CN103284993A - Use of wogonin in preparation of drug for treating chronic kidney disease - Google Patents
Use of wogonin in preparation of drug for treating chronic kidney disease Download PDFInfo
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
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- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
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Abstract
The invention relates to wogonin and derivatives thereof, a prodrug of wogonin as well as medical use of wogonin and biologically-physiologically acceptable salts of wogonin and derivatives thereof for treating a chronic kidney disease, particularly for treating renal fibrosis and renal fibrosis-induced diseases.
Description
Technical field
The invention belongs to pharmaceutical field, the medical usage that relates to wogonin, specifically, the present invention relates to wogonin and derivant thereof, prodrug and physiologically acceptable salt at the medical usage for the treatment of aspect the chronic nephropathy, particularly the medical usage in renal fibrosis and the disease that caused by renal fibrosis.
Background technology
Chronic renal disease is a kind of modal chronic refractory disease.Natural crowd's annual morbidity of chronic renal failure (CRF) is 98-198/100 ten thousand populations, the sickness rate of developed country such as the U.S. and Japan is up to 800-1000 ten thousand/1,000,000 populations, be the trend that index rises over past ten years, China is still based on chronic glomerulonephritis, but the CRF that the Secondary cases factor causes increases year by year.Multiple nephropathy such as renal insufficiency, renal dysfunction develops into the later stage and all may cause renal failure.
Renal fibrosis (comprising glomerule fibrosis, kidney region fibrosis, kidney vascular fibrosis) is the co-channel that nearly all kidney disease proceeds to renal failure in latter stage at end, being one of main pathology performance of various chronic renal diseases, is the final outcome of the disease of matter between various glomerule, blood vessel and tubule own.No matter there are some researches show the nephropathy of which kind of cause of disease, the development of renal fibrosis all is progressive, and its mesonephric glomerulus fibrosis and kidney region fibrosis play an important role in renal fibrosis.Finally developing into CRF is the final final result of renal fibrosis.Therefore, among the present invention, estimate wogonin to the curative effect of chronic nephropathy with the animal model of renal fibrosis.
Radix Scutellariae is the famous Chinese medicine of China, has heat clearing and damp drying, eliminating fire and detoxication, effects such as arresting bleeding and miscarriage prevention.Comprise in the Radix Scutellariae: glycoside compositions such as baicalin, wogonoside reach aglycon constituents such as baicalin, wogonin, oroxylin-A.Our pre-stage test finds, Radix Scutellariae total glucosides unit extract has certain improvement effect for kidney of rats fibrosis due to one-sided ureter ligation and 5/6 nephrectomy.So further wherein chemical compound has been carried out active tracking, has found that wogonin has its better therapeutical effect to renal fibrosis.
Wogonin (structural formula 1) also is present in other labiate, in plants such as Herba Scutellariae Barbatae and apocynaceae plant Chinese yellow eel rattan, separates a kind of important flavone compound that obtains, and it mainly is present in the root and stem of plant.Wogonin has biological activity widely, as antioxidation, antiinflammatory, neuroprotective, antitumor and antiviral etc.The anti-tumor activity of wogonin is the focus of studying both at home and abroad at present, but does not also have report for the research for the treatment of chronic nephropathy.
Summary of the invention
Technical problem to be solved by this invention is prodrug and wogonin and the medical usage of the physiologically acceptable salt of derivant in the treatment chronic nephropathy thereof that proposes wogonin and derivant thereof, wogonin, particularly treats renal fibrosis and the medical usage of the disease (as renal insufficiency) that caused by renal fibrosis.
The structure of wogonin of the present invention is shown in structural formula 1, and its molecular formula is C
16H
12O
5, chemical name is 5,7-dihydroxy-8-methoxyl group-2-phenyl-4H-1-benzofuran-4-ketone.
The derivant of wogonin of the present invention is in the said structure formula 1:
3,6,3 ' and 4 ' is replaced by hydroxyl respectively, or wherein has both or three to be replaced by hydroxyl simultaneously;
3 replaced by hydroxyl after, the hydrogen in this hydroxyl is replaced by monosaccharide groups or disaccharidase base;
Hydrogen in 5 and 7 hydroxyls is replaced by monosaccharide groups or disaccharidase base respectively or simultaneously;
After 6 hydrogen was replaced by hydroxyl, the hydrogen on the hydroxyl was contained two alkyl or alkenyls to four carbon atom again and is replaced;
Methoxyl group in 8 is substituted by hydrogen.
The derivant of wogonin of the present invention specifically comprises following chemical compound:
(1) wogonin glycosides (comprising wogonin 3-O-β-D-glucuronide (M1), 5-O-β-D-glucuronide, 7-O-β-D-glucuronide);
(2) 3,5,7,3 ', 4 '-penta hydroxy group-8-methoxy flavone (C
16H
12O
8);
(3) 5,6,7-trihydroxy-8-methoxy flavone (C
16H
12O6);
(4) 3,5,7,3 ', 4 '-penta hydroxy group-8-methoxyl group-6-isobutenyl flavone (C
20H
19O
5);
In addition, the prodrug of wogonin of the present invention refers to can discharge in vivo the chemical compound of wogonin and derivant thereof after metabolism.
Also have, the invention still further relates to the medical usage of physiologically acceptable salt in the treatment chronic nephropathy of wogonin and derivant thereof.
The embodiment that rear section of the present invention is introduced is according to the pharmacodynamics test of the salt that can introduce on wogonin and derivant, prodrug and the physiology at the renal fibrosis animal model, the result shows that wogonin can improve the body weight of rat model, significantly suppress the serum creatinine of chronic nephropathy animal and the rising of urea nitrogen content, improve creatinine clearance rate, improve renal function; Significantly reduce the nephridial tissue hydroxyproline content, can improve the kidney inflammatory cell infiltration and between the matter damage, reduce the renal fibrosis degree.Wogonin and derivant thereof, prodrug and physiologically acceptable salt is at the medical usage for the treatment of in the chronic nephropathy, particularly treats renal fibrosis and the medical usage of the disease (as renal insufficiency) that caused by renal fibrosis has broad application prospects.
Wogonin and derivant thereof are used for the treatment of chronic nephropathy, renal fibrosis and can be made into tablet, capsule, soft capsule, spray, gel, gel inhalant, oral agents, suspensoid, electuary, patch, pill, powder, injection, freeze dried injection, lipidosome injection, target administration injection, suppository, slow releasing preparation or controlled release preparation during the disease (as renal insufficiency) that caused by renal fibrosis, by mode administrations such as oral, injections.
Description of drawings
Fig. 1. after wogonin was intervened the UUO rat model, nephridial tissue pathological section HE dyeing (20 * 10) is figure (annotating: A sham operated rats, B model group, C losartan group, F wogonin group) as a result.
Fig. 2. after wogonin was intervened the UUO rat model, the scarlet dyeing of nephridial tissue pathological section sky wolf (20 * 10) is figure (annotating: A sham operated rats, B model group, C losartan group, F wogonin group) as a result.
The specific embodiment
Below in conjunction with the drawings and specific embodiments, further set forth the present invention.These embodiment are interpreted as only being used for explanation the present invention and are not used in restriction protection scope of the present invention.After the content of having read the present invention's record, those skilled in the art can make various changes or modifications the present invention, and these equivalences change and modify and fall into claim of the present invention institute restricted portion equally.
Embodiment 1 (wogonin is to the test of pesticide effectiveness of one-sided ureter ligation (UUO) rat model)
1. whether test objective: investigating wogonin has the improvement effect to one-sided urinary catheter ligation (UUO) rat model renal fibrosis.
2. test method:
2.1. animal grouping
Be divided into 5 groups at random: 10 of sham operated rats, 10 of model group groups, 10 of losartan groups, 10 of wogonin low dose group, 10 of wogonin high dose group.
2.2. modelling
Except sham operated rats; the one-sided ureter ligation of other 4 groups of row; method is as follows: behind chloral hydrate (400mg/kg) intraperitoneal anesthesia experimental rat, get rats with left abdomen kidney district otch, separate the left side ureter with the ophthalmology tweezer; with No. four surgical threads; the ligation ureter respectively at renal calices place and inferior pole of kidney place, but not from disconnected ureter, the kidney peplos and protect surrounding tissue of noting during operation not damaging; the operation back places original position to kidney, layer-by-layer suture peritoneum, muscle, skin.Strictly observe the sterile working in the art.Sham operated rats is not except carrying out the ureter ligation, and all the other steps are identical with model group.
2.3. administration and drawing materials
Operation administration on the same day, it is 20mg/kg/d that the losartan group is irritated stomach dosage, and it is 10mg/kg/d that the wogonin low dose group is irritated stomach dosage, and it is 20mg/kg/d that the wogonin high dose group is irritated stomach dosage, and sham operated rats and model group give the equal volume normal saline.
Rat was put to death in administration on the tenth day, put to death and collected the 24h urine and record the urine amount the previous day.After rat used chloral hydrate with 400mg/kg dosage intraperitoneal injection of anesthesia, dorsal position was fixed, and opens the abdominal cavity, situations such as the color of observation kidney, matter, form, volume, adhesion.Through the ventral aorta blood sampling, win left and right sides kidney, weigh, leave and take part nephridial tissue 10% formalin fixed, be used for making the common pathology specimen and be convenient to om observation, part is deposited in-70 ℃ of refrigerators and is preserved, and is used for hydroxyproline content and measures.After 4 ℃ of institute's blood samplings left standstill 2 hours, 3000rpm * 10min was centrifugal, and separation of serum is used for various serum indexs and detects.
2.4. rat body weight, kidney body ratio, left and right sides kidney anharmonic ratio are observed
Rat body weight respectively organized in record before putting to death, and takes out the left and right sides kidney, and record left and right sides kidney is heavy behind the removal kidney peplos, and left kidney records weight after emitting hydrops, calculates kidney body left and right sides kidney ratio when.
Each group of postoperative does not all have rats death.Sham operated rats postoperative rats eating, defecation are normal substantially, and be flexibly movable, is swift in response, and fur is neat, and is little with difference before the art.Model group rat atrichia gloss, the movable minimizing.Positive drug group and the reaction of wogonin group rat are sensitive, and fur is more neat, but obvious minimizing is compared in activity with sham operated rats.From body weight, each group is compared with sham operated rats all and is descended to some extent, and statistical significance (P＜0.01 or P＜0.05) is all arranged.From the kidney body recently, compare with sham-operation, all the other each groups all increase to some extent, and difference has statistical significance (P＜0.01); Compare with model group, each administration group all decreases, and difference has statistical significance (P＜0.05 or P＜0.01).From left and right sides kidney anharmonic ratio, each group all increases to some extent than sham operated rats, and difference has statistical significance (P＜0.01 or P＜0.05).Compare with model group, each administration group all decreases, and difference has statistical significance (P＜0.05 or P＜0.01).The results are shown in Table 1.
Table 1 is respectively organized the comparison of left and right sides kidney anharmonic ratio when of rat body weight, kidney body
Annotate: compare * P＜0.05, * * P＜0.01 with sham operated rats; Compare with model group,
#P＜0.05,
##P＜0.01.
2.5. biochemical indicator and hydroxyproline content are measured
Automatic clinical chemistry analyzer (Hitachi 7080) mensuration serum creatinine (Scr) and blood urea nitrogen (BUN), urine creatine, and calculate according to formula [Ccr=urine creatine/serum creatinine * urine amount (mL/min)] and calculate endogenous creatinine clearance rate.
Accurate weighing kidney after requiring to have prepared sample according to test kit, utilizes microplate reader to detect each sample OD value, draws the kidney hydroxyproline content as calculated, and computing formula is:
The serum creatinine measurement result, each group compares with sham operated rats, all significantly raises; Compare with model group, each administration group all has to a certain degree decline, and with the model group comparing difference statistical significance is arranged.
The determination of urea nitrogen result, each group compares with sham operated rats, all significantly raises; Compare with model group, each administration group blood urea nitrogen all has to a certain degree decline, and each administration group has statistical significance than model group decline.
Compare with sham operated rats, each hydroxyproline content of organizing the kidney of rats tissue all is significantly increased, and difference has statistical significance; Compare with model group, hydroxyproline content all has decline to a certain degree in each administration group kidney of rats tissue, and each administration group difference has statistical significance.The results are shown in Table 2 and table 3.
Table 2. is respectively organized the comparison of kidney of rats function
Annotate: compare * P＜0.05, * * P＜0.01 with sham operated rats; Compare with model group,
#P＜0.05,
##P＜0.01.
Table 3. pair kidney of rats is organized the influence of hydroxyproline content
Annotate: compare * P＜0.05, * * P＜0.01 with sham operated rats; Compare with model group,
#P＜0.05,
##P＜0.01.
2.6. pathological study
Along middle rip cutting, half places 10% formalin solution fixing with the kidney of removing hydrops, and it is frozen that second half puts into-70 ℃ of refrigerators, is used for hydroxyproline content and measures.Gradient alcohol dehydration, paraffin embedding, the routine paraffin wax section, the dimethylbenzene dewaxing after the dehydration of ethanol gradient, is carried out conventional H E dyeing and Sirius red colouring, its pathological change of om observation.The results are shown in Figure 1 and Fig. 2.
2.7. statistical procedures
The result of the test quantitative data with
Expression is used the spss17.0 statistical package and is carried out statistical analysis, and group difference relatively adopts one factor analysis of variance, if heterogeneity of variance, to row one factor analysis of variance after the number conversion.Be that difference has statistical significance with P＜0.05.
3. result of the test: see Table 1,2,3.
4. conclusion (of pressure testing): wogonin improves significantly to one-sided ureter ligation (UUO) rat model renal fibrosis.
In addition, use wogonin 3-O-β-D-glucuronide (M1), 5-O-β-D-glucuronide, 7-O-β-D-glucuronide, 3,5,7 respectively, 3 ', 4 '-penta hydroxy group-8-methoxy flavone (C
16H
12O
8), 5,6,7-trihydroxy-8-methoxy flavone (C
16H
12O
6) and 3,5,7,3 ', 4 '-penta hydroxy group-8-methoxyl group-6-isobutenyl flavone (C
20H
19O
5) replace wogonin and investigate it whether one-sided urinary catheter ligation (UUO) rat model renal fibrosis is had the improvement effect, result of the test is identical with the result of the test of embodiment 1, that is wogonin 3-O-β-D-glucuronide (M1), 5-O-β-D-glucuronide, 7-O-β-D-glucuronide, 3,5,7,3 ', 4 '-penta hydroxy group-8-methoxy flavone (C
16H
12O
8), 5,6,7-trihydroxy-8-methoxy flavone (C
16H
12O
6) and 3,5,7,3 ', 4 '-penta hydroxy group-8-methoxyl group-6-isobutenyl flavone (C
20H
19O
5) all one-sided ureter ligation (UUO) rat model renal fibrosis is improved significantly.
Embodiment 2 (wogonin is to the test of pesticide effectiveness of 5/6 nephrectomy rat model)
1. whether test objective: investigating wogonin has the improvement effect to 5/6 nephrectomy rat model renal fibrosis.
2. test method:
2.1. animal grouping, modelling, administration and draw materials
Rats eating standard food, freely drink water, after adaptability raised for 1 week, be divided into 5 groups at random: 10 of sham-operation (Sham) groups, 10 of model group (5/6 nephrectomy), 10 of losartan groups (20mg/kg), 10 of wogonin low dosage (10mg/kg) groups, 10 of wogonin high dose group (20mg/kg) groups.
Except sham operated rats, all the other are all as the modeling group.With the anesthesia of modeling group rats by intraperitoneal injection, the left kidney of the prostrate exposure of rat district.Behind the preserved skin, from making oblique foreign side otch apart from left ridge rib bone 1.5cm, get kidney through posterior peritoneum, the exposure kidney, peel off perirenal fat and peplos after, camber excises 2/3 nephridial tissue (mainly excising the cortex part).Gelfoam hemostasis by compression, tangent plane do not have the left kidney of residue and sewing up of resetting after the active hemorrhage.Same procedure anesthetized rat behind the 7d, ligation fully behind the kidney base of a fruit of free fully right side.To each group rat administration, model group and sham operated rats give the normal saline of equal volume after the two operations.More than each treated animal sub-cage rearing.
8 week of administration, rat was put to death in the back, and execution is collected the 24h urine and recorded the urine amount the previous day.After rat used chloral hydrate with 400mg/kg dosage intraperitoneal injection of anesthesia, dorsal position was fixed, and opens the abdominal cavity, situations such as the color of observation kidney, matter, form, volume, adhesion.Through the ventral aorta blood sampling, win residual kidney, weigh, leave and take part nephridial tissue 10% formalin fixed, be used for making the common pathology specimen and be convenient to om observation, part is deposited in-80 ℃ of refrigerators and is preserved, and is used for hydroxyproline content and measures.After 4 ℃ of institute's blood samplings left standstill 2 hours, 3000rpm * 10min was centrifugal, and separation of serum is used for various serum indexs and detects.
2.2. rat body weight, residual kidney weight ratio, observation
Rat body weight respectively organized in record before putting to death, and record left side kidney is heavy behind the removal kidney peplos, calculates residual kidney weight ratio.
Body weight is observed, and each group is compared with sham operated rats all and descended to some extent, and only model group difference has statistical significance (P＜0.01).From residual kidney body weight recently, compare with sham-operation, all the other each groups all increase to some extent, and difference has statistical significance (P＜0.01); Compare with model group, each administration group all decreases, and positive drug group and wogonin group difference all have statistical significance (P＜0.05 or P＜0.01).The results are shown in Table 4.
Table 4 is respectively organized the comparison of rat body weight, residual kidney weight ratio
Annotate: compare * P＜0.05, * * P＜0.01 with sham operated rats; Compare with model group,
#P＜0.05,
##P＜0.01.
2.3. biochemical indicator
Automatic clinical chemistry analyzer (Hitachi 7080) is measured urine protein, serum creatinine (SCr), blood urea nitrogen (BUN), urine creatine, and calculates endogenous creatinine clearance rate.
From serum creatinine, each group compares with sham operated rats, all significantly raises; With model group relatively, each administration group all significantly descends, and with the model group comparing difference statistical significance is arranged.The results are shown in Table 5.
The determination of urea nitrogen result, each group compares with sham operated rats, all significantly raises; Compare with model group, each administration group blood urea nitrogen all descends, and each administration group has statistical significance than model group decline.The results are shown in Table 5.
Table 5 is respectively organized the comparison of kidney of rats function
Annotate: compare * P＜0.05, * * P＜0.01 with sham operated rats; Compare with model group,
#P＜0.05,
##P＜0.01.
2.4. statistical procedures
The result of the test quantitative data with
Expression is used the spss17.0 statistical package and is carried out statistical analysis, and group difference relatively adopts one factor analysis of variance, if heterogeneity of variance, to row one factor analysis of variance after the number conversion.Be that difference has statistical significance with P＜0.05.
3. result of the test: see Table 4,5.
4. conclusion (of pressure testing): wogonin improves significantly to 5/6 nephrectomy rat model renal fibrosis.
In addition, use wogonin 3-O-β-D-glucuronide (M1), 5-O-β-D-glucuronide, 7-O-β-D-glucuronide, 3,5,7 respectively, 3 ', 4 '-penta hydroxy group-8-methoxy flavone (C
16H
12O
8), 5,6,7-trihydroxy-8-methoxy flavone (C
16H
12O
6) and 3,5,7,3 ', 4 '-penta hydroxy group-8-methoxyl group-6-isobutenyl flavone (C
20H
19O
5) replace wogonin and investigate it whether 5/6 nephrectomy rat model renal fibrosis is had the improvement effect.Result of the test is identical with the result of the test of embodiment 2, that is wogonin 3-O-β-D-glucuronide (M1), 5-O-β-D-glucuronide, 7-O-β-D-glucuronide, 3,5,7,3 ', 4 '-penta hydroxy group-8-methoxy flavone (C
16H
12O
8), 5,6,7-trihydroxy-8-methoxy flavone (C
16H
12O
6) and 3,5,7,3 ', 4 '-penta hydroxy group-8-methoxyl group-6-isobutenyl flavone (C
20H
19O
5) all 5/6 nephrectomy rat model renal fibrosis is improved significantly.
Embodiment 3 (the wogonin prodrug is to the test of pesticide effectiveness of one-sided ureter ligation (UUO) rat model)
1. whether test objective: investigating the wogonin prodrug has the improvement effect to 5/6 nephrectomy rat model renal fibrosis.
2. test method: be example with wogonin ethyl ester (hydrogen on 7 hydroxyls of wogonin is esterified), method is with embodiment 1.
3. result of the test: the wogonin prodrug can improve the body weight of rat model, significantly suppresses the rising of serum creatinine and the urea nitrogen content of chronic nephropathy animal, improves creatinine clearance rate, improves renal function; Significantly reduce the nephridial tissue hydroxyproline content.
4. conclusion (of pressure testing): the wogonin prodrug has the improvement effect to one-sided ureter ligation (UUO) rat model renal fibrosis.
Embodiment 4 (the wogonin prodrug is to the test of pesticide effectiveness of 5/6 nephrectomy rat model)
1. whether test objective: investigating the wogonin prodrug has the improvement effect to 5/6 nephrectomy rat model renal fibrosis.
2. test method: be example with wogonin ethyl ester (hydrogen on 7 hydroxyls of wogonin is esterified), method is with embodiment 2.
3. result of the test: the wogonin prodrug can improve the body weight of rat model, significantly suppresses the rising of serum creatinine and the urea nitrogen content of chronic nephropathy animal, improves creatinine clearance rate, improves renal function; Significantly reduce the nephridial tissue hydroxyproline content.
4. conclusion (of pressure testing): the wogonin prodrug has the improvement effect to 5/6 nephrectomy rat model renal fibrosis.
Embodiment 5 (test of pesticide effectiveness of the one-sided ureter ligation of the physiologically acceptable salt pair of wogonin (UUO) rat model)
1. whether test objective: investigating the wogonin one-sided ureter ligation of physiologically acceptable salt pair (UUO) rat model renal fibrosis has the improvement effect.
2. test method: be representative with the wogonin sodium salt, method is with embodiment 1.
3. result of the test: the wogonin sodium salt can improve the body weight of rat model, significantly suppresses the rising of serum creatinine and the urea nitrogen content of chronic nephropathy animal, improves creatinine clearance rate, improves renal function; Significantly reduce the nephridial tissue hydroxyproline content.
4. experiment conclusion: the one-sided ureter ligation of the physiologically acceptable salt pair of wogonin (UUO) rat model renal fibrosis has the improvement effect.
Embodiment 6 (test of pesticide effectiveness of physiologically acceptable salt pair 5/6 nephrectomy rat model of wogonin)
1. whether test objective: investigating physiologically acceptable salt pair 5/6 nephrectomy rat model renal fibrosis of wogonin has the improvement effect.
2. test method:: be representative with the wogonin sodium salt, method is with embodiment 2.
3. result of the test: the wogonin sodium salt can improve the body weight of rat model, significantly suppresses the rising of serum creatinine and the urea nitrogen content of chronic nephropathy animal, improves creatinine clearance rate, improves renal function; Significantly reduce the nephridial tissue hydroxyproline content.
4. experiment conclusion: physiologically acceptable salt pair 5/6 nephrectomy rat model renal fibrosis of wogonin has the improvement effect.
Claims (8)
1. wogonin and derivant thereof the purposes in the medicine of preparation treatment chronic nephropathy.
2. wogonin and derivant thereof the purposes in the medicine of preparation treatment renal fibrosis.
3. wogonin and derivant thereof the purposes in the medicine of the disease that preparation treatment is caused by renal fibrosis.
4. purposes according to claim 3 is characterized in that, the disease that is caused by renal fibrosis is renal insufficiency.
5. according to any one described purposes among the claim 1-4, it is characterized in that the derivant of wogonin is wogonin glycosides, 3,5,7,3 ', 4 '-penta hydroxy group-8-methoxy flavone, 5,6,7-trihydroxy-8-methoxy flavone or 3,5,7,3 ', 4 '-penta hydroxy group-8-methoxyl group-6-isobutenyl flavone.
6. purposes according to claim 5 is characterized in that, the wogonin glycosides is wogonin 3-O-β-D-glucuronide, 5-O-β-D-glucuronide or 7-O-β-D-glucuronide.
7. after metabolism, can discharge the chemical compound of wogonin and derivant thereof in vivo, i.e. the purposes of the prodrug of wogonin in the medicine of preparation treatment chronic nephropathy.
8. the purposes of the physiologically acceptable salt of wogonin and derivant thereof in the medicine of preparation treatment chronic nephropathy.
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| CN201210046196.9A CN103284993B (en) | 2012-02-27 | 2012-02-27 | The purposes of wogonin in the medicine of preparation treatment chronic nephropathy |
| PCT/CN2012/073007 WO2013127110A1 (en) | 2012-02-27 | 2012-03-26 | Use of wogonin in preparation of medicine for treating chronic kidney disease |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103877074A (en) * | 2014-03-21 | 2014-06-25 | 贾正平 | Application of 5,6,7,8- trihydroxy-8-methoxyflavone in preparing anti-hypoxic drug |
| CN105287488A (en) * | 2015-10-12 | 2016-02-03 | 安徽医科大学 | Application of wogonin in treating acute kidney injury and medicine prepared by wogonin for treating acute kidney injury |
| CN110237066A (en) * | 2018-03-07 | 2019-09-17 | 上海市计划生育科学研究所 | The application of 3- methoxy flavone and its derivative in the drug that preparation treats or prevents nephrosis |
| CN111920836A (en) * | 2019-06-13 | 2020-11-13 | 江苏苏中药业集团股份有限公司 | Application of abelmoschus manihot extract in preparation of medicine for treating fibrosis |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101455718A (en) * | 2008-12-30 | 2009-06-17 | 上海中医药大学 | Scullcap total-flavonoid aglycone extract, preparation method and use thereof |
-
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- 2012-02-27 CN CN201210046196.9A patent/CN103284993B/en active Active
- 2012-03-26 WO PCT/CN2012/073007 patent/WO2013127110A1/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101455718A (en) * | 2008-12-30 | 2009-06-17 | 上海中医药大学 | Scullcap total-flavonoid aglycone extract, preparation method and use thereof |
Non-Patent Citations (3)
| Title |
|---|
| 肖光艳 等: "中药在肾脏疾病中对核因子-κB的影响", 《牡丹江医学院学报》 * |
| 谢红东 等: "黄芩提取物对大鼠肾间质纤维化的作用及其抗氧化机制", 《中国中西医结合肾病杂志》 * |
| 高燕 等: "黄芩素药理学研究新进展", 《时珍国医国药》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103877074A (en) * | 2014-03-21 | 2014-06-25 | 贾正平 | Application of 5,6,7,8- trihydroxy-8-methoxyflavone in preparing anti-hypoxic drug |
| CN103877074B (en) * | 2014-03-21 | 2017-04-19 | 贾正平 | Application of 5,6,7,8- trihydroxy-8-methoxyflavone in preparing anti-hypoxic drug |
| CN105287488A (en) * | 2015-10-12 | 2016-02-03 | 安徽医科大学 | Application of wogonin in treating acute kidney injury and medicine prepared by wogonin for treating acute kidney injury |
| CN110237066A (en) * | 2018-03-07 | 2019-09-17 | 上海市计划生育科学研究所 | The application of 3- methoxy flavone and its derivative in the drug that preparation treats or prevents nephrosis |
| CN110237066B (en) * | 2018-03-07 | 2022-03-29 | 上海市生物医药技术研究院 | Application of 3-methoxyflavone and derivatives thereof in preparation of medicines for treating or preventing nephropathy |
| CN111920836A (en) * | 2019-06-13 | 2020-11-13 | 江苏苏中药业集团股份有限公司 | Application of abelmoschus manihot extract in preparation of medicine for treating fibrosis |
| CN111920836B (en) * | 2019-06-13 | 2023-04-18 | 苏中药业集团股份有限公司 | Application of abelmoschus manihot extract in preparation of medicine for treating fibrosis |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2013127110A1 (en) | 2013-09-06 |
| CN103284993B (en) | 2015-08-19 |
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