CN113713039A

CN113713039A - Traditional Chinese medicine composition for treating membranous nephropathy and application thereof

Info

Publication number: CN113713039A
Application number: CN202111129511.XA
Authority: CN
Inventors: 雷根平; 李小会
Original assignee: Affiliated Hospital of Shaanxi University of Chinese Medicine
Current assignee: Affiliated Hospital of Shaanxi University of Chinese Medicine
Priority date: 2016-04-21
Filing date: 2016-04-21
Publication date: 2021-11-30
Also published as: CN105853678A

Abstract

The invention relates to a traditional Chinese medicine composition for treating membranous nephropathy and a preparation method thereof, wherein the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 60-120 parts of astragalus membranaceus, 15-30 parts of radix rehmanniae recen, 15-30 parts of prepared rehmannia root, 15-30 parts of semen euryales, 15-30 parts of pyrola, 30-90 parts of rhizoma smilacis glabrae, 30-90 parts of spreading hedyotis herb, 15-30 parts of salvia miltiorrhiza, 0.5-3 parts of raw leech, 6-12 parts of schizonepeta and 6-12 parts of radix sileris; and extracting according to a certain process method, and then mixing with pharmaceutically acceptable auxiliary materials to prepare the traditional Chinese medicine oral preparation. The traditional Chinese medicine composition has the effects of tonifying spleen and kidney, tonifying qi and yin, and promoting diuresis and blood circulation, and is used for treating proteinuria and edema caused by various acute and chronic nephritis and nephrotic syndrome.

Description

Traditional Chinese medicine composition for treating membranous nephropathy and application thereof

The application is a divisional application with the application date of 2016, 21/04, the application number of 201610250386.0, and the name of the invention being 'a traditional Chinese medicine composition for treating membranous nephropathy and a preparation method thereof'.

Technical Field

The invention relates to a traditional Chinese medicine composition for treating membranous nephropathy and a preparation method thereof, and belongs to the technical field of traditional Chinese medicines.

Background

Membranous Nephropathy (IMN) is a group of diseases characterized by immune complex deposition under glomerular basement membrane epithelial cells with diffuse thickening of basement membrane, which can be classified into idiopathic, familial and secondary according to its etiology. Among them, Idiopathic Membranous Nephropathy (IMN) is one of the common pathological types of primary nephrotic syndrome, accounting for about one third of adult nephrotic syndrome. The disease has very different natural disease courses, has different sequelae such as spontaneous remission, continuous proteinuria, renal function deterioration and the like, and no effective treatment method exists at present, and about 30 percent of patients progress to end-stage renal failure within 5-10 years.

The disease belongs to the categories of edema, turbid urine, consumptive disease and the like in the traditional Chinese medicine. Among them, edema of various degrees and a large amount of proteinuria are characteristic clinical manifestations. From the onset and development of the disease, the pathogenesis of deficiency and excess is through the whole process of the disease. The deficiency of the disease is caused by kidney essence deficiency, the spleen and kidney qi is weak, the spleen qi is deficient, the essence is not lifted and leaks downwards, the kidney is not sealed and stored, the essence leaks slightly to cause a great amount of proteinuria, the proteinuria aggravates the kidney essence deficiency for a long time, the red tongue of a membranous nephropathy patient is clinically seen, particularly, the red tongue or the red tongue edge and tip after long-term use of hormone substances is aggravated, or the tongue changes from pale to red, and meanwhile, most patients are accompanied with the external manifestations of kidney essence deficiency such as waist soreness, limb weakness, dysphoria with feverish sensation in the five centers, dry mouth and drinking preference, and the like. This disease is caused by the coexistence of water-dampness, damp-heat and blood stasis. Water retention due to spleen qi deficiency and weakness in transportation and transformation; kidney deficiency governs water failing to function, and water retention can cause edema of face and limbs, hydrothorax, ascites and the like. The long-term accumulation of water-dampness into heat and the application of hormones all cause the generation of damp-heat; qi deficiency failing to circulate blood and water deficiency leading to disease blood can cause blood stasis, resulting in hyperlipidemia and increased blood viscosity. Meanwhile, membranous nephropathy is a pathological type with complications such as thrombus, embolism and the like in nephrotic syndrome, such as renal venous thrombosis, lower limb venous thrombosis, pulmonary embolism and the like, the incidence rate is about 10% -60%, and the importance of blood stasis in the pathogenesis of membranous nephropathy is indicated. In conclusion, the occurrence and development of the IMN are critical to the massive proteinuria, and the hypoproteinemia, the hyperlipidemia, the blood hypercoagulable state and the like are secondary to the massive proteinuria, so that the treatment of the disease is critical to pay attention to the massive proteinuria. Based on the knowledge of the pathogenesis of the IMN, aiming at the treatment of the disease, a method of combining six methods of cultivation, tonifying, fixing, dispersing, clearing and dredging, namely a method of 'cultivating, fixing, dispersing and clearing and dredging' is provided for treating the IMN, and the IMN is treated by a method of cultivating, reinforcing and tonifying the kidney according to experience of many years.

The traditional Chinese medicine for treating IMN can improve clinical symptoms and physical signs of patients, reduce urine protein and delay the progression of renal failure. The incidence of IMN has increased year by year as renal biopsies have become popular in recent years. Although the treatment guidelines such as KDIGO aiming at IMN are available at present, the treatment of the disease is still clinically intractable due to long administration time of the disease, inconsistent sensitivity of patients to hormones and immunosuppressants and a plurality of side effects of the drugs, and belongs to refractory nephropathy. The patient's massive proteinuria is difficult to relieve, and renal function impairment occurs slowly to end up in renal failure. The curative effect of the existing western medicine treatment scheme is still not satisfactory, the toxic and side effects of the immunosuppressant are inevitable, and in addition, almost all immunosuppressants have relapse after drug withdrawal or weight reduction.

The inventor of the application has abundant clinical experience in the aspect of treating the nephropathy proteinuria, and Guangxi traditional Chinese medicine journal (volume 38, 3, 6 month 2015) publishes a text of 'the experience of Regen Zhi ren physicians in treating the nephropathy proteinuria', and has successfully developed 'Qihuang culture tonifying kidney-reinforcing tablet' before, the prescription of the medicine comprises the following components: 60g of astragalus, 30g of radix rehmanniae recen, 30g of gordon euryale seed, 10g of schizonepeta, 30g of oldenlandia diffusa and 15g of salvia miltiorrhiza. The medicine is mainly used for treating primary nephrotic syndrome membranous nephropathy. However, the long-term use of the traditional Chinese medicine proves that the formula has some defects: the raw rehmannia root is cold and cool, which is easy to hurt the spleen and stomach after being taken for a long time, thus causing poor appetite and abdominal distension of patients, thick and greasy tongue coating, so the raw rehmannia root and the prepared rehmannia root can increase the property of kidney essence and warm in nature, and the raw rehmannia root and the prepared rehmannia root can not cause the excessive cold and cool of the spleen and stomach and can tonify the kidney essence when being used together. Because of its greasy taste, the pungent and smooth action of Fang Feng is added, so it has the action of wind-herbs resolving dampness, and the long-term administration of the medicine does not cause the defect of thick and greasy tongue coating; gorgon fruit can secure essence but the power is weaker, increase Lujicao and strengthen the power of reinforcing kidney with the property of acid absorption; salvia miltiorrhiza, which has a light effect of activating blood circulation, often causes thrombosis due to a large amount of proteinuria, has much less effect on thrombolysis and reduction of platelet aggregation and blood viscosity than leeches, so the amount of leeches is usually selected according to the urinary protein amount and blood viscosity index in clinic. The oldenlandia diffusa is mild in effect, and the glabrous greenbrier rhizome and the oldenlandia diffusa are often used together when the membranous nephropathy has serious damp heat, so that the effect is obvious. However, in clinical application, the treatment effect of the medicine is not ideal enough, so that the research and development of a more effective traditional Chinese medicine preparation has great significance for improving the traditional Chinese medicine treatment of IMN.

Disclosure of Invention

The invention aims to provide a traditional Chinese medicine composition for treating membranous nephropathy and a preparation method thereof, wherein the traditional Chinese medicine composition has the effects of tonifying spleen and kidney, tonifying qi and yin, and promoting diuresis and blood circulation, and has the advantages of obvious curative effect and small toxic and side effects.

The astragalus root in the formula is earthed up to produce water, the inventor of the application can use the astragalus root clinically, the astragalus root formula with large dosage is considered to have the effect of promoting diuresis, and when the astragalus root is used as a raw material, the clinical dosage can reach 200 g; sheng Di Huang and Shu Di Huang tonify kidney and replenish essence, in Nei Jing: the essence deficiency means tonifying and flavor-taking, and the herbs are used as monarch drugs to treat the root cause; the ministerial herbs of gordon euryale and pyrola control the symptoms by securing and controlling the essence; treating proteinuria with radix astragali, radix rehmanniae and radix rehmanniae Preparata. Rhizoma smilacis glabrae and oldenlandia diffusa are used for clearing heat and promoting diuresis; the salvia miltiorrhiza and the leech promote the circulation of blood; so that Jing Jie and Fang Feng can ventilate lung and promote Qi movement to remove the therapeutic effect of disease, and they are pungent and pungent in flavor and also greasy in property of Di Huang. The medicines are combined to play the effects of tonifying spleen and kidney, supplementing qi and nourishing yin, and promoting diuresis and blood circulation.

The technical scheme of the invention provides a traditional Chinese medicine composition for treating membranous nephropathy, which is prepared from the following raw material medicines in parts by weight: 60-120 parts of astragalus membranaceus, 15-30 parts of radix rehmanniae recen, 15-30 parts of prepared rehmannia root, 15-30 parts of semen euryales, 15-30 parts of pyrola, 30-90 parts of rhizoma smilacis glabrae, 30-90 parts of spreading hedyotis herb, 15-30 parts of salvia miltiorrhiza, 0.5-3 parts of leech, 6-12 parts of schizonepeta and 6-12 parts of divaricate saposhnikovia root.

Preferably, the traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 90 parts of astragalus membranaceus, 22 parts of radix rehmanniae recen, 22 parts of prepared rehmannia root, 22 parts of semen euryales, 22 parts of pyrola, 60 parts of rhizoma smilacis glabrae, 60 parts of oldenlandia diffusa, 22 parts of salvia miltiorrhiza, 1 part of leech, 10 parts of schizonepeta and 10 parts of radix sileris.

The invention also provides application of the traditional Chinese medicine composition in preparing a medicine for treating membranous nephropathy.

The invention also provides application of the traditional Chinese medicine composition in preparing a medicine for relieving proteinuria.

The invention also provides application of the traditional Chinese medicine composition in preparing a medicine for improving renal function.

The preparation method of the traditional Chinese medicine composition for treating membranous nephropathy comprises the following steps: the preparation method comprises the following steps of taking the astragalus, the radix rehmanniae recen, the prepared rehmannia root, the semen euryales, the pyrola, the glabrous greenbrier rhizome, the spreading hedyotis herb, the salvia miltiorrhiza, the leech, the fineleaf schizonepeta herb and the divaricate saposhnikovia root according to the weight ratio, drying the raw materials, crushing the raw materials into fine powder, uniformly mixing the fine powder to obtain a traditional Chinese medicine mixture, and adding auxiliary materials commonly used in pharmaceutics to prepare various oral preparations.

The preparation method of the traditional Chinese medicine composition for treating membranous nephropathy can also be prepared by the following process steps:

firstly, crushing glabrous greenbrier rhizome and leech into fine powder;

mixing the astragalus, the radix rehmanniae recen, the prepared rehmannia root, the gordon euryale seed, the pyrola, the oldenlandia diffusa, the salvia miltiorrhiza, the schizonepeta and the divaricate saposhnikovia root, adding water which is 7-10 times of the weight of the medicinal materials, decocting for 1-3 times, 0.5-2 hours each time, filtering, mixing filtrates, concentrating and drying under reduced pressure, and crushing into dry paste powder for later use;

taking the fine powder in the step I and the dry paste powder in the step II, fully and uniformly mixing to obtain a traditional Chinese medicine mixture, and adding auxiliary materials commonly used in pharmacy to prepare various oral preparations

As a further preferred aspect of the present invention, the preparation process of the traditional Chinese medicine composition comprises:

firstly, crushing glabrous greenbrier rhizome and leech into 100-mesh fine powder;

mixing the astragalus, radix rehmanniae recen, prepared rehmannia root, semen euryales, pyrola, oldenlandia diffusa, salvia miltiorrhiza, schizonepeta and divaricate saposhnikovia root, adding 9 times of water by weight of the medicinal materials, decocting for 2 times, 1 hour each time, filtering, mixing filtrates, concentrating and drying under reduced pressure, and crushing into dry paste powder for later use;

and fifthly, taking the fine powder in the step and the dry paste powder in the step, fully and uniformly mixing to obtain a traditional Chinese medicine mixture, and adding auxiliary materials commonly used in pharmacy to prepare various oral preparations.

The traditional Chinese medicine composition can be prepared into granules, hard capsules, tablets, dripping pills or pills.

Granules: mixing the obtained Chinese medicinal mixture with appropriate amount of dextrin and sucrose, granulating, drying, and making into granule.

Hard capsule preparation: adding appropriate adjuvant into the obtained Chinese medicinal mixture, granulating, and making into hard capsule.

And (3) tablet preparation: mixing the obtained Chinese medicinal mixture with appropriate amount of starch and dextrin, granulating, and making into tablet.

Dripping pills: mixing the obtained Chinese medicinal mixture with appropriate amount of matrix, and making into dripping pill.

And (3) pill preparation: mixing the obtained Chinese medicinal mixture with appropriate amount of water, Mel, and carboxymethylcellulose sodium, and making into pill.

The medicine properties of the medicines used in the invention are as follows:

astragalus root: sweet and warm in nature and flavor. It enters meridians, lung and spleen meridians. The functional indications are as follows: tonify qi, strengthen superficies, induce diuresis, expel pus, heal wound and promote tissue regeneration. Can be used for treating deficiency of vital energy, asthenia, anorexia, loose stool, collapse of middle-warmer energy, chronic diarrhea, rectocele, hematochezia, metrorrhagia, superficial deficiency, spontaneous perspiration, qi deficiency, edema, carbuncle, cellulitis, intractable ulcer, blood deficiency, debility with yellowish complexion, internal heat, and diabetes; proteinuria due to chronic nephritis and diabetes.

Dried rehmannia root: sweet and cold in nature and flavor. Meridian tropism, main function: clear heat and cool blood, nourish yin, promote the production of body fluid. Can be used for treating fever with deep-red tongue, polydipsia, yin deficiency, internal heat, bone steaming, internal heat, diabetes, hematemesis, epistaxis, macula, and eruption.

Prepared rehmannia root: sweet in nature and taste, slightly warm. It enters meridians, liver and kidney meridians. The functional indications are as follows: to nourish yin, enrich blood, replenish essence and replenish marrow. Can be used for treating deficiency of liver-yin and kidney-yin, soreness of waist and knees, hectic fever, night sweat, nocturnal emission, internal heat, diabetes, blood deficiency, sallow complexion, cardiopalmus, severe palpitation, menoxenia, metrorrhagia, metrostaxis, hemorrhage, giddiness, tinnitus, and early white beard and hair.

Gorgon fruit: sweet, astringent and neutral in nature and flavor. It enters meridians, spleen and kidney meridians. The functional indications are as follows: tonify kidney, secure essence, tonify spleen, check diarrhea, dispel dampness and stop leukorrhagia. Can be used for treating nocturnal emission, enuresis, frequent micturition, spleen deficiency, chronic diarrhea, whitish and turbid urine, and leukorrhagia.

Herba Pyrolae: sweet, bitter and warm in nature and taste. It enters meridians, liver and kidney meridians. The functional indications are as follows: dispel wind-damp, strengthen tendons and bones, stop bleeding. Can be used for treating rheumatalgia, asthenia of waist and knee, menorrhagia, and chronic cough.

Glabrous greenbrier rhizome: sweet, bland and mild in nature and flavor. It enters meridians, liver and stomach meridians. The functional indications are as follows: remove dampness, remove toxicity, and relieve joint pain. Can be used for treating damp-heat stranguria with turbid discharge, leukorrhagia, carbuncle swelling, scrofula, scabies, tinea, syphilis and limb spasm and arthralgia and myalgia caused by mercury poisoning.

Herba Hedyotidis Diffusae: sweet, light and cool in nature and flavor. It enters the meridians, stomach, large intestine and small intestine. The functional indications are as follows: clearing away heat and toxic material, inducing diuresis to alleviate edema, promoting blood circulation to stop pain. Can be used for treating intestinal carbuncle (appendicitis), skin ulcer, furuncle, toxic swelling, jaundice due to damp-heat, and dysuresia; it is externally used for treating sore, furuncle, carbuncle, swelling, and venomous snake bite.

Red sage root: bitter and slightly cold in nature. It enters meridians, heart and liver meridians. The functional indications are as follows: dispel stasis and alleviate pain, activate blood and dredge meridians, clear heart fire and relieve restlessness. Can be used for treating menoxenia, amenorrhea, dysmenorrhea, abdominal mass, thoracico-abdominal pain, arthralgia due to heat, pyocutaneous disease, swelling and pain, vexation, and insomnia; hepatosplenomegaly, angina pectoris.

Leech: the nature and taste are salty, bitter and mild; has little toxicity. It enters meridians and liver meridian. The functional indications are as follows: break blood, dispel stasis and dredge meridians. Can be used for treating abdominal mass, amenorrhea due to blood stasis, traumatic injury.

Herba schizonepetae: pungent and warm in nature. It enters meridians, lung and liver meridians. The functional indications are as follows: relieve exterior syndrome, dispel wind and promote eruption. Can be used for treating common cold, headache, measles, rubella, and initial stage of pyocutaneous disease. Stir-baked into charcoal is indicated for hematochezia, metrorrhagia and metrostaxis and postpartum anemic fainting.

Wind prevention: pungent and sweet in flavor and warm in nature. Meridian tropism includes bladder, liver and spleen meridians. The functional indications are as follows: relieve exterior syndrome, dispel wind, subdue dampness and stop spasm. Can be used for treating common cold, headache, rheumatalgia, rubella, pruritus, and tetanus.

Compared with the prior art, the invention has the following beneficial effects:

through years of clinical experience, the inventor of the application summarizes the traditional Chinese medicine composition with the obvious curative effect on membranous nephropathy, the selected medicinal materials are compatible, the compatibility theory of monarch, minister, assistant and guide of the traditional Chinese medicine is taken as guidance, the medicines are matched to play the role of synergy, so that the traditional Chinese medicine composition has the effects of tonifying spleen and kidney, tonifying qi and nourishing yin, and promoting diuresis and activating blood, and the characteristics of treating both symptoms and root causes, obvious curative effect and small toxic and side effects of the composition are reflected, and the traditional Chinese medicine composition has the obvious curative effect on various patients with proteinuria and edema caused by acute nephritis, chronic nephritis and nephrotic syndrome. Pharmacological experiments show that the Chinese medicinal composition has obvious improvement on the rat urinary protein quantification for 24 hours and serum ALB, TP, TC and TG, has the total clinical effective rate of over 80 percent, has better clinical curative effect than a control group (tonifying and kidney-reinforcing formula), and is suitable for large-scale clinical popularization.

The following is a pharmacological research test on the technical scheme of the present invention, in the research, in order to simplify the experimental operation and save the research cost, the experimental principle of parallel control is followed, the difference of curative effect of each drug group caused by the dosage form itself is eliminated, so as to scientifically highlight the creativity of the technical scheme of the present invention, and the research is performed by taking an intermediate product group of one of the closest technical schemes as a representative, which can be fully deduced by the skilled person in the art to understand the beneficial effects of the technical schemes at other parameter points in the application, so the technical content and the pharmacodynamic results of the present invention are by no means limited to the scope.

Pharmacological experiments

1 materials and methods

1.1 preparation and grouping of Experimental animals and models

50 clean male SD rats with the mass (160 +/-20) g are selected and provided by the animal experiment center of Shanxi Chinese medicine university. 50 rats were acclimatized for 1 week and randomized into 40 building blocks and 10 normal blocks. With reference to the modified Border method, 3 times of tail vein injection of cationized bovine serum albumin (C-BSA) to replicate a membranous nephropathy model per week of model-building rats, and 4 weeks of continuous injection of 0.9% sodium chloride injection with equal volume to the tail vein of a control group to confirm successful model building, the model-building rats are randomly divided into 4 groups: model group, control group, treatment 1 group, treatment 2 groups, each group consisting of 10.

1.2 Experimental drugs, Primary reagents and instruments

The preparation method of the 'control group medicine' is as follows:

decocting 60g of radix astragali, 30g of radix rehmanniae, 30g of semen euryales, 10g of herba schizonepetae, 30g of oldenlandia diffusa and 15g of radix salviae miltiorrhizae for 2 times by using 8 times of water, combining filtrates, filtering, and adding distilled water to prepare a suspension liquid medicine before use.

The preparation method of the medicine for treating group 1 comprises the following steps:

taking 90g of astragalus, 22g of radix rehmanniae recen, 22g of prepared rehmannia root, 22g of gordon euryale seed, 22g of pyrola, 60g of glabrous greenbrier rhizome, 60g of spreading hedyotis herb, 22g of salvia miltiorrhiza, 1g of leech, 10g of fineleaf schizonepeta herb and 10g of divaricate saposhnikovia root; drying the above raw materials, pulverizing into 100 mesh fine powder, mixing, and adding distilled water to obtain suspension liquid medicine before use.

The preparation method of the medicine for treating the 2 groups comprises the following steps:

(1) pulverizing rhizoma Smilacis Glabrae 60g and Hirudo 1g into 100 mesh fine powder;

(2) mixing the astragalus mongholicus 90g, the radix rehmanniae recen 22g, the prepared rehmannia root 22g, the gordon euryale seed 22g, the pyrola herb 22g, the oldenlandia 60g, the salvia miltiorrhiza 22g, the schizonepeta 10g and the divaricate saposhnikovia root 10g, adding water which is 9 times of the weight of the medicinal materials, decocting for 2 times, 1 hour each time, filtering, mixing the filtrates, concentrating and drying under reduced pressure, and crushing into dry paste powder for later use;

(3) and (3) taking the fine powder in the step (1) and the dry paste powder in the step (2), fully and uniformly mixing, and adding distilled water to prepare a suspension liquid medicine to obtain the medicine.

Bovine Serum Albumin (BSA): goat anti-rat PAI-1 polyclonal antibody, Sigma, USA. SABC kit: beijing Zhongshan Biotechnology Ltd; electric heating constant temperature water bath box: h-1, W21-600, Tianjin Tester plant; full-automatic biochemical analyzer: hitachi, model 7170A, Hitachi; microtome, ELCIA; HPIAS-1000 full-automatic color pathological image analysis system, Wuhan thousand-screen image technology, Inc.

1.3 methods of administration

The rats in the normal group and the model group were each administered a 5 mL-dose of physiological saline each time by gavage from day 1 after the end of molding.

From the day one after the molding of the control group, the decoction of the drug in the control group is concentrated to 25.0g/kg in the form of gavage for each rat every day, and the stock solution contains 2.0g of the crude drug per ml for 4 weeks continuously.

Treatment 1 and 2 groups from day 1 after the end of molding, suspensions were prepared with distilled water, and the "treatment 1 group drug" and "treatment 2 group drug" were administered at a dose of 25.0g/kg, 5mL each time, for 4 consecutive weeks.

1.4 detection indexes and methods biochemical index determination:

respectively measuring albumin (Alb), Total Protein (TP), Triglyceride (TC) and total cholesterol (TG) in a serum sample by using a full-automatic biochemical analyzer; and (3) quantifying the urine protein for 24 h: measuring the amount of urine protein for 24h by adopting a biuret method; and (3) immunofluorescence observation: detecting lgG and complement C3 by indirect immunofluorescence; and (3) observing by an electron microscope: observing the change of glomerular basement membrane and foot processes by a Hitachi H7500 type transmission electron microscope; PAI-1 immunohistochemical detection of renal tissues was performed by SABC method (PBS was used as a negative control instead of primary antibody), and light-microscopic observation was performed to show positive dark brown particles in renal parenchyma and interstitial cells.

1.5 statistical treatment

Statistical analysis was performed using the SPSS13.0 software package, with data averaged. + -. standard deviation

Indicating that the parameter data between groups is subjected to LSD-T test, the parameter data between groups is subjected to pairing T test, P<A significant difference is found at 0.05.

2 results

2.1 quantification of urine protein in rats in each group for 24h, and determination of serum TP, ALB, TC, TG are shown in Table 1.

TABLE 1 comparison of the quantification of 24h urine protein, serum ALB, TP, TC, TG in each group

Note: p <0.05 compared to pre-treatment; Δ P <0.05 after treatment compared to control group.

As can be seen from Table 1, except for the normal group, the rats (model group, control group, treatment 1 group and treatment 2 group) in each model group all showed significant proteinuria, and abnormal (P <0.05) serum TP, ALB, TC and TG appeared, indicating that the model formation in the experiment was successful. At the end of 4 weeks of administration, the urine protein quantification, serum TC and TG levels of rats in the control group, the treatment 1 group and the treatment 2 group are obviously lower than those of the model group, and the significant difference exists (P is less than 0.05); the quantitative determination of the urine protein and the improvement of the TC and TG levels of the serum of the rats in the treatment groups 1 and 2 are better than those of the control group. The levels of TP and ALB in the serum of rats in the control group, the treatment 1 group and the treatment 2 group are obviously increased, and compared with the model group, the levels are significantly different (P is less than 0.05). The quantification of urinary protein, serum TP, ALB, TC, TG levels in rats of treatment 1 and treatment 2 had statistical significance compared to the control group (P < 0.05).

2.2 immunofluorescence Observation

The normal group had no immune complex deposition, and the model group, control group, treatment 1 group and treatment 2 group had varying degrees of IgG and C3 deposited as fine particles along the capillary vessel climbing and a portion of the mesentery region. The fluorescence intensity of the model group was significantly increased, and IgG and C3 in the control group, treatment 1 group and treatment 2 group were significantly decreased. The immunofluorescence results showed a significant reduction in deposition in the control, treatment 1, and treatment 2 groups compared to the model group.

2.3 Electron microscopy

The result shows that the glomerular basement membrane of the kidney tissue of the normal rat has no thickening, no electron compact substance deposition under the epithelium and no amalgamation of the foot process; the rat glomerular basement membrane of the model group is thickened and wavy, the secondary processes of podocyte disappear, the podocyte is diffusely fused, most of electron compact matters can be seen under the epithelium, the electron compact matters at different parts are partially dissolved and absorbed, the renal tubule cell gap is widened, and the renal interstitial fiber tissue is proliferated. The thickening of the glomerular basement membrane of the rats in the control group, the treatment 1 group and the treatment 2 group is obviously reduced compared with that of the model group, foot process fusion occasionally occurs, a few electron compact substances are deposited under the epithelium, the renal tubules are approximately normal, and the proliferation of renal interstitial fiber tissues is obviously reduced.

2.4 groups of rats PAI-1 kidney tissue immunohistochemical observations are presented in Table 2.

TABLE 2 expression of PAI-1 groups

Note that compared to the normal group, Δ P < 0.05; p <0.05 compared to control group.

PAI-1 is mainly expressed in glomerulus and renal tubular epithelial cells, and is expressed in trace amount in a normal group, the expression in the kidney tissues of rats in a model group, a treatment 1 group and a treatment 2 group is higher than that in the normal group (P <0.05), and the expression in the kidney tissues of rats in the treatment 1 group and the treatment 2 group is obviously lower than that in the model group (P < 0.05); the values of the regulated PAI-1 in the treatment 1 group and the treatment 2 group are statistically significant (P <0.05), which suggests that the Chinese medicinal composition can inhibit the excessive expression of PAI-1 in the rats with membranous nephropathy.

In the experiment, C-BSA is adopted to establish a rat model of membranous nephropathy, and an immunohistochemical method is used for observing the expression of PAI-1 in the model. Research results show that the traditional Chinese medicine composition can inhibit the expression of PAI-1 in renal tissues of membranous nephropathy, and simultaneously has obvious improvement on 24h urinary protein quantification and serum ALB, TP, TC and TG, thereby proving that the traditional Chinese medicine composition has obvious advantages in treating membranous nephropathy.

Detailed Description

The following are specific examples of the present disclosure, which are used to illustrate technical solutions to be solved in the present disclosure and help those skilled in the art understand the present disclosure, but the present disclosure is not limited to these examples.

Example 1

Taking 90g of astragalus, 22g of radix rehmanniae recen, 22g of prepared rehmannia root, 22g of gordon euryale seed, 22g of pyrola, 60g of glabrous greenbrier rhizome, 60g of spreading hedyotis herb, 22g of salvia miltiorrhiza, 1g of leech, 10g of fineleaf schizonepeta herb and 10g of divaricate saposhnikovia root; drying the above raw materials, pulverizing into 100 mesh fine powder, mixing to obtain Chinese medicinal mixture, mixing with appropriate amount of dextrin and sucrose, granulating, drying, and making into 1000g granule.

Example 2

Taking 120g of astragalus, 30g of radix rehmanniae recen, 15g of prepared rehmannia root, 15g of gordon euryale seed, 30g of pyrola, 90g of glabrous greenbrier rhizome, 30g of spreading hedyotis herb, 30g of salvia miltiorrhiza, 3g of leech, 6g of fineleaf schizonepeta herb and 12g of divaricate saposhnikovia root, drying the raw materials, crushing the raw materials into 100-mesh fine powder, uniformly mixing the fine powder, obtaining a traditional Chinese medicine mixture, uniformly mixing the mixture with a proper amount of starch and dextrin, granulating, and pressing into 1000 tablets.

Example 3

Taking 60g of astragalus, 15g of radix rehmanniae recen, 30g of prepared rehmannia root, 30g of gordon euryale seed, 15g of pyrola, 30g of glabrous greenbrier rhizome, 90g of spreading hedyotis herb, 15g of salvia miltiorrhiza, 0.5g of leech, 12g of schizonepeta and 6g of divaricate saposhnikovia root, drying the raw material medicines, crushing the raw materials into 100-mesh fine powder, uniformly mixing the fine powder to obtain a traditional Chinese medicine mixture, adding calcium carbonate and magnesium stearate, granulating, encapsulating and preparing into 1000 hard capsules.

Example 4

(3) and (3) taking the fine powder in the step (1) and the dry paste powder in the step (2), fully and uniformly mixing to obtain a traditional Chinese medicine mixture, adding a proper amount of honey and water, uniformly stirring, and preparing into 1000 pills.

Example 5

(1) Pulverizing rhizoma Smilacis Glabrae 90g and Hirudo 3g into 100 mesh fine powder;

(2) then 120g of astragalus, 30g of radix rehmanniae recen, 15g of prepared rehmannia root, 15g of gordon euryale seed, 30g of pyrola, 30g of oldenlandia diffusa, 30g of salvia miltiorrhiza, 6g of schizonepeta, 12g of divaricate saposhnikovia root, and the medicinal materials are combined, added with water which is 7 times of the weight of the medicinal materials to be decocted for 3 times, each time lasts for 0.5h, filtered, the filtrates are combined, concentrated and dried under reduced pressure, and crushed into dry paste powder for later use;

(3) and (3) taking the fine powder in the step (1) and the dry paste powder in the step (2), fully and uniformly mixing, then carrying out hot melting on the mixture and PEG4000 matrix, uniformly stirring, carrying out dripping, and preparing into 1000 dripping pills.

Example 6

(1) Pulverizing rhizoma Smilacis Glabrae 30g and Hirudo 0.5g into 100 mesh fine powder;

(2) mixing 60g of astragalus membranaceus, 15g of radix rehmanniae recen, 30g of prepared rehmannia root, 30g of gordon euryale seed, 15g of pyrola, 90g of oldenlandia diffusa, 15g of salvia miltiorrhiza, 12g of schizonepeta and 6g of divaricate saposhnikovia root, adding water which is 10 times of the weight of the medicinal materials, decocting for 1 time and 2 hours each time, filtering, mixing filtrates, concentrating and drying under reduced pressure, and crushing into dry paste powder for later use;

(3) mixing the above fine powder of step (1) and the dry extract powder of step (2) to obtain a Chinese medicinal mixture, adding microcrystalline cellulose and starch, granulating, encapsulating, and making into 1000 hard capsules.

In order to further verify the efficacy of the final preparation of the present invention, we performed corresponding clinical trials on the final granules and pills prepared in the above specific examples 1 and 4, and the results are reported below.

2 clinical observation and curative effect

2.1 general data:

153 patients of Membranous Nephropathy (MN) originated from nephrology inpatients and outpatients of subsidiary hospitals of Shanxi traditional Chinese medicine college from 1 month to 2015 2011 are collected. All cases meet the diagnosis standard of primary nephrotic syndrome, 153 patients are randomly divided into 3 groups and 30 control groups, wherein 19 men and 11 women are selected; age 18-70 years, average age (40.6 + -22.3 years); the course of disease is 6-80 months, and the average course of disease (24.4 +/-11.5) months. Treatment 1 group 65, 37 men and 28 women; age 19-69 years, mean age (38.1 + -19.7 years); the course of disease is 8-78 months, and the average course of disease (21.9 +/-14.6 months); treatment 2 groups of 58, 31 men and 27 women; age 18-70 years, mean age (39.7 ± 18.3 years); the course of disease is 9-76 months, and the average course of disease (22.3 +/-12.3) months. Excluding secondary nephrotic syndrome, recent severe infection, severe cardiovascular and cerebrovascular diseases and liver diseases, pregnant and lactating women, and psychosis patients. Before treatment, the three groups of patients had no significant difference (P >0.05) in terms of sex, age, mean age, course, mean course, urinary protein level, and the like, and were comparable.

2.2 methods of treatment

Basic treatment: low-salt, low-fat and high-quality protein diet is given to 3 groups of patients, ACEI or ARB is used for reducing blood pressure and urine protein, and the blood pressure is controlled below 130/80 mmHg; and can be used for reducing blood fat, inducing diuresis and relieving swelling. For patients with middle-risk and high-risk groups with 24-hour urinary protein quantification larger than 4.0g, hormones (40-60 mg per day, morning-starting administration, and equal amount of methylprednisolone morning-starting administration for patients with liver function impairment) and cyclophosphamide (0.8-1.0 g per month, intravenous drip for two days) are added for treatment.

Control group: the patients in the control group are given the formula for reinforcing and reinforcing the kidney, wherein 60g of astragalus, 30g of radix rehmanniae recen, 30g of semen euryales, 10g of herba schizonepetae, 30g of oldenlandia diffusa and 15g of salvia miltiorrhiza are decocted in water for taking in the morning and evening with warm water. The medicine is taken continuously for 6 months, which is a course of treatment.

Treatment 1 group: the patient administered the Chinese medicinal granules prepared according to the technical scheme of the group of example 12 times daily for oral administration 3 dosage units each time. The medicine is taken continuously for 6 months, which is a course of treatment.

Treatment 2 groups: the patients were administered the Chinese medicinal pills prepared according to the technical scheme of example 4 group orally 2 times a day in the morning and evening with 3 dosage units each time. The medicine is taken continuously for 6 months, which is a course of treatment.

2.3 detection of indicators

Firstly, quantifying urine protein (24U-TP) in 24 hours; ② renal function: serum urea nitrogen (BUN), Creatinine (CREA); ③ liver function: plasma Total Protein (TP), Albumin (ALB); fourthly, blood fat: total Cholesterol (CHOL), Triglyceride (TG).

2.4 evaluation criteria for clinical efficacy

Reference is made to clinical practice guidelines for KDIGO glomerulonephritis. And (3) complete alleviation: the 24-hour urinary protein quantification is less than 0.3g/d, at least 1 week and 2 times, and reaches the standard, and simultaneously, the serum albumin and the blood creatinine are in a normal range; partial mitigation: a 24 hour urinary protein quantification of <3.5g/d and a reduction of at least 50% from peak; reach the standard 2 times at intervals of at least 1 week while serum albumin is normal or improved, and blood creatinine is stable; and (4) invalidation: the above standard is not met.

2.5 statistical methods

SPSS17.0 statistical software is adopted for processing and measuring data

Showing that the comparison among groups adopts t test and P<A difference of 0.05 is statistically significant.

2.6 results

2.6.1 comparison of baseline urine protein levels in three groups of patients, see Table 3.

TABLE 3 comparison of three groups of baseline urine protein levels

2.6.2 the clinical efficacy of the three groups is compared in Table 4.

TABLE 4 comparison of the three groups of therapeutic effects

Note P <0.05 compared to control.

From the experimental results shown in table 4, the total remission rates of the treatment groups 1 and 2 were 81.54% and 87.93%, respectively, while the total remission rate of the control group was 73.33%, and compared with the control group, the total remission rates of the treatment groups 1 and 2 were significantly different (P <0.05), and the treatment group was superior to the control group.

2.6.3 comparison of results for three groups of 24hU-TP, liver function TP, ALB, see Table 5.

TABLE 5 comparison of the quantitative results of three groups of TP, ALB, 24h urine protein

Note: p <0.05, P <0.01 compared to pre-treatment; Δ P <0.05 after treatment compared to control group.

Results table 5 shows that there was no significant difference in 24hU-TP, and ALB before treatment in three groups of patients (P >0.05), 24hU-TP was significantly decreased before treatment in three groups of patients after treatment (P <0.01), TP and ALB were significantly increased (P <0.05 or P <0.01), but the decrease values of 24hU-TP were more significant in treatment 1 and 2 groups than in the control group (P <0.05), and the improvement in TP and ALB was more significant (P < 0.05).

2.6.4 comparison of the relief of different proteinuria levels in three groups, the results are shown in Table 6.

TABLE 6 comparison of Total remission rates for different proteinuria levels in three groups of patients

Note: Δ P <0.05 and Δ P <0.01, compared to the control group.

As can be seen from table 6, after 1 course of treatment, proteinuria of three groups of patients, namely the low-risk group, the medium-risk group and the high-risk group, was significantly alleviated; the proteinuria of the middle-risk group and the high-risk group in the treatment groups 1 and 2 is obviously better than that of the control group (P is less than 0.01).

2.6.5 comparison of three CHOL, TG, CREA results, see Table 7.

TABLE 7 comparison of three groups of CHOL, TG, CREA assay results

Note: p <0.05, P <0.01 compared to pre-treatment.

Experimental results table 7 shows that there was no significant difference in CHOL, TG, CREA in the patients of three groups (control group, treatment 1 group and treatment 2 group) before treatment (P >0.05), and the serum CHOL, TG levels of the patients of three groups after treatment were significantly lower than those before treatment (P <0.01), and there was no significant difference in CREA. The clinical efficacy of the patients in the treatment group 1 and the treatment group 2 is better than that of the treatment group although there is no significant difference (P >0.05) between CHOL and TG after treatment.

From the above, the medicine provided by the invention can effectively relieve the disease condition of the IMN patient, remarkably reduce the 24hU-TP of the patient, improve TP and ALB, and has good clinical curative effect.

Although the present invention has been described with reference to the preferred embodiments, it should be understood that various changes and modifications can be made therein by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.

Claims

1. The traditional Chinese medicine composition for treating membranous nephropathy is characterized by comprising the following raw materials in parts by weight: 60-120 parts of astragalus membranaceus, 15-30 parts of radix rehmanniae recen, 15-30 parts of prepared rehmannia root, 15-30 parts of semen euryales, 15-30 parts of pyrola, 30-90 parts of rhizoma smilacis glabrae, 30-90 parts of spreading hedyotis herb, 15-30 parts of salvia miltiorrhiza, 0.5-3 parts of leech, 6-12 parts of schizonepeta and 6-12 parts of divaricate saposhnikovia root.

2. The traditional Chinese medicine composition for treating nephrotic proteinuria according to claim 1, which comprises the following raw materials in parts by weight: 90 parts of astragalus, 22 parts of radix rehmanniae recen, 22 parts of prepared rehmannia root, 22 parts of gordon euryale seed, 22 parts of pyrola, 60 parts of glabrous greenbrier rhizome, 60 parts of spreading hedyotis herb, 22 parts of salvia miltiorrhiza, 1 part of leech, 10 parts of fineleaf schizonepeta herb and 10 parts of divaricate saposhnikovia root.

3. Use of the Chinese medicinal composition of claim 1 or 2 in the preparation of a medicament for treating membranous nephropathy.

4. Use of the Chinese medicinal composition of claim 1 or 2 in the preparation of a medicament for relieving proteinuria.

5. Use of a Chinese medicinal composition according to claim 1 or 2 in the manufacture of a medicament for improving renal function.

6. The use of any one of claims 3 to 5, wherein the medicament is in the form of granules, tablets, hard capsules, dripping pills or pills.

7. The use according to any one of claims 3 to 6, wherein the process for the preparation of the medicament comprises the steps of: pulverizing the dried raw materials to obtain medicinal powder, and mixing the medicinal powder with adjuvants to obtain medicinal preparation.

8. The use according to any one of claims 3 to 6, wherein the process for the preparation of the medicament comprises the steps of:

pulverizing rhizoma Smilacis Glabrae and Hirudo powder to obtain fine powder;

decocting the medicinal materials to obtain medicinal liquid, removing water in the medicinal liquid to obtain dry extract, and pulverizing the dry extract to obtain dry extract powder;

mixing the fine powder and the dry extract powder to obtain a traditional Chinese medicine mixture, and mixing the traditional Chinese medicine mixture with auxiliary materials to obtain a medicinal preparation;

the medicinal materials are astragalus root, dried rehmannia root, prepared rehmannia root, gordon euryale seed, pyrola, oldenlandia diffusa, salvia miltiorrhiza, schizonepeta and divaricate saposhnikovia root;

the decoction comprises the following steps: mixing the medicinal materials with water, decocting for 1-3 times, and combining filtrates to obtain a liquid medicine;

the weight ratio of the medicinal materials to the water is 1 (7-10); the time for decoction is 0.5-2 h/time.

9. The use according to claim 8, wherein the fine powder has a particle size of 100 mesh or less;

the number of times of decoction is 2; the weight ratio of the medicinal materials to the water is 1: 9; the decoction time is 1 h/time.