CN107837271A - Epalrestat is preparing the application in treating medicine for treating diabetic nephropathy - Google Patents
Epalrestat is preparing the application in treating medicine for treating diabetic nephropathy Download PDFInfo
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- CN107837271A CN107837271A CN201711102437.6A CN201711102437A CN107837271A CN 107837271 A CN107837271 A CN 107837271A CN 201711102437 A CN201711102437 A CN 201711102437A CN 107837271 A CN107837271 A CN 107837271A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
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Abstract
The invention discloses aldose reductase inhibitor Epalrestat to prepare the application in treating medicine for treating diabetic nephropathy, is related to biomedicine technical field.Epalrestat is the domestic aldose reductase inhibitor uniquely listed, by giving Epalrestat to db/db mouse stomaches, it is found that Epalrestat has the urinary albumin excretion for significantly reducing db/db mouse, improves Pathological equivalent damage fruit.Oral administration Epalrestat disclosed by the invention has good Renoprotective Effect, and a drug candidate is provided for the protection renal of clinical diabetes nephrosis crowd.
Description
Technical field
The present invention relates to the application of Epalrestat, and more particularly to Epalrestat is in treatment medicine for treating diabetic nephropathy is prepared
Using belonging to biomedicine technical field.
Background technology
Diabetes are a kind of a kind of metabolic diseases characterized by patient blood glucose is higher than normal value for a long time.Diabetes are alive
The incidence of disease in the range of boundary increasingly raises, it has also become a public health problem.Diabetes have and its serious complication, wherein
Long-term complications include angiocardiopathy, apoplexy, chronic kidney disease, nerve ending and PVR etc..Diabetic nephropathy be by
The kidney damage gradually developed, clinical pathology check visible diffusivity and nodular glomerulosclerosis, and these pathological changes are with kidney
The clinical manifestations such as oedema, albuminuria, finally directly result in renal failure.At present, diabetic nephropathy turns into ESRD
(ESRD) first reason, after diabetic duration 10-20, renal failure can occur for plurality.Therefore, glycosuria
The prevention and treatment of sick nephrosis all should obtain enough attention.So far, it can prevent, terminate or reverting diabetes renal function
The medicine of obstacle there is no the report into clinical practice.It is clinically used for treating the medicine main function of diabetes to reduce blood glucose,
The improvement or protective effect of renal function are not had, some hypoglycemic medicines even have the side effect for causing injury of kidney.
Epalrestat is the aldose reductase inhibitor of the currently the only approval listing in China, available for preventing, improve and control
Treat diabetes complicated nerve ending.It is by reversibly suppressing related to the pathogenesis of diabetic complication more
Glucose is converted into the aldose reductase of sorbierite and improves nerve cell function in first alcohol metabolism.Study and send out through the present inventor
Existing, Epalrestat also has very obvious action to reducing serum uric acid level.Therefore, the present inventor proposes that Epalrestat is used to make
Application in standby treatment hyperuricemia and gout medicine.
The content of the invention
The present invention is proposed Epalrestat applied to the medicine for preparing new diabetic nephropathy.
The present invention is applied to the technological means of clinical peroral dosage form using Epalrestat is made as active component, if
The medicine of new treatment diabetic nephropathy is counted.
The present invention gives Epalrestat using db/db mouse as animal pattern, by gavage and treated, measure urinary albumin row
Flat and lipid peroxicition the pathological study that sluices carries out the evaluation of Epalrestat treatment diabetic nephropathy.Research finds Yi Pasi
He can make the twenty-four-hour urine albumin level of db/db mouse be remarkably decreased, and renal pathology lesion significantly improves.As
Basis, the present invention propose that Epalrestat is preparing the application in treating medicine for treating diabetic nephropathy.
Brief description of the drawings
The Epalrestat structural formula of accompanying drawing 1
Accompanying drawing 2db/db mouse twenty-four-hour urine albumin levels
Wherein, WT is normal wild-type mice, and as a control group, db/db is animal pattern group, WT+Epalrestat
It is respectively that wild type and animal pattern give Epalrestat therapeutic intervention group with db/db+Epalrestat.* * p ＜ 0.001
vs WT；The vs db/db+Epalrestat. of # p ＜ 0.05
The cortex renis PAS of accompanying drawing 3 dyes pathology
Wherein, WT is normal wild-type mice, and as a control group, db/db is animal pattern group, WT+Epalrestat
It is respectively that wild type and animal pattern give Epalrestat therapeutic intervention group with db/db+Epalrestat.
The cortex renis MASSON of accompanying drawing 4 dyes pathology
Wherein, WT is normal wild-type mice, and as a control group, db/db is animal pattern group, WT+Epalrestat
It is respectively that wild type and animal pattern give Epalrestat therapeutic intervention group with db/db+Epalrestat.
The glomerulus electron microscope pathologic structure of accompanying drawing 5
Wherein, WT is normal wild-type mice, and as a control group, db/db is animal pattern group, WT+Epalrestat
It is respectively that wild type and animal pattern give Epalrestat therapeutic intervention group with db/db+Epalrestat.
Embodiment
The present invention carries out detailed explanation by the following examples, but is not meant to that present invention is limited only to this.
Using db/db mouse 24 the, (male, purchased from model animal research institute of Nanjing University, week old of wild-type mice 24
7) tested.Under feeding standard environment (free diet and drinking-water, day alternates with night, each 12 hours), adaptability is raised one week.
Then, db/db mouse stochastic averaginas are divided into 2 groups, i.e., db/db groups and give the db/db+Epalrestat of Epalrestat treatment
Group；C57BKLS mouse stochastic averaginas are divided into 2 groups, i.e., WT groups and give the WT+Epalrestat groups of Epalrestat treatment.
Experimental design and it is grouped as follows：WT groups (12 C57BKLS mouse), WT+Epalrestat groups (12 C57BKLS
Mouse, daily gavage give the Epalrestat that dosage is 20mg/kg body weight), db/db groups (12 db/db mouse) and db/db+
Epalrestat groups (12 db/db mouse, daily gavage give the Epalrestat that dosage is 20mg/kg body weight).After 8 weeks,
Twenty-four-hour urine liquid is collected, 800g/min centrifugations 10min removes arena, and takes kidney in fasting afterwards 12 hours, execution.
It is horizontal using abcam companies mouse Albumin ELISA kits (ab108792) measure urinary albumin；
Nephridial tissue is taken to carry out PAS, MASSON dyeing pathologic finding and electron microscope pathologic finding respectively.
Influence (accompanying drawing 2) of the Epalrestat to db/db mice serum uric acid levels：As a result show, during 15 week old, db/db
Mouse retention albumin level is significantly higher than normal wild type WT groups mouse (p ＜ 0.001), and after 8 weeks Epalrestats are treated,
The urinary albumin level of db/db mouse can be remarkably decreased (p=0.048).
Pathological study is carried out to nephridial tissue, PAS dyes visible db/db groups glomerular volume increase, mesangial cell
Hyperplasia, mesangial region are broadening；, partly there is tubercle in the visible apposition of mesangial region；MASSON dyes visible renal tubule and interstitial goes out
Existing fibrosis lesion.Giving Epalrestat intervention group symptom has obvious mitigation (accompanying drawing 3,4)
Dia-betic rats are observed under electron microscopic examination, it is seen that db/db groups Glomerular mesangium component * deposition is serious, and sertoli cell occurs
Extensive podocytic process fusion and residual adhesion, and symptom significantly mitigates (accompanying drawing 5) after giving Epalrestat.
Claims (7)
1. Epalrestat shown in formula I is preparing the application in treating medicine for treating diabetic nephropathy as active component；
Molecular formula：C15H13NO3S2；Molecular weight：319.399.
2. Epalrestat shown in Formulas I is preparing treatment diabetic nephropathy medicine with pharmaceutically acceptable with the salt that sour combination is formed
Application in thing, the pharmaceutically acceptable acid is citric acid, maleic acid, butanedioic acid, fumaric acid, malic acid, hydrobromic acid, first
Sulfonic acid, pyruvic acid, niacin, lactic acid, orotic acid, ascorbic acid, folic acid, glyceric acid, glycolic, taurine, glycine, smart ammonia
Acid, glutamic acid, lysine, proline, valine.
3. Epalrestat shown in Formulas I is combined formed salt in preparation treatment glycosuria with pharmaceutically acceptable with alkali metal ion
Application in sick nephrosis medicine, the pharmaceutically acceptable alkali metal ion be sodium ion, potassium ion, calcium ion, magnesium ion,
Ammonium ion, lithium ion, iron ion, copper ion, zinc ion, silver ion, barium ions, gold ion.
4. the Epalrestat or its salt according to claim 2-3 are preparing the application in treating medicine for treating diabetic nephropathy, its
It is characterised by：Epalrestat or its salt cross 60 mesh, 80 mesh, 100 mesh, 120 mesh, 150 mesh, 200 mesh, 300 mesh sieves after crushing,
Or by being micronized, being made the techniques such as solid solution, coating, clinically acceptable formulation is made in reprocessing.
5. the Epalrestat or its salt according to claim 2-4 are preparing the application in treating medicine for treating diabetic nephropathy, its
It is characterised by：Epalrestat combines to form compound medicine with other medicines, and clinically acceptable formulation is made in reprocessing.
6. the Epalrestat or its salt according to claim 2-5 are preparing the application in treating medicine for treating diabetic nephropathy, its
It is characterised by：Epalrestat or its salt are made into clinically acceptable formulation, the main formulation for including oral delivery form.
7. application of the Epalrestat in medicine for treating diabetic nephropathy is treated according to claim 2-6, it is characterised in that institute
State formulation for tablet, capsule, oral liquid, supensoid agent, syrup, particle, dripping pill, oral disintegrating tablet, sustained release tablets, patch, micropill, micro-capsule,
Liposome, microballoon, sustained release preparation, controlled release preparation, liquid drugs injection, freeze-dried powder, aseptic powder injection or transfusion.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711102437.6A CN107837271A (en) | 2017-11-07 | 2017-11-07 | Epalrestat is preparing the application in treating medicine for treating diabetic nephropathy |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201711102437.6A CN107837271A (en) | 2017-11-07 | 2017-11-07 | Epalrestat is preparing the application in treating medicine for treating diabetic nephropathy |
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| CN107837271A true CN107837271A (en) | 2018-03-27 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110051668A (en) * | 2019-04-17 | 2019-07-26 | 南通大学附属医院 | A kind of verification method of application of the Epalrestat in preparation pancreatic cancer drug and the inhibiting effect to pancreatic cancer cell secretion excretion body |
| CN112137990A (en) * | 2020-11-04 | 2020-12-29 | 南京康川济医药科技有限公司 | Epalrestat sustained-release preparation and preparation method thereof |
| CN113995751A (en) * | 2021-11-15 | 2022-02-01 | 哈尔滨医科大学 | Application of epalrestat in preparing medicine for preventing and treating cerebral arterial thrombosis |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106619624A (en) * | 2017-03-13 | 2017-05-10 | 中国药科大学 | Application of epalrestat in preparation of drugs for treating hyperuricemia and gout |
-
2017
- 2017-11-07 CN CN201711102437.6A patent/CN107837271A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106619624A (en) * | 2017-03-13 | 2017-05-10 | 中国药科大学 | Application of epalrestat in preparation of drugs for treating hyperuricemia and gout |
Non-Patent Citations (1)
| Title |
|---|
| 马开颜等: "依帕司他片治疗糖尿病肾病43例疗效观察", 《陕西医学杂志》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110051668A (en) * | 2019-04-17 | 2019-07-26 | 南通大学附属医院 | A kind of verification method of application of the Epalrestat in preparation pancreatic cancer drug and the inhibiting effect to pancreatic cancer cell secretion excretion body |
| CN112137990A (en) * | 2020-11-04 | 2020-12-29 | 南京康川济医药科技有限公司 | Epalrestat sustained-release preparation and preparation method thereof |
| CN113995751A (en) * | 2021-11-15 | 2022-02-01 | 哈尔滨医科大学 | Application of epalrestat in preparing medicine for preventing and treating cerebral arterial thrombosis |
| CN113995751B (en) * | 2021-11-15 | 2022-11-01 | 哈尔滨医科大学 | Application of epalrestat in preparing medicine for preventing and treating cerebral arterial thrombosis |
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Application publication date: 20180327 |