CN110917296A - Application of traditional Chinese medicine composition in preparation of medicine for treating diabetic nephropathy - Google Patents

Application of traditional Chinese medicine composition in preparation of medicine for treating diabetic nephropathy Download PDF

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CN110917296A
CN110917296A CN201911223393.1A CN201911223393A CN110917296A CN 110917296 A CN110917296 A CN 110917296A CN 201911223393 A CN201911223393 A CN 201911223393A CN 110917296 A CN110917296 A CN 110917296A
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diabetic nephropathy
traditional chinese
chinese medicine
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肖伟
陶晓倩
曹泽彧
曹亮
王振中
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Jiangsu Kanion Pharmaceutical Co Ltd
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    • A61K36/88Liliopsida (monocotyledons)
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Abstract

The invention provides application of a traditional Chinese medicine composition in preparing a medicine for treating diabetic nephropathy, which is characterized by comprising the following components in part by weight: 100 portions of astragalus root, 100 portions of angelica, 500 portions of radix codonopsis, 100 portions of radix scrophulariae, 500 portions of honeysuckle, 100 portions of dendrobium, 500 portions of achyranthes root and 100 portions of liquorice. The composition and the tongsai tablet provided by the invention have a certain inhibiting effect on the blood sugar level of a diabetic nephropathy rat, can delay the occurrence of urine protein, have a protecting effect on the kidney and can regulate lipid metabolism; can reduce FBG level of mice with early diabetic nephropathy, and improve renal function of mice with early diabetic nephropathy.

Description

Application of traditional Chinese medicine composition in preparation of medicine for treating diabetic nephropathy
Technical Field
The invention relates to application of a traditional Chinese medicine composition, in particular to application of the traditional Chinese medicine composition in preparing a medicine for treating diabetic nephropathy.
Background
In recent years, the incidence of diabetes, particularly type 2 diabetes, has increased year by year and is in a trend of being younger. Diabetic Nephropathy (DN) is one of the most major vascular complications of diabetes, with hidden early-stage lesions that severely affect patient life and are one of the leading causes of patient death. DN has become the first cause of end stage renal disease. As DN patients are often interlaced with complex conditions such as high sugar, abnormal lipid metabolism, hemodynamic disturbance, abnormal oxidative stress state, inflammatory state and the like, the treatment is more difficult than other nephropathy along with the progress of the disease course, the prognosis and survival of the diabetic patients are seriously influenced, but no method capable of effectively curing DN exists at present, and the early prevention and early treatment of DN becomes an important research subject for DN and nephropathy students. However, due to the complex pathogenesis of the DN, the existing treatment measures of the DN can only partially delay the process of the DN and cannot fundamentally block the development of the DN. The currently used related treatment medicines are mainly western medicines and mainly used for symptomatic treatment, so that certain limitations are formed for some patients with complications, and the development of DN cannot be effectively solved. The recent literature indicates that the early prevention and treatment of DN by traditional Chinese medicine can delay the progress of pathological changes and attract the wide attention of experts at home and abroad.
Disclosure of Invention
The invention aims to provide application of a traditional Chinese medicine composition in preparing a medicine for treating diabetic nephropathy, and specifically the traditional Chinese medicine composition comprises the following components: 100 portions of astragalus root, 100 portions of angelica, 500 portions of radix codonopsis, 100 portions of radix scrophulariae, 500 portions of honeysuckle, 100 portions of dendrobium, 500 portions of achyranthes root and 100 portions of liquorice.
Further, the traditional Chinese medicine composition comprises: 500 parts of astragalus mongholicus 400-.
Further, the traditional Chinese medicine composition comprises: 500 parts of astragalus root 450-50 parts, 450-50 parts of angelica, 450-50 parts of radix codonopsis, 450-50 parts of radix scrophulariae, 450-50 parts of honeysuckle, 450-50 parts of dendrobium, 450-50 parts of achyranthes root and 450-50 parts of liquorice.
Further, the traditional Chinese medicine composition comprises: 480 parts of astragalus membranaceus, 480 parts of angelica sinensis, 480 parts of codonopsis pilosula, 480 parts of radix scrophulariae, 480 parts of honeysuckle, 480 parts of dendrobe, 480 parts of achyranthes bidentata and 480 parts of liquorice.
Specifically, the medicament for treating diabetic nephropathy is selected from an oral administration dosage form, an injection administration dosage form or an external administration preparation.
More specifically, the medicine for diabetic nephropathy can be decoction, granules, capsules, tablets, oral liquid, pills, tinctures, syrups, suppositories, gels, sprays and injections.
Further, the medicine for diabetic nephropathy is selected from tongsai tablets. The tongsai tablet can be prepared by the following method:
480g of astragalus, 480g of angelica, 480g of codonopsis pilosula, 480g of radix scrophulariae, 480g of honeysuckle, 480g of dendrobium, 480g of achyranthes and 480g of liquorice are taken according to the above dosage ratio, water is added for decoction twice, each time of decoction is carried out for 1-2 hours, the decoction liquid is combined and kept stand, the supernatant liquid is concentrated into thick paste with the relative density of about 1.2, ethanol is used for precipitation, the alcohol content is 60-70%, the mixture is stirred evenly, kept stand, the ethanol is recovered from the supernatant liquid and concentrated into extract, and then the extract is dried, crushed, screened, prepared into powder, tableted and coated to prepare tablets, and the tablets are prepared into 1000.
Further, the traditional Chinese medicine composition can be prepared by the following method:
weighing the medicinal materials according to the weight ratio, adding water for decocting twice, decocting for 1-2 hours each time, combining the decoctions, standing, concentrating the supernatant into thick paste with the relative density of about 1.2, precipitating with ethanol until the ethanol content reaches 60-70%, stirring uniformly, standing, recovering ethanol from the supernatant, concentrating into an extract, drying and crushing.
Further, the diabetic nephropathy is type II diabetic nephropathy.
The invention also provides application of the traditional Chinese medicine composition in preparing a hypoglycemic medicament, wherein the traditional Chinese medicine composition comprises the following components in parts by weight: 100 portions of astragalus root, 100 portions of angelica, 500 portions of radix codonopsis, 100 portions of radix scrophulariae, 500 portions of honeysuckle, 100 portions of dendrobium, 500 portions of achyranthes root and 100 portions of liquorice.
Wherein, the raw materials in the composition can be directly ground into powder, or can be extracts prepared by conventional methods or other forms. The composition of the present invention may also be directly ground into powder, or may be an extract prepared by a conventional method in the art, etc.
Further, the traditional Chinese medicine composition comprises: 500 parts of astragalus mongholicus 400-.
Further, the traditional Chinese medicine composition comprises: 480 parts of astragalus membranaceus, 480 parts of angelica sinensis, 480 parts of codonopsis pilosula, 480 parts of radix scrophulariae, 480 parts of honeysuckle, 480 parts of dendrobe, 480 parts of achyranthes bidentata and 480 parts of liquorice.
The Tongsai pulse tablet is prepared by combining the modern pharmacodynamic research progress on the basis of the Simiao Yongan decoction from the experimental prescription New compilation and combining the clinical empirical cutting of famous and old traditional Chinese medicine of the Shuangjing traditional Chinese medicine university, and highlights the characteristics of combining both the principal and secondary aspects and differentiating diseases and syndromes. Is prepared from 8 Chinese-medicinal materials including astragalus root, pilose asiabell root, dendrobium, scrophularia root, honeysuckle flower, Chinese angelica root, achyranthes root, liquorice root, etc. and has the functions of nourishing vital energy and blood, nourishing Yin, clearing away heat, promoting blood circulation to disperse blood clots, etc. Since the market appeared in 1982, extensive basic research and clinical application research of modern pharmacy show that the tongxiao tablet has obvious curative effect on qi deficiency and blood stasis.
The prescription of the tongsai tablet is deeply researched, a Diabetic Nephropathy (DN) rat model and an early diabetic nephropathy mouse model (db/db) are established, and pharmacological and pharmacodynamic experiments show that the composition and the tongsai tablet provided by the invention have a certain inhibition effect on the blood sugar level of a diabetic nephropathy rat, can delay the occurrence of urine protein, have a protection effect on the kidney and can regulate lipid metabolism; can reduce FBG level of mice with early diabetic nephropathy, and improve renal function of mice with early diabetic nephropathy. These results show that the composition and the tongsai tablet of the invention have better regulating and improving effects on blood sugar and diabetic nephropathy.
Detailed Description
As mentioned above, the present invention is directed to the use of a Chinese medicinal composition in the preparation of a medicament for treating diabetic nephropathy, which will be described in detail with reference to the following experimental examples.
It is specifically noted that all similar substitutes and modifications for the present invention which are obvious to those skilled in the art are deemed to be included in the present invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention.
If the specific conditions are not indicated, the method is carried out according to the conventional conditions or the conditions suggested by manufacturers, and the used raw material medicines or auxiliary materials and the used reagents or instruments are the conventional products which can be obtained commercially.
The invention is further illustrated by the following examples:
example 1 therapeutic Effect on left nephrectomy in combination with Strenzozoomycin intraperitoneal injection induced Diabetic Nephropathy (DN) rat model
1.1 drug sources
The Tongxiao tablets are sold in the market, are exclusively produced by Jiangsu Kangyuan sunshine pharmaceutical industry Limited liability company, and have the following approval document numbers: chinese medicine standard character Z32020535
1.2 Experimental methods
1.2.1 Experimental grouping, model replication and drug administration
48 male SD rats were randomly divided into 6 groups, control, sham, model, and Tonsil (TSM) high, medium, and low dose groups, 8 per group. After adaptive feeding for 3d, fasting for 12h before all animal experiments, drinking water is not limited, abdominal anesthesia is carried out by 3% pentobarbital sodium (100mg/kg), model group rats pass through dorsal left side nephrectomy, and 50mg/kg Streptozotocin (STZ) is subjected to single abdominal injection for 2 weeks after operation, so as to establish a DN rat model; performing operation incision on a sham operation group without excising the left kidney, and performing intraperitoneal injection by using citric acid buffer solution with the same volume after the operation; control mice were not treated at all. And (3) taking 2 times of random blood sugar larger than 16.7mmol/L within 72 hours after molding as a standard for establishing a diabetes model. After the model is built, the stomach filling administration is started, the stomach filling is carried out by using 1mL of normal saline every day for a control group, a sham operation group and a model group, the stomach filling is carried out by using 13.2g of crude drug/kg, 6.6g of crude drug/kg and 3.3g of crude drug/kg for a Tongxiao tablet group respectively, the administration is carried out for 1 time/d for each group, and the continuous administration is carried out for 4 weeks.
1.2.2 specimen Collection
1d before the experiment is finished, the urine volume of the model rat is collected and measured for 24h by using a metabolism cage. After the medicine drying is finished, 5% chloral hydrate solution is used for intraperitoneal injection anesthesia, blood is taken from an abdominal aorta, serum is separated, and the medicine is stored at the temperature of-70 ℃ for later use.
1.2.3 detection method
All rats are bled from 1 time/peripheral tail vein, fasting blood glucose is measured by adopting a glucometer, 24h urine protein (24h-Upro) is measured by adopting a biuret method, blood creatinine (SCR) is measured by adopting a picric acid method, urea nitrogen (BUN) is measured by adopting a urease method, and Total Cholesterol (TC) and Triacylglycerol (TG) are measured by adopting a phosphotungstic acid precipitation method; the 24h-Upro, SCR, BUN, TC and TG were all performed according to the kit's instructions. The quantitative determination of the microalbumin in urine of 24h after the diabetes is modeled and more than 30mg is taken as the establishment standard of the DN model.
1.4 results of the experiment
1.4.1 DN modeling results
After the STZ is injected for 3 days, the blood sugar of all rats in the model group is higher than 16.7mmol/L, which indicates that the diabetes molding is successful, and the molding rate of the diabetes is 100%.
1.4.2 Fasting Blood Glucose (FBG) and 24h urine protein amount (24h-UPro) of rat
Compared with the model group, the FBG and the 24h-UPro of the rats in the control group and the sham operation group are lower than those of the rats in the model group, and have statistical significance (P is less than 0.05); the FBG and 24h-UPro of the TSM rats in each dose group are lower than those of the model group, and the statistical significance is achieved (P is less than 0.05). See table 1. It shows that TSM has certain inhibition effect on the blood sugar level of diabetic nephropathy rats and can delay the appearance of urine protein.
TABLE 1 influence of TSM on the DN model rat FBG, 24h-UPro ((B))
Figure BDA0002301478960000051
n=8)
Figure BDA0002301478960000061
P <0.05, P <0.01 compared to model group.
1.4.3 Change in Biochemical index of blood of rats in each group
Compared with the model group, rats SCr, BUN, TC and TG in the control group and the sham operation group are lower than those in the model group, and have statistical significance (P is less than 0.05); after 4 weeks of treatment of DN rats with different doses of TSM, the dose-dependent decrease in SCr, BUN, TC and TG levels in each treatment group of TSM was statistically significant (P <0.05) compared to the model group, as shown in Table 2. The TSM tablet has a protective effect on the kidney of a diabetic nephropathy rat and can regulate lipid metabolism.
TABLE 2 influence of TSM on biochemical indices of DN rat blood: (
Figure BDA0002301478960000062
n=8)
Figure BDA0002301478960000063
P <0.05, P <0.01 compared to model group.
EXAMPLE 2 therapeutic Effect on early diabetic nephropathy model mice (db/db)
1.1 drug sources
The Tongxiao tablets are sold in the market, are exclusively produced by Jiangsu Kangyuan sunshine pharmaceutical industry Limited liability company, and have the following approval document numbers: chinese medicine standard character Z32020535
1.2 Experimental methods
1.2.1 grouping and administration of Experimental animals
Male 4-week-old clean-grade diabetic nephropathy model animals db/db mice and 6 control db/m mice are raised under a constant temperature condition, indexes such as body mass, tail vein blood sugar and urine albumin of the mice are detected, and the mice are determined to enter an experimental group after showing blood sugar increase but urine protein is negative: 6 db/m mice were used as a control group, and 32 db/db mice were divided into a model group, a tonsillar vein relaxing Tablet (TSM) high, medium and low dose groups, each group consisting of 8 mice. Performing intragastric administration, wherein the control group and the model group are intragastric with 1mL of normal saline every day, and the Tongxiao tablet group is intragastric with 21.2g crude drug/kg, 10.6g crude drug/kg and 5.3g crude drug/kg respectively, and each group is administered for 1 time/d. The experiment was terminated for 4 weeks until the serum albumin in the model group mice was significantly higher than that in the normal control group mice. Body mass and blood glucose were measured 1 time per week and uroalbumin was measured 1 time every two weeks during the experiment.
1.2.2 detection index
1.2.2.1 blood glucose and 24h urine protein determinations blood was taken from the tail vein before, at the end of 2 weeks, at the end of 4 weeks before dosing and 24h urine was collected on the day using a metabolic cage. Fasting plasma glucose (FBG) was measured with a glucometer and 24h urine protein (24h-UPro) was measured by the biuret method, following the strict instructions.
1.2.2.2 renal function and relative renal weight determination of drug intervention after a 4 week end blood sample was taken and tested for serum urea nitrogen (BUN) and creatinine (Scr) by an OLYMPUS AU600 fully automated biochemical analyzer. Relative kidney weight (KW/BW) ═ kidney weight (mg)/body weight (g). Precisely weighing the weight of the kidney, taking the right kidney in an aseptic operation, removing the capsule, washing with normal saline, sucking the blood stain with filter paper, weighing the weight of the right kidney, and calculating according to a formula.
1.3 results of the experiment
1.3.1 Fasting Blood Glucose (FBG)
Compared with the control group, the blood sugar of the mice in the other groups is obviously increased before the administration, at the end of 2 weeks and at the end of 4 weeks, and the difference has obvious statistical significance (P < 0.01). Before administration, FBG of each dose group of TSM was not statistically different compared to the model group (P > 0.05). FBG was significantly reduced in both the medium and high dose TSM at the end of 2 weeks and the low, medium and high dose at the end of 4 weeks over time, with statistical significance for the difference (P < 0.01). See table 3.
Table 3 effect of TSM on DN model mouse FBG: (
Figure BDA0002301478960000081
n=8)
Figure BDA0002301478960000082
Compared with the control group, the compound of the formula,△△P<0.01; comparison with model group<0.01.
1.3.224 h urine protein amount (24h-UPro)
Before administration, the model group and the TSM high, medium and low dose groups have no obvious increase of 24h-UPro level (P >0.05) compared with the control group, the model group mice have no obvious change of 24h-UPro level compared with the control group after 2 weeks of treatment, and the TSM in each group has no obvious difference of 24h urine protein level (P >0.05) compared with the model group. After 4 weeks of treatment, the 24h-UPro level model group showed an increase compared to the control group mice, and the 24h-UPro level of each group of TSM was significantly decreased compared to the model group (P < 0.01). The results are shown in Table 4.
TABLE 4 Effect of TSM on DN model mice 24h-UPro ((S))
Figure BDA0002301478960000083
n=8)
Figure BDA0002301478960000084
Compared with the control group, the compound of the formula,△△P<0.01; comparison with model group<0.01.
1.3.3 serum creatinine (SCr), Urea Nitrogen (BUN) and relative Kidney weight
Compared with a control group, the SCr and BUN levels and relative renal weight average of a model group and a TSM high, medium and low dose group are obviously increased (P <0.05), the SCr and BUN levels of each TSM group are obviously reduced (P <0.01) compared with the model group after 4 weeks of treatment, the relative renal weight of a high dose in the TSM is obviously reduced (P <0.05), and the relative renal weight of the TSM is positively correlated with the dose; the TSM is suggested to be capable of effectively improving the renal function of DN mice. The results are shown in Table 5.
Table 5 effects of TSM on renal function and relative renal weight in DN mice: (
Figure BDA0002301478960000091
n=8)
Figure BDA0002301478960000092
Compared with the control group, the compound of the formula,P<0.05,△△P<0.01; comparison with model group<0.05,**P<0.01.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims (10)

1. An application of a traditional Chinese medicine composition in preparing a medicine for treating diabetic nephropathy is characterized in that the traditional Chinese medicine composition comprises: 100 portions of astragalus root, 100 portions of angelica, 500 portions of radix codonopsis, 100 portions of radix scrophulariae, 500 portions of honeysuckle, 100 portions of dendrobium, 500 portions of achyranthes root and 100 portions of liquorice.
2. The use of claim 1, wherein the Chinese medicinal composition comprises: 500 parts of astragalus mongholicus 400-.
3. The use of claim 1, wherein the Chinese medicinal composition comprises: 500 parts of astragalus root 450-50 parts, 450-50 parts of angelica, 450-50 parts of radix codonopsis, 450-50 parts of radix scrophulariae, 450-50 parts of honeysuckle, 450-50 parts of dendrobium, 450-50 parts of achyranthes root and 450-50 parts of liquorice.
4. The use of claim 1, wherein the Chinese medicinal composition comprises: 480 parts of astragalus membranaceus, 480 parts of angelica sinensis, 480 parts of codonopsis pilosula, 480 parts of radix scrophulariae, 480 parts of honeysuckle, 480 parts of dendrobe, 480 parts of achyranthes bidentata and 480 parts of liquorice.
5. The use according to any one of claims 1 to 4, wherein the medicament for diabetic nephropathy is selected from the group consisting of an oral administration form, an injection administration form, and an external administration form.
6. The use according to claim 5, wherein the medicament for diabetic nephropathy is selected from the group consisting of decoction, granules, capsules, tablets, oral liquid, pills, tinctures, syrups, suppositories, gels, sprays, injections.
7. The use according to any one of claims 1 to 4, wherein the medicament for diabetic nephropathy is a tonneau tablet.
8. The use of any one of claims 1-4, wherein the preparation method of the Chinese medicinal composition comprises the following steps:
weighing the medicinal materials according to the weight ratio, adding water for decocting twice, decocting for 1-2 hours each time, combining the decoctions, standing, concentrating the supernatant into thick paste with the relative density of about 1.2, precipitating with ethanol until the ethanol content reaches 60-70%, stirring uniformly, standing, recovering ethanol from the supernatant, concentrating into an extract, drying and crushing.
9. The use according to any one of claims 1 to 4, wherein the diabetic nephropathy is type II diabetic nephropathy.
10. An application of a traditional Chinese medicine composition in preparing a hypoglycemic medicament is characterized in that the traditional Chinese medicine composition comprises: 100 portions of astragalus root, 100 portions of angelica, 500 portions of radix codonopsis, 100 portions of radix scrophulariae, 500 portions of honeysuckle, 100 portions of dendrobium, 500 portions of achyranthes root and 100 portions of liquorice.
CN201911223393.1A 2019-12-03 2019-12-03 Application of traditional Chinese medicine composition in preparation of medicine for treating diabetic nephropathy Pending CN110917296A (en)

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