CN103356646A - Application of Chukrasone A in preparation of medicines for treating acute renal failure - Google Patents
Application of Chukrasone A in preparation of medicines for treating acute renal failure Download PDFInfo
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- CN103356646A CN103356646A CN2013102781754A CN201310278175A CN103356646A CN 103356646 A CN103356646 A CN 103356646A CN 2013102781754 A CN2013102781754 A CN 2013102781754A CN 201310278175 A CN201310278175 A CN 201310278175A CN 103356646 A CN103356646 A CN 103356646A
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- chukrasone
- renal failure
- acute renal
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- application
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- 208000033626 Renal failure acute Diseases 0.000 title claims abstract description 35
- 201000011040 acute kidney failure Diseases 0.000 title claims abstract description 35
- 208000009304 Acute Kidney Injury Diseases 0.000 title claims abstract description 34
- 208000012998 acute renal failure Diseases 0.000 title claims abstract description 34
- 239000003814 drug Substances 0.000 title claims abstract description 13
- HZUBWSRMDOJYPS-WPCVKUBSSA-N chukrasone A Natural products C=1([C@@H]2OC(=O)C[C@H]3[C@@]4(O)[C@H](O)C(=O)[C@@]5(O)[C@@H](OC(=O)C(C)C)C(C)(C)[C@@H]([C@]5([C@H]4[C@H](OC(C)=O)C[C@]32C)C)CC(=O)OC)C=COC=1 HZUBWSRMDOJYPS-WPCVKUBSSA-N 0.000 title abstract description 29
- 238000002360 preparation method Methods 0.000 title abstract description 12
- 229940079593 drug Drugs 0.000 title abstract description 4
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims description 6
- 229930187319 chukrasone Natural products 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 241000700159 Rattus Species 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 210000002700 urine Anatomy 0.000 description 7
- 210000003734 kidney Anatomy 0.000 description 6
- 230000006870 function Effects 0.000 description 5
- 206010030302 Oliguria Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000003907 kidney function Effects 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 201000003126 Anuria Diseases 0.000 description 3
- 241001156380 Chukrasia tabularis Species 0.000 description 3
- 108010087141 Kv1.2 Potassium Channel Proteins 0.000 description 3
- 102000006628 Kv1.2 Potassium Channel Human genes 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000010255 intramuscular injection Methods 0.000 description 3
- 239000007927 intramuscular injection Substances 0.000 description 3
- 239000003450 potassium channel blocker Substances 0.000 description 3
- 230000008327 renal blood flow Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 210000005084 renal tissue Anatomy 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 208000001889 Acid-Base Imbalance Diseases 0.000 description 1
- 208000010444 Acidosis Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- 102000004257 Potassium Channel Human genes 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000007950 acidosis Effects 0.000 description 1
- 208000026545 acidosis disease Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a new medical application of Chukrasone A, in particular to an application of Chukrasone A in preparation of medicines for treating acute renal failure. The application of the Chukrasone A in preparation of medicines for treating acute renal failure provided by the invention is disclosed for the first time. As the framework type is a brand new framework type and the inhibitory activity of the Chukrasone A to acute renal failure is unimaginably strong, the probability of giving any enlightenment by other compounds does not exist. The Chukrasone A has remarkable substantial characteristics and meanwhile has remarkable progress in treatment of acute renal failure.
Description
Technical field
The present invention relates to the pharmaceutical chemistry field.Particularly, the present invention relates to the novel medical use of Chukrasone A, i.e. the application of Chukrasone A in preparation treatment acute renal failure medicine.
Background technology
Acute renal failure (Acute Renal Failure, ARF) be the clinical syndrome that is caused by many reasons, be found in the clinical departments patient, sickness rate is high and often have serious consequences, (a few hours are to a couple of days) siddhi can sharply descend its characteristics in a short time, clinical manifestation is acute oliguria (urine amount＜400mLPd) or anuria (urine amount＜100mLPd), nitrogen matter metabolite is discharged and is produced obstacle in the body, azotemia appears rapidly, water and electrolyte, acid base imbalance, and cause each system's corresponding function imbalance of whole body.The principal element that causes acute renal failure is the rapid minimizing of renal blood flow, and because oxidative stress and the cell injury that the nephridial tissue ischemia causes finally causes the deterioration of renal tissue structural damage and function.There is no clinically at present the generally acknowledged effective medicine for the treatment of acute renal failure, only can be by correcting water-electrolyte balance, the symptomatic treatment measures such as correction acidosis improve symptom, and the later stage also needs to keep the body function by hemodialysis.There is the clinical medicine of obvious curative effects rare aspect the Renal tissues damage improving the kidney perfusion obstacle and alleviate.
The Compound C hukrasone A that the present invention relates to is one and delivered (Liu in 2012, H. B. et al., 2012. Chukrasones A and B:Potential Kv1.2 Potassium Channel Blockers with New Skeletons from Chukrasia tabularis. Organic Letters 14 (17), 4438 – 4441.) New skeleton compound, this chemical compound has brand-new framework types, present purposes only relates to potassium-channel and suppresses active (Liu, H. B. et al., 2012. Chukrasones A and B:Potential Kv1.2 Potassium Channel Blockers with New Skeletons from Chukrasia tabularis. Organic Letters 14 (17), 4438 – 4441.), belong to open first for the purposes of the Chukrasone A that the present invention relates in the anti-acute renal failure medicine of preparation, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for acute renal failure, there is not the possibility that is provided any enlightenment by other chemical compounds, possess outstanding substantive distinguishing features, be used for simultaneously anti-acute renal failure and obviously have significant progress.
Summary of the invention
The purpose of this invention is to provide the purposes that Chukrasone A is used for the treatment of acute renal failure, namely for the preparation of the purposes for the treatment of the acute renal failure medicine.
Chukrasone A of the present invention has obvious therapeutical effect to the acute renal failure disease.
Research by us is found, the anuria when Chukrasone A can improve acute renal failure or oliguria symptom, the function of protection kidney.
Described Compound C hukrasone A structure is shown in formula I:
Formula I
The purposes of the Chukrasone A that the present invention relates in the anti-acute renal failure medicine of preparation belongs to open first, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for acute renal failure, there is not the possibility that is provided any enlightenment by other chemical compounds, possess outstanding substantive distinguishing features, be used for simultaneously anti-acute renal failure and obviously have significant progress.
The specific embodiment
The preparation method of Compound C hukrasone A involved in the present invention is referring to document (Liu, H. B. et al., 2012. Chukrasones A and B:Potential Kv1.2 Potassium Channel Blockers with New Skeletons from Chukrasia tabularis. Organic Letters 14 (17), 4438 – 4441.).
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not subjected to any restriction of specific embodiment, but limited by claim.
Embodiment 1: the preparation of Compound C hukrasone A tablet involved in the present invention:
Get 20 and digest compound Chukrasone A, add conventional adjuvant 180 grams of preparation tablet, mixing, conventional tablet machine are made 1000.
Embodiment 2: the preparation of Compound C hukrasone A capsule involved in the present invention:
Get 20 and digest compound Chukrasone A, add conventional adjuvant such as starch 180 grams of preparation capsule, mixing is encapsulatedly made 1000.
Further specify its pharmaceutically active below by pharmacodynamic experiment.
Further specify its pharmaceutically active below by pharmacodynamic experiment.
Experimental example 1 Chukrasone A is to the therapeutical effect of acute renal failure rat
(1) experimental technique
Adopt intramuscular injection glycerol to cause the Acute Renal Failure Rats animal model.Select 60 of the healthy male SD rats of 180 ~ 220g, be divided at random 5 groups: sham operated rats (intramuscular injection normal saline); Model group (intramuscular injection glycerol); Chukrasone A I group (0.3 mg/Kg)); Chukrasone A II group (0.6 mg/Kg)); Chukrasone A III group (1.2 mg/Kg)), each organizes rat immediately tail vein injection saline or Chukrasone A after the glycerol modeling, is administered once after 12 and 24 hours again.
(2) observation index
60 rat lasts give to put into metabolic cage collection twenty-four-hour urine behind Chukrasone A or the normal saline, stay rear 6 hours of urine with 4% chloral hydrate intraperitoneal injection of anesthesia, adopt laser Doppler flowmetry to measure after the modeling and the rear bilateral renal blood flow for the treatment of, average as single animal renal blood flow; Get blood and prepare serum, measure blood BUN and Cre; Get kidney, prepare 10% renal cortex homogenate, measure renal cortex homogenate MDA, GSH, NO(all by the operation of test kit description).
(3) experimental result
1. Chukrasone A can increase acute renal failure Mouse Kidney blood flow
Table 1 Chukrasone A is on the impact of acute renal failure Mouse Kidney blood flow
* P＜0.05vs acute renal failure model group
2. Chukrasone A is to the protective effect of acute renal failure Mouse Kidney function tool
The model group rat significantly reduces than rats in sham-operated group twenty-four-hour urine amount, is respectively 4.57 ± 0.74ml and 11.82 ± 2.36ml; Middle and high dosage Chukrasone A group twenty-four-hour urine amount is significantly higher than model group (P＜0.05), and the urine measurer of three medication therapy groups has dose dependent, is respectively I group 5.43 ± 0.84ml, II group 7.85 ± 1.36ml, III group 9.63 ± 1.54ml.Illustrate that Chukrasone A can improve the oliguria symptom of acute renal failure rat.
Acute renal failure rat intravenous injection normal saline is after 24 hours, and serum BUN is 25.53 ± 1.62mmol/L, and Cre is 168.56 ± 13.01umol/L, apparently higher than sham operated rats, illustrates that model group animal renal function injury is serious.Middle and high dosage Chukrasone A can improve the renal function (P＜0.05) of acute renal failure rat in dose dependent ground.See Table 2.
Each rats in test groups renal function index of table 2 relatively
* P＜0.05vs acute renal failure model group
Conclusion: the anuria when Chukrasone A can improve acute renal failure or oliguria symptom, the function of protection kidney can be used for preparing anti-acute renal failure medicine.
Claims (1)
1.Chukrasone the application of A in treatment acute renal failure medicine, described Compound C hukrasone A structure as
Formula IShown in:
Formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310278175.4A CN103356646B (en) | 2013-07-04 | 2013-07-04 | The application of Chukrasone A in preparation treatment acute renal failure medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310278175.4A CN103356646B (en) | 2013-07-04 | 2013-07-04 | The application of Chukrasone A in preparation treatment acute renal failure medicine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103356646A true CN103356646A (en) | 2013-10-23 |
| CN103356646B CN103356646B (en) | 2015-11-25 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310278175.4A Expired - Fee Related CN103356646B (en) | 2013-07-04 | 2013-07-04 | The application of Chukrasone A in preparation treatment acute renal failure medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103356646B (en) |
-
2013
- 2013-07-04 CN CN201310278175.4A patent/CN103356646B/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| HONG-BING LIU等: "Chukrasones A and B: Potential Kv1.2 Potassium Channel Blockers with New Skeletons from Chukrasia tabularis", 《ORG. LETT.》 * |
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| Publication number | Publication date |
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| CN103356646B (en) | 2015-11-25 |
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| C06 | Publication | ||
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| C10 | Entry into substantive examination | ||
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| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20151027 Address after: 266000 Licang, Qingdao, No. nine East water road, No. 320, No. Applicant after: Gu Xiangmao Address before: 210009 Gulou District, Jiangsu, Nanjing Gu Ping Kong, No. 4 Applicant before: Ding Shengyu |
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| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CB03 | Change of inventor or designer information |
Inventor after: Li Gefeng Inventor before: Ding Shengyu |
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| CB03 | Change of inventor or designer information | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170331 Address after: 065201 Hebei City, Yanjiao Province, the town of Sanhe, the main street south campus, building 2, unit 202, room 5 Patentee after: Li Gefeng Address before: 266000 Licang, Qingdao, No. nine East water road, No. 320, No. Patentee before: Gu Xiangmao |
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| TR01 | Transfer of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20151125 Termination date: 20170704 |
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| CF01 | Termination of patent right due to non-payment of annual fee |