CN101919837B - Application of rosmarinic acid in preparing medicament for treating or preventing renal fibrosis - Google Patents
Application of rosmarinic acid in preparing medicament for treating or preventing renal fibrosis Download PDFInfo
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- CN101919837B CN101919837B CN2010101736495A CN201010173649A CN101919837B CN 101919837 B CN101919837 B CN 101919837B CN 2010101736495 A CN2010101736495 A CN 2010101736495A CN 201010173649 A CN201010173649 A CN 201010173649A CN 101919837 B CN101919837 B CN 101919837B
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Abstract
The invention provides application of rosmarinic acid in preparing medicament for treating or preventing renal fibrosis. The medicament can be of oral administration and injecting administration, wherein the dosage in injecting administration is between 50 and 1,500mg; and the dosage in oral administration is between 100 and 3,000mg.
Description
The application divides an application for application number 200610045376.X's.Original bill application title: the application of rosmarinic acid in the medicine of preparation treatment or prevention hepatic fibrosis and renal fibrosis, the applying date: on June 29th, 2006.
Technical field
The present invention relates to a kind of new medicine use, relate to the application of rosmarinic acid in the medicine of preparation prevention or treatment renal fibrosis particularly.
Background technology
Renal fibrosis (comprising kidney region fibrosis and glomerular sclerosis) is the main pathological basis of the kidney damage final stage that causes of a variety of causes, the renal fibrosis mechanism is comparatively complicated, relevant with multiple factor, wherein main and celliferous propagation of extracellular matrix cell and activation, vaso-active substance, cytokine and extracellular matrix are changed unbalance relevant, and kidney region fibrosis almost is the common pathway that all former or secondary kidney disease proceed to end stage renal failure.
The chemistry of rosmarinic acid (Rosmarinic acid) is called R (+) 2-((3-(3,4-dihydroxy phenyl-(oxidation-2-acrylic) oxygen base) 3,4-dihydroxy benzenes propanoic acid).Rosmarinic acid is water miscible polyphenol compound.Have various active such as antiinflammatory, antioxidant activity, immunosuppressant, antithrombotic and antiplatelet aggregative activity [Liu Yingxiang, meter will loyalty. rosmarinic acid Pharmacological action study progress, World Notes on Plant Medicine, 1993,8 (6): 248～251.; Chen Shuzhen pays rising tone, etc. rosmarinic acid is to the influence that rat neutrophilic granulocyte free radical generates and lysosome discharges, Acta Pharmaceutica Sinica, 1999,34 (12): 881～885.; Peake P.W.PussellB.A, MartynP, etal.The, inhibiton effect of Rosmarinic acid on complement in volves the C5convertase.Int JImmuno pharmacol 13:853～857,1997.; Zou Zhengwu, Xu Lina, Tian Jinying. rosmarinic acid antithrombotic and platelet aggregation effect, Acta Pharmaceutica Sinica, 1993,28 (4): 241～245.].But rosmarinic acid does not appear in the newspapers in the pharmacological action of preparation prevention or treatment renal fibrosis.The inventor is surprised to find rosmarinic acid is having tangible effect aspect prevention or the treatment renal fibrosis.Based on this, the inventor has invented the application of rosmarinic acid at prevention or treatment renal fibrosis.
Summary of the invention
The invention provides the application of rosmarinic acid in the medicine of preparation prevention or treatment renal fibrosis.
The invention provides the application of rosmarinic acid in preparation treatment or prevention renal fibrosis medicine.
Medicine provided by the invention is when being used for renal fibrosis, and the using dosage scope is 50mg～1500mg during its injection; Preferred 50～750mg, the using dosage scope is 100mg～3000mg when oral; Preferred 100～1500mg.
The present invention also provides the medicine of being made up of rosmarinic acid and pharmaceutically acceptable carrier or adjuvant, this medicine can be prepared into tablet, capsule, drop pill, injection, freeze-dried powder or injectable emulsion with the pharmacy conventional method, preferably exists with tablet, drop pill or freeze-dried powder form.
The specific embodiment
The preparation of embodiment 1 rosmarinic acid freeze-dried powder
Get rosmarinic acid 50.0g, add injection water 2000ml and make its dissolving, transfer pH=5.5～7.5 with NaOH, with mannitol 8g, stirring and dissolving, ultrafiltration, obtain apyrogenic clear liquor, pour in the 10ml cillin bottle, 2ml/ only, press the lyophilizing of freeze-dried powder technology, make every freeze-dried powder that contains rosmarinic acid 50.0mg.
Embodiment 2 rosmarinic acid preparation tablets
Prescription:
Rosmarinic acid 100.0g
Icing Sugar 35.0g
Lactose 40.0g
Carboxymethyl starch sodium 23.0g
3%PVP
K30Aqueous solution is an amount of
Magnesium stearate 2.0g
Make 1000 altogether
Operation: cross 100 mesh sieves after taking by weighing the abundant mix homogeneously of rosmarinic acid, Icing Sugar, lactose and carboxymethyl starch sodium of recipe quantity, add 3%PVP
K30Aqueous solution is made soft material in right amount, and 20 mesh sieves are granulated, 60 ℃ of dryings 3 hours, and 18 mesh sieve granulate add the magnesium stearate of recipe quantity, scrobicula stamping behind the mix homogeneously, the heavily about 200mg of adjustment sheet, promptly
Test of the influence of 1 rosmarinic acid to one-sided ureter ligation kidney of rats interstitial fibrosis
1.1 material
Rosmarinic acid is provided by Shandong Province's natural drug Engineering Technical Research Centre, and content is more than 95%, lot number: 041205; Benazepril, Novartis Pharma AG produces, lot number: 040306; Hydroxyproline (HYP) test kit, biotech firm is built up in Nanjing, lot number: 050906; Fibronectin (FN) test kit is available from the Shanghai institute of Biological Products.
Laboratory animal regular grade Wistar rat, male, body weight 150-200g, the SD rat, Shandong greenery natural drug Societe Principia Research Development Experimental Animal Center provides qualified number: SYXK (Shandong) 20030020.
1.2 test method and result
130 of rats, be divided into 13 groups at random, it is sham operated rats, model group, benazepril group is irritated stomach 10mg/kg group, rosmarinic acid intravenous injection 2.5mg/kg group, rosmarinic acid intravenous injection 5mg/kg group, rosmarinic acid intravenous injection 25mg/kg group, rosmarinic acid intravenous injection 75mg/kg group, rosmarinic acid intravenous injection 150mg/kg group, rosmarinic acid is irritated stomach 5mg/kg group, rosmarinic acid is irritated stomach 10mg/kg group, rosmarinic acid is irritated stomach 50mg/kg group, rosmarinic acid is irritated stomach 150mg/kg group, rosmarinic acid is irritated stomach 300mg/kg group, 1 week of animal feeding, each rat with 10% chloral hydrate 3.0mL/kg intraperitoneal injection of anesthesia after, the rat right arm reclining is fixed on the operating-table, use iodine tincture after the cropping, 75% alcohol disinfecting field of operation, row left side abdomen otch, successively cut skin, muscle and each layer of stomach wall, expose and separation left side ureter, sham operated rats is only cut abdominal cavity and free left side ureter, but not ligation and cutting off, other are respectively organized rat and use 4-0 silk thread ligation twice, last one ligation point is positioned at left inferior pole of kidney level, between twice ligation point, cut off ureter then, layer-by-layer suture, postoperative was put to death each treated animal after the chloral hydrate anesthesia in 10 days 10%, get blood, press Fibronectin and measure explanation mensuration fiber connexin (FN).Normal saline is left and taken left kidney after the lavation repeatedly, and nephridial tissue is fixed through 4% paraformaldehyde buffer.Cut an amount of nephridial tissue, press the explanation of hydroxyproline kit measurement and measure hydroxyproline.
Routine pathology is learned and checked 1. macroscopy: sham operated rats kidney color is scarlet, smooth surface, peplos gloss, no adhesion.Other respectively organize the increase of kidney volume, and color is pale, and the surface is graininess, similar human body branny kidney, the adhesion of a few regions kidney peplos.2. light microscopy checking: sham operated rats nephron clear in structure, glomerular capsule do not have expansion or dwindle, and renal cells does not have obvious degeneration and necrosis, do not have come off epithelial cell or cast, no vasodilation or cell infiltration in the matter in the tube chamber.The large stretch of renal tubular necrosis of model control group, the hyperplasia of kidney interstitial fibers, tubular ectasia, in a large amount of pale brown color refractive power materials or the downright bad epithelial cell that comes off are arranged, the glomerule decreased number, part glomerule fibrosis and with the adhesion of bag Man cyst wall, blister cavities disappears.Administration respectively organizes pathological changes and model control group is similar, but all has morphology in various degree to improve, and irritates heavy dose of each group of stomach significantly with rosmarinic acid especially, with model control group notable difference is arranged relatively.
Each group FN, HYP are carried out the T check.The results are shown in Table 1, rosmarinic acid intravenous injection 5mg/kg organizes, rosmarinic acid intravenous injection 25mg/kg organizes, rosmarinic acid intravenous injection 75mg/kg organizes, rosmarinic acid intravenous injection 150mg/kg organizes, rosmarinic acid filling stomach 10mg/kg organizes, rosmarinic acid filling stomach 50mg/kg organizes, rosmarinic acid filling stomach 150mg/kg organizes, rosmarinic acid filling stomach 300mg/kg organizes obvious reduction FN, HYPP level (comparing p＜0.05 or 0.01 with model control group).The stomach 150mg/kg group of irritating rosmarinic acid reduces FN, HYP level and rosmarinic acid and irritates stomach 300mg/kg group relatively, there was no significant difference; Rosmarinic acid intravenous injection 75mg/kg group reduces FN, HYP level and rosmarinic acid intravenous injection 150mg/kg group relatively, there was no significant difference.
Table 1 rosmarinic acid is to the influence of one-sided ureter ligation kidney of rats interstitial fibrosis
*, p＜0.05,
*, compare with model group p＜0.01
Claims (4)
1. the application of rosmarinic acid in the medicine of preparation treatment or prevention renal fibrosis.
2. application according to claim 1 is characterized by drug administration by injection or oral administration.
3. application according to claim 2, its drug administration by injection dosage is 50-1500mg, oral administration dosage is 100-3000mg.
4. application according to claim 3, drug administration by injection dosage are 50-750mg, and oral administration dosage is 100-1500mg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101736495A CN101919837B (en) | 2006-06-29 | 2006-06-29 | Application of rosmarinic acid in preparing medicament for treating or preventing renal fibrosis |
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| CN2010101736495A CN101919837B (en) | 2006-06-29 | 2006-06-29 | Application of rosmarinic acid in preparing medicament for treating or preventing renal fibrosis |
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| Application Number | Title | Priority Date | Filing Date |
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| CN200610045376XA Division CN101095668B (en) | 2006-06-29 | 2006-06-29 | Application of rosmarinic acid in the preparation of medicines for treating or preventing liver fibrosis and kidney fibrosis |
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| CN101919837A CN101919837A (en) | 2010-12-22 |
| CN101919837B true CN101919837B (en) | 2011-08-03 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1315863A (en) * | 1998-05-16 | 2001-10-03 | 财团法人牧岩生命工学研究所 | Use of rosmarinic acid and derivatives thereof as immunosuppressant or inhibitor of SHz-mediated process |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1315863A (en) * | 1998-05-16 | 2001-10-03 | 财团法人牧岩生命工学研究所 | Use of rosmarinic acid and derivatives thereof as immunosuppressant or inhibitor of SHz-mediated process |
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| CN101919837A (en) | 2010-12-22 |
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Effective date of registration: 20170613 Address after: 264670, No. 15, pioneering Road, hi tech Zone, Shandong, Yantai Patentee after: Shandong Luye Pharma Co., Ltd. Address before: 264003 Laishan, Shandong Province Bao Road, No. 9 District, No. Patentee before: Luye Natural Medicinal Research Developing Co., Ltd., Shandong Prov. |
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