CN115708851B - A fructus Chebulae and flos Chrysanthemi oral preparation, and its preparation method and application - Google Patents
A fructus Chebulae and flos Chrysanthemi oral preparation, and its preparation method and application Download PDFInfo
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Abstract
The invention relates to a myrobalan and chrysanthemum oral preparation, which is prepared from raw material medicines of myrobalan, chicory root, colchicory, aloe and chicory seed, and is prepared into an oral preparation by crushing, extracting, removing impurities and concentrating. The preparation has effects of regulating abnormal body fluid quality, activating block, relieving inflammation, detumescence, and cleaning kidney, and is suitable for oral preparation for treating gouty arthritis and hyperuricemia nephropathy caused by hyperuricemia.
Description
Technical Field
The invention relates to a myrobalan chrysanthemum oral preparation, a preparation method and application thereof, wherein the oral preparation has the effects of regulating abnormal body fluid quality, opening blocks, resisting inflammation, reducing swelling and cleaning kidneys, and is clinically used for treating gouty arthritis and hyperuricemia nephropathy caused by hyperuricemia.
Background
Gout (gout) is a metabolic disease in which purine metabolism is impaired, so that the uric acid content in the body is increased, and accumulation and precipitation occur, and clinically, hyperuricemia, gouty nephropathy caused by the involved kidneys and recurrent gouty arthritis are mainly caused. Recent epidemiological surveys show that 3.9% of adults (> 20 years) in the united states diagnose gout, and that gout incidence rates in the last 10 years of our country are also as high as 0.86% -2.20%, and that gout incidence rates show a significant rising trend worldwide.
Acute gouty arthritis (acute gouty arthritis, AGA) is the first symptom of acute onset of gout, has close relation with hyperuricemia caused by various reasons, and causes uric acid crystals locally precipitated in joints to deposit on articular cartilage, synovium and surrounding tissues, so as to stimulate the production of inflammatory cytokines such as tumor necrosis factor-a and the secretion of pro-inflammatory substances such as leukocyte cofactors and the like, release various chemotactic inflammatory factors such as IL-1 beta, TNF-alpha, IL-6 and the like, and can cause acute inflammatory symptoms of gout.
Hyperuricemia (HUA) refers to a state in which the body is disturbed in purine metabolism, uric Acid (UA) is hypersecreted or renal excretion is dysfunctional, and Uric Acid accumulates in the blood. Epidemiological studies have shown that in recent years, with increasing standard of living, people have a trend toward increasing protein and high purine-rich dietary intake, increasing the incidence of hyperuricemia, and toward younger age. Hyperuricemia is a great hazard to human bodies and is an important factor for inducing gouty arthritis and hyperuricemia nephropathy.
Hyperuricemia nephropathy refers to kidney damage caused directly or indirectly by high concentrations of serum uric acid. Uric acid may cause kidney damage through its soluble uric acid form or sodium urate crystal form. Soluble urates produce inflammatory responses by damaging vascular endothelial function, activate renin-angiotensin-aldosterone system (renin angiotensin aldosterone system, RAAS), raise blood pressure and intraglomerular pressure, and ultimately lead to reduced renal function and renal fibrosis; the sodium urate crystal form is mainly deposited on the kidney to cause acute inflammatory injury of the kidney. Meanwhile, research shows that hyperuricemia and the occurrence of a plurality of diseases, such as hypertension, coronary heart disease, diabetes, obesity and the like, are a certain positive correlation, and become independent risk factors independent of hyperglycemia, hypertension and hyperlipidemia, and become a new 'fourth highest'. Therefore, finding a new drug that is promising for the treatment of hyperuricemia is a focus of industry attention.
Disclosure of Invention
The invention aims to develop an oral preparation of myrobalan and chrysanthemum, which is prepared from raw materials of myrobalan, chicory root, colchicory, aloe and chicory seed, and is prepared into an oral preparation by crushing, extracting, removing impurities and concentrating. The preparation has effects of regulating abnormal body fluid quality, activating block, relieving inflammation, detumescence, and cleaning kidney, and is suitable for oral preparation for treating gouty arthritis and hyperuricemia nephropathy caused by hyperuricemia.
The invention relates to a myrobalan and chrysanthemum oral preparation, which is prepared from the following raw materials of myrobalan, chicory root, colchicory, aloe and chicory seed, wherein the content of each component in 1 part is as follows: 30-150 g of myrobalan, 40-180 g of chicory root, 20-150 g of colchicory, 25-210 g of aloe and 30-190 g of chicory seed, and the specific operation is carried out according to the following steps:
a. pulverizing 30-150 g of myrobalan, 40-180 g of chicory root, 20-150 g of colchicory, 25-210 g of aloe and 30-190 g of chicory seed by a pulverizer according to a conventional method, and sieving with a 40-120 mesh sieve to obtain a mixture;
b. placing the mixture obtained in the step a into an extraction tank, adding 4-12 times of water, decocting for 2 times, wherein the first time is 30 minutes-2 hours, filtering, and the second time is 20 minutes-1.5 hours, filtering;
c. mixing the two filtrates obtained in step b, standing for 6-12 hr, filtering, concentrating the filtrate to obtain soft extract with relative density of 1.05-1.30 and temperature of 40-80deg.C, and making into oral preparation by conventional method.
A preparation method of a myrobalan and chrysanthemum oral preparation is carried out according to the following steps:
a. the content of each component in each 1 part is as follows: pulverizing 30-150 g of myrobalan, 40-180 g of chicory root, 20-150 g of colchicory, 25-210 g of aloe and 30-190 g of chicory seed by a pulverizer according to a conventional method, and sieving with a 40-120 mesh sieve to obtain a mixture;
b. placing the mixture obtained in the step a into an extraction tank, adding 4-12 times of water, decocting for 2 times, wherein the first time is 30 minutes-2 hours, filtering, and the second time is 20 minutes-1.5 hours, filtering;
c. mixing the two filtrates obtained in step b, standing for 6-12 hr, filtering, concentrating the filtrate to obtain soft extract with relative density of 1.05-1.30 and temperature of 40-80deg.C, and making into oral preparation by conventional method.
The application of the myrobalan oral preparation in preparing medicines for treating gouty arthritis caused by hyperuricemia.
The application of the myrobalan oral preparation in preparing medicines for treating hyperuricemia nephropathy.
Drawings
FIG. 1 is a visual observation of ankle joints of each group 24 hours after molding according to the present invention, wherein A: blank control group; b: a model group; indomethacin group C; d: high dose group of myrobalan; e: dose group in myrobalan; f: low dose group of myrobalan;
FIG. 2 is a graph of HE staining results (x 100) of the ankle synovial tissue of each group of rats according to the present invention, wherein A: blank control group; b: a model group; indomethacin group C; d: low dose group of myrobalan; e: dose group in myrobalan; f: high dose group of myrobalan;
FIG. 3 is a graph showing the effect of the present invention on body weight of hyperuricemia mice;
FIG. 4 is a graph showing the results of the general observation of kidney tissue from groups of mice in accordance with the present invention;
FIG. 5 is a graph showing the results of the kidney histopathological examination (HE, 100 μm) of hyperuricemia mice according to the invention.
Detailed Description
Example 1
a. The content of each component in each 1 part is as follows: weighing 80 g of myrobalan, 40 g of chicory root, 50 g of colchicory, 25 g of aloe and 30 g of chicory seed, crushing the five medicinal materials by a conventional method by using a crusher, and sieving the crushed medicinal materials by a sieve of 40-120 meshes to obtain a mixture;
b. placing the mixture obtained in the step a into an extraction tank, adding 10 times of water, decocting for 2 times, wherein the first time is 1.5 hours, filtering, and the second time is 20 minutes, filtering;
c. mixing the two filtrates obtained in step b, standing for 8 hr, filtering, concentrating the filtrate to obtain soft extract with relative density of 1.05 and temperature of 80deg.C, and making into oral preparation by conventional method.
Example 2
a. The content of each component in each 1 part is as follows: pulverizing 30 g of myrobalan, 80 g of chicory root, 20 g of colchicory, 50 g of aloe and 80 g of chicory seed by a pulverizer according to a conventional method, and sieving with a 40-120 mesh sieve to obtain a mixture;
b. placing the mixture obtained in the step a into an extraction tank, adding 4 times of water, decocting for 2 times, wherein the first time is 30 minutes, filtering, and the second time is 50 minutes, and filtering;
c. mixing the two filtrates obtained in step b, standing for 6 hr, filtering, concentrating the filtrate to obtain soft extract with relative density of 1.30 and temperature of 40deg.C, and making into oral preparation by conventional method.
Example 3
a. The content of each component in each 1 part is as follows: pulverizing 100 g of myrobalan, 160 g of chicory root, 70 g of colchicory, 90 g of aloe and 100 g of chicory seed by a pulverizer according to a conventional method, and sieving with a 40-120 mesh sieve to obtain a mixture;
b. placing the mixture obtained in the step a into an extraction tank, adding 8 times of water, decocting for 2 times, filtering the first decoction for 2 hours, and filtering the second decoction for 1 hour;
c. mixing the two filtrates obtained in step b, standing for 12 hr, filtering, concentrating the filtrate to obtain soft extract with relative density of 1.18 and temperature of 70deg.C, and making into oral preparation by conventional method.
Example 4
a. The content of each component in each 1 part is as follows: pulverizing 150 g of myrobalan, 40 g of chicory root, 100 g of colchicory, 210 g of aloe and 190 g of chicory seed by a pulverizer according to a conventional method, and sieving with a 40-120 mesh sieve to obtain a mixture;
b. placing the mixture obtained in the step a into an extraction tank, adding 5 times of water, decocting for 2 times, wherein the first time is 80 minutes, filtering, and the second time is 1.5 hours, and filtering;
c. mixing the two filtrates obtained in step b, standing for 7 hr, filtering, concentrating the filtrate to obtain soft extract with relative density of 1.15 and temperature of 50deg.C, and making into oral preparation by conventional method.
Example 5
a. The content of each component in each 1 part is as follows: pulverizing fructus Chebulae 70 g, herba Cichorii root 50 g, colchicine 40 g, aloe 180 g and herba Cichorii seed 170 g by conventional method, sieving with 40-120 mesh sieve to obtain mixture;
b. placing the mixture obtained in the step a into an extraction tank, adding 7 times of water, decocting for 2 times, wherein the first time is 1.5 hours, filtering, and the second time is 50 minutes, filtering;
c. mixing the two filtrates obtained in step b, standing for 9 hr, filtering, concentrating the filtrate to obtain soft extract with relative density of 1.25 and temperature of 60deg.C, and making into oral preparation by conventional method.
Example 6
a. The content of each component in each 1 part is as follows: pulverizing fructus Chebulae 30, herba Cichorii root 180 g, colchicine 150 g, aloe 210 g and herba Cichorii seed 190 g by conventional method, and sieving with 40-120 mesh sieve to obtain mixture;
b. placing the mixture obtained in the step a into an extraction tank, adding 12 times of water, decocting for 2 times, wherein the first time is 30 minutes, filtering, and the second time is 1.5 hours, filtering;
c. mixing the two filtrates obtained in step b, standing for 10 hr, filtering, concentrating the filtrate to obtain soft extract with relative density of 1.30 and temperature of 40deg.C, and making into oral preparation by conventional method.
Example 7
a. The content of each component in each 1 part is as follows: pulverizing 150 g of myrobalan, 40 g of chicory root, 20 g of colchicory, 25 g of aloe and 30 g of chicory seed by a pulverizer according to a conventional method, and sieving with a 40-120 mesh sieve to obtain a mixture;
b. placing the mixture obtained in the step a into an extraction tank, adding 12 times of water, decocting for 2 times, filtering the first decoction for 2 hours, and filtering the second decoction for 20 minutes;
c. mixing the two filtrates obtained in step b, standing for 6 hr, filtering, concentrating the filtrate to obtain soft extract with relative density of 1.05 and temperature of 80deg.C, and making into oral preparation by conventional method.
Example 8
The application of the myrobalan oral preparation in preparing the medicine for treating gouty arthritis caused by hyperuricemia comprises the following steps:
establishing an acute gouty arthritis model, and observing the influence of different doses of myrobalan oral preparations on detumescence and anti-inflammation of rats with the acute gouty arthritis model;
research on anti-inflammatory and detumescence effects of myrobalan oral preparation on acute gouty arthritis:
1. grouping animals, preparing disease models and treatment thereof:
1.1 animal grouping and model establishment:
after raising 60 SD male rats for 1 week, dividing the rats into 6 groups, namely a blank control group, a model group, an indometacin group and a low, medium and high dose group of the myrobalan oral preparation, wherein each group comprises 10 SD male rats; modeling a model group, a myrobalan oral preparation, a medium-high dose group and an indometacin group according to a classical Coderre rat animal model, injecting 0.2mL of sodium urate solution with the concentration of 25mg/mL into the right ankle joint cavity of a rat before the 12d gastric lavage, completing model establishment, and injecting an equal volume of physiological saline solution into corresponding parts in a blank control group;
1.2 administration:
according to the ratio of the dosage of the low, medium and high dose groups of the myrobalan oral preparation to 1:2:4, the low dose group of the myrobalan oral preparation is filled with the drug suspension by 0.56g/kg per day, the medium dose group is filled with 1.12g/kg per day, and the high dose group is filled with 2.24g/kg per day; the indomethacin group irrigates the indomethacin enteric-coated tablet suspension with 7.75mg/kg daily; respectively administering distilled water with the same volume to the blank control group and the model group for stomach irrigation; 1 time per day, and continuously lavage for 14 days; starting to perform right ankle joint modeling from the 12d of the stomach irrigation, and continuing to irrigate the stomach for 2d after establishing a model;
1.3, observation indexes and detection methods:
1.3.1 ankle swelling index measurement:
measuring the ankle joint swelling degree of the rat by adopting a toe volume device before molding and after molding for 6, 12, 24, 36 and 48 hours respectively; swelling= (post-molding volume-pre-molding volume)/pre-molding volume×100%, the whole experimental process is operated by the same person (accuracy of measurement is ensured as much as possible), each group of data is repeated 3 times, and an average value is obtained; the ankle joint visual observation of each group after 24 hours of molding shows that the model group (B in figure 1) has obvious joint swelling compared with the other groups, and the model group is shown in figure 1;
1.3.2 After HE staining, the pathological changes of the synovial tissue of the ankle joint were observed:
killing the rat after the last administration for 2 hours, dehydrating and waxing the extracted ankle synovial tissue, embedding and slicing, staining the slices by HE staining, and finally observing pathological changes under a microscope and microscopically collecting images;
1.3.3 ELISA (enzyme Linked immunosorbent assay) for detecting the contents of TNF-alpha, IL-1 beta and IL-6 in ankle synovial flushing fluid:
killing the rat after the last gastric lavage for 2 hours, adding 1ml of physiological saline to wash the joint cavity, collecting the flushing fluid, centrifuging for 10 minutes at 3000r/min, and taking the supernatant to be measured; strictly according to ELISA kit instruction, determining the content of TNF-alpha, IL-1 beta and IL-6 in each sample;
2.4 statistical methods:
data were processed using SPSS 26.0 software, data expressed as x±s: the comparison between groups adopts One-Way ANOVA single factor analysis of variance, LSD test is selected when the variances are uniform, dunnett T3 test is selected when the variances are not uniform; rank sum test is selected when the normalization is not satisfied. The difference of P <0.05 is statistically significant;
3 results:
3.1 ankle swelling index comparison for each group of rats:
compared with a blank control group, the swelling indexes of each time phase of each dose group of the model group, each dose group of the myrobalan oral preparation and each time phase of the indometacin group are obviously increased, the difference has statistical significance (P < 0.05), and the model is successfully established; compared with the model group, the swelling indexes of each dose group of the myrobalan and chrysanthemum oral preparation and the indometacin group are reduced to different degrees after molding for 6h, 12h, 24h, 36h and 48h, and the difference is statistically significant (P < 0.05); compared with indometacin groups, the swelling degree difference of the low-dose groups of the myrobalan oral preparation is larger at 6h and 12h after molding, the difference has statistical significance (P < 0.05), the swelling index of each of the medium-dose group and the high-dose group is slightly higher, and the difference has no statistical significance (P > 0.05); except for the blank control group, the rest groups have swelling peak value 24h after molding, then swelling subsides, the joint swelling degree of rats in each dose group of the myrobalan chrysanthemum oral preparation is reduced along with the increase of the dose, the negative correlation trend is presented, and a certain dose-effect relationship is shown in table 1:
table 1 ankle swelling ratio at various time phases after molding of rats of each group
Note that: p <0.05 compared to the placebo group; compared to model group, #p <0.05; compared to indomethacin group, < P <0.05; compared with the low-dose group of myrobalan, & P <0.05; compared with the dose group in myrobalan, +.P <0.05.
3.2 pathological changes of the synovial tissue of the rat ankle in each group:
the ankle synovium tissue form and tissue structure of the rat in the blank control group are normal, and no small blood vessel generation and leukocyte infiltration are found; model group synovial membrane swelling, obvious proliferation of cells, disordered structural arrangement, massive leukocyte infiltration, and visible small angiogenesis and fibroblast; indometacin group synovial tissue slightly swells, cells slightly proliferate, and a small amount of leucocytes and fibroblasts infiltrate; the chebula oral preparation has the advantages that the synovial tissue of a low-dose group is swollen, the cells are proliferated, the structural arrangement is disordered, and the infiltration of leucocytes and the generation of small blood vessels are visible; the dose group synovial tissue in the myrobalan oral preparation has swollen cells, the structural arrangement is disordered, and leukocyte infiltration and fibroblast can be seen; the high-dose group synovium tissue of the myrobalan oral preparation has slight swelling, slight hyperplasia of cells, slightly disordered structural arrangement, and no white blood cells and fibroblasts basically; the myrobalan oral preparation is shown to obviously reduce inflammatory response of ankle synovial tissue, and is shown in figure 2;
3.3 comparison of TNF-alpha, IL-1 beta and IL-6 content in the rinse solution of the ankle synovial tissue of each group of rats:
compared with a blank control group, the amounts of TNF-alpha, IL-1 beta and IL-6 in each dose group and indometacin group of the model group, the myrobalan oral preparation are all increased, and the difference has statistical significance (P < 0.05); compared with the model group, the contents of TNF-alpha, IL-1 beta and IL-6 in each dosage group, indometacin group of the myrobalan oral preparation are reduced, and the difference has statistical significance (P < 0.05); compared with the indomethacin group, the content of TNF-alpha, IL-1 beta and IL-6 in each dosage group of the myrobalan oral preparation is slightly higher, wherein the difference between the low dosage group and the indomethacin group in the myrobalan oral preparation is statistically significant (P < 0.05), and the difference between the high dosage group TNF-alpha, IL-1 beta and IL-6 and the indomethacin group is not statistically significant (P > 0.05), as shown in Table 2:
TABLE 2 comparison of TNF- α, IL-1 β, IL-6 content in the synovial tissue washes of the groups (pg/mL)
Note that: p <0.05 compared to the placebo group; compared to model group, #p <0.05; compared to indomethacin group, < P <0.05; compared with the low-dose group of myrobalan, & P <0.05; compared with the dose group in myrobalan, +.P <0.05.
Acute gouty arthritis is closely related to hyperuricemia caused by various reasons, and the hyperuricemia promotes uric acid crystals locally precipitated from joints to deposit on articular cartilage, synovium and surrounding tissues, stimulates the production of inflammatory cytokines such as tumor necrosis factor-a and the secretion of pro-inflammatory substances such as leukocyte auxiliary factors and the like, releases various chemotactic inflammatory factors such as IL-1 beta, TNF-alpha, IL-6 and the like, and can cause acute inflammatory symptoms of gout; at present, the gouty arthritis treatment medicine mainly comprises non-steroidal anti-inflammatory drugs, colchicine, glucocorticoid and interleukin-1 antagonist, but the medicines are easy to cause adverse reactions such as gastrointestinal tract and the like, and complications can be relieved only by reducing dosage and even stopping medicines; the myrobalan and chrysanthemum oral preparation has the effects of regulating abnormal body fluid, opening blocks, resisting inflammation, reducing swelling and cleaning kidneys, and is used for treating gouty arthritis and hyperuricemia nephropathy caused by hyperuricemia; according to the invention, sodium urate is injected into the ankle joint cavity on the right side of a rat to cause acute gouty arthritis, and the falling off of synovial epithelium, vascular hyperplasia and massive inflammatory cell infiltration of different degrees can be seen under a light mirror; the oral preparation of myrobalan has slight swelling of synovial tissue, slight hyperplasia of cells, and no white blood cells and fibroblasts. The medicine shows that the myrobalan oral preparation can obviously reduce the inflammatory reaction of the ankle synovial tissue;
sodium urate crystals (MUS) in vivo stimulate platelets, neutrophils, synovial cells and monocytes to release various inflammatory mediators, and these inflammatory cytokines play important roles in the onset of gouty arthritis; IL-1β, IL-6 as inflammatory chemokines and activators play an important role in the development and progression of gouty arthritis, and IL-1β is considered to be a primary cytokine in the pro-inflammatory network chain, whereas IL-6 is a secondary pro-inflammatory cytokine induced by IL-1β, TNF- α; studies have also shown that: the various inflammatory factors such as TNF-alpha, IL-1 beta, IL-6 and the like play an important role in the pathogenesis of gouty arthritis, and MSU can enable an organism to release the various inflammatory factors such as TNF-alpha, IL-1 beta, IL-6 and the like and further cause infiltration of inflammatory cells, thereby generating inflammatory cascade reaction and inducing the acute onset of gouty arthritis [16-18]. The myrobalan and chrysanthemum oral preparation can reduce the levels of TNF-alpha, IL-1 beta and IL-6 in rat acute gouty arthritis synovial tissue, and can obviously reduce pathological damage of joints. The mechanism is related to reducing the content of inflammatory factors in joint fluid, reducing the release of inflammatory mediators and relieving the inflammatory symptoms of redness, swelling, heat and pain of the diseased joint.
Example 9
The application of the myrobalan oral preparation in preparing the medicine for treating hyperuricemia nephropathy comprises the following steps:
establishing an acute hyperuricemia model animal and a kidney injury model thereof, and observing the prevention and treatment effects of the myrobalan oral preparation on the acute hyperuricemia model animal and the kidney injury model thereof:
protective effect of myrobalan oral preparation on acute hyperuricemia and kidney injury:
1. grouping animals, preparing disease models and treatment thereof:
after 48 male KM mice are normally fed with common feed for 3 days, the mice are divided into a blank group, a model group, an allopurinol group, and a low, medium and high dose group of the myrobalan oral preparation, 6 groups and 8 groups each; after the grouping is completed, the low (1.23 g/kg), medium (2.43 g/kg) and high (4.86 g/kg) groups of the myrobalan oral preparation are respectively filled with liquid medicine with corresponding dosage concentration, the positive medicine group is given with allopurinol solution (0.063 g/kg), the blank control group and the model control group are filled with equal volumes of pure water, and each group is continuously administered for 14 days according to the administration volume of 0.2ml/10g, 1 time a day;
referring to the "pharmacological experiment methodology" and the results of the preliminary experiments, the mice of each group were given normal gastric administration on day 14 of administration, and after 1 hour of administration, the mice of each group were filled with hypoxanthine (500 mg. Kg. D-1) and were intraperitoneally injected with potassium oxazinate (450 mg. Kg. D-1) to create an acute hyperuricemia model. Taking blood from eyeball after molding for 1 hour, centrifuging for 15min at 3000 r.min < -1 >, taking supernatant and placing in a refrigerator at-80 ℃ for standby; immediately killing the mice after blood taking, taking kidney and liver tissues at one side of the animals, freezing the kidney and liver tissues by dry ice, transferring the kidney and liver tissues to a refrigerator with the temperature of-80 ℃ for standby, taking kidney tissues at the other side of the mice, and fixing the kidney tissues by 4% paraformaldehyde solution;
2. detecting the index:
2.1 changes in body mass, kidney mass and kidney index for each group of mice: the general condition of the mice is observed every day and weighed, and the weight change of each mouse is calculated;
2.2 biochemical detection of serum: detecting uric acid and urea nitrogen levels in serum of each group of mice according to the use instructions of the kit;
2.3 determination of serum adenosine deaminase and hepatic xanthine oxidase activity of mice: detecting the activity of adenosine deaminase and liver xanthine oxidase in serum of each group of mice according to the use instruction of the kit;
2.4ELISA method for detecting PRPS and PRPPAT levels in kidney tissue IL-1 beta, TNF-alpha and liver tissue: after the protein of the kidney of the mice is quantified by a BCA method, the IL-1 beta, the TNF-alpha and the PRPS and PRPPAT levels of the kidney of the mice in each group and the PRPS and PRPPAT levels of liver tissues are detected by an ELISA method according to the instruction of the kit of the IL-1 beta, the TNF-alpha and the PRPS and the PRPPAT of the kidney of the mice;
2.5 kidney HE staining histopathological detection of mice: taking out the kidney of the mouse from 4% paraformaldehyde solution, cutting into small blocks, placing the small blocks in an embedding box, flushing the small blocks for 2 hours by using running water, dehydrating the small blocks by using gradient ethanol, immersing paraffin, embedding, slicing, HE staining, observing under a microscope, and collecting images to analyze the damage condition of the kidney;
2.6 statistical methods: the experimental result is expressed by mean ± standard deviation, SPSS23.0 statistical software is adopted to conduct data analysis, t-test is used for two groups of comparison, single-factor variance analysis is used for comparison among multiple groups, LSD is adopted to conduct analysis on intra-group differences in pairs, and p <0.05 is the difference, so that the statistical significance is achieved;
3. results:
3.1 mice weight gain status:
there was no significant difference in the change in body weight of the mice in the remaining groups except the positive control group during the dosing period; and the body weight of the mice in the positive group did not increase at the seventh day of administration, see fig. 3;
3.2 comparison of serum UA and renal BUN levels in mice of each group:
compared with a blank control group, the uric acid level of mice in the model group is obviously increased (p is less than 0.01), and the success of establishing the hyperuricemia model is verified; compared with the model group, uric acid level of each administration group of the myrobalan oral preparation is obviously reduced, and the medium and high dosage groups are more obvious (P < 0.05), which indicates that the myrobalan oral preparation can reduce uric acid with dose dependency; mice in the model group had significantly elevated serum urea nitrogen (BUN) levels (P < 0.01) compared to the blank group; compared with the model group, the BUN level of each administration group of the myrobalan oral preparation is obviously reduced (P < 0.01), and the allopurinol group is obviously increased (P < 0.01), as shown in Table 3:
TABLE 3 Effect of oral Chebula preparation on serum uric acid and Urea Nitrogen levels in hyperuricemia mice
Note that: comparison to the blank: * P (P)<0.05，**P<0.01; comparison to model set: # P<0.05， ## P<0.01。
3.3 effects on liver XOD, ADA, PRPS and PRPPAT activity in mice of each group:
uric acid is the end product of purine metabolism, and liver is the main site of uric acid production, with Xanthine Oxidase (XOD), adenosine Deaminase (ADA), phosphoribosyl pyrophosphate synthetase (PRPS), phosphoribosyl pyrophosphate acyltransferase (PRPPAT) being key enzymes for uric acid production; compared with the blank group, the liver XOD, ADA, PRPS and PRPPAT activity of the mice in the model group are obviously increased (P < 0.05); compared to the model group, liver XOD, ADA, PRPS and PRPPAT activity were significantly reduced (P <0.05 or P < 0.01) in mice in each of the dosing groups, with the dose group being more pronounced in the myrobalan oral formulation, as shown in table 4:
TABLE 4 Effect of oral Chebula formulation on hyperuricemia mouse liver XOD, ADA, PRPS and PRPPA Activity
Note that: comparison to the blank: * P (P)<0.05，**P<0.01; comparison to model set: # P<0.05， ## P<0.01。
3.4 myrobalan oral preparation improves kidney function and alleviates pathological damage of kidney tissues:
compared with the blank group, the levels of TNF-alpha and IL-6 in the kidneys of the mice in the model group are obviously increased (P < 0.05), and the levels of TNF-alpha and IL-6 in the kidneys of the mice in the model group are obviously reduced (P < 0.05) compared with the model group, as shown in table 5 and fig. 4, the kidneys of the mice in the blank group are full, uniform in texture, bright red and uniform in color; compared with a blank group, the model group mice have obviously increased kidneys, and have uneven color of the kidneys with spots; allopurinol group mice have smaller kidneys and whitish colors; compared with the model group, the surface of the kidney of the mice in the terminalia chebula oral preparation intervention group is reddish brown and smooth, and the damage degree is smaller than that of the model group; the result of kidney histopathology is shown in fig. 5, and kidney pathological sections of the model group mice can be seen in pathological changes such as tubular dilatation degeneration, glomerular atrophy, sclerosis and cavitation, interstitial mass scattering in inflammatory cell infiltration and the like; the kidney damage condition of mice can be relieved after the intervention of the myrobalan oral preparation, and the kidney tubule is slightly dilated and denatured in the low dose group, so that the kidney glomerulus is atrophic; kidney architecture was essentially normal in the medium dose group; the high dose group can see slight tubular atrophy; indicating that the myrobalan oral preparation can alleviate kidney diseases caused by hyperuricemia;
TABLE 5 Effect of oral Chebula preparation on liver TNF-alpha and IL-6 Activity in hyperuricemia mice
Note that: comparison to the blank: * P<0.05， ** P<0.01; comparison to model set: # P<0.05， ## P<0.01。
the results show that: the myrobalan oral preparation can obviously reduce serum uric acid level of hyperuricemia mice caused by hypoxanthine combined with potassium oxazinate; compared with a blank control group, the model group has obviously raised uric acid, XOD and other key enzyme activities; compared with the model group, the uric acid level of the myrobalan oral preparation is obviously reduced, and the activity of key enzymes such as XOD and the like is reduced; the myrobalan oral preparation has better uric acid reducing effect, and the uric acid reducing mechanism of the myrobalan oral preparation is possibly related to the inhibition of the activities of key enzymes such as XOD and the like in the liver;
the study showed that: the myrobalan oral preparation obviously reduces the content of uric acid and BUN in serum of mice with hyperuricemia models, and reduces the expression of proinflammatory factors such as IL-6, TNF alpha and the like; this is consistent with the results of earlier studies of the subject group on the ability of the myrobalan oral formulation to alleviate inflammatory responses; the observation of pathological sections shows that the myrobalan oral preparation improves the pathological changes of glomerular atrophy, tubular dilation, renal fibrosis and inflammatory cell infiltration of renal interstitial of mice with hyperuricemia; the above results indicate that: the myrobalan oral preparation can play a role in protecting kidney by improving kidney injury parameters, resisting inflammation, resisting fibrosis and the like;
studies have shown that: there is a link between hyperuricemia and the development of kidney disease; the experimental results suggest that lowering uric acid treatment may prevent the progression of kidney disease, suggesting that high uric acid concentration in serum may be one of the risk factors causing exacerbation of chronic kidney disease; based on the research, the reduction of hyperuricemia and targeted inhibition of hyperuricemia-related kidney signal abnormality can have great effect on improving kidney structure and function; the molecular mechanism of the myrobalan oral preparation for regulating uric acid level and improving kidney injury is clarified by establishing a chronic hyperuricemia kidney disease model through research, and a theoretical basis is provided for the potential application of the myrobalan oral preparation in hyperuricemia treatment; in conclusion, the myrobalan and chrysanthemum oral preparation has the effects of preventing and treating hyperuricemia. The myrobalan oral preparation not only plays a role in reducing uric acid by regulating key enzymes such as XOD and the like in the uric acid generation process, but also protects the kidney by improving the kidney function and reducing the inflammatory factor level. Therefore, the myrobalan and chrysanthemum oral preparation can be an effective therapeutic drug for treating gouty arthritis and hyperuricemia nephropathy caused by hyperuricemia.
Claims (4)
1. The myrobalan and chrysanthemum oral preparation for treating gouty arthritis and hyperuricemia nephropathy caused by hyperuricemia is characterized by being prepared from raw material medicines of myrobalan, chicory root, colchicory, aloe and chicory seed, wherein the content of each 1 part of each component is as follows: 30-150 g of myrobalan, 40-180 g of chicory root, 20-150 g of colchicory, 25-210 g of aloe and 30-190 g of chicory seed, and the specific operation is carried out according to the following steps:
a. pulverizing 30-150 g of myrobalan, 40-180 g of chicory root, 20-150 g of colchicory, 25-210 g of aloe and 30-190 g of chicory seed by a pulverizer according to a conventional method, and sieving with a 40-120 mesh sieve to obtain a mixture;
b. placing the mixture obtained in the step a into an extraction tank, adding 4-12 times of water, decocting for 2 times, wherein the first time is 30 minutes-2 hours, filtering, and the second time is 20 minutes-1.5 hours, filtering;
c. mixing the two filtrates obtained in step b, standing for 6-12 hr, filtering, concentrating the filtrate to obtain soft extract with relative density of 1.05-1.30 and temperature of 40-80deg.C, and making into oral preparation by conventional method.
2. A method for preparing the myrobalan oral formulation according to claim 1, wherein: the method comprises the following steps of:
a. pulverizing the five medicinal materials by a pulverizer according to a conventional method, and sieving with a 40-120 mesh sieve to obtain a mixture;
b. placing the mixture obtained in the step a into an extraction tank, adding 4-12 times of water, decocting for 2 times, wherein the first time is 30 minutes-2 hours, filtering, and the second time is 20 minutes-1.5 hours, filtering;
c. mixing the two filtrates obtained in step b, standing for 6-12 hr, filtering, concentrating the filtrate to obtain soft extract with relative density of 1.05-1.30 and temperature of 40-80deg.C, and making into oral preparation by conventional method.
3. Use of the myrobalan oral formulation according to claim 1 or 2 in the manufacture of a medicament for the treatment of gouty arthritis caused by hyperuricemia.
4. Use of an oral formulation of myrobalan according to claim 1 or 2 for the preparation of a medicament for the treatment of hyperuricemia nephropathy.
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| CN113876896A (en) * | 2021-09-08 | 2022-01-04 | 福建中医药大学 | Three-rice-drink traditional Chinese medicine formula composition for reducing uric acid and relieving gout and preparation process thereof |
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| CN1557352A (en) * | 2004-01-19 | 2004-12-29 | 北京中医药大学 | Novel usage of chicory aqueous extract |
| CN113876896A (en) * | 2021-09-08 | 2022-01-04 | 福建中医药大学 | Three-rice-drink traditional Chinese medicine formula composition for reducing uric acid and relieving gout and preparation process thereof |
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