Traditional Chinese medicine compound preparation for treating nephrotic syndrome and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine compound preparation for treating nephrotic syndrome and a preparation method of the traditional Chinese medicine compound preparation, and belongs to the technical field of nephrotic syndrome treatment.The synbiotic microcapsule is prepared by compatibility of traditional Chinese medicines such as safflower, scutellaria baicalensis and perilla frutescens, and the synbiotic microcapsule is prepared by embedding traditional Chinese medicine extracts such as astragalus membranaceus and lily with lactobacillus acidophilus and bifidobacterium; and the wall material is prepared from mannose grafted meadowfoam seed extract, sodium alginate and fucoidin sulfate. The synbiotics microcapsule utilizes a Maillard reaction modified wall material to enhance gastric acid erosion resistance, realizes intestinal targeted colonization through mannose residues, protects probiotics, directionally releases traditional Chinese medicine active components, adjusts intestinal flora balance and inhibits uremia toxin generation. The traditional Chinese medicine components such as the safflower and the scutellaria baicalensis improve kidney blood circulation, relieve inflammatory response and regulate lipid metabolism by inhibiting an NF-kappa B channel, activating an AMPK channel and the like; the components such as the Chinese yam and the Chinese wolfberry can repair the permeability of glomerular basement membrane and improve the hypoproteinemia.

Description

Technical Field

[0001] This invention belongs to the field of nephrotic syndrome treatment technology, and particularly relates to a traditional Chinese medicine compound preparation for treating nephrotic syndrome and its preparation method. Background Technology

[0002] Nephrotic syndrome (NS) is a complex clinical syndrome caused by abnormal glomerular filtration function. Its core pathological feature is a significantly increased permeability of the glomerular filtration membrane, leading to massive leakage of plasma proteins and subsequently causing a series of metabolic disorders and organ damage. Specific clinical manifestations include:

[0003] Massive proteinuria: 24-hour urine protein quantification exceeding 3.5g (adult standard) is a direct result of the dual damage to the charge barrier and mechanical barrier of the glomerular filtration membrane, commonly seen in podocyte injury or degradation of basement membrane components (such as type IV collagen and laminin).

[0004] Hypoproteinemia: Plasma albumin levels below 30 g / L. Due to continuous protein loss exceeding the liver's compensatory synthesis capacity, it can further induce edema and immune dysfunction.

[0005] Severe edema: Due to the decrease in plasma colloid osmotic pressure, water seeps from the blood vessels into the interstitial space, often manifesting as eyelid edema upon waking and pitting edema of both lower limbs. In severe cases, ascites and pleural effusion may occur.

[0006] Hyperlipidemia: The liver compensates by increasing the synthesis of lipoproteins while reducing the breakdown and metabolism of lipoproteins, resulting in a significant increase in serum cholesterol, triglycerides, and low-density lipoprotein, which accelerates renal vascular endothelial damage and atherosclerosis.

[0007] Treatment of nephrotic syndrome requires a comprehensive strategy, encompassing multiple dimensions including drug intervention, dietary control, and lifestyle optimization. In the field of drug therapy, current clinical practice primarily relies on glucocorticoids and immunosuppressants. However, long-term use of these Western medicines not only requires vigilance regarding drug side effects, drug resistance, and potential infusion reactions, but also raises concerns about their long-term impact on the patient's overall metabolism and immune function. Regarding dietary and lifestyle management, patients should adhere to a low-salt, low-fat, and high-quality protein diet, while also reducing the burden on the kidneys through adequate rest, avoiding fatigue and infection. However, relying solely on Western medicine or lifestyle adjustments cannot fully address the complexity of the disease. The symptomatic treatment nature of Western medicine makes it difficult to address deeper pathological mechanisms such as renal fibrosis and intestinal microecological disorders. While traditional Chinese medicine emphasizes holistic regulation and syndrome differentiation, existing compound formulas often suffer from limitations in compatibility, making it difficult to achieve synergistic effects across multiple targets. Furthermore, traditional Chinese medicine's regulation of the intestinal flora is largely based on the theory of "strengthening the spleen and stomach," but lacks targeted regulatory strategies for specific bacterial groups. For example, kidney disease patients often experience a decline in the abundance of beneficial bacteria in their gut due to long-term use of antibiotics or immunosuppressants. Existing traditional Chinese medicine formulas do not specifically supplement probiotics, making it difficult to rebuild the intestinal barrier function and inhibit the production of uremic toxins. Furthermore, the effective components of traditional Chinese medicine, such as flavonoids (e.g., baicalin) and polysaccharides (e.g., poria cocos polysaccharides), are easily degraded by gastric acid after oral administration, resulting in insufficient local drug concentrations in the glomeruli. Summary of the Invention

[0008] In response to the above situation and to overcome the shortcomings of the existing technology, this invention prepares probiotic microcapsules by combining probiotics with extracts of traditional Chinese medicine such as astragalus and lily, and scientifically combines them with other traditional Chinese medicines such as safflower and scutellaria to form a multi-target synergistic treatment system. This not only solves the problems of insufficient regulation of intestinal flora and easy degradation of effective ingredients by gastric acid in traditional Chinese medicine, but also makes up for the side effects of long-term use of Western medicine.

[0009] To achieve the above objectives, the following technical solution is adopted: On the one hand, the present invention provides a traditional Chinese medicine compound preparation for treating nephrotic syndrome, which is made from the following components by weight: 20-40 parts of Heshengyuan microcapsules, 8-15 parts of safflower, 10-18 parts of scutellaria baicalensis, 6-12 parts of perilla, 10-20 parts of mulberry, 5-10 parts of codonopsis pilosula, 3-8 parts of charred areca nut, 12-20 parts of euryale ferox, 15-25 parts of jujube, 10-18 parts of wolfberry, 15-25 parts of yam, 8-15 parts of asparagus, 10-20 parts of cornus officinalis, 5-10 parts of oroxylum indicum, 3-8 parts of cardamom, 6-12 parts of Murraya paniculata, 10-18 parts of Lespedeza bicolor, and 8-15 parts of Ajuga decumbens.

[0010] Safflower is pungent in flavor and warm in nature, and it pertains to the heart and liver meridians, having the effects of promoting blood circulation to dredge meridians, dissipating stasis and relieving pain. Due to kidney lesions in patients with nephrotic syndrome, the local blood circulation in the kidneys is not smooth, and there is a pathological state of blood stasis blockage. Safflower can improve the blood circulation in the kidneys, increase the blood flow in the kidneys, and promote the repair and regeneration of kidney tissues by promoting blood circulation and removing blood stasis.

[0011] Perilla is pungent in flavor and warm in nature, and it pertains to the lung and spleen meridians, having the effects of relieving exterior syndrome and dispelling cold, regulating qi and harmonizing the stomach. Perilla mainly regulates the spleen and stomach functions of patients by regulating qi and harmonizing the stomach. Due to long-term illness and the use of drugs in patients with nephrotic syndrome, it is easy to have disharmony of the spleen and stomach functions, resulting in symptoms such as loss of appetite, nausea and vomiting. The effect of perilla in regulating qi and harmonizing the stomach can improve the spleen and stomach functions of patients, enhance appetite, promote digestion and absorption, and provide sufficient nutritional support for the body.

[0012] Mulberry is sweet and sour in flavor and cold in nature, and it pertains to the heart, liver and kidney meridians, having the effects of nourishing yin and tonifying blood, promoting the production of body fluid and moistening dryness. Most patients with nephrotic syndrome have the condition of deficiency of kidney yin. Mulberry can nourish kidney yin and improve the symptoms of deficiency of kidney yin by nourishing yin and tonifying blood. Its abundant nutritional components, such as polysaccharides and flavonoids, have antioxidant and anti-aging effects, can reduce the oxidative stress damage of kidney tissues, protect kidney cells, and delay the progression of kidney diseases.

[0013] Chinese bellflower root is sweet and slightly bitter in flavor and slightly cold in nature, and it pertains to the lung, spleen and liver meridians, having the effects of moistening the lung and resolving phlegm, nourishing yin and harmonizing the stomach, and detoxifying. Chinese bellflower root can improve the symptoms of cough and dry throat caused by yin deficiency in patients by nourishing yin and moistening the lung, and harmonizing the stomach and detoxifying, and at the same time regulate the spleen and stomach functions and enhance the resistance of the body. Its components such as polysaccharides and sterols have certain immunomodulatory and antioxidant effects, which help to reduce kidney inflammatory reactions and protect kidney functions.

[0014] Areca nut is pungent and bitter in flavor and warm in nature, and it pertains to the stomach and large intestine meridians, having the effects of killing parasites and eliminating accumulation, promoting qi circulation and promoting diuresis. Raw areca nut has certain toxicity. After being roasted, its toxicity is reduced, and at the same time, the effect of promoting qi circulation and promoting diuresis is retained. In the treatment of nephrotic syndrome, the effect of roasted areca nut in promoting qi circulation and promoting diuresis can promote the metabolism and excretion of body fluids, and reduce the symptoms of edema. Modern research has found that areca alkaloids can activate the AMPK pathway, promote lipid metabolism, and have a good regulatory effect on nephrosis complicated with hyperlipidemia.

[0015] Gordon euryale seed is sweet and astringent in flavor and neutral in nature, and it pertains to the spleen and kidney meridians, having the effects of tonifying the kidney and astringing essence, strengthening the spleen and stopping diarrhea, and removing dampness and arresting leukorrhea. Gordon euryale seed can astringe the essence of the kidney and reduce the loss of protein from urine by tonifying the kidney and astringing essence. Its effect of strengthening the spleen and stopping diarrhea can improve the spleen and stomach functions of patients, promote the absorption of nutrients, and enhance the resistance of the body. At the same time, the effect of Gordon euryale seed in removing dampness and arresting leukorrhea helps to reduce the pathogenic dampness in the body and relieve the symptoms of edema. Modern pharmacological research shows that components such as flavonoids and polysaccharides in Gordon euryale seed have antioxidant and anti-inflammatory effects, which can protect kidney tissues and reduce kidney damage.

[0016] Red dates are sweet and warm in nature, and they enter the spleen, stomach, and heart meridians. They have the effects of tonifying the middle energizer, replenishing qi, nourishing blood, and calming the mind. Red dates can enhance the function of the spleen and stomach by tonifying the middle energizer and promoting the generation of qi and blood. Patients with long-term proteinuria leading to qi and blood deficiency can benefit from the blood-nourishing effect of red dates, which can replenish qi and blood and improve the patient's anemia symptoms.

[0017] Goji berries are sweet in taste and neutral in nature, and they enter the liver and kidney meridians. They have the effects of nourishing the liver and kidneys, benefiting essence and improving eyesight. Patients with nephrotic syndrome often have liver and kidney yin deficiency. Goji berries can nourish the liver and kidneys, thus improving symptoms such as lower back and knee pain, dizziness, and blurred vision.

[0018] Yam is sweet in taste and neutral in nature, and it enters the spleen, lung, and kidney meridians. It has the effects of tonifying the spleen and stomach, promoting body fluid production and benefiting the lungs, and tonifying the kidneys and astringing essence. In the treatment of nephrotic syndrome, yam can enhance the spleen and stomach's digestive function by tonifying them, promoting the absorption of nutrients and providing sufficient nutritional support to the body. Its kidney-tonifying and essence-astringent effect can consolidate kidney essence and reduce proteinuria. At the same time, yam also has the effect of promoting body fluid production and benefiting the lungs, which can improve symptoms such as dry mouth and cough caused by deficiency of both qi and yin in patients.

[0019] Asparagus root is sweet and bitter in taste, cold in nature, and enters the lung and kidney meridians. It has the effects of nourishing yin and moistening dryness, clearing the lungs and promoting the production of body fluids. Patients with nephrotic syndrome are prone to symptoms of yin deficiency and internal heat. Asparagus root, by nourishing yin and moistening dryness, can nourish kidney yin, clear internal heat, and relieve symptoms such as hot flashes and night sweats. Its effect of clearing the lungs and promoting the production of body fluids can improve respiratory symptoms and reduce pulmonary inflammation.

[0020] Cornus officinalis has a sour and astringent taste, is slightly warm in nature, and enters the liver and kidney meridians. It has the effects of tonifying the liver and kidneys, and astringing and consolidating. In the treatment of nephrotic syndrome, Cornus officinalis can improve the state of liver and kidney yin deficiency by tonifying the liver and kidneys, and enhance kidney function. Its astringent and consolidating effect can consolidate kidney essence, reduce proteinuria, and also has a certain effect on improving symptoms such as frequent urination and enuresis caused by kidney qi deficiency.

[0021] The flavor of *Oroxylum indicum* is sweet and bitter, and its nature is cool. It enters the lung, liver, and stomach meridians, and has the effects of clearing the lungs and relieving sore throat, soothing the liver and harmonizing the stomach. Its liver-soothing and stomach-harmonizing effects can regulate the patient's emotions, improve spleen and stomach function, promote appetite, and enhance the body's resistance.

[0022] Murraya paniculata has a pungent and slightly bitter taste, and is warm in nature. It enters the liver and stomach meridians and has the effects of promoting qi circulation, relieving pain, and invigorating blood circulation. Murraya paniculata can alleviate symptoms such as lower back pain caused by kidney disease by promoting qi circulation and relieving pain. Its effect of invigorating blood circulation and removing blood stasis can improve blood circulation in the kidneys and promote the repair and regeneration of kidney tissue.

[0023] Cardamom has a pungent and warm flavor, and enters the spleen and stomach meridians. It has the effects of drying dampness, promoting qi circulation, warming the middle jiao, and stopping vomiting. In the treatment of nephrotic syndrome, cardamom can improve the state of dampness and qi stagnation in patients by drying dampness and promoting qi circulation, and promote the digestive function of the spleen and stomach.

[0024] Lespedeza spicata has a slightly bitter and pungent taste, and is neutral in nature. It possesses the functions of clearing heat and dampness, promoting blood circulation and unblocking collaterals. In the treatment of nephrotic syndrome, its heat-clearing and dampness-removing effects can eliminate damp-heat pathogens from the body and reduce inflammatory responses in the kidneys. Its blood-activating and collateral-unblocking effects can improve renal blood circulation, promote kidney tissue repair, and have an auxiliary effect in alleviating the symptoms of nephrotic syndrome.

[0025] Ajuga decumbens has a bitter taste and is cold in nature. It enters the lung, liver, and kidney meridians and has the effects of clearing heat and detoxifying, cooling blood and reducing swelling. Ajuga decumbens can clear heat and toxins from the body and reduce kidney inflammation. Its blood-cooling and swelling-reducing effects can alleviate symptoms such as edema and hematuria caused by kidney disease.

[0026] Furthermore, the synbiotic microcapsules are prepared through the following steps:

[0027] S1. Preparation of inner layer extracts: Astragalus membranaceus was pulverized, and 10 times its weight of 70% ethanol was added. The mixture was refluxed twice at 60℃ for 2 hours each time. The extracts were combined and concentrated under reduced pressure to a relative density of 1.1-1.2 to obtain Astragalus membranaceus extract. Lily bulbs were sliced, and 8 times its weight of water was added. After boiling, the mixture was simmered three times for 1.5 hours each time. The decoctions were combined, filtered, and the filtrate was concentrated under reduced pressure to a thick paste to obtain lily bulb extract. Poria cocos was pulverized and passed through a 60-mesh sieve. 10 times its weight of water was added, and the mixture was ultrasonically extracted at 80℃ for 30 minutes, twice. The extracts were combined, centrifuged at 4000 r / min for 10 minutes, and the supernatant was collected and concentrated under reduced pressure to obtain Poria cocos extract. Cubeb was pulverized, defatted twice by reflux with petroleum ether, and then 95% ethanol was added at a material-to-liquid ratio of 1:8 for reflux extraction twice, 1.5 hours each time. The ethanol extracts were combined, and the ethanol was recovered to obtain cubeb extract.

[0028] S2. Probiotic Treatment: Inoculate Lactobacillus acidophilus, Bifidobacterium, and Lactobacillus plantarum into MRS medium and incubate at 37℃ for 18-24 hours. Centrifuge at 5000 rpm for 10 minutes to collect the bacterial cells. Wash the cells 2-3 times with sterile physiological saline and adjust the bacterial suspension concentration to 1×10⁻⁶. 9 -1×10 10 CFU / mL;

[0029] S3. Preparation of the inner layer mixture: The Astragalus extract, Lily extract, Poria extract, and Piper cubeba extract are mixed in proportion, dissolved in sterile water, and prepared into a mixed solution with a concentration of 20-30 mg / mL. Then, the treated probiotic suspension is added to achieve a final probiotic concentration of 1×10⁻⁶.8 -1×10 9 CFU / mL was used to obtain the inner layer mixture;

[0030] S4. Preparation of wall material solution: Add 15 times the amount of water to the agar seeds, stir and extract at 60℃ for 3 hours, filter, concentrate the filtrate and freeze dry, pulverize and pass through a 100-mesh sieve to obtain agar seed extract. Mix the agar seed extract with mannoprotein at a mass ratio of 1:1–1:5, dissolve in phosphate buffer at pH=7.0-9.0 to prepare a mixed solution with a mass fraction of 10-20%, react at 60-70℃ for 18-24 hours, dialysis and lyophilize to obtain mannosyl-grafted agar seed extract. Add the mannosyl-grafted agar seed extract and sodium alginate to deionized water and dissolve in a water bath at 50-60℃ to prepare a first solution with a mass fraction of 3%-5%. Then dissolve fucoidan sulfate in an acetate-sodium acetate buffer solution at pH=4.5-5.5 to prepare a second solution with a mass fraction of 1%-2%. Then mix the first and second solutions and stir evenly to obtain the wall material solution.

[0031] S5. Microcapsule preparation: The inner layer mixture is slowly added dropwise to the wall material solution while stirring at 800-1000 r / min to form an O / W type emulsion. After stirring for 30 min, the emulsion is added dropwise to a 0.2-0.3 mol / L calcium chloride solution. The ion crosslinking reaction is carried out for 1-2 h under magnetic stirring to form a gel network between sodium alginate and calcium ions. The microcapsules are washed 2-3 times with deionized water to remove residual calcium chloride solution on the surface. Then, the washed microcapsules are dispersed in deionized water to prepare a suspension with a solid content of 10%-15%, which is then spray-dried to obtain dried Synbiotic microcapsules.

[0032] Astragalus has a sweet taste and slightly warm nature. It enters the spleen and lung meridians and has the effects of tonifying qi and raising yang, consolidating the exterior and stopping sweating, and promoting diuresis and reducing edema. Patients with nephrotic syndrome often experience symptoms such as massive proteinuria and hypoalbuminemia. Astragalus, by tonifying qi and raising yang, can enhance the function of the spleen and lungs, making the spleen function smoothly and the lung qi sufficient, thereby strengthening the retention of essential substances and reducing proteinuria. Modern pharmacological studies have shown that astragalus polysaccharides can regulate the body's immune function, enhance the body's resistance, and reduce the risk of infection caused by low immune function in patients with nephrotic syndrome. Astragalus saponins have anti-inflammatory and antioxidant effects, which can reduce glomerular inflammation, protect the integrity of the glomerular filtration membrane, reduce its permeability, and thus reduce protein leakage.

[0033] Lily bulbs are sweet and cold in nature, and enter the heart and lung meridians. They nourish yin and moisten the lungs, clear the heart and calm the mind. Patients with nephrotic syndrome, due to long-term illness and the use of hormones and other medications, are prone to symptoms such as yin deficiency with internal heat, irritability, and insomnia. The yin-nourishing properties of lily bulbs can nourish kidney yin, improve the state of yin deficiency with excessive fire, and alleviate symptoms such as hot flashes and night sweats caused by yin deficiency. At the same time, its calming and mind-clearing effects help regulate the patient's emotions, improve sleep quality, and positively contribute to improving the patient's quality of life.

[0034] Poria cocos is sweet and bland in taste, neutral in nature, and enters the heart, lung, spleen, and kidney meridians. Patients with nephrotic syndrome often experience severe edema, which Traditional Chinese Medicine (TCM) attributes to internal retention of dampness and its overflow into the skin. Poria cocos, by promoting diuresis and eliminating dampness, can facilitate the excretion of excess water from the body, thus alleviating edema symptoms. Furthermore, Poria cocos also strengthens the spleen; the spleen governs transformation and transportation, and a healthy spleen ensures the normal transformation and transportation of dampness, helping to fundamentally improve the condition of internal dampness retention. Modern pharmacological studies show that Poria cocos polysaccharides can regulate intestinal flora, improve the intestinal microecological environment, promote nutrient absorption, and enhance the body's resistance; Poria cocos extract has antioxidant and anti-inflammatory effects, reducing oxidative stress damage and inflammatory responses in kidney tissue and protecting kidney function.

[0035] Long cubeb has a pungent and warm nature, and enters the spleen, stomach, kidney, and bladder meridians. It has the effects of warming the middle jiao (spleen and stomach), dispelling cold, promoting qi circulation and relieving pain, and warming the kidneys and invigorating yang. The kidney-warming effect of long cubeb helps enhance the kidney's qi transformation function and assists in promoting diuresis and reducing swelling. Modern research shows that the volatile oils and other components in long cubeb have antibacterial and anti-inflammatory effects, which can inhibit kidney inflammation and protect kidney tissue.

[0036] Agaric seeds are the seeds of the false groundcherry. They taste sweet and slightly bitter, and are neutral in nature. They have the effects of clearing heat and relieving summer heat, and promoting diuresis and reducing swelling. They have a good relieving effect on the symptoms of heat and dampness stagnation in patients with nephrotic syndrome. Agaric seeds can clear heat from the body and reduce the inflammatory response of the kidneys by clearing heat. By promoting diuresis and reducing swelling, they can promote the excretion of excess water in the body, relieve edema symptoms, reduce the pressure on the kidneys, and improve the blood circulation of the kidneys.

[0037] The extract of *Gynostemma pentaphyllum* seeds contains a large amount of highly esterified pectin polysaccharides, which can form a gel network in solution, exhibiting excellent film-forming ability. When used to prepare microcapsule wall materials, under processes such as spray drying or drop preparation, the pectin polysaccharide molecules can rapidly form a continuous and dense film through interactions such as hydrogen bonding, hydrophobic interactions, and ionic cross-linking, completely encapsulating core materials such as probiotics and traditional Chinese medicine extracts. In the acidic environment of the stomach, the gel structure of the wall material can maintain relative stability, preventing the probiotics and traditional Chinese medicine components from being destroyed by gastric acid. This gel network is porous, allowing water molecules to slowly penetrate, causing the wall material to gradually swell and release the core material, achieving a sustained-release effect of the drug. After the gel network of *Gynostemma pentaphyllum* seed pectin polysaccharides is cross-linked with sodium alginate through calcium ions, it can form a more stable composite gel structure, enhancing the mechanical strength and acid resistance of the wall material; while combining with fucoidan sulfate can further optimize the surface properties and pore structure of the wall material, improving the targeting and controlled-release performance of the microcapsules.

[0038] Furthermore, in step S2, the mass ratio of Lactobacillus acidophilus, Bifidobacterium, and Lactobacillus plantarum is 3-5:1-3:1-3.

[0039] Furthermore, in step S3, the mass ratio of Astragalus membranaceus extract, lily extract, Poria cocos extract, and Piper cubeba extract is 3-8:2-5:1-3:1-3.

[0040] Furthermore, in step S4, the mass ratio of mannose-grafted Lithops seed extract to sodium alginate in the first solution is 1:1 to 3:1.

[0041] Furthermore, in step S4, the volume ratio of the first solution to the second solution is 3:1 to 5:1.

[0042] Furthermore, in step S5, the volume ratio of the inner layer mixture to the wall material solution is 1:5 to 1:8.

[0043] Furthermore, the inlet air temperature of the spray dryer is 110-130℃, the outlet air temperature is 50-70℃, and the atomization pressure is 0.2-0.3MPa.

[0044] On the other hand, the present invention also provides a method for preparing the traditional Chinese medicine compound preparation for treating nephrotic syndrome, comprising the following steps:

[0045] (1) After crushing all components except the synbiotic microcapsules, mix them evenly, pass them through a 200-mesh sieve, add 8-10 times the mass of ethanol for extraction, extract 3 times, each extraction for 1 hour, combine the extracts, and concentrate the extract to a thick paste with a relative density of 1.10-1.15.

[0046] (2) Add 70% ethanol to the thick paste obtained in step (1), let it stand for 24 hours, remove the supernatant, centrifuge the remaining precipitate at 4000 r / min for 15 min, combine the filtrates, and concentrate to obtain the refined extract.

[0047] (3) Mix the refined extract obtained in step (2) with the synbiotic microcapsules and dry to obtain a traditional Chinese medicine compound preparation.

[0048] Furthermore, the traditional Chinese medicine compound preparation also includes pharmaceutically acceptable fillers, lubricants, and flavoring agents.

[0049] Furthermore, the filler is one or more selected from cyclodextrin, lactose, microcrystalline cellulose, starch, methylcellulose, carboxymethylcellulose, dicalcium phosphate, and mannitol.

[0050] Furthermore, the lubricant is one or more of magnesium stearate, silica gel, talc, glyceryl behenate, hydrogenated vegetable oil, and sodium lauryl sulfate.

[0051] Furthermore, the flavoring agent is one or more of rock sugar, honey, citric acid, glycyrrhizic acid, and hawthorn acid.

[0052] Furthermore, the traditional Chinese medicine compound preparation is a clinically acceptable preparation, and the traditional Chinese medicine compound preparation is one of the following: tablets, capsules, solutions, granules, ointments, pills, suspensions, pills, powders, decoctions, and oral preparations.

[0053] The beneficial effects of this invention are:

[0054] This invention combines probiotics with extracts of traditional Chinese medicines such as Astragalus membranaceus, lily bulb, and Poria cocos to form microcapsule structures. This not only protects the probiotics from stomach acid but also allows for targeted release in the intestines. The probiotics can regulate the balance of intestinal flora and reduce the accumulation of uremic toxins, while the components of traditional Chinese medicines such as Astragalus membranaceus synergistically improve kidney function through immunomodulation and anti-inflammatory effects. Studies have shown that synbiotics can significantly reduce the expression of genes related to kidney fibrosis and inhibit kidney damage.

[0055] Grafting mannose onto agar seed extract via Maillard reaction not only enhances the hydrophilicity and biocompatibility of the wall material through sugar chain modification, but also significantly improves the colonization efficiency of microcapsules in the intestine through the specific binding ability of mannose residues to intestinal mucosal epithelial cells, prolonging the drug's retention time in the intestine and improving bioavailability. The sulfate ester groups of fucoidan carry a strong negative charge, which can form an electrostatic synergistic effect with the carboxylic acid groups of sodium alginate, increasing the cross-linking density and mechanical strength of the wall material gel network. At the same time, its helical structure can be embedded in the gel pores of sodium alginate and calcium ions, significantly improving the microcapsules' resistance to gastric acid erosion.

[0056] The compound contains flavonoids such as safflower, scutellaria, and lespedeza, which can inhibit the NF-κB pathway and reduce the release of inflammatory factors. Roasted areca nut promotes lipid metabolism by activating the AMPK pathway and alleviates nephropathy complicated with hyperlipidemia. Dioscorea and wolfberry improve hypoproteinemia by regulating blood sugar and protein metabolism. The polyphenols in mulberry and cornus officinalis can reduce oxidative stress damage and repair glomerular basement membrane permeability. Detailed Implementation

[0057] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0058] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention. The preferred embodiments and materials described herein are for illustrative purposes only and do not limit the scope of this application.

[0059] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, and the experimental materials used in the following examples are all purchased from commercial channels.

[0060] The traditional Chinese medicine compound preparation in the embodiments of the present invention is a granule.

[0061] Example 1: A traditional Chinese medicine compound preparation for treating nephrotic syndrome, made from the following components by weight: 30 parts of Heshengyuan microcapsules, 12 parts of safflower, 15 parts of scutellaria baicalensis, 8 parts of perilla, 12 parts of mulberry, 8 parts of codonopsis pilosula, 5 parts of charred areca nut, 15 parts of euryale ferox, 18 parts of jujube, 14 parts of wolfberry, 18 parts of yam, 10 parts of asparagus, 16 parts of cornus officinalis, 8 parts of oroxylum indicum, 5 parts of cardamom, 8 parts of Murraya paniculata, 12 parts of Lespedeza bicolor, and 12 parts of Ajuga decumbens.

[0062] The synbiotic microcapsules are prepared through the following steps:

[0063] S1. Preparation of inner layer extracts: Astragalus membranaceus was pulverized, and 10 times its weight of 70% ethanol was added. The mixture was refluxed twice at 60℃ for 2 hours each time. The extracts were combined and concentrated under reduced pressure to a relative density of 1.1-1.2 to obtain Astragalus membranaceus extract. Lily bulbs were sliced, and 8 times its weight of water was added. After boiling, the mixture was simmered three times for 1.5 hours each time. The decoctions were combined, filtered, and the filtrate was concentrated under reduced pressure to a thick paste to obtain lily bulb extract. Poria cocos was pulverized and passed through a 60-mesh sieve. 10 times its weight of water was added, and the mixture was ultrasonically extracted at 80℃ for 30 minutes, twice. The extracts were combined, centrifuged at 4000 r / min for 10 minutes, and the supernatant was collected and concentrated under reduced pressure to obtain Poria cocos extract. Cubeb was pulverized, defatted twice by reflux with petroleum ether, and then 95% ethanol was added at a material-to-liquid ratio of 1:8 for reflux extraction twice, 1.5 hours each time. The ethanol extracts were combined, and the ethanol was recovered to obtain cubeb extract.

[0064] S2. Probiotic Treatment: Inoculate Lactobacillus acidophilus, Bifidobacterium, and Lactobacillus plantarum at a mass ratio of 4:2:2 into MRS medium, incubate at 37℃ for 24 hours, centrifuge at 5000 rpm for 10 minutes, collect the bacterial cells, wash 2-3 times with sterile physiological saline, and adjust the bacterial suspension concentration to 1×10⁻⁶. 10 CFU / mL;

[0065] S3. Preparation of the inner layer mixture: The Astragalus extract, Lily extract, Poria extract, and Piper cubeba extract are mixed in a mass ratio of 5:3:2:2, dissolved in sterile water to prepare a mixed solution with a concentration of 25 mg / mL. Then, the prepared probiotic suspension is added to achieve a final probiotic concentration of 1 × 10⁻⁶. 9 CFU / mL was used to obtain the inner layer mixture;

[0066] S4. Preparation of wall material solution: Add 15 times the amount of water to the agar seeds, stir and extract at 60℃ for 3 hours, filter, concentrate the filtrate and freeze dry, pulverize and pass through a 100-mesh sieve to obtain agar seed extract. Mix the agar seed extract with mannoprotein at a mass ratio of 1:3, dissolve in phosphate buffer at pH=7.4 to prepare a 15% mass fraction mixed solution, react at 80℃ for 24 hours, dialysis and lyophilize to obtain mannosyl-grafted agar seed extract. Add the mannosyl-grafted agar seed extract and sodium alginate at a mass ratio of 2:1 to deionized water, dissolve in a 55℃ water bath to prepare a 4% mass fraction first solution. Then dissolve fucoidan sulfate in an acetate-sodium acetate buffer solution at pH=5.0 to prepare a 1.5% mass fraction second solution. Then mix the first solution and the second solution at a volume ratio of 4:1, stir evenly to obtain the wall material solution.

[0067] S5. Microcapsule preparation: The inner layer mixture was slowly added dropwise to the wall material solution at a volume ratio of 1:6, while stirring at 900 r / min to form an O / W emulsion. After stirring for 30 min, the emulsion was added dropwise to a 0.2 mol / L calcium chloride solution. An ionic cross-linking reaction was carried out for 1.5 h under magnetic stirring to form a gel network between sodium alginate and calcium ions. The microcapsules were washed three times with deionized water to remove residual calcium chloride solution from the surface. The washed microcapsules were then dispersed in deionized water to prepare a suspension with a solid content of 12%. Spray drying was performed at an inlet air temperature of 120℃, an outlet air temperature of 60℃, and an atomization pressure of 0.2 MPa to obtain dried Synbiotic microcapsules.

[0068] The preparation method of the traditional Chinese medicine compound preparation for treating nephrotic syndrome includes the following steps:

[0069] (1) After crushing all components except the synbiotic microcapsules, mix them evenly, pass them through a 200-mesh sieve, add 8-10 times the mass of ethanol for extraction, extract 3 times, each extraction for 1 hour, combine the extracts, and concentrate the extract to a thick paste with a relative density of 1.10-1.15.

[0070] (2) Add 70% ethanol to the thick paste obtained in step (1), let it stand for 24 hours, remove the supernatant, centrifuge the remaining precipitate at 4000 r / min for 15 min, combine the filtrates, and concentrate to obtain the refined extract.

[0071] (3) Mix the refined extract obtained in step (2) with the synbiotic microcapsules and dry to obtain a traditional Chinese medicine compound preparation.

[0072] Example 2: A traditional Chinese medicine compound preparation for treating nephrotic syndrome, made from the following components by weight: 20 parts of Heshengyuan microcapsules, 8 parts of safflower, 10 parts of scutellaria baicalensis, 6 parts of perilla, 10 parts of mulberry, 5 parts of codonopsis pilosula, 3 parts of charred areca nut, 12 parts of euryale ferox, 15 parts of jujube, 10 parts of wolfberry, 15 parts of yam, 8 parts of asparagus, 10 parts of cornus officinalis, 5 parts of oroxylum indicum, 3 parts of cardamom, 6 parts of Murraya paniculata, 10 parts of Lespedeza bicolor, and 8 parts of Ajus lanceolata. The rest are the same as in Example 1.

[0073] Example 3: A traditional Chinese medicine compound preparation for treating nephrotic syndrome, made from the following components by weight: 40 parts of Heshengyuan microcapsules, 15 parts of safflower, 18 parts of scutellaria baicalensis, 12 parts of perilla, 20 parts of mulberry, 10 parts of codonopsis pilosula, 8 parts of charred areca nut, 20 parts of euryale ferox, 25 parts of jujube, 18 parts of wolfberry, 25 parts of yam, 15 parts of asparagus, 20 parts of cornus officinalis, 10 parts of oroxylum indicum, 8 parts of cardamom, 12 parts of Murraya paniculata, 18 parts of Lespedeza bicolor, and 15 parts of Ajuga decumbens. The rest are the same as in Example 1.

[0074] Example 4: A traditional Chinese medicine compound preparation for treating nephrotic syndrome, made from the following components by weight: 25 parts of Heshengyuan microcapsules, 10 parts of safflower, 10 parts of scutellaria baicalensis, 8 parts of perilla, 10 parts of mulberry, 6 parts of codonopsis pilosula, 4 parts of charred areca nut, 12 parts of euryale ferox, 18 parts of jujube, 15 parts of wolfberry, 18 parts of yam, 6 parts of asparagus, 15 parts of cornus officinalis, 6 parts of oroxylum indicum, 4 parts of cardamom, 8 parts of Murraya paniculata, 12 parts of Lespedeza bicolor, and 10 parts of Ajus lanceolata. The rest are the same as in Example 1.

[0075] Example 5: A traditional Chinese medicine compound preparation for treating nephrotic syndrome, made from the following components by weight: 28 parts of Heshengyuan microcapsules, 12 parts of safflower, 15 parts of scutellaria baicalensis, 8 parts of perilla, 15 parts of mulberry, 6 parts of codonopsis pilosula, 4 parts of charred areca nut, 15 parts of euryale ferox, 18 parts of jujube, 16 parts of wolfberry, 18 parts of yam, 12 parts of asparagus, 12 parts of cornus officinalis, 7 parts of oroxylum indicum, 7 parts of cardamom, 7 parts of Murraya paniculata, 12 parts of Lespedeza bicolor, and 9 parts of Ajus lanceolata. The remainder is the same as in Example 1.

[0076] Example 6: A traditional Chinese medicine compound preparation for treating nephrotic syndrome, made from the following components by weight: 30 parts of Heshengyuan microcapsules, 10 parts of safflower, 12 parts of scutellaria baicalensis, 11 parts of perilla, 13 parts of mulberry, 7 parts of codonopsis pilosula, 5 parts of charred areca nut, 15 parts of euryale ferox, 18 parts of jujube, 13 parts of wolfberry, 18 parts of yam, 13 parts of asparagus, 15 parts of cornus officinalis, 8 parts of oroxylum indicum, 5 parts of cardamom, 10 parts of Murraya paniculata, 12 parts of Lespedeza bicolor, and 10 parts of Ajuga decumbens. The remainder is the same as in Example 1.

[0077] Example 7: A traditional Chinese medicine compound preparation for treating nephrotic syndrome, made from the following components by weight: 35 parts of Heshengyuan microcapsules, 10 parts of safflower, 16 parts of scutellaria baicalensis, 8 parts of perilla, 15 parts of mulberry, 8 parts of codonopsis pilosula, 6 parts of charred areca nut, 14 parts of euryale ferox, 18 parts of jujube, 15 parts of wolfberry, 18 parts of yam, 9 parts of asparagus, 17 parts of cornus officinalis, 7 parts of oroxylum indicum, 7 parts of cardamom, 9 parts of Murraya paniculata, 12 parts of Lespedeza bicolor, and 9 parts of Ajus lanceolata. The remainder is the same as in Example 1.

[0078] Example 8: A traditional Chinese medicine compound preparation for treating nephrotic syndrome, made from the following components by weight: 25 parts of Heshengyuan microcapsules, 12 parts of safflower, 13 parts of scutellaria baicalensis, 9 parts of perilla, 13 parts of mulberry, 7 parts of codonopsis pilosula, 8 parts of charred areca nut, 14 parts of euryale ferox, 20 parts of jujube, 15 parts of wolfberry, 21 parts of yam, 9 parts of asparagus, 12 parts of cornus officinalis, 9 parts of oroxylum indicum, 3 parts of cardamom, 9 parts of Murraya paniculata, 12 parts of Lespedeza bicolor, and 11 parts of Ajus lanceolata. The rest are the same as in Example 1.

[0079] Example 9: Animal experiments on the traditional Chinese medicine compound preparation of the present invention

[0080] (1) Experimental animals: SPF-grade male SD rats, 6 weeks old, weighing 200-220g, a total of 60 rats, were purchased from Shanghai Jihui Experimental Animal Breeding Co., Ltd. The breeding environment was: temperature 22±2℃, relative humidity 50±10%, 12h day and night alternation, free food and water.

[0081] (2) Modeling method: The tail vein injection of doxorubicin was used to establish the model. The rats were fixed on the rat board, the tail was disinfected with 75% alcohol, and the needle was inserted at the distal 1 / 3 of the tail vein. Doxorubicin solution (concentration 1mg / mL, solvent is physiological saline) was slowly injected. The injection dose was 5mg / kg body weight. After the injection, the rats continued to be fed. 24h urine was collected every week, and urine protein was detected by biuret method. When the 24h urine protein quantification was ≥100mg / 24h, the model was considered to be successful.

[0082] (3) Experimental grouping:

[0083] Normal control group (10 animals): No modeling treatment was performed. The animals were given an equal volume of physiological saline by gavage daily for 4 consecutive weeks.

[0084] Model control group (10 animals): After successful modeling, the animals were given an equal volume of physiological saline by gavage daily for 4 consecutive weeks.

[0085] Low-dose group of traditional Chinese medicine compound preparation (10 animals): After successful modeling, the animals were administered the raw drug at a concentration of 0.5 g / kg / d by gavage (equivalent to 1 / 10 of the clinical adult dose) for 4 consecutive weeks.

[0086] Medium-dose group of traditional Chinese medicine compound preparation (10 animals): After successful modeling, the animals were administered the raw drug at a content of 1.0 g / kg / d by gavage (equivalent to 1 / 5 of the clinical adult dose) for 4 consecutive weeks.

[0087] High-dose group of traditional Chinese medicine compound preparation (10 animals): After successful modeling, the animals were administered the raw drug at a content of 2.0 g / kg / d by gavage (equivalent to 1 / 2 of the clinical adult dose) for 4 consecutive weeks.

[0088] Positive control group (10 animals): After successful modeling, the animals were administered methylprednisolone tablet suspension (5 mg / kg / day, dissolved in 0.5% sodium carboxymethyl cellulose) by gavage daily for 4 consecutive weeks.

[0089] (4) Analytical methods:

[0090] Urine parameters: 24-hour urine was collected after the last administration, and urinary protein was quantitatively detected (biuret method).

[0091] Blood parameters: After the last administration, blood was drawn from the abdominal aorta to test serum albumin (bromocresol green method), serum creatinine (enzymatic method), blood urea nitrogen (urease method), and total cholesterol (TC).

[0092] Histopathology: Right kidney tissue was taken, fixed in 4% paraformaldehyde, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (HE) to observe glomerular morphology. Masson staining was used to detect the degree of renal interstitial fibrosis and the renal fibrosis area was calculated.

[0093] Gut microbiota: Fecal samples were collected, DNA was extracted, and changes in the abundance of Bifidobacteria in the gut were analyzed.

[0094] (5) Statistical methods: Data were analyzed using SPSS 26.0. One-way ANOVA was used for comparisons between groups. P < 0.05 was considered statistically significant.

[0095] The experimental results are shown in Table 1.

[0096] Table 1: Comparison Table of Animal Experiment Results

[0097]

[0098] Compared with the model control group, * indicates P<0.05, ** indicates P<0.01, and data are expressed as mean ± standard deviation.

[0099] Table 1 shows that in the normal control group, 24-hour urinary protein quantification, serum albumin levels, serum creatinine, and blood urea nitrogen levels were all within the normal range, indicating normal renal filtration function and protein metabolism in normal rats. In the model control group, urinary protein quantification increased after modeling, serum albumin decreased significantly, and serum creatinine increased, suggesting a successful doxorubicin-induced nephrotic syndrome model, with rats exhibiting typical proteinuria, hypoalbuminemia, and renal function impairment. In the high-dose group, urinary protein quantification decreased compared to the model group, serum albumin rebounded, and serum creatinine decreased, approaching normal levels. The medium-dose and low-dose groups also showed dose-dependent improvement, with the high-dose group showing an inhibitory effect on proteinuria comparable to the positive control drug methylprednisolone, and even superior in the magnitude of serum albumin rebound.

[0100] The total cholesterol level in the model control group was significantly higher than that in the normal group, and the area of ​​renal fibrosis was increased, suggesting that nephrotic syndrome is accompanied by severe lipid metabolism disorders and renal fibrosis. The high-dose traditional Chinese medicine group reduced total cholesterol and decreased the area of ​​renal fibrosis, indicating that this preparation improves renal pathological damage through multiple mechanisms by regulating blood lipids and inhibiting renal interstitial fibrosis.

[0101] The relative abundance of Bifidobacteria in the model control group was lower than that in the normal group, while it could be restored to near normal levels in the high-dose traditional Chinese medicine group. Gut microbiota dysbiosis is closely related to the inflammatory response and intestinal barrier function impairment in nephrotic syndrome. The recovery of Bifidobacteria abundance can alleviate renal inflammatory response by improving intestinal immune homeostasis.

[0102] Example 10: Clinical trial of the traditional Chinese medicine compound preparation of the present invention

[0103] (1) Case selection:

[0104] Eighty patients with nephrotic syndrome admitted between January 2023 and January 2025 were selected and randomly divided into a control group and an experimental group, with 40 patients in each group.

[0105] Control group: 23 males and 17 females; age range 22-64 years, mean (45.23±3.03) years; disease duration 6-24 months, mean (12.5±2.8) months.

[0106] Experimental group: 22 males and 18 females; age range 23-65 years, mean (45.33±3.01) years; disease duration 5-26 months, mean (13.2±3.1) months.

[0107] The baseline data (gender, age, disease duration, quantified urine protein, etc.) of the two groups were comparable (P>0.05). The study followed basic principles of medical ethics and met the ethical standards established by the ethics review committee.

[0108] (2) Inclusion and exclusion criteria:

[0109] The patient meets the diagnostic criteria for NS in the "Guidelines for the Diagnosis and Treatment of Nephrotic Syndrome": 24-hour urinary protein quantification ≥3.5g, plasma albumin ≤30g / L, accompanied by edema and / or hyperlipidemia.

[0110] Age 18-70, gender not limited.

[0111] (3) Exclusion criteria:

[0112] It is complicated by secondary kidney diseases such as diabetic nephropathy and lupus nephritis.

[0113] Severe liver and kidney dysfunction, malignant tumors, and coagulation disorders.

[0114] Allergy or intolerance to any of the ingredients in this preparation.

[0115] Pregnant or breastfeeding women.

[0116] (4) Treatment plan and medication:

[0117] Basic treatment: Both groups of patients received routine treatments such as diuretics (furosemide), anticoagulation (low molecular weight heparin), antihypertensive drugs (ACEI / ARB), and lipid-lowering drugs (statins).

[0118] Control group: Oral methylprednisolone tablets, initial dose 0.8 mg / kg / day (maximum dose 48 mg / day), taken once in the morning, and the dose was reduced by 10% every 2 weeks after 4 weeks.

[0119] Experimental group: In addition to the control group, the traditional Chinese medicine compound preparation of this invention was added, one dose each time, containing 10g of raw herbs, three times a day, taken with warm water.

[0120] (5) Observation indicators:

[0121] Kidney function indicators: Before treatment and 2 months after treatment, 24-hour urine protein quantification (biuret method), plasma albumin (bromocresol green method), serum creatinine (enzymatic method), and blood urea nitrogen (urease method) were tested.

[0122] Blood lipid indicators: Total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL-C) were measured before treatment and 2 months after treatment.

[0123] Safety indicators: Record adverse reactions (such as gastrointestinal discomfort, infection, abnormal blood sugar, etc.) during treatment.

[0124] Symptom scoring: Before treatment and 2 months after treatment, the symptom scoring scale was used to assess TCM syndromes such as edema (0-3 points), fatigue (0-3 points), and soreness of the waist and knees (0-3 points). The total score was 0-9 points, and the lower the score, the milder the symptoms.

[0125] (6) Criteria for evaluating therapeutic efficacy:

[0126] The following standards are formulated with reference to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs":

[0127] Significant effect: 24-hour urine protein quantification decreased by ≥60%, plasma albumin ≥35g / L, TCM syndrome score decreased by ≥70%, edema symptoms basically disappeared, and blood lipid indicators returned to normal or close to normal.

[0128] Effective: 24-hour urine protein quantification decreased by 30%-59%, plasma albumin decreased by 30-35g / L, TCM syndrome score decreased by 30%-69%, edema symptoms were significantly improved, and blood lipid indicators were significantly improved.

[0129] Invalid: The above criteria were not met, or the condition worsened.

[0130] Overall effectiveness rate = (number of cases with significant effect + number of cases with effective effect) / total number of cases × 100%.

[0131] (7) Statistical methods: SPSS 26.0 was used for data analysis. Quantitative data were expressed as (x±s), and the t-test was used for comparisons between groups. Count data were analyzed by χ² test. Ordinal data were analyzed by Ridit analysis. P<0.05 was considered statistically significant.

[0132] The results of the above experiments are shown in Tables 2, 3 and 4.

[0133] Table 2: Comparison Table of Renal Function Indicators in Clinical Trials

[0134]

[0135] Table 3: Comparison Table of Blood Lipid Indicators in Clinical Trials

[0136]

[0137] Table 4: Comparison Table of Adverse Reaction Rates and Symptom Scores in Clinical Trials

[0138]

[0139] In Tables 2 and 3, the comparisons before and after treatment within each group are shown. * indicates P<0.05, and ** indicates P<0.01. The data are expressed as mean ± standard deviation.

[0140] As can be seen from Tables 2-4, after 2 months of treatment, the 24-hour urinary protein quantification in the control group decreased, plasma albumin increased, serum creatinine decreased, and blood urea nitrogen decreased. In contrast, the improvement in urinary protein quantification, plasma albumin, serum creatinine, and blood urea nitrogen in the experimental group was significantly better than that in the control group. This indicates that the combination of the traditional Chinese medicine compound and hormones in this invention can enhance the proteinuria-reducing effect and accelerate the recovery of renal function.

[0141] After two months of treatment, the total cholesterol, triglycerides, and low-density lipoprotein levels in the experimental group decreased significantly, with a more pronounced decrease than that in the control group. This indicates that the traditional Chinese medicine compound of the present invention can reduce renal fat deposition and lower the risk of cardiovascular complications by regulating lipid metabolism.

[0142] In terms of TCM syndrome scores, the experimental group's score decreased from 6.6 to 2.1, significantly better than the control group's 3.8, especially in the improvement of symptoms such as edema, fatigue, and soreness in the lower back and knees. This is related to the fact that the TCM compound can improve water metabolism and the state of qi and blood deficiency by regulating the spleen and kidney qi transformation functions.

[0143] The adverse reaction rate in the control group was 32.5%, while it was only 12.5% ​​in the experimental group. The reason why this traditional Chinese medicine compound can reduce the immunosuppression and gastrointestinal mucosal damage caused by hormones is related to its spleen-strengthening, stomach-nourishing, qi-tonifying, and surface-strengthening components. For example, if the traditional Chinese medicine compound contains Astragalus membranaceus, Atractylodes macrocephala, and other drugs, it can enhance the body's immunity and reduce the risk of infection; if it contains Poria cocos, Citrus reticulata, and other drugs, it can improve gastrointestinal function and reduce the gastrointestinal reactions caused by hormones.

[0144] The results above show that the addition of the traditional Chinese medicine compound of this invention to methylprednisolone tablets has a significant effect on nephrotic syndrome, which is beneficial to improving renal function, regulating blood lipid levels, and reducing adverse reactions.

[0145] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

[0146] The present invention and its embodiments have been described above. This description is not restrictive, and the embodiments shown are only one of the embodiments of the present invention. The actual application is not limited to this. In conclusion, if those skilled in the art are inspired by this description and design similar methods and embodiments without departing from the spirit of the present invention, they should all fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine compound preparation for treating nephrotic syndrome, characterized in that: Is made of the following components by weight: 20-40 parts of synbiotic microcapsules, 8-15 parts of safflower, 10-18 parts of scutellaria, 6-12 parts of perilla, 10-20 parts of mulberry, 5-10 parts of white ginseng, 3-8 parts of roasted areca nut, 12-20 parts of gordon euryale, 15-25 parts of red dates, 10-18 parts of medlar, 15-25 parts of yam, 8-15 parts of asparagus, 10-20 parts of dogwood, 5-10 parts of belvedere, 3-8 parts of cardamom, 6-12 parts of nine fragrant, 10-18 parts of slender hujiuzi, 8-15 parts of muscle grass; ​ The synbiotic microcapsules are prepared by the following steps: S1, preparation of inner layer extract: after the astragalus root medicinal material is crushed, 10 times the mass of 70% ethanol is added, and reflux extraction is carried out at 60°C water bath for 2 times, each for 2h, the extract is combined, and concentrated under reduced pressure to relative density 1.1-1.2 to prepare astragalus extract; the lily medicinal material is sliced, 8 times the mass of water is added, and after boiling, it is decocted for 3 times, each for 1.5h, the decoction is combined, filtered, and the filtrate is concentrated under reduced pressure to a thick paste to prepare lily extract; the poria cocos medicinal material is crushed through a 60 mesh sieve, 10 times the mass of water is added, and ultrasonic extraction is carried out at 80°C for 30min, 2 times, the extract is combined, centrifuged at 4000r / min for 10min, the supernatant is taken, and concentrated under reduced pressure to prepare poria cocos extract; After the piper longum is crushed, it is defatted with petroleum ether by reflux extraction for 2 times, then 95% ethanol is added at a material-liquid ratio of 1:8 to extract by reflux extraction for 2 times, each for 1.5h, the ethanol extract is combined, and the ethanol is recovered to prepare piper longum extract; S2, processing probiotics: Lactobacillus acidophilus, Bifidobacterium, Lactobacillus plantarum are inoculated in MRS medium, incubated at 37°C for 18-24h, centrifuged at 5000r / min for 10min, the bacterial body is collected, washed with sterile physiological saline for 2-3 times, and then the concentration of bacterial suspension is adjusted to 1×10 9 -1×10 10 CFU / mL; S3, preparation of inner layer mixed solution: the Astragalus extract, Lily extract, Poria cocos extract, and Cubeb extract are mixed according to the proportion, and then dissolved in sterile water to prepare a mixed solution with a concentration of 20-30 mg / mL. Then, the prepared probiotic bacterial suspension is added to obtain an inner layer mixed solution with a final concentration of 1×10 8 CFU / mL. 9 CFU / mL, to obtain an inner layer mixed solution. S4, wall material solution preparation: the stone flower seeds are added into 15 times the amount of water, stirred and extracted at 60°C for 3h, filtered, and the filtrate is concentrated and freeze-dried, crushed through a 100 mesh sieve to prepare stone flower seed extract, the stone flower seed extract is mixed with mannose protein at a mass ratio of 1:1-1:5, dissolved in a phosphate buffer solution with pH=7.0-9.0, and prepared into a mixed solution with a mass fraction of 10-20%, reacted at 60-70°C for 18-24h, purified by dialysis, and freeze-dried to prepare mannose grafted stone flower seed extract, the mannose grafted stone flower seed extract and sodium alginate are added into deionized water, dissolved in a water bath at 50-60°C to prepare a first solution with a mass fraction of 3%-5%, the fucoidan sulfate is dissolved in an acetic acid-sodium acetate buffer solution with pH=4.5-5.5 to prepare a second solution with a mass fraction of 1%-2%, then the first solution and the second solution are mixed and stirred uniformly to obtain the wall material solution; S5, microcapsule preparation: slowly drop the inner layer mixed solution into the wall material solution, while stirring at a speed of 800-1000 r / min, forming an O / W emulsion, after stirring for 30 min, drop the emulsion into 0.2-0.3 mol / L calcium chloride solution, under magnetic stirring, ion crosslinking reaction for 1-2 h, sodium alginate and calcium ions form a gel network, washed with deionized water for 2-3 times, remove the surface residual calcium chloride solution, then disperse the washed microcapsules in deionized water, prepare a suspension with a solid content of 10%-15%, spray drying, get dried probiotic microcapsules.

2. The traditional Chinese medicine compound preparation for treating nephrotic syndrome according to claim 1, characterized in that: The mass ratio of Lactobacillus acidophilus, Bifidobacterium and Lactobacillus plantarum in step S2 is 3-5:1-3:1-3.

3. The traditional Chinese medicine compound preparation for treating nephrotic syndrome according to claim 1, characterized in that: The mass ratio of Huangqi extract, Baihe extract, Fuling extract and Bajingqie extract in step S3 is 3-8:2-5:1-3:1-3.

4. The traditional Chinese medicine compound preparation for treating nephrotic syndrome according to claim 1, characterized in that: The mass ratio of mannose grafted Shihua seed extract and sodium alginate in the first solution in step S4 is 1:1-3:

1.

5. The traditional Chinese medicine compound preparation for treating nephrotic syndrome according to claim 1, characterized in that: The volume ratio of the first solution to the second solution in step S4 is 3:1-5:

1.

6. The traditional Chinese medicine compound preparation for treating nephrotic syndrome according to claim 1, characterized in that: The volume ratio of the inner layer mixed solution to the wall material solution in step S5 is 1:5-1:

8.

7. The traditional Chinese medicine compound preparation for treating nephrotic syndrome according to claim 1, characterized in that: The inlet air temperature of the spray drying is 110-130℃, the outlet air temperature is 50-70℃, and the atomization pressure is 0.2-0.3 MPa.

8. A preparation method of the traditional Chinese medicine compound preparation for treating nephrotic syndrome according to any one of claims 1-7, characterized in that: (1) grinding and mixing the components except the probiotic microcapsules uniformly, passing through a 200 mesh screen, adding 8-10 times the mass of ethanol for extraction, extracting 3 times, each time for 1 h, combining the extract, and concentrating the extract to a thick paste with a relative density of 1.10-1.15; (2) adding 70% ethanol to the thick paste obtained in step (1), standing for 24 h, removing the supernatant, centrifuging the remaining precipitate at 4000 r / min for 15 min, and then combining the filtrate and concentrating to obtain the refined extract; (3) mixing the refined extract obtained in step (2) with the probiotic microcapsules, drying, and obtaining the traditional Chinese medicine compound preparation.

9. The preparation method of the traditional Chinese medicine compound preparation for treating nephrotic syndrome according to claim 8, characterized in that: The traditional Chinese medicine compound preparation further comprises a pharmaceutically acceptable filler, lubricant and flavoring agent; the filler is one or more of cyclodextrin, lactose, microcrystalline cellulose, starch, methyl cellulose, carboxymethyl cellulose, calcium hydrogen phosphate and mannitol; the lubricant is one or more of magnesium stearate, silica gel, talc, glyceryl behenate, hydrogenated vegetable oil and sodium lauryl sulfate; and the flavoring agent is one or more of granulated sugar, honey, citric acid, glycyrrhizic acid and maslinic acid.

10. The preparation method of the traditional Chinese medicine compound preparation for treating nephrotic syndrome according to claim 9, characterized in that: The traditional Chinese medicine compound preparation is a clinically acceptable preparation, and the traditional Chinese medicine compound preparation is one of tablets, capsules, solutions, granules, pastes, pills, suspensions, pills, powders, decoctions and oral preparations.

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