CN114377052A - Preparation for regulating immune imbalance of diabetic nephropathy and preparation method thereof - Google Patents
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- CN114377052A CN114377052A CN202210042881.8A CN202210042881A CN114377052A CN 114377052 A CN114377052 A CN 114377052A CN 202210042881 A CN202210042881 A CN 202210042881A CN 114377052 A CN114377052 A CN 114377052A
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Abstract
The invention relates to the technical field of traditional Chinese medicine application, in particular to a preparation for regulating immune imbalance of diabetic nephropathy. The method comprises the following steps: a preparation body; the preparation body is selected according to the following components in parts: 1500 parts of Tripterygium hypoglaucum, 200 parts of starch, 3-10 parts of talcum powder and 1-8 parts of magnesium stearate. The preparation method comprises the following steps: taking Tripterygium hypoglaucum, removing root bark, cutting into slices, decocting with water for three times, mixing filtrates, filtering, and concentrating the filtrate to obtain fluid extract; step two: adding ethanol into the concentrated fluid extract, stirring, standing, filtering, recovering ethanol from the filtrate, and concentrating to obtain soft extract to obtain active ingredient of the substance. Reducing the expression levels of diabetic nephropathy p-PI3K, p-AKT and p-NF-k B proteins, and the relative immune index of phosphorylated total protein proportion; reducing glycosylated hemoglobin, renal index, urinary microalbumin and creatinine, urinary albumin/creatinine ratio, and total cholesterol, triglyceride, low density lipoprotein, TNF-alpha and IL-1 beta levels in serum, and increasing high density lipoprotein level in diabetic nephropathy.
Description
Technical Field
The invention relates to the technical field of traditional Chinese medicine application, in particular to a preparation for regulating immune imbalance of diabetic nephropathy and a preparation method thereof.
Background
Epidemiological survey data published by the international diabetes union in 2019 show that about 4.63 million of the 20-79-year-old adults worldwide are diagnosed with Diabetes (DM) and the incidence rate reaches 9.3%, wherein the diabetes patients in China reach 1.16 million, and the diabetes patients in China are the most countries of the diabetes patients worldwide. With the increasing prevalence of DM, the number of End Stage Renal Disease (ESRD) caused by DM is increasing dramatically. The proportion of incorporated DM in ESRD patients worldwide has increased from 19.0% in 2000 to 29.7% in 2015, with the proportion caused by DM in newly-discovered ESRD rising from 22.1% in 2000 to 31.3% in 2015, and the annual incidence of ESRD rising from 375.8/million in 2000 to 1016/million in 2015 in ESRD-incorporated DM patients.
Diabetic nephropathy (DKD) refers to chronic kidney disease caused by diabetes, mainly manifested by urinary albumin/creatinine ratio (UACR) of not less than 30mg/g and/or estimated glomerular filtration rate (eGFR) <60 ml/min/(1.73 m 2), and persists for more than 3 months, DKD is already a leading cause of ESRD in developed countries and regions, and DKD prevalence also increases proportionally with significant increase in diabetic prevalence. In foreign reports, 20-40% of DM patients have combined DKD, while the DKD prevalence rate of type2 diabetes mellitis (T2 DM) patients in China is 21.8%, so that the development of prevention and treatment research on diabetic nephropathy is important.
Tripterygium hypoglaucum is root of plant of Tripterygium of Celastraceae, and has effects of dispelling pathogenic wind, removing dampness, promoting blood circulation, stopping bleeding, relieving rigidity of muscles, setting bone, removing toxic substance, and killing parasite. Clinically, the traditional Chinese medicine composition is usually used for treating rheumatic arthralgia, hemiplegia, hernia pain, dysmenorrheal, menorrhagia, postpartum abdominal pain, ceaseless bleeding, acute infectious hepatitis, chronic nephritis, lupus erythematosus, cancer and swelling, traumatic fracture, osteomyelitis, bone tuberculosis, paratuberculosis, sore toxicity, psoriasis and neurodermatitis.
In terms of the current research, a preparation prepared from the substance has a large number of clinical researches and basic researches on the aspects of rheumatoid arthritis, psoriasis, lupus erythematosus, acute infectious hepatitis and the like to verify that the curative effect is exact, but the research on the treatment effect and the action pathway mechanism of diabetic nephropathy is lack of relevant researches.
Disclosure of Invention
The scheme aims to provide a preparation for regulating the immune imbalance of diabetic nephropathy and a preparation method thereof.
In order to achieve the above objects, the present invention provides a preparation for regulating immune imbalance of diabetic nephropathy and a method for preparing the same, comprising: a preparation body; the preparation body is selected according to the following components in parts: 1500 parts of Tripterygium hypoglaucum, 200 parts of starch, 3-10 parts of talcum powder and 1-8 parts of magnesium stearate.
The scheme provides a preparation method of a preparation for regulating the immune imbalance of diabetic nephropathy, and the preparation method comprises the following steps:
the method comprises the following steps: taking Tripterygium hypoglaucum, removing root bark, cutting into slices, decocting with water for three times, mixing filtrates, filtering, and concentrating the filtrate to obtain fluid extract;
step two: adding ethanol into the concentrated fluid extract, stirring, standing, filtering, recovering ethanol from the filtrate, and concentrating to obtain soft extract to obtain the active ingredient of the substance.
The scheme has the beneficial effects that: aiming at the problem that the basis of pharmacodynamic substances of the tripterygium hypoglaucum which regulate the imbalance of the 'immunity-inflammation' of the diabetic nephropathy is unclear, through the series excavation and in-vivo and in-vitro experimental verification of network pharmacology on the interaction network of the 'disease genes-drug targets-action pathways-biological functions' of the tripterygium hypoglaucum, the invention identifies the action components and the targets of the 'immunity-inflammation' imbalance of the diabetic nephropathy which can be regulated by the preparation prepared by the tripterygium hypoglaucum in a specific extraction mode. In vivo verification experiment shows that the preparation can effectively reduce glycosylated hemoglobin, renal index, urine microalbumin, creatinine and urine albumin/creatinine ratio in diabetic nephropathy, and levels of Total Cholesterol (TC), Triglyceride (TG), low density lipoprotein (LDL-C), TNF-alpha and IL-1 beta in serum, and improve high density lipoprotein (HDL-C) level. In vitro verification experiments show that the preparation can effectively reduce the expression levels of p-PI3K, p-AKT and p-NF-k B proteins of diabetic nephropathy, and relevant immune indexes such as phosphorylated total protein proportion, and inhibit the activation of PI 3K/AKT/NF-k B signal pathways. Lays a foundation for treating the 'immune-inflammatory' imbalance of diabetic nephropathy.
Further, the substances obtained in the second step are added with auxiliary materials to be prepared into tablets, capsules, granules, pills or oral liquid preparations.
Furthermore, in the first step, the decoction is carried out for 1.5 hours for the first time, and the decoction is carried out for 1 hour for the second time and the third time respectively.
Further, adding ethanol into the concentrated fluid extract in the second step to make the alcohol content reach 70%.
Further, the standing time in the second step is 12 hours.
And further adding starch, talcum powder and magnesium stearate into the thick paste obtained in the step two, uniformly mixing, granulating, drying and tabletting to obtain the tablet.
Further, the preparation body also comprises: 10-20 parts of radish seeds.
Furthermore, the preparation body is also used for treating rheumatoid arthritis, psoriasis, lupus erythematosus and acute infectious hepatitis.
Further, a package is arranged outside the capsule; the package comprises: a left chamber and a right chamber; the left cavity and the right cavity are connected through a sealing strip, and the sealing strip is arranged in an S shape; a supporting plate is arranged in the left cavity in a sliding manner, and a groove for placing capsules is formed in the supporting plate; and one side of the groove is communicated with the channel. Water for melting capsules is placed in the right cavity; the sugar coatings outside the capsules are arranged in an up-and-down connection mode, the upper sugar coatings and the lower sugar coatings are wrapped in a round shape, and the sugar coatings connected in the middle are arranged in a rectangular shape; the top and the bottom of the left cavity are both provided with wedge openings for tearing. The sugar coating ensures that in the extrusion process, the sugar coating connected in the middle can utilize the thrust caused by the deformation process to the sugar coatings at the upper part and the lower part, so that the sugar coating is broken. If the normal capsule is used, the wedge opening is directly torn open and the capsule can be taken out, the support plate can also ensure that the hand does not contact with the medicament, and a user holds the support plate and pours the medicament into the mouth. Not only can carry out the adjustment of safety and sanitation to the demand change of the medicament of different crowds in the unused period, can guarantee simultaneously when taking, clean health need not to prepare other appurtenance alright realize taking. For patients taking a large amount of medicines, the supporting plate can also replace a hand-held or other supporting object, and is clean and sanitary. The quantity of recess in the backup pad can set up according to the demand of medicament, if to the old person patient of less clarity, with medicine direction backup pad.
Drawings
Figure 1 is a flow chart of an assay for the modulation of an "immune-inflammatory" imbalance in diabetic nephropathy based on networked pharmacological discovery of agents.
FIG. 2 is a flow chart of a method for preparing a formulation for modulating an "immune-inflammatory" imbalance in diabetic nephropathy according to an embodiment of the present invention.
Figure 3 is a graphical illustration of a network regulatory machine for intervention of agents in diabetic nephropathy based on network pharmacology discovery.
FIGS. 4A-D are graphs showing the changes in the metabolic indices of the preparation against weight, urine volume, blood glucose, serum insulin, C-peptide sugar, hemoglobin and serum lipids in diabetic nephropathy rats.
FIGS. 5A-B are graphs showing the changes in renal index, urine microalbuminuria and creatinine, and inflammation in each group of SD rats.
Fig. 6A-C are graphs of the effect of H & E staining to observe the effects of agents on the pathological changes in the kidney of DKD rats and the effect of immunohistochemical methods to detect the expression of ECM markers in kidney tissue.
FIGS. 7A-B are graphs showing ELISA for the detection of the expression levels of fibronectin, collagen type I, TNF- α, and IL-1 β in high-sugar treated HK-2 cells.
FIG. 8A is a western blot banding pattern for the target protein.
FIG. 8B is a graph of the relative amounts of protein expression of PI3K, p-PI3K, the ratio of p-PI3K to PI3K, AKT, p-AKT, the ratio of p-AKT to AKT, NF-. kappa.B (p65), p-NF-. kappa.B (p65), p-NF-. kappa.B (p65) and NF-. kappa.B (p 65).
FIG. 9A is a protein western blot band.
FIG. 9B is a graph of the relative protein expression levels of PI3K, p-PI3K, p-PI3K to PI3K, AKT, p-AKT to AKT, NF-k B (p65), p-NF-k B (p65), p-NF-k B (p65), and NF-k B (p65) in high glucose treated HK-2 cells.
FIG. 10A is a graph showing the expression and distribution of NF-. kappa.B (p65) protein in renal tissue of rats with diabetic nephropathy.
FIG. 10B is a graph of the ratio of the number of nuclear translocating NF-. kappa.B (p65) cells in DKD rat kidney tissue cells to the total number of nuclear NF-. kappa.B (p65) cells, the overlap factor and the relative IOD value.
Fig. 11 is a graph of the formulation relieving DKD mechanisms.
Fig. 12 is a top view of an embodiment of the present invention.
Fig. 13 is a schematic structural diagram of an embodiment of the present invention.
Detailed Description
The following is further detailed by way of specific embodiments:
the reference numbers in the drawings of the specification include: left cavity 1, right cavity 2, backup pad 3, recess 4, medicament 5, passageway 6, sealing strip 7
The embodiment of the invention provides a preparation for regulating the immune imbalance of diabetic nephropathy: the method comprises the following steps: a preparation body; the preparation body is selected according to the following components in parts: 1500 parts of Tripterygium hypoglaucum, 200 parts of starch, 3-10 parts of talcum powder and 1-8 parts of magnesium stearate.
As shown in fig. 2, the preparation method of the preparation for regulating immune imbalance of diabetic nephropathy provided by the embodiment of the invention comprises the following steps:
(1) taking Tripterygium hypoglaucum, removing root bark, slicing, decocting in water for three times (1.5 hr for the first time and 1 hr for the second and third times respectively), mixing filtrates, filtering, and concentrating the filtrate to obtain fluid extract with certain relative density;
(2) adding ethanol into the concentrated fluid extract to make ethanol content reach 70%, stirring, standing for 12 hr, filtering, recovering ethanol from the filtrate, and concentrating to obtain soft extract with certain relative density to obtain the active ingredient of the material.
(3) Adding certain amount of starch, pulvis Talci, and magnesium stearate into the soft extract, mixing, granulating, drying, and tabletting to obtain tablet.
The application effect of the invention is described in detail by integrating multidimensional biological network excavation and animal-cell in vivo and vitro experimental verification.
10-20g of radish seeds are added into the preparation, and the radish seeds have the effect of relieving thunder god vine in the tripterygium hypoglaucum hutch and can protect the liver. Meanwhile, the gastrointestinal motility can be enhanced, and the gastrointestinal reaction of the tripterygium hypoglaucum can be improved.
1. Active ingredient screening and target prediction of preparation
CRT chemical compositions were retrieved via ETCM database (http:// www.tcmip.cn/ETCM/Index. php/Home/Index/, 2018); then, the principle of 'drug property class' in the ADME parameters of the pharmacokinetics of the components (QED > 0.49) is used as a condition to further screen CRT bioactive components; finally, active ingredients with similarity scores above 0.80 were selected for further study using the MedChem Studio 3.0 software, based on structural and functional similarity of the ingredients.
2. Diabetic nephropathy-associated gene collection
Drugs for the treatment of diabetic nephropathy were collected via the drug bank database (http:// www. drug bank. ca/, version 5.1.8) and their target gene sets were extracted. In addition, The HPO database (The Human genotype Ontology, https:// HPO. jax. org/app/, updated at 2021, 6.8 th) and The DisGeNet database (http:// www.disgenet.org/, version 7.0) were searched to collect clinical symptoms related to diabetic nephropathy and to obtain a disease gene of diabetic nephropathy.
3. Functional enrichment analysis
Enrichment analysis was performed on CRT active based on HPO symptoms and KEGG pathway data (http:// www.genome.jp/KEGG/, latest updated at 16/10/2012) in DAVID database (https:// DAVID. ncifcrf. gov/tools. jsp, version 6.7), retaining only HPO clinical symptoms and data of P <0.05 in KEGG pathway (Bonferroni method correction).
4. Construction and analysis of disease gene-drug target interaction network
Based on STRING database (Search Tool for Known and Predicted Protein-Protein Interactions, http:// STRING-db.org/, version 10.0), obtaining the incidence relation between the genes related to diabetic nephropathy and CRT candidate targets, and constructing the 'disease gene-drug target' interaction network. And (3) retaining genes with the gene-gene interaction score higher than 0.7, calculating three topological characteristics of node degree, distance between nodes and node compactness, and screening nodes with important topological characteristics in the network. And finally, dividing the nodes highly associated in the network into different functional modules by using a Markov clustering algorithm, and visualizing the network by using Cytoscape software (version 3.8.0).
5. In vivo experimental verification
5.1 ethical statement
All experimental protocols are approved by the ethical committee of the institute of traditional Chinese medicine of the Chinese academy of sciences (accession number: IACUC-G16045). The animal experiment is carried out according to the instruction and the regulation of the nursing and use of experimental animals in Beijing experimental animal nursing center of Chinese academy of traditional Chinese medicine.
5.2 animals and methods of study
48 SD male rats, weighing 190-. Prior to the experiment, rats were given an acclimation period of 1 week. 48 SD rats were randomly divided into a normal control group (n = 8) and a model group (n = 40), and given a standard diet and a high fat diet (HFD, 60% fat, 20% carbohydrate and 20% protein, # D12492, Research Diets, inc., NJ, USA), respectively. After 4 weeks of feeding, rats on the high-fat diet were intraperitoneally injected with 35mg/kg streptozotocin (STZ, dissolved in pre-cooled citric acid buffer, pH 4.5, # V900890, Sigma-Aldrich, St. Louis, MO, USA) twice a week. Blood sugar is detected by blood sampling of the tail vein after one week, and the success of molding is shown when the blood sugar is more than 11.1 mmol/L. The model rats were then divided into diabetic nephropathy (n = 8), metformin (135 mg/kg, n =8, # PHR1084, Sigma-Aldrich, St. Louis, MO, USA), CRT low dose (CRT-L, 145mg/kg, n =8, CRT provided by chongqing chinese institute pharmaceutical limited, lot number: 20200901), CRT medium dose (CRT-M, 290mg/kg, n = 8), CRT high dose (CRT-H, 580mg/kg, n = 8); meanwhile, rats (CON) in a normal control group are injected with streptozotocin solution solvent. During the administration, rats in both the model group and the administration group were given a high fat diet until the end of the experiment (week 9). Mortality in the diabetic nephropathy rat model is about 20%.
5.3 Biochemical index detection
The body weight, blood glucose, urine volume of the rats were measured every week while blood samples were taken and the insulin, C-peptide and glycated hemoglobin levels were measured. At the end of the experiment on day 63, fasting was performed for 12 hours, then urine was collected in metabolic cages and urine was assayed for microalbumin and creatinine levels, as well as IL-1 β, TNF- α, Total Cholesterol (TC), Triglycerides (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) levels in serum, and IL-1 β, TNF- α, type I collagen, fibronectin levels in cell culture media by ELISA.
5.4 pathological tissue examination
Different groups of kidney tissues were taken for H & E staining and histopathological changes were observed. Rat kidneys were fixed with 10% formalin. From the obtained paraffin sections, 3 mm thick sections were obtained according to a conventional procedure, and the sections were dewaxed and rehydrated and stained with hematoxylin and eosin. All sections were examined under an optical microscope (ML 31, minmei optoelectronics limited, guangzhou, china).
5.5 immunohistochemical staining
Immunohistochemical staining was performed using ultrasensitive SP (mouse/rabbit) Immunohistochemical (IHC) KIT (# KIT-9706, KIT-9701, KIT-9709; New Biotechnology Inc., Fuzhou, China) containing endogenous peroxidase blocking solution, serum, secondary antibody, streptavidin peroxidase and Diaminobenzidine (DAB) substrate-chromogen. Rat kidney tissue sections were incubated overnight at 4 ℃ with antibodies to type I collagen (diluted 1:800, # PAB46098, Bei Yinlai Biotechnology Co., Ltd., Wuhan, China) and fibronectin (diluted 1:800, # PAB46097, Bei Yinlai Biotechnology Co., Ltd., Wuhan, China), respectively. After washing, the sections were incubated with avidin-coupled secondary antibodies in a hypersensitivity SP (mouse/rabbit) IHC KIT (1: 800, # KIT-0305; McXin Biotechnology Ltd., Fuzhou, China) and left at room temperature for 30 minutes. The staining of the target protein was observed with streptavidin-peroxidase labeled polymer (50 mL, 15min at room temperature) and substrate-chromogen (100 mL, 2min at room temperature).
Staining intensity scores were determined according to the method of Handala et al [1 ]. Given the heterogeneity of protein staining, tumor specimens were scored in a semi-quantitative manner. The percentage groupings were as follows: 0 (0%), 1 (1% -10%), 2 (11% -50%) and 3 (> 50%). The dyeing intensity is divided into: 0, negative; 1, weak; 2, moderate; 3, strong. The final score for each slice is the product of the percentage and the intensity score.
5.6 immunofluorescence assay
Formalin-fixed rat kidney paraffin sections (thickness 3 mm) were deparaffinized prior to antigen retrieval. Endogenous peroxidase was blocked by incubation with 3% H2O2 in methanol for 15 min. Kidney sections were blocked with Phosphate Buffered Saline (PBS) containing 0.05% Triton X-100 (EZ 1609D315, seiko biotechnology limited, guangzhou, china) and 10% goat serum, and then mixed with 1: 100 dilutions of NF-kB (# 14220-1-AP, Proteintech, IL, USA) and pNF-kB (# YP0191, Immuno Way, TX, USA) antibodies were incubated overnight at 4 ℃. After washing, the sections were incubated with Cy 3-labeled donkey anti-rabbit (GB 21403, Severe Biotech Co., Ltd., Wuhan, China) and FITC-labeled donkey anti-rabbit (GB 22403, Severe Biotech Co., Ltd., Wuhan, China), respectively. After standing at room temperature for 45min, ProLong Gold anti-fading agent (# P36941, Thermo Fisher Science, CA, USA) was washed and incubated, nuclei were stained with 4', 6-diamino-2-phenylindole (DAPI, 1: 1000, Thermo Fisher Scientific/Invitgen, MA, USA) for 2 min. Immunofluorescence results were observed under a fluorescence microscope (Nikon Eclipse C1, Nikon, Japan) and analyzed by ImageJ (version 1.52e, national institutes of health, USA; http:// image j. NIH. gov/ij) for two images per field. The nuclear translocation level of NF-kB was shown by measuring the optical density value (IOD) of NF-kB in the nucleus and calculating the ratio of the number of cells nuclear translocated by NF-kB (p65) to the total number of cells.
6. In vitro test verification
Human tubular epithelial cells (HK-2, # GDC0152, China center for type culture Collection, Wuhan, China) were used for in vitro experimental validation. DMEM low-sugar medium (# SH30022-01B, Thermo Scientific/HyClone, MA, USA) supplemented with 10% fetal bovine serum was used for culture at 37 ℃ in a 5% CO2 incubator. After 80% -90% of the HK-2 cells had grown, they were digested with trypsin. Cells are planted on a 6-well plate at the density of 1.5 multiplied by 105 cells/well, and after the cells are attached to the wall, the culture medium containing 0.5 percent serum is replaced for starvation culture for 24 hours, so that the cells are in a resting stage. The medium was then discarded and the HK-2 cells were divided into control (CON, glucose 5.6 mmol/L), high carbohydrate (HG, glucose 30 mmol/L), CRT low dose (CRT-L, 10 μ g/mL), CRT high dose (CRT-H, 50 μ g/mL), dapagliflozin (DAP, 10 μmol/L). All treatment groups were cultured in high-sugar medium (glucose 30 mmol/L). After placing in the incubator for further incubation for 48 h, the supernatant and cells were collected for further analysis.
7. Western blot analysis
Proteins were extracted using RIPA lysis buffer (# P0013B, bi yun biotechnology limited, shanghai, china) and protease inhibitor (# ST506, bi yun biotechnology limited, shanghai, china), and centrifuged at 12000rpm for 15min to obtain cell supernatants. Protein quantification was performed using BCA quantification kit (# P0012S, Byuntian Biotech Co., Ltd., Shanghai, China), and separated by 10% SDS-PAGE gel electrophoresis, and then transferred to PVDF membrane. The membranes were blocked with 10% skim milk (# 7198868, Difco/Becton Dickinson, USA) and incubated overnight with primary antibody at 4 ℃. The details of the antibodies are as follows: (# 4249, CST, MA, USA), p-PI3K (# bs-3332R, Boaosen Biotechnology Ltd, Beijing, China), AKT (# ab89402, abcam, MA, USA), p-AKT (# ab81283, abcam, MA, USA), NF-. kappa.B (p65) (# YM3111, Immuno Way, TX, USA), p-NF-. beta.p 65) (# YP0191, Immuno Way, TX, USA) and GAPDH 2118, CST, MA, USA). After three washes with Tris Buffered Saline (TBST) containing Tween 20, incubation was continued for half an hour with horseradish peroxidase (HRP) -labeled secondary antibody (# C2226, Propley Gene technology Co., Ltd., Beijing, China) and three washes with Tris Buffered Saline (TBST) were continued. Finally, protein bands were detected using a chemiluminescence imaging analysis system (5200, Tianneng Biotech Co., Ltd., Shanghai, China), and the grey values of protein expression were quantified using ImageJ software (NIH).
8. Statistical analysis
All experiments in this study were performed in triplicate. Statistical analysis was performed using GraphPad Prism (7.0). Data are expressed as means ± standard deviation, followed by LSD test using one-way analysis of variance. P <0.05 indicates significance.
9. The preparation has potential of relieving diabetic nephropathy
And collecting and predicting 672 CRT candidate targets by utilizing a Chinese medicine encyclopedia database ETCM and a Chinese medicine integrated pharmacology network computing platform TCMIP. Meanwhile, 3472 genes related to diabetic nephropathy are collected from a human phenotype ontology database HPO, a human disease related gene database DisGeNet and a drug database drug, wherein 390 are CRT candidate targets. Further gene function enrichment analysis shows that the CRT candidate target can be obviously enriched in diabetic nephropathy related symptoms (P < 0.05) such as frequent micturition, diabetic neuropathy, inflammation, diabetic retinopathy, hypertension and the like. From the enriched biological functions, CRT candidate targets were significantly involved in immune system regulation, substance metabolism, energy synthesis and decomposition, and hormone synthesis and metabolism related functions (P < 0.05), suggesting that CRT may have the potential to alleviate pathological changes in diabetic nephropathy.
10. The preparation can relieve diabetic nephropathy by reversing immune-inflammation imbalance
By utilizing the interaction information among biological molecules, a multi-dimensional interaction network of CRT aiming at 'disease genes-drug targets-action pathways-biological functions' related to diabetic nephropathy is constructed. Wherein 23,923 pairs of interactions occurred between 561 CRT targets and 2851 genes associated with diabetic nephropathy. And (3) screening 231 key candidate targets for intervention of the CRT in the diabetic nephropathy through network node topological feature calculation. Further gene function enrichment analysis shows that key candidate targets for CRT intervention in diabetic nephropathy are significantly enriched in 5 functional modules, including: modulating immune inflammatory responses, reducing renal basement membrane pathology, modulating renal blood rheology abnormalities, modulating the nervous system and energy metabolism (figure 3). Notably, modulating the immunoinflammatory module is the most prominent functional module for CRT candidate target enrichment. Therefore, this study selects action targets associated with CRT-mediated immune function and anti-inflammatory action as in vivo and in vitro experimental validation subjects.
11. The preparation is effective in reducing blood sugar of diabetic nephropathy rat, and relieving insulin resistance and metabolic disorder
High fat diet/streptozotocin-induced diabetic nephropathy model rats showed significant weight loss, increased urine volume, and increased blood glucose compared to normal control rats, which were significantly improved 2 weeks after CRT treatment (fig. 4A). In addition, serum insulin and C-peptide levels in diabetic nephropathy model rats were significantly elevated at 6-9 weeks and returned to normal after high dose CRT administration (fig. 4B). The glycosylated hemoglobin can accurately reflect the long-term blood sugar control degree and is the gold standard for blood sugar control of type II diabetic patients. As shown in fig. 4C, glycosylated hemoglobin levels were significantly elevated in diabetic nephropathy model rats, while levels were significantly reduced after CRT administration. Considering that metabolic disorders are the main feature of diabetic nephropathy, the levels of serum lipid metabolism-related indicators of each group were further examined. As a result, it was found that administration of different doses of CRT significantly reduced serum TC, TG, LDL-C levels and increased HDL-C levels (FIG. 4D).
12. The preparation can effectively improve renal function and inflammatory reaction of diabetic nephropathy rat
In renal function, diabetic nephropathy model rats kidney index, urinary microalbumin and creatinine levels, and urinary albumin/creatinine ratio were all significantly increased, while they were significantly decreased after administration of high dose CRT (fig. 5A). In addition, the serum TNF-alpha and IL-1 beta levels of the diabetic nephropathy model rats are also obviously higher than those of normal rats, while the serum TNF-alpha and IL-1 beta levels of the CRT treatment group are obviously reduced. The expression of TNF-. alpha.and IL-1. beta. in the high-sugar-treated HK-2 cells also showed the same trend (FIG. 5B; FIG. 7B).
In terms of histopathological changes in the kidney, glomeruli of the model animals were lobulated, glomerular vessels were severely constricted (blue arrows), mesangial matrix was significantly increased (green arrows), tubular epithelial cells were enlarged, cytoplasm was vacuolated (red arrows), and inflammatory infiltration and proliferation of tubular interstitium occurred (black arrows). The above histopathological changes in the kidney were effectively improved after 4 weeks of high dose CRT treatment (see fig. 6A).
Alterations in the extracellular matrix (ECM) are one of the key pathological changes in diabetic nephropathy. This study examined the expression of fibronectin and type I collagen using immunohistochemistry. As shown in fig. 6B and 6C, after administration of CRT to diabetic nephropathy rats, the positive immunoreactions of fibronectin and type I collagen were significantly attenuated, while the number of positive immunoreactive cells was significantly decreased (P < 0.05). The expression of the above-mentioned markers also showed the same trend in the high-sugar-treated HK-2 cells (FIG. 7A).
13. The preparation can inhibit the activation of PI 3K/AKT/NF-kappa B signal pathway in vivo and in vitro
Network analysis results show that key network targets for CRT intervention in diabetic nephropathy are all significantly enriched in PI 3K/AKT/NF-k B pathway (figure 3), which indicates that the pathway may play a key role in improving inflammatory response of diabetic nephropathy. Meanwhile, Western blot detection results show that in diabetic nephropathy rat kidney tissues and high-glucose-induced HK-2 cells, the expression levels of p-PI3K, p-AKT and p-NF-k B proteins and the ratios of p-PI3K/PI3K, p-AKT/AKT and p-NF-k B/NF-k B are all remarkably increased. Further, CRT was effective in reducing the expression levels of p-PI3K, p-AKT, and p-NF-. kappa.B proteins, as well as their phosphorylation to total protein ratio in vitro and in vivo models (FIGS. 8A and B; FIGS. 9A and B). Meanwhile, immunofluorescence detection results also show that the fluorescent-labeled NF-. kappa.B (p65) in renal tissues of diabetic nephropathy rats is significantly translocated into nuclei, and the conditions are effectively reversed after administration (FIGS. 10A and B).
The result of the invention shows that the candidate network target for the CRT intervention in diabetic nephropathy is probably obviously related to the inhibition of immune inflammation and the alleviation of the related pathways of renal basement membrane lesion. Key network target recognition and functional module analysis show that PI 3K/AKT/NF-k B/IL-1 beta/TNF-alpha signal mediated 'immune-inflammatory' reaction is probably a key link for improving diabetic nephropathy by CRT. In vitro and in vivo verification experiments show that the preparation effectively reduces the blood sugar of a rat with high-fat feed/streptozotocin-induced diabetic nephropathy, improves insulin resistance, reduces the accumulation of ECM protein, improves renal function and renal histopathological abnormality, and reduces the nuclear accumulation of NF-k B protein and the levels of downstream cytokines IL-1 beta and TNF-alpha by inhibiting the activation of PI3K, AKT and NF-k B protein. The results are also verified in the high-sugar induced HK-2 cells, and the pathological changes can be effectively reversed, so that the development of diabetic nephropathy is alleviated.
As shown in fig. 12 and 13:
in this embodiment, for different needs of different users for medicines, for example, it is difficult to swallow medicines, and medicines such as oral liquid or granule need to be taken orally according to different needs in the later period, and in such a case, a user purchases a large amount of medicines 5, but not all the medicines can be used up, and cannot be taken continuously after expiration, so that a large amount of waste is caused.
The embodiment sets a preservation package for capsules and granules or oral medicines 5 according to the requirements of users, wherein the preservation package comprises a left cavity 1 and a right cavity 2, and the interiors of the left cavity 1 and the right cavity 2 are both aseptically arranged so as to ensure the cleanness of the medicines 5.
The backup pad 3 is placed to left side 1 inside in chamber, is equipped with recess 4 in the backup pad 3, and the capsule preparation is placed to recess 4 inside, and recess 4 slightly is greater than the size of capsule, and the top of recess 4 is equipped with the passageway 6 that communicates with it, and is little than the width of capsule, guarantees that the capsule can block in recess 4, can not be in the same direction as passageway 6 roll-off.
Inside the right chamber 2 is placed water for the user to melt the formulation, and the water content is such as to be able to melt the granules inside the capsule.
In this embodiment, the mode setting of connecting about the sugar-coat that the capsule adopted adopts, and the sugar-coat of upper portion and lower part is circular parcel, and the sugar-coat that the middle part is connected is the rectangle setting, and the purpose is guaranteed to be in the extrusion process, and the sugar-coat that the middle part is connected can utilize the thrust that deformation process caused upper portion and lower part sugar-coat for the sugar-coat breaks.
The left cavity 1 and the right cavity 2 are connected through a sealing strip 7, and the top of the sealing strip 7 is in an S-shaped arrangement. The purpose is to guarantee that when being squeezed, the part of "S" type destroys at first for left side chamber 1 and right chamber 2 intercommunication realize that the inside water in right chamber 2 enters into right chamber 2, and then damage at the outside sugar-coat of capsule, inside granule expose the back, realize the granule and sleep and get fused.
3 middle parts of backup pad are sunken, slope setting all around, and the purpose is in guaranteeing that hydroenergy enough equal flow to recess 4, with the abundant integration of granule.
In this embodiment, if the normal capsule 5 is used, the wedge is directly torn open and taken out, and the support plate 3 can ensure that the human hand does not contact with the medicament 5, so that the user can take the support plate 3 with his hand and pour the medicament into the mouth.
This embodiment not only can carry out the adjustment of safety and sanitation to the demand change of the different crowds to medicament 5 in the unused period, can guarantee simultaneously when taking, and is clean sanitary, need not to prepare other appurtenances alright realize taking. For patients taking a large amount of medicines, the supporting plate 3 can also replace a hand-held or other supporting object, so that the patient is clean and sanitary.
The quantity of recess 4 in the backup pad 3 can set up according to the demand of medicament 5, if to the old person patient of less clarity, with medicine direction backup pad 3, the 5 numbers of medicament that correspond 4 quantity of recess just are the measurement of taking, and is more convenient to the old man.
The double-deck packing of 1 outside dress in left side chamber, outside packaging layer are equipped with the iron powder, and set up in the bottom of backup pad 3, in extrusion sealing strip 7 and medicament 5, utilize the effect of iron powder atress heating, heat the medicament 5 that melts, can accelerate melting of 5 outside glazes of medicament simultaneously, more can make the 5 heats of medicament after melting, the better entry of the person of being convenient for, reinforcing person's the effect of taking.
The foregoing is merely an example of the present invention and common general knowledge of known specific structures and features of the embodiments is not described herein in any greater detail. It should be noted that, for those skilled in the art, without departing from the structure of the present invention, several changes and modifications can be made, which should also be regarded as the protection scope of the present invention, and these will not affect the effect of the implementation of the present invention and the practicability of the patent. The scope of the claims of the present application shall be determined by the contents of the claims, and the description of the embodiments and the like in the specification shall be used to explain the contents of the claims.
Claims (10)
1. A formulation for modulating an immune imbalance in diabetic nephropathy, comprising: a preparation body; the preparation body is selected according to the following parts of substances: 1500 parts of Tripterygium hypoglaucum, 200 parts of starch, 3-10 parts of talcum powder and 1-8 parts of magnesium stearate.
2. The preparation method of the preparation for regulating the immune imbalance of the diabetic nephropathy specifically comprises the following steps:
the method comprises the following steps: taking Tripterygium hypoglaucum, removing root bark, cutting into slices, decocting with water for three times, mixing filtrates, filtering, and concentrating the filtrate to obtain fluid extract;
step two: adding ethanol into the concentrated fluid extract, stirring, standing, filtering, recovering ethanol from the filtrate, and concentrating to obtain soft extract to obtain the active ingredient of the substance.
3. The method for preparing a preparation for regulating immune imbalance of diabetic nephropathy according to claim 2, wherein the substance obtained in step two is added with adjuvants to prepare tablets, capsules, granules, pills or oral liquid preparations.
4. The method for preparing a preparation for regulating immune imbalance of diabetic nephropathy according to claim 2, wherein the first decoction is 1.5h, and the second and third decoctions are 1 h.
5. The method for preparing a preparation for regulating immune imbalance of diabetic nephropathy according to claim 2, wherein ethanol is added to the concentrated fluid extract in the second step to make the alcohol content reach 70%.
6. The method for preparing a preparation for regulating immune imbalance of diabetic nephropathy according to claim 2, wherein the standing time in the second step is 12 h.
7. The method for preparing the preparation for regulating the immune imbalance of diabetic nephropathy according to claim 3, wherein the starch, the talcum powder and the magnesium stearate are added into the thick paste obtained in the second step, and the mixture is uniformly mixed, granulated, dried and tableted to obtain the tablet.
8. The formulation for modulating diabetic nephropathy immune imbalance of claim 1, wherein the formulation body further comprises: 10-20 parts of radish seeds.
9. The formulation for modulating an immune imbalance of diabetic nephropathy according to claim 1, wherein the formulation is also for use in the treatment of rheumatoid arthritis, psoriasis, lupus erythematosus and acute infectious hepatitis.
10. The formulation for modulating immune imbalance of diabetic nephropathy according to claim 3, wherein the capsule is provided with a package on the outside; the package comprises: a left chamber and a right chamber; the left cavity and the right cavity are connected through a sealing strip, and the sealing strip is arranged in an S shape; a supporting plate is arranged in the left cavity in a sliding manner, and a groove for placing capsules is formed in the supporting plate; a channel communicated with one side of the groove; water for melting capsules is placed in the right cavity; the sugar coatings outside the capsules are arranged in an up-and-down connection mode, the upper sugar coatings and the lower sugar coatings are wrapped in a round shape, and the sugar coatings connected in the middle are arranged in a rectangular shape; the top and the bottom of the left cavity are both provided with wedge openings for tearing.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101641071A (en) * | 2007-03-30 | 2010-02-03 | 先灵公司 | Multi-compartment package |
| CN107088158A (en) * | 2017-05-16 | 2017-08-25 | 傅书华 | It is a kind of to facilitate capsule to pack |
| CN113862390A (en) * | 2021-10-26 | 2021-12-31 | 重庆市药研院制药有限公司 | Primer and method for identifying root and mixed counterfeit product of herba Humuli Scandentis |
-
2022
- 2022-01-14 CN CN202210042881.8A patent/CN114377052A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101641071A (en) * | 2007-03-30 | 2010-02-03 | 先灵公司 | Multi-compartment package |
| CN107088158A (en) * | 2017-05-16 | 2017-08-25 | 傅书华 | It is a kind of to facilitate capsule to pack |
| CN113862390A (en) * | 2021-10-26 | 2021-12-31 | 重庆市药研院制药有限公司 | Primer and method for identifying root and mixed counterfeit product of herba Humuli Scandentis |
Non-Patent Citations (3)
| Title |
|---|
| 周静波等: "火把花根片与厄贝沙坦片治疗糖尿病肾病的效果比较", 《西南国防医药》 * |
| 方玲娜等: "火把花根对糖尿病肾病大鼠肾脏Angptl2和NF-κB表达的影响", 《现代中西医结合杂志》 * |
| 杨小红等: "火把花根片治疗糖尿病肾病30例临床研究", 《新中医》 * |
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| CB02 | Change of applicant information |
Country or region after: China Address after: No. 10 Bitong Road, Xinshi Street, Changshou District, Chongqing 401220 Applicant after: Chongqing Pharmaceutical Research Institute Pharmaceutical Co.,Ltd. Address before: 401220 Zhongke Future City, Xinshi Street, Changshou District, Chongqing Applicant before: Chongqing Pharmaceutical Research Institute Pharmaceutical Co.,Ltd. Country or region before: China |