CN103340850A - Application of Aphanamgrandiol A in preparation of drugs for treating acute renal failure - Google Patents
Application of Aphanamgrandiol A in preparation of drugs for treating acute renal failure Download PDFInfo
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- CN103340850A CN103340850A CN2013102859725A CN201310285972A CN103340850A CN 103340850 A CN103340850 A CN 103340850A CN 2013102859725 A CN2013102859725 A CN 2013102859725A CN 201310285972 A CN201310285972 A CN 201310285972A CN 103340850 A CN103340850 A CN 103340850A
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- aphanamgrandiol
- renal failure
- acute renal
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- application
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- 208000033626 Renal failure acute Diseases 0.000 title claims abstract description 32
- 201000011040 acute kidney failure Diseases 0.000 title claims abstract description 32
- 208000009304 Acute Kidney Injury Diseases 0.000 title claims abstract description 31
- 208000012998 acute renal failure Diseases 0.000 title claims abstract description 31
- 239000003814 drug Substances 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 229940079593 drug Drugs 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 6
- 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
- 230000008327 renal blood flow Effects 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
- XBZYWSMVVKYHQN-MYPRUECHSA-N (4as,6as,6br,8ar,9r,10s,12ar,12br,14bs)-10-hydroxy-2,2,6a,6b,9,12a-hexamethyl-9-[(sulfooxy)methyl]-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxylic acid Chemical compound C1C[C@H](O)[C@@](C)(COS(O)(=O)=O)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C XBZYWSMVVKYHQN-MYPRUECHSA-N 0.000 description 3
- 201000003126 Anuria Diseases 0.000 description 3
- 240000003906 Aphanamixis grandifolia Species 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 238000010255 intramuscular injection Methods 0.000 description 3
- 239000007927 intramuscular injection Substances 0.000 description 3
- 210000003734 kidney Anatomy 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
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 208000010444 Acidosis Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 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
- 239000002775 capsule Substances 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
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 230000005764 inhibitory process 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
- 210000004185 liver Anatomy 0.000 description 1
- 239000000463 material Substances 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
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 210000005084 renal tissue Anatomy 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
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Landscapes
- 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 Aphanamgrandiol A, namely an application of the Aphanamgrandiol A in preparation of drugs for treating acute renal failure. The application of the Aphanamgrandiol A in preparation of drugs for treating acute renal failure is disclosed for the first time, as the framework type belongs to a totally new framework type and the Aphanamgrandiol A has incredible high inhibitory activity to acute renal failure, no other compounds give any prediction, the Aphanamgrandiol A has remarkable substantive features, and simultaneously the Aphanamgrandiol A has a remarkable improvement for resisting acute renal failure.
Description
Technical field
The present invention relates to the new purposes of compd A phanamgrandiol A, relate in particular to the application of Aphanamgrandiol 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 multiple reason, 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, occur azotemia rapidly, 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.Still there is not at present the effective medicine for the treatment of acute renal failure of generally acknowledging clinically, only can be by correcting water-electrolyte balance, 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 nephridial tissue damage improving renal blood flow perfusion obstacle and alleviate.
The compd A phanamgrandiol A that the present invention relates to is one and delivered (Qi Zeng in 2013, Bin Guan, Jie Ren, et al.Aphanamgrandiol A, a new triterpenoid with a unique carbon skeleton from Aphanamixis grandifolia.Fitoterapia, 86 (2013) 217 – 221.) noval chemical compound, this chemical compound has brand-new framework types, present purposes only relates to inhibition gastric cancer, ovarian cancer, colon cancer, the increment of liver epithelial cancerous cell (Qi Zeng, Bin Guan, Jie Ren, et al.Aphanamgrandiol A, a new triterpenoid with a unique carbon skeleton from Aphanamixis grandifolia.Fitoterapia, 86 (2013) 217 – 221.), the purposes of the Aphanamgrandiol A that the present invention relates in preparation treatment acute renal failure medicine belongs to open first.
Summary of the invention
The objective of the invention is to provides the application of Aphanamgrandiol A in the anti-acute renal failure medicine of preparation according to not finding that it has the present situation of the report of anti-acute renal failure activity in the existing Aphanamgrandiol A research.
By our discovering, the anuria when Aphanamgrandiol A can improve acute renal failure or oliguria symptom, the function of protection kidney.
Described compd A phanamgrandiol A, structure is shown in formula I:
Formula I
The purposes of the Aphanamgrandiol 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 anti-acute renal failure simultaneously and obviously have obvious improvement.
The specific embodiment
The preparation method of compd A phanamgrandiol A involved in the present invention is referring to document (Qi Zeng, Bin Guan, Jie Ren, et al.Aphanamgrandiol A, a new triterpenoid with a unique carbon skeleton from Aphanamixis grandifolia.Fitoterapia, 86 (2013) 217 – 221.)
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 compd A phanamgrandiol A tablet involved in the present invention:
Get 5 and digest compound Aphanamgrandiol A, add dextrin material 195 grams, mixing, conventional tabletting are made 1000.
Embodiment 2: the preparation of compd A phanamgrandiol A capsule involved in the present invention:
Get 5 and digest compound Aphanamgrandiol A, add starch 195 grams, mixing is encapsulatedly made 1000.
Further specify its pharmaceutically active below by pharmacodynamic experiment.
The therapeutical effect of the acute renal failure rat of experimental example 1Aphanamgrandiol A
(1) experimental technique
Adopt intramuscular injection glycerol to cause the acute renal failure rat animal model.Select 60 of the healthy male SD rats of 180～220g for use, be divided into 5 groups at random: sham operated rats (intramuscular injection normal saline); Model group (intramuscular injection glycerol); Aphanamgrandiol A I group (0.3mg/Kg)); Aphanamgrandiol A II group (0.6mg/Kg)); Aphanamgrandiol A III group (1.2mg/Kg)), each organizes rat tail vein injection saline or Aphanamgrandiol A immediately 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 Aphanamgrandiol A or the normal saline, stay back 6 hours of urine with 4% chloral hydrate intraperitoneal injection of anesthesia, adopt laser Doppler flowmetry to measure after the modeling and treatment back bilateral renal blood flow amount, 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.Aphanamgrandiol A can increase acute renal failure mice renal blood flow
The influence of the acute renal failure mice of table 1Aphanamgrandiol A renal blood flow
* P＜0.05 contrasts with the acute renal failure model group
2.Aphanamgrandiol the acute renal failure mice of A renal function tool protective effect
The model group rat significantly reduces than sham operated rats rat twenty-four-hour urine amount, is respectively 4.86 ± 0.26ml and 11.43 ± 2.53ml; Middle and high dosage Aphanamgrandiol 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 5.16 ± 0.65ml, II group 7.93 ± 1.43ml, III group 9.86 ± 1.39ml.Illustrate that Aphanamgrandiol 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 28.73 ± 1.62mmol/L, and Cre is 171.63 ± 14.37umol/L, apparently higher than sham operated rats, illustrates that model group animal renal function injury is serious.Middle and high dosage Aphanamgrandiol 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＜0.05 contrasts with the acute renal failure model group
Conclusion: the anuria when Aphanamgrandiol 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.Aphanamgrandiol the application of A in preparation treatment acute renal failure medicine, described compd A phanamgrandiol A structure is shown in formula I:
Formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013102859725A CN103340850A (en) | 2013-07-05 | 2013-07-05 | Application of Aphanamgrandiol A in preparation of drugs for treating acute renal failure |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013102859725A CN103340850A (en) | 2013-07-05 | 2013-07-05 | Application of Aphanamgrandiol A in preparation of drugs for treating acute renal failure |
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| Publication Number | Publication Date |
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| CN103340850A true CN103340850A (en) | 2013-10-09 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2013102859725A Pending CN103340850A (en) | 2013-07-05 | 2013-07-05 | Application of Aphanamgrandiol A in preparation of drugs for treating acute renal failure |
Country Status (1)
| Country | Link |
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| CN (1) | CN103340850A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101965184A (en) * | 2008-01-11 | 2011-02-02 | 里亚塔医药公司 | Synthetic triterpenoid compound and method in order to cure the disease |
-
2013
- 2013-07-05 CN CN2013102859725A patent/CN103340850A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101965184A (en) * | 2008-01-11 | 2011-02-02 | 里亚塔医药公司 | Synthetic triterpenoid compound and method in order to cure the disease |
Non-Patent Citations (1)
| Title |
|---|
| QI ZENG ET AL.: "Aphanamgrandiol A, a new triterpenoid with a unique carbon skeleton from Aphanamixis grandifolia", 《FITOTERAPIA》 * |
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Application publication date: 20131009 |