阅读说明：本技术 一种治疗肾病的组合物、颗粒剂及制备方法 (Composition and granules for treating nephropathy and preparation method ) 是由 李强 于 2021-06-30 设计创作，主要内容包括：本发明公开了一种治疗肾病的组合物、颗粒剂及制备方法,所述组合物由黄芪、山萸肉、柴胡、当归、菟丝子和僵蚕组成,所述颗粒剂包括所述的组合物和医学上可接受的辅料,所述制备方法,包括S1浸膏的制备：将配方量的黄芪、山萸肉、柴胡、当归、菟丝子和僵蚕混合,加水浸泡后,煎煮、滤过、合并提取液、浓缩,得到浸膏；S2向步骤S1得到的浸膏中加入糊精混匀,烘干后粉碎,得到混合粉；S3向步骤S2得到的混合粉中加入乙醇,制成湿颗粒,干燥、整粒,即得。相比现有技术,本发明通过黄芪、山萸肉、柴胡、当归、菟丝子和僵蚕的复配,可显著改善DKD动物模型的肾损害及EMT相关蛋白的表达水平,保护肾功能。(The invention discloses a composition for treating nephropathy, granules and a preparation method, wherein the composition comprises astragalus, cornus officinalis, radix bupleuri, angelica sinensis, semen cuscutae and stiff silkworm, the granules comprise the composition and medically acceptable auxiliary materials, and the preparation method comprises the following steps of preparing an S1 extract: mixing radix astragali, Corni fructus, bupleuri radix, radix Angelicae sinensis, semen Cuscutae and Bombyx Batryticatus, soaking in water, decocting, filtering, mixing extractive solutions, and concentrating to obtain extract; s2, adding dextrin into the extract obtained in the step S1, uniformly mixing, drying and crushing to obtain mixed powder; s3 adding ethanol into the mixed powder obtained in step S2, making into wet granules, drying, and grading. Compared with the prior art, the kidney damage and the expression level of EMT related protein of the DKD animal model can be obviously improved and the kidney function can be protected by compounding the astragalus, the cornus, the radix bupleuri, the angelica, the semen cuscutae and the stiff silkworm.)

1. A composition for treating nephropathy is characterized by comprising the following raw materials: radix astragali, Corni fructus, bupleuri radix, radix Angelicae sinensis, semen Cuscutae and Bombyx Batryticatus.

2. The composition according to claim 1, which is characterized by consisting of the following raw materials in parts by weight: 30-800 parts of astragalus, 10-300 parts of cornus, 10-300 parts of radix bupleuri, 10-300 parts of angelica, 10-300 parts of semen cuscutae and 10-300 parts of stiff silkworm.

3. The composition of claim 2, wherein the weight ratio of astragalus root, dogwood fruit, bupleurum root and batryticated silkworm is 3:1:1: 1.

4. Use of a composition according to any one of claims 1 to 3 in the manufacture of a medicament for the treatment of renal disease.

5. The use according to claim 4, wherein the medicament is in the form of capsules, tablets, granules or pills.

6. A granule for treating kidney disease, comprising the composition of any one of claims 1 to 3 and a pharmaceutically acceptable excipient.

7. The granule according to claim 6, wherein the excipients comprise dextrin and ethanol.

8. A method of preparing the granule of claim 6, comprising the steps of:

s1, preparing an extract: mixing radix astragali, Corni fructus, bupleuri radix, radix Angelicae sinensis, semen Cuscutae and Bombyx Batryticatus, soaking in water, decocting, filtering, mixing extractive solutions, and concentrating to obtain extract;

s2, adding dextrin into the extract obtained in the step S1, uniformly mixing, drying and crushing to obtain mixed powder;

s3, adding ethanol into the mixed powder obtained in the step S2, preparing wet granules, drying and finishing the granules to obtain the granules.

9. The preparation method according to claim 8, wherein the mass ratio of the dextrin to the extract in step S2 is 1: 1.

10. the method according to claim 8, wherein the ethanol is added in an amount of 25 to 40% by weight based on the mixed powder in step S3.

Technical Field

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

Background

Diabetic nephropathy (DKD) is a common microvascular complication of diabetes, and is also one of the major causes of End-stage renal disease (ESRD). DKD is hidden, has unobvious early symptoms, then causes albuminuria, edema and glomerular filtration rate reduction, finally enters ESRD, and is one of the main death reasons of the diabetics. According to statistics, the prevalence rate of diabetes of adults in China is continuously increased, and the prevalence rate of renal complications of diabetic patients is as high as 41.4%. The traditional Chinese medicine accumulates abundant experience in the aspect of prevention and treatment of DKD and obtains good curative effect.

CN110787263A discloses an application of a traditional Chinese medicine composition in preparation of a medicine for treating diabetes, wherein the traditional Chinese medicine composition comprises astragalus mongholicus, wolfberry fruits, Chinese yam, coix seeds, radix scrophulariae, radix glehniae, eclipta, human placenta, eucommia ulmoides, pseudo-ginseng, motherwort, leeches, periostracum cicada, semen plantaginis and achyranthes bidentata. Meanwhile, the composition has good effect of preventing and treating the fibrosis of the renal tubular epithelial cells.

CN110917296A discloses an application of a Chinese medicinal composition in preparing a medicament for treating diabetic nephropathy, the Chinese medicinal composition comprises: 100 portions of astragalus root, 100 portions of angelica, 500 portions of codonopsis pilosula, 100 portions of figwort, 500 portions of honeysuckle, 100 portions of dendrobium, 500 portions of achyranthes root and 100 portions of liquorice, and the traditional Chinese medicine composition can reduce the FBG level of mice with early diabetic nephropathy and improve the renal function of the mice with early diabetic nephropathy.

The mechanism of DKD generation has not been elucidated, and under the limitation, it is mainly used for symptomatic treatment such as controlling blood sugar and blood pressure, reducing proteinuria, and the like, and there is a lack of drugs capable of blocking DKD progression. Therefore, finding effective intervention measures is of great importance.

In traditional Chinese medicine, DKD is classified into diabetes, and the disease is caused by kidney deficiency, qi transformation disorder and emotional disorder due to insufficient endowment, improper diet, excessive desire and emotional disorder. The basic pathogenesis of DKD is the mixture of principal deficiency, secondary excess and deficiency and excess. The deficiency refers to the deficiency of the spleen and kidney, while the excess refers to qi stagnation, blood stasis, phlegm-dampness and turbid toxin. The traditional Chinese medicine considers that the spleen is the acquired root of the human body, the source of qi and blood generation, and the spleen has the functions of dissipating essence, ascending clear and consolidating. Blood sugar is food essence, when spleen qi is deficient and transportation and transformation are disordered, which means that insulin is absolutely or relatively insufficient, food essence accumulates slightly to generate dampness and transform turbidity, which means that blood sugar is increased and diabetes is caused. Spleen qi deficiency can lead to failure of the spleen to consolidate, and failure of the spleen to take up can lead to loss of essence and urine, which can lead to urinary protein. If the diabetes is treated by mistake, the condition gradually develops and can affect the kidney, which causes the deficiency of both the spleen and the kidney. The spleen deficiency failing to take up and store, the kidney deficiency failing to store and the loss of essence aggravate, which is manifested as the continuous increase of proteinuria. The progress of diabetes to DKD stage is the five zang organs with extreme weakness and must be ascribed to the kidney, which is inevitable due to deficiency. Therefore, DKD mostly starts from spleen injury and spleen deficiency, affects the kidney in the later period, the spleen qi can not control essence, the kidney qi can not store essence, the essence can not flow downwards, qi and blood can not flow, qi and blood channels are stagnated, so that the circulation of body fluid and blood is not smooth, phlegm stasis is formed, dampness, stasis, phlegm and stagnation are mutually caused, and the DKD is cemented in the collaterals of the kidney, thereby promoting the development of DKD, and therefore, the DKD is suitable for strengthening spleen and tonifying kidney, and promoting blood circulation.

Therefore, it is necessary to provide a composition for treating nephropathy according to the theory of the traditional Chinese medicine.

Disclosure of Invention

The invention aims to provide a composition for treating nephropathy, granules and a preparation method thereof aiming at the traditional Chinese medicine theory. The composition can significantly improve renal function of spontaneous diabetes db/db model mice and expression level of EMT related proteins, thereby improving renal damage of DKD animal models and protecting renal function.

In order to achieve the purpose, the invention adopts the following technical scheme:

a composition for treating nephropathy comprises the following raw materials: radix astragali, Corni fructus, bupleuri radix, radix Angelicae sinensis, semen Cuscutae and Bombyx Batryticatus.

Astragalus membranaceus is a perennial herb of Leguminosae, namely dried root of Astragalus membranaceus Bge Astragalus membranaceus Fisch. var. mongholicus Hsiao or Astragalus membranaceus Fisch. Bge. has the effects of tonifying qi, strengthening exterior, promoting urination, expelling pus, healing sore, promoting granulation and the like. The radix astragali mainly contains effective components such as flavone, saponin, and polysaccharide, wherein astragaloside A and astragalan are the main active components, and have pharmacological effects of resisting inflammation, resisting oxidation, regulating immunity, and resisting tumor. Research shows that astragalus membranaceus can delay the renal fibrosis process of DN mice, reduce proteinuria and protect kidney functions.

Dogwood is dry mature pulp of Cornus officinalis of Cornus genus (Cornus) of Cornaceae family (Cornaceae), set zucc, first reported in shennong's herbal, and has the effects of tonifying liver and kidney, arresting seminal emission, arresting spontaneous emission, etc. Corni fructus contains terpenoids, flavone, tannin, organic acid, polysaccharide, etc., and has effects of lowering blood sugar, resisting tumor, protecting myocardium, lowering blood sugar, regulating bone metabolism, and resisting inflammation. Research shows that the dogwood can inhibit a Wnt/beta-catenin signal channel so as to inhibit YKL-40 expression and improve kidney injury of DN rats.

Dodder (Cuscutae Semen), an annual stem parasitic plant Cuscuta chinensis (Cuscuta chinensis Lam.) and Cuscuta chinensis (Cuscuta australis r.br.) of the genus Cuscuta of the family Convolvulaceae, was originally recorded in Shennong Bencao Jing, and had the efficacies of tonifying liver and kidney, securing essence, reducing urination, preventing miscarriage, improving eyesight, and the like.

Angelica sinensis is the dried root of Angelica sinensis (Oliv.) Diels of Umbelliferae, and has effects of replenishing blood, promoting blood circulation, regulating menstruation, relieving pain, loosening bowel, and relieving constipation. The angelica mainly contains volatile oil, polysaccharide, amino acid, organic acid, flavone and other components, and has the functions of promoting erythropoiesis, reducing blood fat, resisting oxidation, improving kidney function and the like. Research shows that the active ingredients of angelica can reduce the inflammation level of the kidney of DN rats by regulating TLR 4/NF-kB signal channel and delay the progression of renal fibrosis.

Radix bupleuri is the dry root of Bupleurum chinense DC or Bupleurum scorzonerifolium Willd belonging to the family Umbelliferae, wherein the former is called "North Bupleurum chinense" and the latter is called "south Bupleurum chinense", which is recorded in Shennong Ben Cao Jing, and has the effects of relieving exterior syndrome, reducing fever, lifting yang qi, soothing liver and relieving depression. Research shows that the bupleurum contains a plurality of chemical components such as saponin, polysaccharide, flavone and the like, and has pharmacological effects of resisting inflammation, protecting heart, liver and kidney, resisting tumor, resisting depression and the like.

Bombyx Batryticatus is a dry body killed by Beauveria bassiana (balss.) Beauveria bassiana (Vuillant) infected (or artificially inoculated) by 4-5-year-old larva of Bombyx mori Linnaeus, which is an insect in Bombyx of Bombycidae, and has the effects of dispelling wind, relieving pain, eliminating phlegm, resolving masses, calming wind, relieving spasm and the like. Modern pharmacology indicates that the stiff silkworm contains components such as beauvericin, ammonium oxalate, quercetin, kaempferol and the like, has the effects of resisting coagulation, resisting thrombus, promoting microcirculation, enhancing immunity, resisting bacteria, resisting convulsion, resisting tumor, reducing blood sugar and the like, and is widely applied to the research of various diseases such as kidney diseases and the like.

Preferably, the composition for treating nephropathy consists of the following raw materials in parts by weight: 30-800 parts of astragalus, 10-300 parts of cornus, 10-300 parts of radix bupleuri, 10-300 parts of angelica, 10-300 parts of semen cuscutae and 10-300 parts of stiff silkworm.

Further preferably, the mass ratio of the astragalus root, the dogwood fruit, the bupleurum root and the stiff silkworm is 3:1:1: 1.

Most preferably, the mass ratio of the astragalus to the pulp of dogwood fruit to the Chinese thorowax root to the Chinese angelica to the seed of Chinese dodder to the stiff silkworm is 3:1:1:1: 1.

The invention also provides application of the composition for treating the nephropathy in preparation of a medicine for treating the nephropathy.

Preferably, the medicament is in the form of capsules, tablets, granules or pills.

The invention also provides granules for treating the nephropathy, which comprise the composition for treating the nephropathy and medically acceptable auxiliary materials.

Preferably, the excipients include, but are not limited to, dextrin and ethanol.

The invention also provides a preparation method of the granules for treating nephropathy, which comprises the following steps:

s1, preparing an extract: mixing radix astragali, Corni fructus, bupleuri radix, radix Angelicae sinensis, semen Cuscutae and Bombyx Batryticatus, soaking in water, decocting, filtering, mixing extractive solutions, and concentrating to obtain extract;

s2, adding dextrin into the extract obtained in the step S1, uniformly mixing, drying and crushing to obtain mixed powder;

s3, adding ethanol into the mixed powder obtained in the step S2, preparing wet granules, drying and finishing the granules to obtain the granules.

Preferably, the mass ratio of the dextrin to the extract in step S2 is 1: 1.

preferably, the ethanol is added in an amount of 25-40% by weight of the mixed powder in step S3.

The invention has the beneficial effects that:

(1) the composition for treating the nephropathy is prepared by selecting six traditional Chinese medicines of astragalus, cornus, radix bupleuri, angelica sinensis, semen cuscutae and stiff silkworm for compounding, wherein the astragalus is used as a monarch drug, is sweet in taste and slightly warm in nature, and can supplement yang qi of lung, spleen and kidney, so that the spleen can be absorbed by the spleen when the spleen and kidney are healthy and strong, and the kidney can consolidate essence and slightly discharge and stop. The dogwood and the dodder are used as ministerial drugs, and are matched with the astragalus, so that the yin and yang are combined, and the mutual promotion and mutual transformation are realized, so that the effects of tonifying spleen and kidney, astringing spleen essence and stopping leakage and turbidity are achieved. The Chinese angelica is used for assisting in the effects of tonifying qi and activating blood circulation, taking the meanings that tangible blood cannot be fast-growing, intangible qi should be fast-consolidating and qi tonifying can be blood-growing; the stiff silkworm takes the property of clearing and expelling the pathogenic factors, has the effect of expelling exterior and benefiting the evacuation of exogenous pathogenic factors, dredges and is benefiting the removal of damp toxin, and takes the stiff silkworm and the radix bupleuri as guiding drugs, so that the stiff silkworm can clear and expel the pathogenic factors lightly, clear and expel the pathogenic factors, dredge and benefit the triple energizer to lead the pathogenic factors to exit, and can be operated in a pivot machine to facilitate the simultaneous tonification of the spleen and the kidney, and the stiff silkworm and the radix bupleuri have the effects of tonifying the kidney and the spleen, and promoting the circulation of blood.

Experiments show that the composition for treating nephropathy can obviously improve the renal function of a spontaneous diabetic db/db model mouse and the expression level of EMT (acute renal failure) related proteins, thereby improving the renal damage of a DKD (renal dysfunction syndrome) animal model and protecting the renal function.

(2) The extract of the invention has high viscosity, and the conventional granulation method needs a large amount of auxiliary materials (more than 5 times of the weight of the extract), so the extract can not meet the requirements of Chinese pharmacopoeia; the invention improves the granulation process, and improves the forming rate of the granules under the condition of meeting the requirements of pharmacopoeia by the steps of screening auxiliary materials, adjusting the process and the like.

Drawings

FIG. 1 is a graph showing the effect of granules for treating renal diseases prepared in example 2 of the present invention on the expression level of EMT-associated proteins in the kidney of db/db mice.

Detailed Description

The embodiments of the present invention are described below in conjunction with specific embodiments, and before the embodiments of the present invention are further described, it is to be understood that the scope of the present invention is not limited to the specific embodiments described below; it is also to be understood that the terminology used in the examples is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

The sources of the raw materials adopted by the invention are not limited, and the raw materials adopted by the invention are all common commercial products in the technical field. The sources of the raw materials given in the examples have no limiting effect on the technical solution of the present invention.

The source of the raw materials in the examples is shown in table 1.

TABLE 1 sources of raw materials

Raw materials	Batch number	Manufacturer of the product
			Astragalus membranaceus	20200302	Dongguan national medicine group Chinese herbal pieces Limited
Pulp of dogwood fruit	20200301	Dongguan national medicine group Chinese herbal pieces Limited
			Bombyx Batryticatus prepared from rhizoma Zingiberis recens	200201	Dongguan national medicine group Chinese herbal pieces Limited
Radix Angelicae sinensis	20200302	Dongguan national medicine group Chinese herbal pieces Limited
			Bupleuri radix	20200401	Dongguan national medicine group Chinese herbal pieces Limited
Salted semen cuscutae	20191008	Dongguan national medicine group Chinese herbal pieces Limited
			Dextrin		Xiaxilong pharmaceutical Co Ltd
Medicinal ethanol	80v/v％	Zhongshan Huashida chemical Co., Ltd

Basic embodiment

A composition for treating nephropathy is prepared from the following raw materials in parts by weight: 30-900 parts of astragalus, 10-300 parts of cornus, 10-300 parts of radix bupleuri, 10-300 parts of angelica, 10-300 parts of semen cuscutae and 10-300 parts of stiff silkworm.

Preferably, the mass ratio of the astragalus to the pulp of dogwood fruit to the Chinese thorowax root to the stiff silkworm is 3:1:1: 1.

Most preferably, the mass ratio of the astragalus to the pulp of dogwood fruit to the Chinese thorowax root to the Chinese angelica to the seed of Chinese dodder to the stiff silkworm is 3:1:1:1: 1.

The invention also provides application of the composition for treating the nephropathy in preparation of a medicine for treating the nephropathy.

Preferably, the medicament is in the form of capsules, tablets, granules or pills.

The invention also provides granules for treating the nephropathy, which comprise the composition for treating the nephropathy and medically acceptable auxiliary materials.

Preferably, the excipients include, but are not limited to, dextrin and ethanol.

The invention also provides a preparation method of the granules for treating nephropathy, which comprises the following steps:

s1, preparing an extract: mixing radix astragali, Corni fructus, bupleuri radix, radix Angelicae sinensis, semen Cuscutae and Bombyx Batryticatus, soaking in water, decocting, filtering, mixing extractive solutions, and concentrating to obtain extract;

s2, adding dextrin into the extract obtained in the step S1, uniformly mixing, drying and crushing to obtain mixed powder;

in the step S2, the mass ratio of the dextrin to the extract is 1: 1;

s3, adding ethanol into the mixed powder obtained in the step S2, preparing wet granules, drying and finishing the granules to obtain the granules;

in the step S3, the adding amount of the ethanol is 25-40% of the weight of the mixed powder.

The components of the compositions for treating kidney disease in examples 1-5 are shown in FIG. 2.

TABLE 2 EXAMPLES 1-5 Components and amounts (parts by weight) of compositions for the treatment of nephropathy

Components	Example 1	Example 2	Example 3	Example 4	Example 5
						Astragalus membranaceus	30	789	900	800	100
Pulp of dogwood fruit	10	263	300	200	50
						Bombyx Batryticatus prepared from rhizoma Zingiberis recens	10	263	300	100	50
Radix Angelicae sinensis	300	263	10	200	30
						Bupleuri radix	10	263	300	200	30
Salted semen cuscutae	10	263	300	200	20

The preparation method of the granules for treating the nephropathy comprises the following steps:

weighing six traditional Chinese medicinal materials of astragalus, dogwood fruit, angelica, bupleurum chinense, salted dodder and stiff silkworm according to the prescription amount, adding water to soak for 30 minutes, decocting twice, decocting for 1 hour each time, combining the decoction, filtering, concentrating the filtrate into thick paste with the density of 1.25-1.35 (measured at 60 ℃), adding dextrin into the thick paste according to the mass ratio of 1:1, uniformly mixing, drying, crushing, adding 80% ethanol accounting for 30% of the total amount of the extract and the dextrin into the crushed mixed powder, preparing wet granules under a 10-mesh sieve, drying at 70 ℃, finishing granules and preparing the granules.

Comparative example 1

The comparative example differs from example 2 in that: radix Codonopsis and Atractylodis rhizoma are used to replace Corni fructus and bupleuri radix respectively.

Comparative example 2

The comparative example differs from example 2 in that: the composition for treating nephropathy comprises 800 parts of radix astragali, 200 parts of fructus Corni, 300 parts of rhizoma corydalis and 300 parts of Bombyx Batryticatus, wherein the mass ratio of radix astragali to fructus Corni to radix bupleuri to Bombyx Batryticatus is 8:2:3: 3.

Comparative example 3

The comparative example differs from example 2 in that: the preparation method of the granules for treating the nephropathy comprises the following steps:

weighing six traditional Chinese medicinal materials of astragalus, dogwood fruit, angelica, bupleurum chinense, salted dodder and stiff silkworm according to the prescription amount, adding water to soak for 30 minutes, decocting twice, decocting for 1 hour each time, combining the decoction, filtering, concentrating the filtrate into thick paste with the density of 1.25-1.35 (measured at 60 ℃), and mixing the thick paste according to the mass ratio of 1: 2 adding dextrin into the thick paste, mixing well, drying, pulverizing, adding 90% ethanol with the total amount of the extract and dextrin being 20% into the pulverized mixed powder, making into wet granules under 10 mesh sieve, drying at 70 deg.C, grading, and making into granules.

Comparative example 4

The comparative example differs from example 2 in that: the preparation method of the granules for treating the nephropathy comprises the following steps:

weighing six traditional Chinese medicinal materials of astragalus, dogwood fruit, angelica, bupleurum chinense, salted dodder and stiff silkworm according to the prescription amount, adding water to soak for 30 minutes, decocting twice, decocting for 1 hour each time, combining the decoction, filtering, concentrating the filtrate into thick paste with the density of 1.25-1.35 (measured at 60 ℃), and mixing the thick paste according to the mass ratio of 1: 0.8 adding dextrin into the soft extract, mixing, oven drying, pulverizing, adding 70% ethanol accounting for 45% of the total amount of the extract and dextrin into the pulverized mixed powder, sieving with 10 mesh sieve to obtain wet granule, drying at 70 deg.C, grading, and making into granule.

Experimental example I evaluation of granule quality

Quality tests were carried out on the molding rate and dissolution rate of the granules prepared in examples 1 to 3 and comparative examples 3 and 4, as follows:

1. molding rate

Taking a certain amount of particles, determining according to a double-screening method under the general rules of pharmacopoeia, weighing the particles which can pass through a first screen and cannot pass through a fifth screen as qualified particles, and calculating according to the following method.

The molding ratio is the mass of particles that can pass through the sieve No. 1 but cannot pass through the sieve No. 5/total weight of particles × 100%.

2. Melting rate

Accurately weighing 0.50g of qualified granules, putting into a centrifugal tube with constant weight, accurately adding 5mL of boiling water with the temperature of 100 ℃, stirring and shaking for 5 min. Centrifuging in a centrifuge for 15min, discarding supernatant, oven drying the residue at 80 deg.C to constant mass, and precisely weighing, and calculating by the following method:

melting rate is the mass of melted particles/total mass of particles.

The results are shown in Table 3.

TABLE 3

Group of	Molding ratio%	The dissolution rate is%
			Example 1	86.25	89.41
Example 2	88.93	90.05
			Example 3	84.56	87.82
Comparative example 3	55.33	82.12
			Comparative example 4	64.07	83.01

As can be seen from the above table, the granules prepared by the invention have high molding rate and good dissolution rate. And it was found from comparative examples 3 and 4 that the molding rate and dissolution rate of the granules were greatly affected when the preparation method was changed.

Experimental example II evaluation of Effect of treating nephropathy

1. Test animal

135 male db/db mice (Lepr) ko/ko of grade 6 weeks old (Specific pathogen free, SPF) and 15 male wt/wt mice of the same week old (Lepr) purchased from Jiangsu Jiejiaokang Biotech, Inc., weighing 22-50 g. Animals were housed in the SPF animal house at the animal laboratory center of river-south university. The daily food intake is 4-6g, the water is freely drunk, the light/black circulation is carried out for 12 hours, and the indoor temperature is kept constant (24 +/-1) DEG C and the constant humidity is kept constant (45 +/-10)%.

2. Medicaments and agents

Preparing a suspension of the lovastatin (10 mg/kg): 500mg of the medicine is added into 500ml of physiological saline and is stored at normal temperature for standby. Blood glucose strips and glucometers are available from bayer, germany. The Elisa kit for detecting serum cystatin C, urinary microalbumin and urinary creatinine is purchased from Guangzhou Seiko Biotech limited.

3. Modeling and grouping

The model of type 2 diabetes mellitus derived from autosomal recessive inheritance of the inbred strain of db/db C57BL/KsJ mice was used in this experiment. Strain: lebrm 2cd479/Gpt, genotype: (Lepr) ko/ko. The model is that the Leptin signal channel is obstructed due to the Leptin receptor point mutation, so that the mouse has symptoms of hyperglycemia, insulin resistance, obesity and the like.

The control group is a same-group heterozygote mouse, and the genotype: (Lepr) wt/wt.

The experiments were divided into 4 groups: normal control group: 15 mice heterozygous for the same population, 10 mL/kg^-1·d^-1Perfusing the stomach with normal saline for 12 weeks; model group: 15 db/db mice, 10mL kg^-1·d^-1Perfusing the stomach with normal saline for 12 weeks; (iii) treatment group: the treatment components are 7 groups including an example 1 group, an example 2 group, an example 3 group, an example 4 group, an example 5 group, a comparative example 1 group and a comparative example 2 group, 15 db/db mice in each group, and the granules for treating nephropathy prepared in the examples 1-5 and the comparative examples 1-2 are respectively gavaged at a gavage dose of 2.4 g.kg^-1·d^-1Intragastric administration 12Week; four statin group: 15 db/db mice, 10mg kg^-1·d^-1Lostatin, gastric lavage for 12 weeks.

The model group and the treatment group are grouped by adopting a random drawing grouping method, and the mice enter an animal room environment to adapt to 1 week, namely, the mice begin to gavage at the age of 7 weeks, and the times are 1 time per day.

The results of the experiment are shown in table 4.

Table 4 effect of compositions for the treatment of renal disease on biochemical indices of db/db mice (n 15,)

group of

n

Dosage form

Blood sugar (mmol/L)

ACR

Microalbuminuria (mg)

Cystatin C (mg/L)

Normal group

15

10mL·kg-1·d-1

3.83±0.24

21.54±2.65

14.20±0.75

0.98±0.10

Model set

15

10mL·kg-1·d-1

17.71±1.96#

47.89±4.15#

38.51±4.83#

4.77±0.34#

EXAMPLE 1 group

15

2.4g·kg-1·d-1

18.12±0.85#

40.45±4.93#*

36.12±1.96#

2.13±0.45*

EXAMPLE 2 group

15

2.4g·kg-1·d-1

17.96±0.53#

30.00±4.64**

39.43±2.82#

1.25±0.31**

EXAMPLE 3 group

15

2.4g·kg-1·d-1

19.14±1.15#

42.24±5.06#*

40.14±2.45#

2.68±0.23*

EXAMPLE 4 group

15

2.4g·kg-1·d-1

16.53±0.93#

46.45±5.14#

38.64±3.56#

4.01±0.42#*

EXAMPLE 5 group

15

2.4g·kg-1·d-1

19.44±2.13#

45.72±4.44#

39.77±2.51#

4.28±0.38#*

Comparative example 1 group

15

2.4g·kg-1·d-1

20.16±1.23#

46.78±3.82#

41.67±3.12#

4.81±0.30#

Comparative example 2 group

15

2.4g·kg-1·d-1

19.57±0.87#

46.69±4.92#

40.84±3.75#

4.44±0.33#

New group of statins

15

10mg·kg-1·d-1

18.60±3.16#

43.58±3.64#*

38.32±3.41#

1.61±0.24**

Note: compared to the normal group, # P < 0.05; p <0.05, P <0.01 compared to model group.

As can be seen from Table 4, the blood sugar, ACR, urine microalbumin and cystatin C of the model group mice were significantly different compared to the normal group, indicating that the db/db mice were successfully modeled.

Compared with the model control group, the mice in the example 2 group have very significant difference (P <0.01) in both ACR and cystatin C, the mice in the example 1 group and the mice in the example 3 group have significant difference (P <0.05), and the mice in the example 4 group and the mice in the example 5 group have significant difference (P <0.05) in only cystatin C.

From the above-mentioned example 1 group to example 5 group, it was found that the composition is effective for improving kidney loss and protecting kidney function when the mass ratio of astragalus, cornus officinalis, bupleurum and bombyx batryticatus is 3:1:1:1 (examples 1 and 3 groups), and the composition is most effective when the mass ratio of astragalus, cornus officinalis, bupleurum, angelica, dodder and bombyx batryticatus is 3:1:1:1:1 (example 2 group).

Meanwhile, according to the single factor tests of the group of the comparative example 1 and the group of the comparative example 2, compared with the model group, when the mass ratio of the traditional Chinese medicine components in the composition or the mass ratio of the astragalus, the cornus, the radix bupleuri and the stiff silkworm in the composition is changed, no significant difference exists on the blood sugar, the ACR, the urine microalbumin and the cystatin C of a db/db mouse, and the results show that when the mass ratio of the traditional Chinese medicine components in the composition or the mass ratio of the astragalus, the cornus, the radix bupleuri and the stiff silkworm in the composition is changed, the effect of the granules for treating the nephropathy is greatly influenced.

The expression levels of EMT-related proteins in kidney tissues of db/db mice in a normal group, a model group and a treatment group (example 2 group) were measured at the same time, and the results are shown in FIG. 1. compared with the model group, the expression levels of EMT-related proteins a-SMA, fibrinectin, N-cadherin and E-cadherin of db/db mice in granules for treating nephropathy prepared in example 2 were significantly decreased in the treatment group.

In conclusion, the composition for treating the nephropathy is prepared by selecting six traditional Chinese medicines of astragalus, dogwood fruit, radix bupleuri, angelica sinensis, semen cuscutae and stiff silkworm for compounding, wherein the astragalus is used as a monarch drug, is sweet in taste and slightly warm in nature, and can tonify yang qi of lung, spleen and kidney, so that the spleen can be absorbed by the spleen when the spleen and kidney qi is healthy and strong, and the kidney can consolidate essence and slight purgation. The dogwood and the dodder are used as ministerial drugs, and are matched with the astragalus, so that the yin and yang are combined, and the mutual promotion and mutual transformation are realized, so that the effects of tonifying spleen and kidney, astringing spleen essence and stopping leakage and turbidity are achieved. The Chinese angelica is used for assisting in the effects of tonifying qi and activating blood circulation, taking the meanings that tangible blood cannot be fast-growing, intangible qi should be fast-consolidating and qi tonifying can be blood-growing; the stiff silkworm takes the property of clearing and expelling the pathogenic factors, has the effect of expelling exterior and benefiting the evacuation of exogenous pathogenic factors, dredges and is benefiting the removal of damp toxin, and takes the stiff silkworm and the radix bupleuri as guiding drugs, so that the stiff silkworm can clear and expel the pathogenic factors lightly, clear and expel the pathogenic factors, dredge and benefit the triple energizer to lead the pathogenic factors to exit, and can be operated in a pivot machine to facilitate the simultaneous tonification of the spleen and the kidney, and the stiff silkworm and the radix bupleuri have the effects of tonifying the kidney and the spleen, and promoting the circulation of blood.

Tests show that the composition and the medicament for treating nephropathy can obviously improve the renal function of a spontaneous diabetic db/db model mouse and the expression level of renal EMT related proteins, thereby improving the renal damage of a DKD animal model and protecting the renal function.

In addition, because the extract of the invention has high viscosity, a large amount of auxiliary materials (more than 5 times of the weight of the extract) are required by adopting the conventional granulation method, and the requirements of Chinese pharmacopoeia cannot be met; the invention improves the granulation process, and improves the forming rate of the granules under the condition of meeting the requirements of pharmacopoeia by the steps of screening auxiliary materials, adjusting the process and the like.

The present invention has been further described with reference to specific embodiments, which are only exemplary and do not limit the scope of the present invention. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.