CN109223992B

CN109223992B - Traditional Chinese medicine composition for preventing and treating proteinuria and application thereof

Info

Publication number: CN109223992B
Application number: CN201811158174.5A
Authority: CN
Inventors: 杨茗橘; 程芬
Original assignee: Shanghai Resurrection Stone Medical Technology Co Ltd
Current assignee: Shanghai Resurrection Stone Medical Technology Co Ltd
Priority date: 2018-09-30
Filing date: 2018-09-30
Publication date: 2021-07-06
Anticipated expiration: 2038-09-30
Also published as: CN109223992A

Abstract

The invention discloses a traditional Chinese medicine composition for preventing and treating proteinuria, which consists of the following raw material medicines in parts by weight: 1-20 parts of silkworm cocoon shell, 1-20 parts of corn stigma, 0-20 parts of astragalus membranaceus, 0-20 parts of salvia miltiorrhiza and 0-20 parts of ligusticum wallichii. In addition, the invention also discloses application of the traditional Chinese medicine composition in preparing medicines and health-care products for preventing and treating proteinuria. Animal experiments and clinical trials prove that the Chinese medicinal composition has good safety and good curative effect, and can be used for reducing proteinuria caused by different causes of diseases such as diabetic nephropathy, membranous nephropathy, primary nephritis, IgA nephropathy, purpuric nephritis, lupus nephritis, hypertensive nephropathy, gouty nephropathy, chronic renal failure, chronic nephritis, nephrotic syndrome, lupus nephritis, urinary tract infection and the like. The traditional Chinese medicine composition has the advantages of good effect of improving clinical symptoms, small toxic and side effects, good clinical application prospect, simple extraction process, easy preparation and preparation cost reduction.

Description

Traditional Chinese medicine composition for preventing and treating proteinuria and application thereof

Technical Field

The invention relates to the technical field of traditional Chinese medicine compositions, and particularly relates to a traditional Chinese medicine composition for preventing and treating proteinuria and application thereof.

Background

Worldwide, Chronic Kidney Disease (CKD) has been recognized as a major public health problem. Statistically, 10% to 16% of people in asia, europe, australia and the united states suffer from different degrees of chronic kidney disease. Since most chronic kidney disease patients take several years to gradually transition to the end stage of chronic renal insufficiency, it is essential to delay or even reverse the changes in renal pathology in chronic kidney disease patients. Proteinuria (proteinuria) occurs when kidney disease occurs with increased permeability of the glomerular filtration membrane; when renal tubular reabsorption dysfunction, protein reabsorption in glomerular filtrate is reduced, also resulting in proteinuria. Proteinuria is often caused by glomerular interstitial diseases such as diabetic nephropathy, pyelonephritis, analgesic nephropathy, antibiotic renal damage, heavy metal poisoning, congenital polycystic kidney disease and various congenital renal tubular diseases. Proteinuria is widely recognized as a marker of the severity of changes in renal pathology and can predict a reduction in the filtration rate of distant glomeruli and the progression of end-stage renal failure. More importantly, the reduction of proteinuria can obviously play a role in protecting the kidney function of a large number of proteinuria patients from being reduced, and the treatment of the proteinuria can be considered to protect the kidney to the maximum extent. Therefore, how to control and reduce proteinuria is an important research direction for protecting kidney function and delaying the development of kidney damage.

In long-term clinical practice, western medicine has no medicine for proteinuria, mainly aims at treatment of causes of diseases, commonly used medicines such as adrenocortical hormone, immunosuppressive drugs, angiotensin converting enzyme inhibitors, angiotensin n receptor antagonists and the like have certain effects, but all have certain side effects, and the western medicine is not easy to be taken by patients for a long time. The proteinuria does not have a corresponding name in the traditional Chinese medicine, and belongs to the components of essence, yin essence and essence qi in the theory of the traditional Chinese medicine. Ming, carrying Yuan Li (key for syndrome treatment) cloud: the three kinds of diseases are relieved for a long time, the urine is not smelly, the sweet qi is reversed, the urine flows in the drowning, the urine floats and is like lard, the essence is forbidden, the essence is extracted from , the color is like thick oil, a floating membrane is arranged on the urine, the urine is turbid like paste, the urine floats and is drowned, the face like lard is a micro substance of the human body, the protein is equivalent to the protein of modern medicine, the substance basis of the body activity is that the spleen and the stomach transport and transform the essence of food, and the essence is distributed to the five zang organs and the six fu organs to maintain the physiological functions of the viscera, and people who are full of the essence are sealed by the kidney and should not be stored and excreted. The "fine substances" are discharged with urine to form proteinuria after being sealed. The traditional Chinese medicine considers that kidney can not store essence, essence slightly flows downwards, spleen deficiency can not take essence, clear qi sinks, turbid qi overflows, lung can not control qi and the like, and the traditional Chinese medicine is a recognized mechanism for proteinuria in the traditional Chinese medicine at present. The pathogenesis of proteinuria is that the principal is deficiency with secondary excess, the principal is deficiency, and the pathogenic wind, damp-heat and blood stasis are combined, and they can affect each other. The traditional Chinese medicine has the advantages of treating both symptoms and root causes, improving symptoms, having small side effect, being not easy to relapse and the like in the aspect of treating proteinuria.

Chinese patent application CN201810007858.9 discloses a traditional Chinese medicine composition for treating proteinuria, a preparation method and application thereof, wherein the traditional Chinese medicine composition comprises cocoon shell polypeptide and corn silk polysaccharide. Because cocoon shell polypeptide and corn silk polysaccharide in the patent are only partial active ingredients of cocoon shells and corn silk, the extraction process of polysaccharide and polypeptide is complex, and the quality control is difficult, so that the cost is higher.

Disclosure of Invention

The invention aims to solve the technical problem of providing a traditional Chinese medicine composition for preventing and treating proteinuria.

The second technical problem to be solved by the invention is to provide the application of the traditional Chinese medicine composition.

In one aspect of the invention, the traditional Chinese medicine composition for preventing and treating proteinuria is prepared from the following raw material medicines in parts by weight: 1-20 parts of silkworm cocoon shell, 1-20 parts of corn stigma, 0-20 parts of astragalus membranaceus, 0-20 parts of salvia miltiorrhiza and 0-20 parts of ligusticum wallichii.

The traditional Chinese medicine composition can be prepared from 1-20 parts of silkworm cocoon shells and 1-20 parts of corn silk; or 1-20 parts of cocoon shell, 1-20 parts of corn silk and 1-20 parts of astragalus root, or 1-20 parts of cocoon shell, 1-20 parts of corn silk and 1-20 parts of salvia miltiorrhiza, or 1-20 parts of cocoon shell, 1-20 parts of corn silk and 1-20 parts of ligusticum wallichii.

As a preferred technical scheme, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 15-20 parts of silkworm cocoon shell, 15-20 parts of corn stigma, 1-5 parts of astragalus membranaceus, 1-5 parts of salvia miltiorrhiza and 1-5 parts of ligusticum wallichii. Wherein, the most preferable weight ratio is: 15 parts of silkworm cocoon shell, 15 parts of corn stigma, 5 parts of astragalus membranaceus, 3 parts of salvia miltiorrhiza and 3 parts of ligusticum wallichii.

The traditional Chinese medicine adopted by the invention has the advantages of definite curative effect, safety, reliability and obvious curative effect. The silkworm cocoon shell is the cocoon shell of the silkworm moth (Bombyx mori L.) which is an insect in the family Bombycidae, and is also called as follows: silkworm clothing, silkworm cocoon, cotton silkworm, and silkworm cocoon shell. Sweet taste and warm nature. Has hemostatic, thirst quenching, toxic materials removing, and sore healing effects. Stigma Maydis is stigma and stigma of Zea mays L. Many traditional Chinese medicine books have been recorded with corn stigma, which is sweet and bland in taste and mild in nature. Salvia miltiorrhiza is the dried root and rhizome of Salvia miltiorrhiza bge, Salvia milirhizorrhiza bge, a plant of Labiatae, described in Chinese pharmacopoeia (2015 edition). Astragalus membranaceus is dried root of Astragalus membranaceus (Astragalus membranaceus) Membranaceae (Fisch.) of Leguminosae, Var. mongholicus (bge.) Hsiao or Astragalus membranaceus (Astragalus membranaceus) bge. Rhizoma Ligustici Chuanxiong is dried rhizome of Umbelliferae rhizoma Ligustici Chuanxiong (academic name: Ligusticum chuanxiong Hort) recorded in Chinese pharmacopoeia (2015 edition).

The traditional Chinese medicine is a reasonable formula according to the theory of traditional Chinese medicine, an effective traditional Chinese medicine compound is clinically applied, and in the formula, the silkworm cocoon shells tonify the kidney and replenish essence, and the corn stigma can promote urination and reduce swelling; huang Qi can tonify qi and strengthen superficies, Dan Shen and Chuan Xiong can activate blood and resolve stasis. The whole formula can tonify the kidney, replenish essence, tonify qi and remove blood stasis, is used for treating the symptoms of deficiency of kidney essence and qi, and has good curative effect on clinical proteinuria. The traditional Chinese medicine composition is a compound based on the guidance of the theory of traditional Chinese medicine, is an organic whole, and the exertion of the curative effect is not completely replaced by one component or a certain traditional Chinese medicine, and experimental research shows that the traditional Chinese medicine composition has the best curative effect as a whole and has obvious combined synergistic effect compared with the using effect of a single medicine.

The traditional Chinese medicine composition can be directly prepared into various traditional Chinese medicine oral conventional medicaments for preventing and treating proteinuria with pharmaceutically acceptable medicine carriers according to conventional methods in the field or after extraction and processing. The extraction process can be performed by using traditional Chinese medicine extraction methods known in the art, such as but not limited to steam distillation, solvent extraction (including but not limited to methanol, ethanol, acetone, etc.), sublimation, supercritical extraction, etc.

The pharmaceutical formulation may be in any pharmaceutically acceptable dosage form including: tablets, sugar-coated tablets, film-coated tablets, enteric-coated tablets, capsules, hard capsules, soft capsules, oral liquids, buccal agents, granules, pills, powders, ointments, pellets, suspensions, powders, solutions, injections, suppositories, ointments, plasters, creams, sprays, drops, patches; oral dosage forms are preferred, such as: capsule, tablet, oral liquid, granule, pill, powder, pellet, and unguent. The oral dosage forms may contain conventional excipients such as binders, fillers, diluents, tabletting agents, lubricants, disintegrating agents, coloring agents, flavoring agents and wetting agents, and the tablets may be coated if necessary. Suitable fillers include cellulose, mannitol, lactose and other similar fillers; suitable disintegrants include starch, polyvinylpyrrolidone and starch derivatives, such as sodium starch glycolate; suitable lubricants include, for example, magnesium stearate. Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulfate and the like.

The second aspect of the invention provides application of the traditional Chinese medicine composition in preparing medicines and health-care products for preventing and treating proteinuria. The proteinuria is caused by various diseases such as diabetic nephropathy, membranous nephropathy, primary nephritis, IgA nephropathy, purpuric nephritis, lupus nephritis, hypertensive nephropathy, gouty nephropathy, chronic renal failure, chronic nephritis, nephrotic syndrome, lupus nephritis, urinary tract infection and the like.

Experimental results prove that the traditional Chinese medicine composition has an obvious effect of treating proteinuria. Animal experiments and clinical tests prove that the traditional Chinese medicine composition has good safety and good curative effect, can effectively treat proteinuria, has good effect of improving clinical symptoms, has small toxic and side effects, and has good clinical application prospect. Experimental example 1 shows that the compound of the components has better treatment effect on proteinuria of diabetic nephropathy rats than single medicine, and suggests that the traditional Chinese medicines in the compound have synergistic effect. Experimental example 2 comparative study on proteinuria of diabetic nephropathy rats by using the traditional Chinese medicine composition with different proportions proves that, on the one hand, the proteinuria level of diabetic nephropathy rats can be remarkably reduced by using the traditional Chinese medicine composition with different proportions, wherein the most preferable proportion by weight is as follows: 15 parts of silkworm cocoon shell, 15 parts of corn stigma, 5 parts of astragalus membranaceus, 3 parts of salvia miltiorrhiza and 3 parts of ligusticum wallichii. In the second aspect, the fact that the traditional Chinese medicine compound composition consisting of the silkworm cocoon shells and the corn silks is superior to the extract of the silkworm cocoon shell polypeptide and the corn silk polysaccharide (1: 1) (the extraction method refers to Chinese invention patent application CN 201810007858.9), the blood sugar level and the UAE and BUN are remarkably lower (P is less than 0.05), the extraction process is simple, the preparation is easy, the preparation cost is reduced, and the unexpected technical effect is achieved. In the third aspect, the combination of three medicines (compound H, compound I and compound J), the combination of four medicines (compound B and compound C) and the combination of five medicines (compound D and compound E) are all superior to the combination effect of two medicines, have significant difference (P is less than 0.05), and show that the combination of three medicines, four medicines and five medicines all have synergistic effect. Experimental example 3 clinical research proves that the traditional Chinese medicine composition can treat diabetic nephropathy and hyperproteinemia, and the treatment effective rate is 76.7%. Experimental example 4 proves that the traditional Chinese medicine composition can treat the hyperproteinemia of membranous nephropathy. In conclusion, the traditional Chinese medicine composition can effectively reduce proteinuria caused by chronic kidney disease.

Detailed Description

The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out according to conventional conditions or according to conditions recommended by the manufacturers. All percentages, ratios, proportions, or parts are by weight unless otherwise specified.

Example 1: oral liquid

Taking the following raw materials in parts by weight: 300 g of silkworm cocoon shell, 300 g of corn silk, 100g of astragalus root, 60 g of salvia miltiorrhiza and 60 g of ligusticum wallichii. Decocting the above 5 materials in water for 2 times, boiling for 1 hr each time, adding 10 times of water for the first time, adding 8 times of water for the second time, mixing the decoctions, cooling, centrifuging at 3000rpm for 10 min, removing supernatant, concentrating, adding appropriate adjuvant, making into oral liquid 1L according to known method, and packaging with 10ml per bottle for 3 times per day, 1 bottle per time.

Example 2: granules

Taking the following raw materials in parts by weight: 300 g of silkworm cocoon shell, 300 g of corn silk, 100g of astragalus root, 60 g of salvia miltiorrhiza and 60 g of ligusticum wallichii. Decocting the above 5 materials in water for 2 times, wherein the boiling time is 1 hour each time, 10 times of water is added for the first time, 8 times of water is added for the second time, after the decoction is finished, the two decoctions are combined, the mixture is cooled and centrifuged at 3000rpm for 10 minutes, supernatant is removed, the mixture is concentrated to extract with the specific gravity of 1.35, a proper amount of dextrin and powdered sugar is added, the mixture is dried at 70 ℃, prepared into 1000 g of granules, and the granules are prepared, and are subpackaged according to 5g per bag, so that the traditional Chinese medicine is obtained, wherein the traditional Chinese medicine is orally taken for.

The extraction method of the sugar-free granules is the same as that of the sugar-containing granules, and after the extract is prepared into 1.35 extractum, a proper amount of dextrin, microcrystalline cellulose and polyvinyl pyrrolidone alcoholic solution are added for granulation. Drying, granulating into 1000 g granule, and packaging 5g per bag to obtain sugar-free granule, which is orally administered 3 times per day, 1 bag per time.

Example 3: tablet formulation

Taking the following raw materials in parts by weight: 300 g of silkworm cocoon shell, 300 g of corn silk, 100g of astragalus root, 60 g of salvia miltiorrhiza and 60 g of ligusticum wallichii. Decocting the above 5 materials in water for 2 times, boiling for 1 hr each time, adding 10 times of water for the first time, adding 8 times of water for the second time, mixing the decoctions, cooling, centrifuging at 3000rpm for 10 min, collecting supernatant, concentrating to obtain dry extract, and making into tablet with weight of 0.3 g per tablet, 3 times per day and 3 tablets each time.

Example 4: pill preparation

Taking the following raw materials in parts by weight: 300 g of silkworm cocoon shell, 300 g of corn silk, 100g of astragalus root, 60 g of salvia miltiorrhiza and 60 g of ligusticum wallichii. Decocting with appropriate amount of water for 2 times, boiling for 1 hr each time, mixing decoctions, concentrating to obtain dry extract powder, and adding appropriate amount of adjuvants. And then the powder is prepared into 1000 water-honeyed pills according to the known method in the prior art, wherein each pill is 0.5g, and the powder is orally taken for 3 times every day, and 5 pills each time. Orally administered 3 times daily, 5 granules each time.

Example 5: decoction preparation

The ten traditional Chinese medicine compound compositions for treating proteinuria provided in the table 1 are weighed according to the weight proportion, and respectively form ten traditional Chinese medicine compound compositions of a compound A, a compound B, a compound C, a compound D, a compound E, a compound F, a compound G, a compound H, a compound I and a compound J, wherein the formula table is shown in the table 1, and the dosage is 100G per part in the table 1. Adding proper amount of water, decocting for 2 times, timing from boiling, each time for 1 hour, after the decoction, combining the two decoctions, and the administration method is as follows: is administered twice a day.

TABLE 1 table of five Chinese medicinal compound compositions

The following experiments demonstrate the efficacy of the Chinese medicinal composition of the present invention:

test example 1: the traditional Chinese medicine composition of the invention is used for comparative research on the curative effect of the proteinuria of rats

Taking the following raw materials in parts by weight: 300 g of silkworm cocoon shell, 300 g of corn silk, 100g of astragalus root, 60 g of salvia miltiorrhiza and 60 g of ligusticum wallichii. Decocting with appropriate amount of water for 2 times, boiling for 1 hr each time, mixing decoctions, concentrating under reduced pressure, lyophilizing to obtain lyophilized powder (ZHW); in addition, 400 g of cocoon shells, 400 g of corn silk, 100g of astragalus membranaceus, 60 g of salvia miltiorrhiza and 60 g of ligusticum wallichii are respectively taken, decocted and concentrated according to the preparation method of the composition to prepare freeze-dried powder, and the cocoon shell extract (CJK), the corn silk extract (YMX), the astragalus membranaceus extract (HQ), the salvia miltiorrhiza extract (DS) and the ligusticum wallichii extract (CX) are respectively prepared for later use.

SD rats are purchased and fed adaptively for 7 days, and the test is started when blood sugar is checked to be normal, urine protein qualitative test is negative, and animal health conditions are good. Two groups were randomly assigned by body weight, namely blank control group (blank group) and early model group. At the beginning of the experiment, rats in the early stage of the experiment were given a high-sugar, high-fat diet (20% sucrose, 10% lard, 2.5% cholesterol in conventional diet), while the blank control group had free access to ordinary diet and both groups had free access to water. After 8 weeks, after fasting, the rats in the early diabetic nephropathy group were anesthetized by intraperitoneal injection of 3.5ml/kg of a 10% chloral hydrate solution, and the injection volume was 0.3ml/100g of body weight. After confirmation of anesthesia, left nephrectomy was performed: fixing the rat in prone position on an operating table, removing hair, exposing skin, sterilizing with conventional iodophor, cutting skin and muscle layer from left vertebral column and bone, exposing kidney and fat capsule around the kidney, ligating at renal hilum, completely removing left kidney, checking no hemorrhage, and suturing muscle layer and skin. 2 weeks after operation, after fasting for 18 h, each group of rats is administered with Streptozotocin (STZ) -intraperitoneal injection for 50mg/kg, namely, the specific dosage is body weight (citric acid buffer solution used before use is dissolved, equivalent citric acid buffer solution is injected into a blank concentration control group, after STZ 72h is injected, tail vein blood is sampled to measure blood sugar, 24h urine is reserved, the blood sugar level is more than or equal to 16.7mmol/L, urine sugar is positive and stable for 5 days, and urine protein is positive after 2 weeks, the urine protein is measured to serve as an early animal model establishment standard and is listed as an observation object, the rats successfully molded are randomly divided into a model control group (for short model group) and a benazepril hydrochloride group (for short positive drug group), a silkworm cocoon extract (CJK) group, a corn stigma extract (YMX) group, a radix astragali extract (HQ) group, a salvia miltiorrhiza extract (DS) group, a test section, a section, the rhizoma Ligustici Chuanxiong extract group (CX) and composition (ZHW) each comprise 12 animals, each group is numbered and fed in a single cage, and the comparison of blood sugar and urine protein between rats in each group has no statistical significance (P > 0.05).

After the model is made, CJK, YMX, HQ, DS, ZHW and benazepril hydrochloride (positive medicine group) are treated respectively. The dosage of each group is 50 mg/kg/day, the dosage of the positive medicine is 0.9 mg/kg/day, and the medicine is administrated by gastric lavage. The normal control group and the model group were administered with the same amount of distilled water, respectively, and the experiment was terminated by 4 weeks after the start of administration.

The results are shown in tables 2, 3 and 4. The experimental result shows that compared with the blank administration, the blood sugar and the urine microalbumin (UAE) of the model group and each treatment group are obviously increased, which indicates that the molding is successful. After treatment, the positive medicine group, the HQ group, the DS group and the CX group have no obvious effect on blood sugar, the CJK group, the YMX group and the ZHW group can obviously reduce the blood sugar to a certain degree, and the ZHW group has the most obvious reduction degree, so that ZHW has the synergistic effect of reducing the blood sugar. In addition, the group of positive drugs, HQ group, CX group and DS group have a certain effect of reducing urinary microalbumin (UAE), but all the groups are inferior to the group of CJK, YMX and ZHW, and the ZHW group has very obvious effect at 2 weeks and 4 weeks of treatment and has more obvious effect than the CJK group and the YMX group alone, which shows that the ZHW group has the effect of synergistically reducing urinary protein. In addition, CJK, YMX and ZHW decreased serum creatinine (Scr) and urea nitrogen (BUN) levels. In summary, ZHW has the effect of improving symptoms of diabetic nephropathy, and has more obvious curative effect than the single use of each drug.

TABLE 2 comparison of blood glucose in rats at 0, 2 and 4 weeks end: (

）

Note comparison of P < 0.01 with model group, P < 0.01 with ZHW

TABLE 3 comparison of urine microalbumin (UAE) for different treatment sessions in each group: (

）

Note comparison of P < 0.01 with model group, P < 0.01 with ZHW group

Table 4 comparison of serum creatinine (Scr) and urea nitrogen (BUN) at the end of experiment: (

）

Note comparison of P < 0.01 with model group; group # vs ZHW P < 0.01

Test example 2: the traditional Chinese medicine composition with different proportions of the invention is used for the research on the proteinuria effect and the blood sugar comparison of diabetic nephropathy

Taking the six compounds A, B, C, D, E, F, G, H and I prepared in example 5 as experimental subjects, and duplicating the diabetic nephropathy model of the rat according to the method adopted in test example 1.

After the model is made, compound A, compound B, compound C, compound D, compound E, compound F, compound G, compound H, compound I, benazepril hydrochloride (positive drug group), corn stigma polysaccharide and silkworm cocoon polypeptide extract 1:1 (positive drug group, extraction method refers to patent application No. 201810007858.9) are respectively given for treatment. The administration dose is 50 mg/kg/day, the positive drug group dose is 0.9 mg/kg/day, and the administration is performed by gastric lavage. The normal control group and the model group were administered with the same amount of distilled water, respectively, and the experiment was terminated by 4 weeks after the start of administration.

The experimental results are shown in table 5, and the results show that compared with blank administration, the blood sugar and the urine microalbumin (UAE) of the model group and each treatment group are obviously increased, which indicates that the molding is successful. After treatment, the positive medicine group has no obvious effect on blood sugar, while the compound A, the compound B, the compound C, the compound D, the compound E, the compound F, the compound G, the compound H and the compound I can obviously reduce the effects of blood sugar, UAE, BUN and Scr to a certain extent, and the compound D group has the most obvious reduction degree, and the result shows that the traditional Chinese medicine compound with different proportions has good effect of reducing the proteinuria of diabetic kidney, and the compound D has the best effect. Meanwhile, the study also finds that the compound G is obviously superior to the two groups of positive medicines, namely the traditional Chinese medicine compound composition consisting of the silkworm cocoon shells and the corn silk is superior to the silkworm cocoon shell polypeptide and corn silk polysaccharide extract (1: 1), the blood sugar level, the UAE and the BUN are obviously lower (P is less than 0.05), the extraction process is simple, the preparation is easy, the preparation cost is reduced, and the unexpected technical effect is achieved. In addition, the combination of the three medicines (compound H, compound I and compound J), the combination of the four medicines (compound B and compound C) and the combination of the five medicines (compound D and compound E) are superior to the combination of the two medicines, and have significant difference (P is less than 0.05), and further prove that the three, four and five medicines have synergistic effect.

TABLE 5 mixture of different combinations on blood glucose and urine microalbumin levels in diabetic nephropathy rats: (

）

Test example 3: clinical research on treatment of diabetic nephropathy and hyperproteinemia by using traditional Chinese medicine composition

In order to show the clinical curative effect of the invention, 60 patients with diabetic nephropathy are screened, according to renal disease division "diabetic nephropathy diagnosis, syndrome differentiation and curative effect evaluation criteria (trial solution)" of the chinese medical society in 2007:

firstly, the traditional Chinese medicine has a definite history of diabetes, and the course of the disease is usually more than 6-10 years; ② the reagent which accords with Mogensen diabetic nephropathy diagnosis staging standard belongs to diabetic nephropathy III, namely continuous albuminuria, the urine albumin/creatinine ratio is more than 300ug/mg or the urine albumin excretion rate is more than 200ug/min or the urine albumin ration is more than 300mg/24h or the urine albumin ration is more than 0.5g/24 h. Eliminate serious liver and kidney dysfunction, pregnant women and women in lactation period. The test results were divided into an observation group (sugar-free granule prepared in example 2, abbreviated as ZHW) and a basic treatment group (metformin + antihypertension agent treatment group), each of which was 30 cases. In addition, a random number table is generated by simulation of an SAS statistical software package, the cases of the standard group are included and excluded according to a research scheme, and the subjects enter a treatment group and a control group in sequence according to the sequence of the included research and the random number. Treatment groups: the sugar-free granules prepared by the method of example 2 are subpackaged by 5g per bag, and the sugar-free granules are orally taken 3 times a day, 1 bag per time. Basal treatment group: the metformin and the hypotensor are used for treating, the specification is 10 mg/tablet, one tablet is taken every day, and the dosage is taken at night. The treatment course of the two groups is 2 weeks.

The judgment of the curative effect is made by referring to the evaluation standard of the curative effect of the diabetic nephropathy published by the evaluation standards (trial) of the diagnosis and the curative effect of the diabetic nephropathy in Chinese medical and pharmaceutical association of China in 2007. (see Table 6)

Table 6 comprehensive evaluation grading quantization table

The test results are shown in tables 7 and 8, and the clinical test results show that the traditional Chinese medicine composition can obviously reduce 24h urine protein amount (24 hPro) and urine microalbumin (mALB) of diabetic nephropathy patients, has a very obvious improvement effect on renal function, and has a certain improvement effect on blood sugar level. In conclusion, ZHW has obvious improvement effect on diabetic renal symptoms. The specific results are as follows:

(1) proteinuria results analysis

After treatment, the 24h urine protein (24 hPro) and urine microalbumin (mAB) values of the patients in the basal group were significantly reduced compared to those before treatment, while ZHW showed a very significant reduction (P < 0.01) in 24h urine protein (24 hPro) and urine microalbumin (mAB) (see Table 7).

TABLE 7 comparison of proteinuria in different treatment groups: (

）

Significant differences in P < 0.05 compared to pre-treatment; very significant differences in P < 0.01 compared to pre-treatment

(2) Analysis of renal function results

After treatment, the basic treatment group has a remarkable improvement effect on glomerular filtration rate (eGFR), serum urea nitrogen (BUN) basically keeps stable, and serum creatinine (Scr) is increased; and the ZHW groups all have obvious improvement on creatinine, urea nitrogen and glomerular filtration rate, which indicates that the effect on improving renal function is obvious (see table 8).

TABLE 8 renal function comparison of different treatment groups: (

）

Differences were statistically significant P < 0.05 compared to pre-treatment.

(3) Blood glucose outcome analysis

After treatment, the Fasting Blood Glucose (FBG) and the 2h Postprandial Blood Glucose (PBG) of the basal treatment group are both improved remarkably, the Fasting Blood Glucose (FBG) and the 2h Postprandial Blood Glucose (PBG) of the ZHW group are both improved remarkably, the relative degree is lower than that of the basal treatment group, and the statistical significance is achieved (P is less than 0.05) (see table 9).

TABLE 9 patient FBG and PBG Change after different treatment modalities: (

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Differences were statistically significant P < 0.05 compared to pre-treatment.

(4) The treatment effective rate of ZHW groups was found to be 76.7% higher than that of the control according to the evaluation criteria of diabetic nephropathy curative effect in Table 6, and the results are summarized in Table 10. It was shown that ZHW group had good therapeutic effects.

TABLE 10 comparison of efficacy between different treatment groups

Test example 4: experimental study on treatment of membranous nephropathy and hyperproteinemia by using traditional Chinese medicine composition

After the rats are adaptively fed for 1 week, urine is collected for 24h in a metabolism cage, and the urine protein quantification (24 h-Upro) is determined to be less than 5 mg after 24h, and the rats are randomly divided into a normal group (15) and a model group (30). The membranous nephropathy was induced by cationic bovine serum albumin (C-BSA), and 30 mg of C-BSA was dissolved in 15 mL of physiological saline and mixed with an equal amount of incomplete Freund's adjuvant, and the mixture was emulsified thoroughly. 1 mL of the emulsion is taken to be injected subcutaneously at a plurality of points on the back, groin and oxter of a rat in a model group for pre-immunization, 1 time every other day and 3 times in total. The immunization was then performed 3 times a week for 4 consecutive weeks with C-BSA administered at 16 mg/kg/d tail vein each time. Urine is collected in a metabolism cage for 24 hours, and the success of molding is indicated by measuring 24 hours-UPro to be more than 20 mg. Normal group rats were injected with an equal volume of saline in the tail vein each time. The rats survived after the molding is finished and the success of the molding is confirmed by 24 h-UPro detection, and the number of the rats is 24. 24 rats were randomly divided into model groups, composition groups (ZHW groups), and 12 rats each. ZHW groups were administered with the granules prepared in "example 2" at a dose of 50mg/kg, and the normal control group and the model group were administered with distilled water at equal amounts, respectively, until the end of the experiment at the end of 4 weeks after the start of administration.

The experimental results are shown in table 11, and the results show that compared with the blank group (namely the normal control group), the blood sugar and the urine microalbumin (UAE) of the model group and each treatment group are obviously increased, which indicates that the molding is successful. After treatment, ZHW groups all have the effect of obviously reducing blood sugar, UAE, BUN and Scr to a certain extent, and the result shows that ZHW groups can effectively reduce the proteinuria level of the membranous nephropathy high proteinuria disease.

TABLE 11 influence of the Chinese medicinal composition on the indices of membranous nephropathy with albuminuria (A)

）

(Note: comparison with model group. P<0.05, with very significant differences, P<0.01 very significant difference).

Claims

1. A traditional Chinese medicine composition for preventing and treating proteinuria is characterized in that: the traditional Chinese medicine is prepared by decocting the following raw materials in parts by weight in water: 15-20 parts of silkworm cocoon shell, 15-20 parts of corn stigma, 1-5 parts of astragalus membranaceus, 1-5 parts of salvia miltiorrhiza and 1-5 parts of ligusticum wallichii.

2. The traditional Chinese medicine composition according to claim 1, which is prepared from the following raw materials in parts by weight: 15 parts of silkworm cocoon shell, 15 parts of corn stigma, 5 parts of astragalus membranaceus, 3 parts of salvia miltiorrhiza and 3 parts of ligusticum wallichii.

3. A traditional Chinese medicine composition for preventing and treating proteinuria is characterized in that: is prepared by decocting the following raw materials in water: silkworm cocoon shell, corn silk, astragalus root and salvia miltiorrhiza, and the dosage ratio is as follows: 8:2:1:2.

4. A traditional Chinese medicine composition for preventing and treating proteinuria is characterized in that: is prepared by decocting the following raw materials in water: silkworm cocoon shell, corn silk, astragalus root and ligusticum wallichii, and the dosage ratio is as follows: 10:5:6:6.

5. Use of the Chinese medicinal composition according to claim 1 or 2 in the preparation of a medicament for the prevention or treatment of proteinuria.

6. The use according to claim 5, wherein the proteinuria is proteinuria caused by various diseases including diabetic nephropathy, membranous nephropathy, primary nephritis, IgA nephropathy, purpuric nephritis, lupus nephritis, hypertensive nephropathy, gouty nephropathy, chronic renal failure, chronic nephritis, nephrotic syndrome, lupus nephritis, and urinary tract infection.