusticum wallichii, 10-15 parts of peach kernels, 10-30 parts of rhizoma atractylodis macrocephalae (fried), 10-15 parts of rhizoma alismatis, 10-30 parts of poria cocos, 15-30 parts of rhizoma dioscoreae nipponicae, 15-30 parts of oldenlandia diffusa and 9-30 parts of plantain herb. Pharmacodynamic experiments prove that the radix astragali, radix angelicae sinensis and radix paeoniae alba formula has an obvious improvement effect on membranous nephropathy experimental models and related edema, proteinuria and renal functions of idiopathic membranous nephropathy patients.

Description

Technical Field

[0001] The present invention belongs to the field of medicine, and particularly relates to a traditional Chinese medicine composition for treating idiopathic membranous nephropathy and a preparation method thereof. Background Art

[0002] 1.1 The prevalence of idiopathic membranous nephropathy in China has been increasing year by year, and the clinical demand has not been met. Idiopathic membranous nephropathy (IMN) is an in-situ immune complex-mediated glomerulopathy. The prevalence of PMN in China accounts for about 20%-30% among nephropathy patients. The 2018 cross-sectional study of glomerular diseases across the country showed that in North China and Northeast China, PMN has now exceeded IgA nephropathy and become the most common primary glomerular disease; in other regions of China, the prevalence of PMN also shows a steady growth trend, and environmental factors and autoimmune mechanisms may be important inducements [1-3]. In 2023, the number of PMN patients in China was about 2.2 million, with a compound annual growth rate of 2.9% from 2018 to 2023. It is expected that the number of patients will increase to 2.7 million by 2032, with a compound annual growth rate of 2.5% from 2023 to 2032 [4].

[0003] Clinically, IMN mostly presents as nephrotic syndrome (24-hour urinary protein quantification > 3.5 g, serum albumin < 30 g / L, accompanied by hyperlipidemia and edema) or asymptomatic proteinuria; about 80% of patients have varying degrees of edema, and severe cases often have pleural effusion and ascites; less than 10% of patients are found to have renal insufficiency at the onset, and the remaining about 50% of patients, although with more proteinuria, can have relatively stable renal function for a long time. The other 50% of patients gradually develop renal impairment and progress to chronic renal failure 5 - 10 years after the onset. 10% - 60% have thromboembolic complications; increased infection events and malnutrition are also common. Treatment and evaluation mostly refer to the "Membranous Nephropathy" chapter in the 2021 Kidney Disease: Improving Global Outcomes (KDIGO). According to "proteinuria, plasma albumin, estimated glomerular filtration rate, serum anti-PLA2R antibody titer, response to RAS blocker treatment, and the presence of life-threatening complications", IMN is divided into "low, medium, high, and very high risk". The KDIGO guidelines recommend initiating immunosuppressive therapy for patients in the medium-high risk group and very high risk group with at least 1 disease progression factor. Commonly used drugs include alkylating agents (cyclophosphamide), glucocorticoids combined with calcineurin blockers (cyclosporine, tacrolimus), and rituximab, which can increase the complete remission rate and partial remission rate; the guidelines also point out the risks of the above drug treatments and require cautious use and monitoring of their risks [5]. However, in randomized clinical trials of recommended immunosuppressive therapy, up to 68% of patients failed to achieve remission within 12 months [6]. A large proportion of patients are in a state of severe nephrotic syndrome complications and disease progression for a long time, and the treatment cost is high.

[0004] Traditional Chinese medicine has a long history of preventing and treating kidney diseases. According to the different clinical manifestations of IMN, it can be classified into the categories of "edema", "turbid urine", and "consumptive disease" in traditional Chinese medicine. In 2021, led by the Chinese Association of Traditional Chinese Medicine, through systematic sorting of clinical research literature and expert questionnaires, the "Guidelines for Traditional Chinese Medicine Clinical Practice in Idiopathic Membranous Nephropathy" [7] was formed. The recommended opinion is that for low-risk IMN patients, on the basis of supportive treatment, single use of traditional Chinese medicine for 3 - 12 months can achieve a good overall remission rate; for medium-high risk IMN patients, on the basis of the commonly used immunosuppressive therapy regimen, combined use of traditional Chinese medicine or Chinese patent medicine can be considered, and the treatment course is at least 6 months. The drugs recommended by experts include: preparations of Tripterygium wilfordii, Shenyan Kangfu Tablets, Huangkui Capsules, Huobahua Gen Tablets, Kunxian Capsules, and Yishen Huashi Granules, but the recommended grades are all C or D; generally speaking, there is still a lack of satisfactory efficacy for medium-high risk IMN.

[0005] For IMN patients, whether the edema subsides or not is not only about improving symptoms, but also the main criterion for judging the effectiveness of treatment from the patient's perspective. If a certain treatment can reduce "edema", it will greatly improve the patient's compliance with treatment. Although various Western medicine diuretics are effective, long-term use poses risks such as electrolyte disorders, exacerbation of hyperuricemia, and disorders of sugar and lipid metabolism. Even inappropriate diuresis can bring risks such as acute kidney injury, hypotension, and thromboembolic events caused by increased blood viscosity. The drugs recommended in the "Clinical Practice Guidelines for Traditional Chinese Medicine in Idiopathic Membranous Nephropathy" mentioned above generally have weak diuretic and detumescence effects. Therefore, there is a great clinical need for a traditional Chinese medicine that can both promote the remission of membranous nephropathy and improve the symptoms of edema.

[0006] 2.2 The origin, formula analysis and clinical application of "Qifang Guishao Decoction" Professor Dai Xiwen, an old expert in our department, combined the classical Chinese medicine (《Inner Canon》, 《Synopsis of the Golden Chamber》) and his learning from famous Chinese medicine masters such as Yue Meizhong and Huang Jianbai, as well as the modern medical research on the mechanism of edema in nephrotic syndrome, and put forward the idea of differentiating and treating "edema" from the aspects of "qi, blood, and water". He believes that "qi, blood, and water" are mutually generated and transformed physiologically and interact pathologically [8]. Just as 《Synopsis of the Golden Chamber》 says: "When blood circulation is impaired, it will turn into water." 《Treatise on Blood Syndromes》 states: "If water accumulates and fails to transform, externally, the qi of Taiyang cannot reach, and sweating cannot occur; internally, body fluids cannot be generated, and phlegm and fluid interact. This is the case where qi disorder leads to water disorder." The general principle of nephrotic edema is "qi deficiency, blood stasis, and water retention", and good curative effects have been achieved by treating with "Fangji Huangqi Decoction or Fangji Fuling Decoction combined with Danggui Shaoyao Powder" [9]. Danggui Shaoyao San was first recorded in "Treatise on Febrile and Miscellaneous Diseases - Treatment of Miscellaneous Diseases of Women during Pregnancy" for "a pregnant woman with pain in the abdomen" and in "Miscellaneous Diseases of Women" for "various abdominal pains in women". It is composed of three liang of Angelica sinensis, one jin of Paeonia lactiflora, four liang of Poria cocos, four liang of Atractylodes macrocephala, half a jin of Alisma orientale, and half a jin of Ligusticum wallichii. "Formulary of the Taiping Benevolent Dispensary Bureau in the Song Dynasty" stipulates the proportion as: Paeonia lactiflora, Ligusticum wallichii, Alisma orientale, Angelica sinensis, Poria cocos, Atractylodes macrocephala in the ratio of 8:4:4:2:2:2; Efficacy: nourishing blood and regulating the liver, strengthening the spleen and promoting diuresis; In the formula, Angelica sinensis, Paeonia lactiflora, and Ligusticum wallichii soothe the liver, promote qi movement, and activate blood circulation; Poria cocos, Atractylodes macrocephala, and Alisma orientale strengthen the spleen and promote diuresis, being a representative formula for activating blood circulation and promoting diuresis. Fangji Huangqi Tang was first recorded in "Treatise on Febrile and Miscellaneous Diseases - Treatment of Spasms, Dampness, and Heatstroke": "For wind-dampness, with floating pulse, heavy body, sweating, and aversion to wind, Fangji Huangqi Tang is the main treatment." It is composed of "one liang of Stephania tetrandra, half liang of Glycyrrhiza uralensis (fried), seven qian and a half of Atractylodes macrocephala, and one liang and one fen of Astragalus membranaceus (removing the root sheath)"; It mainly treats edema caused by the deficiency of the exterior and the insecurity of the defensive qi, the invasion of the wind-damp pathogen into the muscle surface, and the stagnation of water-dampness in the muscle interstices. Fangji Fuling Tang was first recorded in "Treatise on Febrile and Miscellaneous Diseases - Treatment of Edema Disorders": "For skin edema, with swelling of the four limbs, water qi in the skin, and the four limbs twitching slightly" and is composed of "three liang of Stephania tetrandra, three liang of Astragalus membranaceus, three liang of Cinnamomum cassia, six liang of Poria cocos, and two liang of Glycyrrhiza uralensis"; The difference in the drug composition of the two formulas is that both use Stephania tetrandra, Astragalus membranaceus, and Glycyrrhiza uralensis to benefit qi, dispel wind, and promote diuresis; However, in Fangji Huangqi Tang, the disease is more on the exterior and the swelling is still mild; Fangji Fuling Tang is more towards the interior, and there is insufficiency of defensive yang, so Poria cocos is used heavily, Cinnamomum cassia is added, and the amount of Stephania tetrandra is also larger; For treating the syndrome of fluid retention in the muscles due to deficiency of the exterior, Dr. Dai would flexibly use these two formulas in combination with Danggui Shaoyao San according to the newness or duration of the onset of the patient, the severity of the swelling, and whether there is yang deficiency syndrome.

[0007] Based on the inheritance of Dr. Dai's academic experience and combined with the clinical application situation in our department, and in combination with the pathogenesis of IMN and the research progress of traditional Chinese medicine pharmacology, we modified and adjusted the drug doses of "Fangji Huangqi Tang or Fangji Fuling Tang combined with Danggui Shaoyao San", added new components, formed a new formula, named "Qi Fang Gui Shao Fang", and accumulated a large number of effective cases of using "Qi Fang Gui Shao Fang" to treat membranous nephropathy

[10] .

[0008] To further enhance the clinical value of this compound prescription, we conducted research on the pharmaceutics, summarized the clinical application, and carried out animal experiments, aiming to provide a new treatment option for patients with membranous nephropathy. Summary of the Invention

[0009] In view of the problem that the existing proprietary Chinese medicines for treating the symptoms of "proteinuria and edema" in idiopathic membranous nephropathy cannot meet the clinical needs, the present invention provides a traditional Chinese medicine composition for treating membranous nephropathy.

[0010] To achieve the above object, the present invention is realized through the following technical solutions: A traditional Chinese medicine composition for treating idiopathic membranous nephropathy is made from the following raw materials in parts by mass: 12 - 45 parts of astragalus (raw), 10 - 15 parts of stephania tetrandra, 10 - 20 parts of angelica sinensis, 10 - 20 parts of white peony root, 10 - 15 parts of chuanxiong rhizome, 10 - 15 parts of peach kernel, 10 - 30 parts of atractylodes macrocephala (fried), 10 - 15 parts of alisma orientale, 10 - 30 parts of poria cocos, 15 - 30 parts of dioscorea nipponica, 15 - 30 parts of oldenlandia diffusa, 9 - 30 parts of plantain herb.

[0011] Preferably, the traditional Chinese medicine composition is made from the following raw materials in parts by mass: 30 parts of astragalus (raw), 15 parts of stephania tetrandra, 15 parts of angelica sinensis, 15 parts of white peony root, 15 parts of chuanxiong rhizome, 15 parts of peach kernel, 15 parts of atractylodes macrocephala (fried), 15 parts of alisma orientale, 22.5 parts of poria cocos, 30 parts of dioscorea nipponica, 30 parts of oldenlandia diffusa, 22.5 parts of plantain herb.

[0012] The raw materials for making the traditional Chinese medicine composition of the present invention are in parts by mass as the ratio. During production, it can be increased or decreased according to the corresponding ratio. For example, in large - scale production, it can be in kilograms or tons, and in small - scale production, it can also be in grams. The weight can be increased or decreased, but the mass ratio of the raw materials among the components remains unchanged.

[0013] The present invention also provides a preparation method of the above - mentioned traditional Chinese medicine composition.

[0014] The preparation method of the above - mentioned traditional Chinese medicine composition provided by the present invention includes the following steps: Mix the twelve traditional Chinese medicine materials for making the traditional Chinese medicine composition, soak them in water and then decoct. After the decoction is completed, filter and collect the decoction liquid, thus obtaining the water - decocted agent (decoction) of the traditional Chinese medicine composition.

[0015] In order to further obtain a solid traditional Chinese medicine composition, the method further includes: Concentrate and dry the water - decocted agent (decoction) of the traditional Chinese medicine composition to make a dry extract, and then crush the dry extract to obtain the powder of the traditional Chinese medicine composition.

[0016] In the above method, the soaking conditions are: Add 5 - 10 times the total mass of the traditional Chinese medicine materials of water and soak for 30 - 60 minutes; Preferably, the soaking conditions are: Add 10 times the total mass of the traditional Chinese medicine materials of water and soak for 45 minutes.

[0017] In the above method, the decoction is preferably carried out 3 times, each time for 0.5 hours, then filter and combine the decoction liquids of the 3 times.

[0018] In the above method, the specific method for concentrating and drying the water - decocted agent (decoction) of the traditional Chinese medicine composition is as follows: Concentrate the water - decocted agent (decoction) of the traditional Chinese medicine composition under reduced pressure to a relative density of 1.25 - 1.30 (50 °C), and then dry it under vacuum at 60 °C with a pressure of 0.08 MPa - 0.1 Mpa to obtain a dry extract.

[0019] Furthermore, the powder of the Chinese medicine composition can be used as a raw material, and auxiliary materials can be added to prepare solid preparations such as granules. The specific preparation method is as follows: add dextrin (about 0.4-0.5 times the amount) to the Chinese medicine combination powder, mix evenly, use 85% ethanol by volume as a wetting agent, the amount is 8-10%, mix for 10-15 minutes, and prepare soft materials; the qualified soft materials are granulated with a 14-mesh sieve using a swing granulator, dried at 50-60°C for 2-4 hours, and the dry granules are screened with 16-mesh and 40-mesh sieves, and the undersize of the 40-mesh sieve is collected, and the qualified granules are packaged in aluminum foil bags, 8-8.6g per bag.

[0020] At the same time, in order to facilitate the adjustment and avoid the step of decoction, each Chinese herbal medicine (such as Chinese herbal medicine slices) can be replaced with a corresponding amount of raw medicine in the market. The Chinese herbal medicine granules of each Chinese herbal medicine can be directly mixed. When using, it can be taken with boiled water.

[0021] "Chinese herbal formula granules" refer to single-ingredient Chinese herbal pieces that are extracted according to the Chinese herbal preparation extraction method, using appropriate solvents and procedures to extract the soluble active ingredients, and then concentrated and dried to make powders or granules. Single-ingredient quantitative packaging is implemented, so that pharmacy personnel can follow the doctor's instructions and prescribe according to the prescribed dosage for direct consumption by patients. Chinese herbal formula granules are full-ingredient extracts of traditional herbal pieces. The clinical efficacy is equivalent to that of herbal pieces, and there are corresponding preparation requirements and quality control standards. They have obvious advantages over mixed decoctions of Chinese herbal pieces in terms of stability and controllability.

[0022] At the same time, the medicine for treating idiopathic membranous nephropathy prepared with the Chinese medicine composition provided by the present invention as the active ingredient also belongs to the protection scope of the present invention.

[0023] The pharmaceutical composition can be prepared directly or by adding pharmaceutically acceptable excipients to any pharmaceutically acceptable dosage form. Oral preparations include granules, capsules, tablets, oral liquids, powders, pills, dripping pills, sustained-release preparations, oral liquids, mixtures and syrups. The drugs in the above dosage forms can be prepared according to conventional methods in the pharmaceutical field.

[0024] The present invention also protects the use of the above-mentioned traditional Chinese medicine composition in preparing medicine for treating idiopathic membranous nephropathy.

[0025] The present invention also protects a medicine for treating idiopathic membranous nephropathy.

[0026] The active ingredient of the medicine for treating idiopathic membranous nephropathy is the above-mentioned traditional Chinese medicine composition.

[0027] The treatment of idiopathic membranous nephropathy in the present invention includes treating proteinuria and / or edema associated with idiopathic membranous nephropathy.

[0028] The efficacy of the traditional Chinese medicine composition of the present invention: Tonifying qi and activating blood circulation, promoting diuresis and reducing swelling; Indications: It is used for membranous nephropathy of nephrotic syndrome belonging to the syndrome of qi deficiency and blood stasis, and internal retention of water-dampness, manifested as limb or facial swelling, proteinuria, accompanied by fatigue, enlarged tongue with tooth marks, pale and dull tongue proper, white or white and greasy tongue coating, deep or deep and thready pulse; It can be used alone or in combination with immunomodulatory therapy to promote the remission of nephrotic syndrome; It can also be used for primary nephrotic syndrome, such as adjuvant treatment of minimal change type and focal segmental glomerulosclerosis type.

[0029] The formula analysis of this traditional Chinese medicine composition is as follows: Astragalus membranaceus (fresh) is used as the monarch drug, which can tonify qi and generate yang, especially effective in tonifying the qi of the lung and spleen, and also has the effect of promoting diuresis; Angelica sinensis and Paeonia lactiflora can nourish blood and activate blood circulation, Poria cocos enters the heart, spleen, lung and kidney meridians, promoting diuresis by percolating dampness, and tonifying the spleen and protecting the kidney as the minister drugs; Ligusticum chuanxiong promotes qi circulation and activates blood circulation, Prunus persica activates blood circulation and removes stasis, both of which enter the liver meridian and assist the minister drugs Angelica sinensis and Paeonia lactiflora in nourishing blood and activating blood circulation; Atractylodes macrocephala (fried) is bitter and warm, enters the spleen and stomach meridians, strengthens the spleen and replenishes qi, and dries dampness, assisting Astragalus membranaceus and Poria cocos in promoting qi and activating water circulation; Stephania tetrandra is bitter, pungent and cold, enters the bladder and lung meridians, and can clear heat and promote diuresis by its bitter and cold nature, and is good at descending and discharging damp-heat in the lower jiao bladder. Alisma orientale is sweet and cold, promoting diuresis, enters the kidney and bladder meridians, and Plantago asiatica enters the liver, kidney, lung and small intestine meridians, clearing heat and promoting diuresis, cooling blood, and detoxifying, all of which are used as the guiding drugs to direct the drugs to enter the kidney; Dioscorea nipponica and Hedyotis diffusa in the formula are the unique features of the formula. Through modern pharmacological research and clinical observation, it is found that Dioscorea nipponica is warm in nature, good at dispelling wind-dampness, dredging tendons and collaterals, promoting blood circulation and relieving pain, and has the effects of antioxidant stress, hypoglycemic, anti-inflammatory, immunomodulatory, uric acid-lowering and proteinuria-reducing

[11] ; Hedyotis diffusa is bitter and cold in nature, and has the effects of clearing heat and detoxifying, anti-tumor and immunomodulating

[12] ; It is a targeted treatment for the immune mechanism of membranous nephropathy.

[0030] The application prospect and social benefits of the "QFGS formula" of the present invention: The formula of the "QFGS formula" is based on the theory of "qi, blood, body fluid (water)" in traditional Chinese medicine, and its effective application scenarios include: Membranous nephropathy evaluated as low-risk in the "Guideline" can be used alone on the basis of supportive treatment; For membranous nephropathy evaluated as medium- and high-risk in the "Guideline", combined with glucocorticoids and immunosuppressants, it can better improve symptoms (such as edema, proteinuria, fatigue, etc.); Reduce the exposure to glucocorticoids and immunosuppressants; Reduce the recurrence of the disease during the process of reducing the dosage of glucocorticoids and immunosuppressants. It reflects the simplicity, convenience, effectiveness and affordability of traditional Chinese medicine, and creates good social and economic benefits. Brief Description of the Drawings

[0031] Figure 1 It is the flow chart of the retrospective study; Figure 2 It is the PAS staining results of the renal tissues of rats in each group at 6 weeks; Note: A: Control group; B: Model group; C: QFGS group; D: Losartan group. Detailed Description of the Invention

[0032] The present invention will be further described in detail below in conjunction with specific embodiments. The provided embodiments are only for clarifying the present invention and not for limiting the scope of the present invention. The following provided embodiments can be used as a guide for those of ordinary skill in the art to make further improvements and do not constitute any limitation to the present invention in any way.

[0033] In the experimental methods in the following embodiments, unless otherwise specified, they are all conventional methods, carried out according to the techniques or conditions described in the literature in this field or according to the product specifications. The materials, reagents, etc. used in the following embodiments, unless otherwise specified, can all be obtained from commercial channels.

[0034] The materials, reagents, etc. used in the following embodiments, unless otherwise specified, can all be obtained from commercial channels.

[0035] Astragalus membranaceus, Stephania tetrandra, Angelica sinensis, Paeonia lactiflora, Ligusticum wallichii, Prunus persica, Atractylodes macrocephala, Alisma orientale, Poria cocos, Dioscorea nipponica, Plantago asiatica, etc. used in the following embodiments all comply with the relevant regulations under each medicinal material item in Part I of the Chinese Pharmacopoeia (2020 Edition). Before feeding, through identification, the physical objects of each medicinal material match the names and the quality meets the standards. Hedyotis diffusa Willd. complies with the relevant regulations under the medicinal material item in the Chinese Herbal Medicine Dictionary. Before feeding, through identification, the physical objects of each medicinal material match the names and the quality meets the standards.

[0036] Example 1 Preparation of Qifang Guishao Granules 1. Prescription and preparation process

Prescription

[0037]

Preparation method

[0038]

Dosage and Administration

[0039]

Specification

[0040]

Appearance

[0041]

Identification

[0042] Stephania Root Take 5.0 g of the granules of this product, add 40 mL of absolute ethanol and extract by ultrasonic for 30 min, filter, take all the subsequent filtrate, evaporate to dryness, dissolve the residue in 1 mL of ethanol to obtain the test solution. Separately take tetrandrine reference substance and fangchinoline, dissolve them in chloroform to prepare a mixed solution containing 1 mg per 1 mL as the reference solution. According to the thin - layer chromatography method (General Rule 0502) in Part IV of the Chinese Pharmacopoeia 2020 edition, accurately pipette 10 μL of the above - mentioned test solution and reference solution respectively, spot them on the same silica gel G thin - layer plate, use chloroform - acetone - methanol - 5% concentrated ammonia test solution (6:1:1:0.1) as the developing agent, develop, take out, dry in air, and spray with dilute bismuth potassium iodide test solution. In the chromatogram of the test solution, at the corresponding position of the chromatogram of the reference solution, spots of the same color appear.

[0043] Angelica Root Take 10.0 g of the granules of this product, add 30 mL of ether, ultrasonically treat for 10 min, filter, evaporate the filtrate to dryness, dissolve the residue in 1 mL of ethanol to obtain the test solution. Separately take 0.5 g of angelica reference crude drug and prepare a reference crude drug solution in the same method. According to the thin - layer chromatography method (General Rule 0502) in Part IV of the Chinese Pharmacopoeia 2020 edition, absorb 10 μL of each of the above two solutions respectively, spot them on the same silica gel G thin - layer plate, use n - hexane - ethyl acetate (4:1) as the developing agent, develop, take out, dry in air, and examine under ultraviolet light at 365 nm. In the chromatogram of the test solution, at the corresponding position of the chromatogram of the reference solution, fluorescent spots of the same color appear.

[0044] For Ligusticum wallichii, take 10.0 g of the granules of this product, add 30 mL of ethyl ether, ultrasonically treat for 10 min, filter, evaporate the filtrate to dryness, dissolve the residue in 1 mL of ethyl acetate to prepare the test solution; take another 1 g of the reference medicinal material of Ligusticum wallichii, add 20 mL of ethyl ether, reflux under heating for 1 hour, filter, evaporate the filtrate to dryness, dissolve the residue in 2 mL of ethyl acetate to prepare the reference medicinal material solution. Then take the reference substance of osthole, add ethyl acetate to prepare a solution containing 0.1 mg per 1 mL as the reference substance solution. According to the thin-layer chromatography method (General Principles 0502) in Part IV of the Chinese Pharmacopoeia (2020 Edition), precisely pipette 10 μL of each of the above-mentioned test solution, reference medicinal material solution, and reference substance solution, respectively spot them on the same silica gel GF254 thin-layer plate, use n-hexane-ethyl acetate (3:1) as the developing solvent, develop, take out, dry in air, and examine under ultraviolet light (254 nm). In the chromatogram of the test sample, spots of the same color should appear at the corresponding positions as those in the chromatograms of the reference medicinal material and the reference substance.

[0045] For Prunus persica, take 5.0 g of the granules of this product, add 40 mL of absolute ethanol, ultrasonically treat for 30 min, filter, evaporate the filtrate to dryness, dissolve the residue in 1 mL of ethanol to prepare the test solution. Take another reference substance of amygdalin, add methanol to prepare a solution containing 2 mg per 1 mL as the reference substance solution. According to the thin-layer chromatography method (General Principles 0502) in Part IV of the Chinese Pharmacopoeia (2020 Edition), precisely pipette 10 μL of each of the above two solutions, respectively spot them on the same silica gel G thin-layer plate, use the lower layer solution obtained by placing chloroform-ethyl acetate-methanol-water (15:40:22:10) at 5 - 10 °C for 12 hours as the developing solvent, develop, take out, immediately spray with phosphomolybdic acid-sulfuric acid solution (2 g of phosphomolybdic acid, dissolve it in 20 mL of water, then slowly add 30 mL of sulfuric acid and mix well), and heat at 105 °C until the spots are clearly developed. In the chromatogram of the test sample, spots of the same color should appear at the corresponding positions as those in the chromatogram of the reference substance.

[0046]

Inspection

[0047]

Particle Size

[0048]

Water Content

[0049]

Solubility

[0050]

Difference in Fill Weight

[0051]

Microbial Limit

[0052]

Indications and Functions

[0053]

Dosage and Administration

[0054]

Specification

[0055]

Storage

[0056] Example 2. Preparation of the Granules of the Chinese Medicine Composition of Qifang Guishao Formula 1. Prescription Composition Astragalus membranaceus (raw) 300 g, Stephania tetrandra 150 g, Angelica sinensis 150 g, Paeonia lactiflora 150 g Ligusticum chuanxiong 150 g, Prunus persica 150 g, Atractylodes macrocephala (parched) 150 g, Alisma orientale 150 g Poria cocos 225 g, Dioscorea nipponica 300 g, Hedyotis diffusa 300 g, Plantago asiatica 225 g The total raw drug amount of the whole prescription is 2400 g.

[0057] 2. Preparation Method: Weigh the Chinese medicine formula granules corresponding to the raw drug amounts of each medicinal material in the above prescription, and directly mix the above Chinese medicine formula granules to obtain the granules of the Chinese medicine composition, a total of 30 doses; sub-pack into 120 bags.

[0058] Take 1 dose every day, that is, 2 bags each time, 2 times a day, and take it by dissolving in boiling water after meals in the morning and evening.

[0059] Example 3. Summary of the Clinical Efficacy of Qifang Guishao Formula 1. Retrospective Cohort Study 1.1 Research object: Outpatients with idiopathic membranous nephropathy (IMN) who visited the Nephrology Department of Guang'anmen Hospital, China Academy of Chinese Medical Sciences from January 1, 2018 to December 31, 2022 were selected as the research object. Information was retrieved by the hospital's information department according to the diagnosis of "nephrotic syndrome membranous nephropathy", including patient gender, age, comorbidity diagnosis, test results (biochemistry, blood routine, urine routine, urinary protein quantification) during this period, and prescription information (Chinese and Western medicines, Chinese herbal medicines). The data was "desensitized" to form a database.

[0060] 1.2 Inclusion and exclusion criteria: 1.2.1 Inclusion: (1) Age ≥ 18 years old; (2) Diagnosed with "idiopathic membranous nephropathy", baseline eGFR > 60 ml / min•1.73m 2 ; (3) "Qifang Guishao Decoction" decoction pieces or Chinese herbal formula granules, calculated as 1 dose per day, and the cumulative number of days of taking medicine is not less than 50% of the follow-up days; (4) Have follow-up records of more than 6 months; (5) Have at least 2 or more laboratory tests, and the interval between 2 tests is more than 3 months.

[0061] 1.2.2 Exclusion: Cases that do not meet the inclusion criteria.

[0062] 1.2.3 Screening of the exposed group and the non-exposed group Exposed group, that is, the "Qifang Guishao Decoction" treatment group: Syndrome differentiation of traditional Chinese medicine is qi deficiency and blood stasis syndrome, taking "Qifang Guishao Decoction" decoction pieces or Chinese herbal formula granules.

[0063] Non-exposed group, that is, the control group: Patients who do not take "Qifang Guishao Decoction" Chinese herbal decoction pieces or Chinese herbal formula granules.

[0064] There are no special regulations on the basic treatment of the 2 groups of patients such as RAS blockers and immunosuppressants, but they are recorded and analyzed; the comorbidities and medications are recorded and analyzed.

[0065] To ensure the comparability of the baselines of the treatment group and the control group, 1:1 propensity score matching was performed according to the gender, age, baseline (the first test report during the observation period) 24-hour urinary protein quantification and eGFR (EPI formula) of the 2 groups of patients. Those who were successfully matched entered the efficacy study.

[0066] 1.3 Efficacy judgment: 1.3.1 Main efficacy indicators Changes in 24-hour urinary protein quantification (24-UTP), serum albumin (ALB), and estimated glomerular filtration rate (eGFR) during the follow-up period; the usage rates of glucocorticoids and immunosuppressants.

[0067] 1.3.2 Safety indicators: Changes in ALT and HGB before and after treatment 1.4 Results 1.4.1 Flow chart of the inclusion of research subjects is as Figure 1 shown 1.4.2 Comparison of baseline conditions between the treatment group and the control group in a retrospective study Table 1. Comparison of baseline conditions between the QFGS treatment group and the control group

[0068] Note: Among the research subjects included during the data extraction period of the study (2018 - 2022), some had been diagnosed and started treatment before inclusion, so some patients were already in a remission state.

[0069] After matching the demographic characteristics, comorbidities, and baseline balance of basic treatments (RAS blockers, lipid regulation, blood sugar control, etc.) of the two groups of patients, they were comparable.

[0070] 1.4.3 Efficacy indicators 1.4.3.1 Changes in 24-hour urinary protein quantification (24hUTP) in the treatment group and the control group Table 2. Comparison of changes in 24hUTP (mg) in the two groups of patients during the follow-up period

[0071] Note: Compared with before treatment in this group, *p < 0.05; compared with the control group at the same time, △p < 0.05.

[0072] There was no significant difference in 24hUTP between the two groups at baseline and at 3 months of follow-up (p > 0.05); the urinary protein quantification in the treatment group decreased compared with the baseline at the 6th, 9th, and 12th months of follow-up (p < 0.05); the UTP in the control group decreased significantly compared with the baseline at 3 months of follow-up, but there was no significant improvement in the urinary protein quantification at subsequent time points compared with its baseline (p > 0.05); at 3 months of the follow-up period, the UTP in the control group seemed to be less than that in the treatment group, but it did not reach statistical significance (p = 0.119); at the 9th and 12th months, the improvement of UTP in the treatment group was better than that in the control group (p < 0.05), suggesting that the condition of some patients in the control group may have relapsed.

[0073] 1.4.3.2 Changes in renal function in the treatment group and the control group during the follow-up period Table 3. Comparison of changes in eGFR (ml / min•1.73m2) in the two groups of patients during the follow-up period

[0074] There was no significant change in renal function eGFR at each time point during the follow-up period in each group, that is, renal function was stable.

[0075] 1.4.3.3 ALB Changes in the Treatment Group and the Control Group during the Follow-up Period Table 4 Comparison of ALB (g / L) Changes in the Two Groups of Patients during the Follow-up Period

[0076] Note: Compared with before treatment in the same group, *p < 0.05; compared with the control group at the same time, △p < 0.05.

[0077] During the follow-up period, the blood ALB levels of the two groups of patients increased at each time point compared with the baseline, indicating that membranous nephropathy had a remission trend. However, the treatment group had an advantage in September and December compared with the control group, suggesting that it might be related to the recurrence of the condition in some patients in the control group after 6 months of follow-up.

[0078] 1.4.3.4 Comparison of the Usage of Glucocorticoids and Immunosuppressants in the Treatment Group and the Control Group during the Follow-up Period Table 5 Comparison of the Usage of Glucocorticoids and Immunosuppressants in the Two Groups during the Follow-up Period

[0079] During the follow-up period, the usage rates of glucocorticoids and immunosuppressants in the treatment group were 13.4% lower than those in the control group. However, the statistical results showed that there was no significant difference in the overall usage rates of glucocorticoids and immunosuppressants between the two groups of patients.

[0080] 1.4.4 Safety Indicators in the Treatment Group and the Control Group during the Follow-up Period 1.4.4.1 HGB during the Follow-up Period Table 6 Comparison of HGB (g / L) Index Changes in the Two Groups of Patients during the Follow-up Period

[0081] There was no obvious change in HGB at each time point during the follow-up period in each group, indicating stable renal function.

[0082] 1.4.4.2 Liver Function (ALT) during the Follow-up Period Table 7 Comparison of ALT (U / L) Index Changes in the Two Groups of Patients during the Follow-up Period

[0083] There was no obvious change in ALT at each time point during the follow-up period in each group, indicating no obvious liver function impairment.

[0084] Retrospective cohort studies have shown that for patients with membranous nephropathy who have achieved complete remission or partial remission after treatment, Qifang Guishao Decoction may reduce the risk of recurrence; for patients with low-risk membranous nephropathy, Qifang Guishao Decoction combined with supportive treatment may have advantages over simple supportive treatment in reducing proteinuria and increasing ALB; it is suggested that using Qifang Guishao Decoction in the treatment of membranous nephropathy with moderate, high, and extremely high risks (requiring initiation of immunosuppressive therapy) may enable patients to reduce the risk of exposure to immunosuppressive therapy, improve the remission rate, and has good long-term safety.

[0085] 2. Prospective cohort study 2.1 Study subjects and design: A single-group prospective cohort, including patients with idiopathic membranous nephropathy (IMN) who were hospitalized and followed up in the nephrology ward and outpatient clinic of Guang'anmen Hospital, China Academy of Chinese Medical Sciences from January 1, 2023 to April 30, 2025.

[0086] 2. Inclusion and exclusion criteria 2.2.1 Inclusion criteria: (1) Aged 18 years or older; (2) Meeting the diagnostic criteria for idiopathic membranous nephropathy (positive renal biopsy or blood PLA2R); (3) Patients with chronic kidney disease stages 1-3 (estimated glomerular filtration rate ≥ 30 mL / min / 1.73m 2 ) (4) TCM syndrome differentiation conforming to the syndrome of spleen-kidney qi deficiency and blood stasis with fluid retention. The patient voluntarily took the "Qifang Guishao Decoction Granules" prepared in Example 1, 2 bags each time, twice a day, taken orally with warm water after breakfast and dinner; taking the medicine for > 3 months (5) Informed consent obtained from the patient.

[0087] 2.2.2 Exclusion criteria (1) Renal biopsy pathology complicated with other renal damage; (2) Patients with secondary membranous nephropathy caused by hepatitis, malignant tumor, systemic lupus erythematosus, autoimmune diseases, etc.; (3) Patients with severe cardiovascular diseases, peptic ulcers, or malignant tumors; (4) Women planning pregnancy or in the lactation period; (5) Patients with poor compliance; (6) Patients with incomplete clinical data.

[0088] 2.3 Main efficacy indicators: Clinical outcome of MN Using the first visit information as the baseline, collect the clinical data of the patients at the 3rd, 6th, 9th, and 12th months, and evaluate whether clinical remission (complete or partial remission) is achieved at the above time points for outcome determination.

[0089] 2.3.1 Complete remission: 24-hour urine total protein (24hUTP) quantitative <0.3g, confirmed by two examinations with an interval of at least 1 week between the two examinations, blood albumin (ALB) ≥35g / L, and normal renal function; 2.3.2 Partial remission: 24hUTP <3.5g / 24h, and decreased by ≥50% compared with baseline, confirmed at least 1 week after two examinations, accompanied by blood albumin ≥30g / L, and no change or improvement in renal function.

[0090] 2.3.3 No relief: 24hUTP decreases by less than 50% compared with the pre-treatment baseline or is still greater than 3.5g / 24h or renal function worsens (serum creatinine increases by >15% compared with baseline).

[0091] Total remission (TR) = complete remission (CR) + partial remission (PR), Total remission rate = (complete remission + partial remission) / total number of cases in the group * 100%.

[0092] Post-remission relapse: The nephrotic syndrome state occurs after achieving complete or partial remission.

[0093] Nephrotic syndrome status: 24-UTP>3.5g and ALB<30g / L.

[0094] 2.4 Treatment options: 2.4.1 Conduct a “risk” assessment for patients according to KDIGO. The reference standards are shown in Table 8.

[0095] Table 8 Risk Assessment Notation

[0096] 2.4.2 Different treatment options according to "risk" level: (1) Low risk: Supportive treatment based on RAS blockade, and taking the "Qifang Guishao Fang Granules" prepared in Example 1 at the same time, 2 bags / time, twice a day, in the morning and evening after meals, washed down with boiled water; the course of treatment is 3 months or until complete remission is achieved.

[0097] (2) Medium, high, and very high risk: On the basis of RAS blockade, hormones and immunosuppressants are used as appropriate (for patients who are already using hormones and immunosuppressants at the time of inclusion, the dose of immunosuppressants will not be increased; if adverse events occur in the original treatment regimen, the treatment regimen will be changed). When the condition improves, the dose of hormones and immunosuppressants is gradually reduced until it is stopped; at the same time, take the "Qifang Guishao Fang Granules" prepared in Example 1, 2 bags / time, twice a day, in the morning and evening after meals, with boiled water; the course of treatment is 3 months or until complete relief is achieved.

[0098] (3) Management of complications: For patients with hypertension or diabetes, antihypertensive drugs (CCB, β-blockers, etc.) and hypoglycemic drugs (insulin, oral SGLT-2i, etc.) are used to control blood pressure and blood sugar to reach the standard; for those at risk of thrombosis, anticoagulant therapy is given; for patients with microbial infections, corresponding treatment is provided (records of those occurring during follow-up are regarded as adverse events).

[0099] (4) Patients are followed up once a month for vital sign assessment, recording of adverse events, and at the same time, blood routine, urine routine, liver and kidney function, electrolytes, and 24-hour urine protein quantification tests are conducted.

[0100] 2.4.3 Efficacy evaluation: (1) Main efficacy evaluation: Clinical outcomes during the follow-up period: the number and percentage of cases with complete remission, partial remission, non-remission, and recurrence after remission; (2) Secondary efficacy evaluation Ⅰ. Time to first occurrence of partial remission and complete remission Ⅱ. Whether corticosteroid immunosuppressants are still being used at the end of the follow-up period Ⅲ. Dynamic changes in 24-hour urine protein quantification, blood Scr, and ALB at the 3rd, 6th, 9th, and 12th months of the follow-up period (3) Safety indicators Comparison of HGB and ALT at baseline and at the 12th month or the end of the follow-up; Occurrence of adverse events during the follow-up period: Adverse events refer to infections, thrombosis, abnormal liver function, electrolyte disorders, gastrointestinal bleeding, etc.

[0101] 2.5 Statistical analysis: Data analysis is performed using SPSS 25.0 software. Measurement data are expressed as mean ± SE or median (interquartile range). According to the results of normality analysis, paired t-tests or non-parametric tests are used for efficacy evaluation before and after treatment; count data are presented as the number of cases (%). P < 0.05 is considered statistically significant.

[0102] 3. Research results: 3.1 Baseline conditions of the prospective cohort As of April 30, 2025, a total of 32 cases were included, with an average follow-up time of 17.5 (7.5) months, the shortest being 4 months and the longest being 28 months.

[0103] Table 9 Baseline conditions of 32 patients in the prospective cohort of "Qifang Guishao Decoction" at the time of inclusion

[0104] 3.2. Main efficacy indicators - Clinical remission rate and remission time during the follow-up period As of April 30, 2025, 19 patients (59.4%) achieved partial remission and 13 patients (40.6%) achieved complete remission. The average time for patients to first achieve partial remission was 4.0 (3.0) months, with the shortest being 1 month. The average time for patients to first achieve complete remission was 11.5 (7.6) months, with the shortest being 3.5 months. There were no cases of relapse after remission during the follow-up period.

[0105] 3.3 Secondary Efficacy Indicators 3.3.1 Dynamic Changes of 24h UTP, ALB, and Scr within 12 Months of Follow-up Table 10 Dynamic Changes of 24h UTP, ALB, and Scr within 12 Months of Follow-up

[0106] *Compared with the baseline, *p < 0.05 It can be seen that the 24-hour urinary protein quantification of patients decreased by about 50% compared with the baseline at 3 months, and ALB increased to 33.7 g / L, which was basically consistent with the average time of 4.0 (3.0) months for patients to first achieve partial remission we observed. As the follow-up time extended, the proteinuria and ALB of patients showed a progressive increasing trend. All patients achieved complete or partial remission within 12 months, and the overall remission rate was better than the results of existing RCT studies on the treatment of IMN

[13] . At the time points of 3, 6, 9, and 12 months, Scr showed a slight downward trend (but the difference did not reach statistical significance, p > 0.05), indicating that the overall renal function of patients was stable.

[0107] 3.3.2 Safety Index Evaluation (1) HGB and ALT Table 11 Comparison of HGB and ALT during the Follow-up Period

[0108] The overall HGB and ALT of patients were stable during the follow-up period, and there was no severe impairment of the hematological system or liver function.

[0109] (2) Incidence and Disposal of Adverse Events Table 12 Incidence and Disposal of Adverse Events during the Follow-up Period

[0110] It can be seen that no severe adverse reactions related to QFGS occurred during the follow-up period of patients.

[0111] 3.3.3 Usage of Hormones and Immunosuppressants during the Follow-up Period Table 13 Usage of Hormones and Immunosuppressants during the Follow-up Period

[0112] At the time of inclusion, 24 patients were already receiving hormone and / or inhibitor treatment. During the follow-up observation, as the condition improved, 19 patients discontinued the hormone and / or inhibitor, and there was no recurrence after discontinuation; 5 patients were still using it, and the dose of the immunosuppressant had been reduced by more than 50% compared to the time of inclusion. That is, for low-risk IMN patients, the use of QFGS alone based on supportive treatment can relieve nephrotic syndrome; in patients with medium or higher risk who have already received hormone and / or inhibitor treatment, the combination of QFGS can promote the remission of the condition, reduce the exposure of patients to hormones and / or inhibitors, and maintain the stability of the condition after reducing or discontinuing hormones and / or inhibitors.

[0113] 4. Differences and advantages between the retrospective analysis of the current case series, prospective cohort and comparison with "prior art": In 2001, relevant literature published by the members of this project team reported the experience and case summary of Professor Dai Xiwen using the "classical prescription" - the combined use of Fangji Huangqi Decoction and Danggui Shaoyao Powder with additions and subtractions to form "Yishen Jiangya Prescription" for the treatment of renal parenchymal hypertension. The drug composition is: Astragalus membranaceus 15 - 30g, Stephania tetrandra 12g, Angelica sinensis 12g, Paeonia lactiflora 12g, Atractylodes macrocephala 10g, Paeonia veitchii 12g, Scutellaria baicalensis 15g, Achyranthes bidentata 12, Leonurus japonicus 15g, Ligusticum wallichii 10g, Poria cocos 12g, Alisma orientale 15g, Plantago asiatica 15g; its main treatment (indications) is renal parenchymal hypertension.

[0114] There are obvious differences from the drug composition of the prescription of the present invention (Qi-Fang Danggui Shaoyao Prescription) (Astragalus membranaceus, Stephania tetrandra, Angelica sinensis, Paeonia lactiflora, Ligusticum wallichii, Atractylodes macrocephala, Alisma orientale, Poria cocos, Plantago asiatica, Persica vulgaris, Dioscorea nipponica, Hedyotis diffusa); the main treatment of this prescription is edema caused by qi deficiency and blood stasis, and internal retention of water-dampness, with symptoms such as fatigue, limb or facial swelling, swelling being lighter in the morning and heavier in the evening, pitting on pressure, soreness and swelling of the limbs; oliguria, enlarged tongue with tooth marks, pale and dull tongue, white and greasy tongue coating with tooth marks, deep, thin and slow pulse; chronic kidney disease with the above syndromes; and it also has a certain adjuvant therapeutic effect on reducing proteinuria and improving renal function.

[0115] In January 2025, Liu Aixia et al. reported "Observation on the Efficacy of Modified Danggui Shaoyao Powder in the Treatment of Idiopathic Membranous Nephropathy"

[14] , without reporting the risk stratification and traditional Chinese medicine syndrome types of the included patients with membranous nephropathy. The prescription composition is: Angelica sinensis 15g, stir-fried Paeonia lactiflora 10g, Astragalus membranaceus 10g, Panax ginseng 10g, stir-fried Atractylodes macrocephala 15g, Poria cocos 10g, Alisma orientale 10g, Ligusticum wallichii 10g, Hirudo 6g, roasted Glycyrrhiza uralensis 6g; there are obvious differences from this prescription, and all patients in this study were treated with the combination of "modified Danggui Shaoyao Powder" on the basis of receiving hormone plus cyclophosphamide injection, which is different from the treatment plan of this study; and the treatment observation period was only 2 months, and the overall effective rate of the combined traditional Chinese medicine group was 88.4%, and the recurrence situation was not reported.

[0116] In February 2025, Chen Chen et al. reported "The Effect of Modified Fangji Huangqi Decoction Combined with Wupi Decoction in the Treatment of Idiopathic Membranous Nephropathy"

[15] . The included patients were diagnosed as stage II (pathological stage) according to the Ehrenreich-Churg membranous nephropathy staging criteria, and 60 patients with spleen-kidney deficiency and kidney collaterals stasis were differentiated by traditional Chinese medicine. The prescription composition for treatment was: Fangji 15g, Huangqi 20g, fried Baizhu 15g, Baifuling 12g, Bixie 9g, Chenpi 9g, Zelan 10g, Shuizhi 6g, Danshen 12g, Haifengteng 12g, Sumu 6g, Qian Shi 15g, roasted Gancao 6g; the overall effective rate for 3 courses of treatment was 93.3%. There were differences in the Chinese and Western medicine characteristics and prescriptions of the observation objects compared with this study; the blood ALB situation (a key indicator for membranous nephropathy risk assessment) of the included patients was not reported in the study, nor was the recurrence reported.

[0117] Example 4. Summary of the Pharmacodynamic Effects of Qifang Danggui Shaoyao Prescription in Animal Experiments A rat model of chronic membranous nephropathy was constructed to observe the improvement of proteinuria, renal function (creatinine), renal pathological indexes, and liver function (alanine aminotransferase) in the modeled rats by "Qifang Danggui Shaoyao Prescription".

[0118] 1. Experimental Method 1.1 Construction of a Rat Model of Chronic Kidney Disease A rat passive Heymann nephritis model (PHN model) was used; 26 healthy male SPF-grade SD rats, 5 weeks old, with a body weight of 150 - 180g each. After 1 week of adaptive feeding, the urine protein of the rats was detected using a urine protein test strip before modeling. The test result was negative. Then, the rats were divided into the modeling group (20 rats) and the blank group (6 rats) using a random number table. Anti-FX1A serum (ptx-002S, PROBETEX) was melted at room temperature before use and centrifuged at 3000 rpm for 5 minutes at 4°C, and the precipitate was discarded for standby. Inhaled anesthetic isoflurane was used, connected to a small animal anesthesia machine, and the output flow was adjusted (500 mL / min). After the anesthetic filled the induction box, the rats were placed in the induction box, and the modeling started when they entered the anesthetic state. A PHN rat model was established by a single tail vein injection of anti-FX1A serum, with an injection dose of 5 ml / kg of the rat body weight, injected slowly for a duration of 30 s. Low-dose induction anesthesia was used, and the rats could wake up quickly after the injection. Rats in the blank group were injected with 5 ml / kg of the rat body weight of normal saline via the tail vein, and the anesthesia method and injection operation were the same as those in the modeling group.

[0119] The urinary protein in the random urine of the rats in the model group was monitored using a urinary protein test strip. After 2 weeks of modeling, the urinary protein of most rats in the model group was positive, while the urinary protein test result of the rats in the blank group remained negative. All rats were placed in separate metabolic cages, and their 24-hour urine was collected and their 24-hour UTP was measured. One rat in the control group and one rat model group with 24-hour UTP > 20 mg / 24 h were randomly selected for kidney pathological examination.

[0120] 1.2 Experimental grouping and intervention dose setting The 15 rats with successful modeling were randomly divided into 3 groups, namely: Model group (model group), QFGS (medium-dose group of Qifang Guishao Decoction), and positive control drug group (losartan, Losartan group).

[0121] Basis for calculating experimental drugs and gavage doses: (1)QFGS: "Qifang Guishao Decoction Granules" prepared in Example 1; the equivalent dose of the drug for rats was calculated by converting the daily clinical dose of humans according to body surface area. The medium dose was 6.3 times the adult dose. The gavage volume for rats was 10 ml / kg▪per day, dissolved in sterile drinking water, and gavaged once a day.

[0122] (2)Positive control drug: Losartan potassium tablets (LST, 100 mg / tablet, Merck Sharp & Dohme) were ground thoroughly and formulated into a 1 mg / ml suspension; the equivalent dose of the drug for rats was calculated by converting the daily clinical dose of humans according to body surface area. The dose for rats was 6.3 times the adult dose, that is, (100 mg / 60 kg) * 6.3 = 10.5 mg / kg.

[0123] The gavage doses for each group were as follows: Control group (n = 5), gavaged with an equal volume of normal saline once a day; Model group (n = 5), gavaged with normal saline at 10 ml / kg once a day; QFGS-M group (n = 5), gavaged with QFGS once a day; LST group (n = 5), gavaged with the LST suspension diluted with normal saline to an equal volume of the QFGS-M solution at 10.5 mg / kg•per day once a day Each group of rats was gavaged for 6 weeks.

[0124] 1.3 Efficacy evaluation indicators: (1)24-hour urinary protein excretion: At the 0th, 3rd, and 6th weeks after administration, the rats were placed in separate metabolic cages, allowed to drink water but fasted, and their 24-hour urine was collected while the total urine volume was recorded. 3 ml of the collected urine was centrifuged to obtain the supernatant, and the urine protein concentration was examined by the biuret method. The 24-hour urinary protein excretion was calculated by multiplying the urine protein concentration by the urine volume.

[0125] (2)Serum Scr and ALB: After the experiment ended (at the end of 6 weeks), the rats were anesthetized and blood was collected from the abdominal aorta. The serum was obtained by centrifugation and detected using an automatic biochemical analyzer.

[0126] (3)Kidney pathology (glomerulosclerosis index) After the blood collection operation was completed, the rats were dissected, and the bilateral kidneys of the rats were taken. The capsule and non-renal tissues were stripped off and rinsed with pre-cooled 4°C ice saline. At the renal hilum, the left and right kidneys were cut along the coronal plane, 1.5 mm thick, 2 slices each, and fixed in 4% paraformaldehyde. Light microscopy was used with PAS staining to evaluate the pathological changes of the kidneys.

[0127] 1.4 Safety index: ALT, the method is the same as before 1.5 Statistical analysis: SPSS 25.0 was used for statistical analysis. All data were first tested for normality and homogeneity of variance. For data that were normal and had homogeneous variance, one-way ANOVA was used, and LSD test was used for multiple comparisons between groups. For data that were non-normal or had inhomogeneous variance, non-parametric tests were used, and Kruskal-Wallis H test was used for comparisons of multiple independent samples. A P < 0.05 was considered statistically significant.

[0128] 2. Experimental results and analysis 2.1 Comparison of changes in 24-hour urinary protein levels in rats of each group at different time points The results are shown in Table 14: The urinary protein level in the Control group rats showed no obvious change at each time point and remained at a low level; compared with the Control group, the urinary protein in the Model group began to increase after modeling and maintained a stable upward trend during the 6-week intervention period; compared with the Model group, the urinary protein excretion in the QFGS-M group and the Losartan group decreased at the 3rd and 6th weeks (P < 0.05); the change in urinary protein in the QFGS-M group was very close to that in the Losartan group.

[0129] Table 14 Comparison of changes in 24-hour urinary protein levels in each group during the 6-week intervention

[0130] Note: Contral: Control group; Model: Model group; QFGS: Qifang Guishao group; LST: Losartan potassium group (Positive control drug); *P<0.05 v.s. Contral#P<0.05 v.s.Model 2.2 Comparison of renal function, ALB, and ALT of rats in each group at the end of 6 weeks of drug administration Table 15 Comparison of renal function, ALB, and ALT of rats in each group at the end of 6 weeks of drug administration

[0131] Note: *P<0.05 v.s. Contral#P<0.05 v.s.Model As shown in Table 15, there were no significant differences in Scr and ALT among the groups, that is, after 6 weeks of different interventions, there were no differences in the renal and liver functions of rats in each group; the ALB of the three groups of rats with the model was lower than that of the Control group, among which the Model group was the lowest, while the QFGS and LST groups were higher than the Model group.

[0132] 2.3 Comparison of glomerulosclerosis index in each group (PAS-positive in glomerulus / glomerular area) The PAS staining results of renal tissues of rats in each group at 6 weeks were as Figure 2 shown.

[0133] Renal pathology: Observed by PAS staining under light microscopy, compared with the Contral group, the glomeruli in the Model group were enlarged, the glomerular basement membrane was thickened, and the mesangial matrix showed mild diffuse hyperplasia ( Figure 2 B), and the two treatment groups (QFDG group and Losartan group) also showed enlarged glomeruli and thickened glomerular basement membrane, but the degree was reduced compared with the Model group.

[0134] To sum up, through the rat passive Heymann nephritis model, the characteristics of massive proteinuria, hypoproteinemia, thickening of the renal pathological basement membrane, and glomerulosclerosis similar to human membranous nephropathy were successfully created; and it was confirmed that the intervention of "Qi-Fang Gui-Shao Decoction" could reduce proteinuria and increase the blood albumin level in the model rats, which was equivalent to the positive control drug losartan.

[0135] The above has detailed the present invention. For those skilled in the art, without departing from the purpose and scope of the present invention and without unnecessary experiments, the present invention can be implemented within a relatively wide range under equivalent parameters, concentrations, and conditions. Although specific embodiments of the present invention are given, it should be understood that the present invention can be further improved. In short, according to the principle of the present invention, this application intends to include any changes, uses, or improvements to the present invention, including those that depart from the scope disclosed in this application and are made using conventional techniques known in the art. Some basic features can be applied according to the scope of the following appended claims.

[0136] References: [1]XU [2] Shang Ruihua, Zhu Yongjun, Lin Ziyan, et al. Comparison and clinical analysis of the changes in pathological types of primary glomerular diseases in Henan and Hainan[J]. Journal of Clinical Nephrology, 2021, 21(2): 111-118. DOI: 10.3969 / j.issn.1671-2390.w20-216 [3] Zhan Yuan, Lu Chaohang, Hua Meiling, et al. Clinical pathology and epidemiology analysis of 4314 renal biopsies in a single center in Jiangxi Province[J]. Practical Clinical Medicine, 2022, 23(06): 103-107. [4]China Insights Consulting, Tianguang Practical Strategies Guide (2024), Great Wall Securities Industry Finance Research Institute.

[0137] [5] Kidney Disease: Improving Global Outcomes (KDIGO) GlomerularDiseases work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases[J]. Kidney Int, 2021, 100(4S): S1-276. DOI: 10.1016 / j.kint.2021.05.021. [6]Kidney Disease: Improving Global Outcomes (KDIGO) GlomerularDiseases Work Group. KDIGO 2021 Clinical practice guideline for themanagement of glomerular diseases. Kidney Int 2021; 100:50–5. [7]Nephrology Branch of China Association of Chinese Medicine, Nephrology Professional Committee of Guangdong Association of Chinese Medicine. Guidelines for Traditional Chinese Medicine Clinical Practice of Idiopathic Membranous Nephropathy (2021) [J]. Chinese General Practice, 2023, 26(6): 647-658. [8]Zhan Yongli. Academic Thoughts of Professor Dai Xiwen in Treating Idiopathic Membranous Nephropathy (Edema) from the Perspective of "Qi, Blood and Water" [A]. Kidney Disease Professional Committee of Chinese Association of Integrated Traditional and Western Medicine. Proceedings of the 2016 Annual Academic Conference of the Kidney Disease Professional Committee of Chinese Association of Integrated Traditional and Western Medicine [C]. Kidney Disease Professional Committee of Chinese Association of Integrated Traditional and Western Medicine:, 2016:1. [9]Bao Cuijie, Rao Xiangrong. Summary of Professor Dai Xiwen's Experience in Treating Nephrotic Syndrome [J]. Chinese Journal of Information on Traditional Chinese Medicine, 2007(02): 73-74.

[10] Han Dongyan, Zhao Chen, Rao Xiangrong, Wang Li, Zhang Gaihua, Zhan Yongli. Clinical Observation on Treating Idiopathic Membranous Nephropathy from the Perspectives of Qi, Blood and Water [J]. Chinese Journal of Basic Medicine in Traditional Chinese Medicine, 2013, 11: 1311-1313.

[11] Jin Lixia, Han Meini, Tong Chunxue, etc. Research Progress on Dioscorea nipponica Makino in the Treatment of Chronic Kidney Disease [J]. Chinese Archives of Traditional Chinese Medicine, 2023, 41(08): 29-33.

[12] Li Hui, Li Jun, Xu Rui. Research Progress on the Anti-tumor Mechanism of Hedyotis diffusa Willd [J]. Drugs & Clinic, 2024, 39(07): 1921-1926.

[13] Rojas-Rivera J, Fervenza FC, Ortiz A. Recent clinical trials insights into the treatment of primary membranous nephropathy. Drugs 2022;82:109–32.

[14] Liu Aixia, Wang Yuanyuan, Lei Lina. Clinical Observation on Modified Danggui Shaoyao Powder in Adjuvant Treatment of Idiopathic Membranous Nephropathy [J]. Journal of Practical Traditional Chinese Medicine, 2025;41: 74-75.

[15] Chen Chen, Liu Guangzhen. Effect of Modified Fangji Huangqi Decoction Combined with Wupi Decoction in the Treatment of Idiopathic Membranous Nephropathy [J / OL]. Liaoning Journal of Traditional Chinese Medicine. 2025, 52(04).

Claims

1. A Chinese medicine composition for treating idiopathic membranous nephropathy, prepared from the following raw materials in parts by mass: 12-45 parts of astragalus (raw), 10-15 parts of tetrandra, 10-20 parts of angelica, 10-20 parts of white peony, 10-15 parts of ligusticum chuanxiong, 10-15 parts of peach kernel, 10-30 parts of atractylodes (fried), 10-15 parts of oriental rhizome, 10-30 parts of tuckahoe, 15-30 parts of rhizoma strychnifoliae, 15-30 parts of oldenlandia diffusa, and 9-30 parts of plantain.

2. The Chinese medicine composition for treating idiopathic membranous nephropathy according to claim 1, characterized in that: The Chinese medicine composition is prepared from the following raw materials in parts by weight: 30 parts of astragalus (raw), 15 parts of tetrandra, 15 parts of angelica, 15 parts of white peony root, 15 parts of ligusticum chuanxiong, 15 parts of peach kernel, 15 parts of atractylodes (fried), 15 parts of oriental water chestnut, 22.5 parts of tuckahoe, 30 parts of rhizoma strychnifoliae, 30 parts of oldenlandia diffusa and 22.5 parts of plantain.

3. A method for preparing the Chinese medicine composition for treating idiopathic membranous nephropathy according to claim 1 or 2, comprising the following steps: mixing the twelve Chinese medicinal materials for making the Chinese medicine composition, soaking them in water and then decocting them, filtering them after the decocting is completed, and collecting the decoction to obtain a water decoction of the Chinese medicine composition.

4. The preparation method according to claim 3, characterized in that: The method further comprises: concentrating and drying the water decoction of the traditional Chinese medicine composition to obtain a dry extract, and then crushing the dry extract to obtain a powder of the traditional Chinese medicine composition.

5. The preparation method according to claim 3 or 4, characterized in that: The soaking condition is: adding water 5-10 times the total mass of the Chinese medicinal materials, soaking for 30-60 minutes; preferably, the soaking condition is: adding water 10 times the total mass of the Chinese medicinal materials, soaking for 45 minutes; And / or, the decoction is preferably performed 3 times, each decoction lasting 0.5 hours, filtered, and the 3 decoctions are combined; And / or, the specific method for concentrating and drying the water decoction of the traditional Chinese medicine composition is as follows: the water decoction (decoction) of the traditional Chinese medicine composition is concentrated under reduced pressure to a relative density of 1.25-1.30 (50°C), and then vacuum dried at 0.08MPa-0.1Mpa and 60°C to obtain a dry extract.

6. The preparation method according to claim 4 or 5, characterized in that: The method further comprises: using the powder of the Chinese medicine composition according to claim 4 as a raw material, adding auxiliary materials to prepare granules; The specific method is as follows: add dextrin to the Chinese medicine combination powder described in claim 4, mix evenly, use 85% ethanol by volume as a wetting agent, mix for 10-15 minutes, and prepare a soft material; granulate the qualified soft material with a swing granulator through a 14-mesh sieve, dry, and screen the dry granules with 16-mesh and 40-mesh sieves in turn, collect the sieve under the 40-mesh sieve, and pack the qualified granules in aluminum foil bags.

7. The preparation method according to claim 6, characterized in that: The amount of dextrin used is 0.4-0.5 times the mass of the powder of the traditional Chinese medicine composition; And / or, the amount of 85% ethanol by volume is 8-10% of the sum of the mass of the Chinese medicine combination powder and dextrin; And / or, the drying condition is 50-60° C. for 2-4 hours.

8. A medicine for treating idiopathic membranous nephropathy, the active ingredient of which comprises the Chinese medicine composition according to claim 1 or 2.

9. The drug according to claim 8, characterized in that: The dosage form of the Chinese medicine composition is an oral dosage form; further, the oral dosage form is selected from any one of the following: granules, capsules, tablets, oral liquids, powders, pills, pellets, sustained-release preparations, oral liquids, mixtures and syrups.

10. Use of the Chinese medicine composition according to claim 1 or 2 in the preparation of a drug for treating idiopathic membranous nephropathy; further, the treatment of idiopathic membranous nephropathy includes treating proteinuria and / or edema associated with idiopathic membranous nephropathy.

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