CN102836145B - Applications of pterostilbene in preparation of medicines for preventing and treating chronic glomerular disease - Google Patents
Applications of pterostilbene in preparation of medicines for preventing and treating chronic glomerular disease Download PDFInfo
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- VLEUZFDZJKSGMX-UHFFFAOYSA-N pterostilbene Natural products COC1=CC(OC)=CC(C=CC=2C=CC(O)=CC=2)=C1 VLEUZFDZJKSGMX-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 239000003814 drug Substances 0.000 title claims abstract description 31
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 29
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Abstract
The invention relates to new medical applications of a natural monomer compound pterostilbene, in particular to applications of the pterostilbene in preparation of medicines for preventing and treating a chronic glomerular disease, and applications of pterostilbene in preparation of medicines for preventing and treating progressive chronic glomerular disease. Animal test results show that the pterostilbene has an obvious effect on prevention and improvement of a glomerular function and an organic injury of a fructose model rat renal. The pterostilbene is matched up with relevant adjuvants, a conventional preparation method can be utilized to obtain a health care product or a medicine aiming at preventing and treating the glomerular disease. The above health care product and the medicine can be used for the diseases relevant to the chronic glomerular lesion, such as diabetes and metabolic syndrome and the like, so that the glomerular progressive course in the relevant diseases can be delayed and improved.
Description
One, technical field:
The present invention relates to the new medical use of natural plant active component Pterostilbene, specifically relate to the application of Pterostilbene in preparation prevention and treatment chronic glomerulus disease medicament, particularly relate to for the preparation of the application in progressive chronic glomerulus disease prevention agent and therapeutic agent.
Two, background technology:
Pterostilbene (Pterostilbene, CAS 537-42-8), is a kind of active skull cap components, belongs to Verakanol derivative, is the important activity composition in Fructus Vitis viniferae, blueberry, Sanguis Draxonis goods, Indian Kino tree and India's anti-diabetic medical herbs " Bijasar ".
Diabetes mellitus in China prevalence is 9.7%, surpass the world average level 6.4%, become the first in the world diabetes big country.China's High-risk Group of Diabetes is up to 1.5 hundred million people.Along with the increase year by year of diabetic nephropathy sickness rate, in the complication of diabetes, the sickness rate of chronic glomerulus disease has risen to first.
The ratio of diabetic nephropathy morbidity rear steering renal failure in latter stage (needing dialysis) is very high; Similar with it, other chronic glomerulus disease is along with course advancement turns to when dialysis, there will be equally the social significant problems such as medical expense is surging.Therefore, very strong for the relevant prevention of chronic glomerulus progression of disease and healing potion demand.
With regard to chronic glomerulus disease, podocyte (podocyte) pathological changes, at it, evolution occurs is very important pathology affair.Podocyte is the visceral layer epithelial cell that is positioned at GCBM outside, gains the name because its endochylema forms pseudo-Microfilament on basement membrane surface.Slit membrane (split mernbrane) between podocytic process is last one barrier of glomerular filtration, and therefore Podocytes in Renal Tissue will cause albuminuria to occur.Along with to the going deep into of podocyte biological study, especially, after finding some specific proteins molecules that podocyte is expressed, podocyte has been considered to participate in the key cells of various constitutionales or secondary glomerulopathy progress.Constitutional podocyte is sick often falls ill with the form of expression of minute lesion, FSGS and membranous nephropathy; And Secondary cases podocyte disease is common in infection dependency, drug-associated, metal species drug-associated, autoimmunity, cancer-related, renal transplantation dependency membranous nephropathy.
Not yet there is becoming with glomerulopathy at present the medicine of specific aim target both at home and abroad, change to dialysis for suppressing or postpone the course of disease, clinical conventional medicament comprises: steroid medicine, anticoagulant, immunosuppressant, Angiotensin Ⅱ receptor antagonist class etc.Said medicine improvement effect is limited, and side effect is obvious.
Three, summary of the invention:
The object of the present invention is to provide the new medical use of natural plant active component Pterostilbene, specifically relate to the application of Pterostilbene in preparation prevention and treatment chronic glomerulus disease medicament, particularly relate to preparation prevention and treat the application in progressive chronic glomerulus disease medicament.
Technical solution of the present invention:
The application of Pterostilbene in preparation prevention and treatment chronic glomerulus disease medicament is provided.
The application of Pterostilbene in preparation prevention and treatment chronic glomerulus disease medicament, is characterized in that described chronic glomerulus disease is glomerular podocyte disease.
The application of Pterostilbene in preparation prevention and treatment chronic glomerulus disease medicament, is characterized in that described chronic glomerulus disease is IgA nephropathy.
The application of Pterostilbene in preparation prevention and treatment chronic glomerulus disease medicament, is characterized in that described chronic glomerulus disease is FGS.
The application of Pterostilbene in preparation prevention and treatment chronic glomerulus disease medicament, is characterized in that described chronic glomerulus disease is membranous nephropathy.
The application of Pterostilbene in preparation prevention and treatment chronic glomerulus disease medicament, is characterized in that described chronic glomerulus disease is membrano proliferative glomerulonephritis.
This application has comprised taking Pterostilbene as major ingredient, be equipped with the known pharmaceutic adjuvant of those skilled in the art (excipient, cosolvent, controlled release agent etc.), make the known dosage form of those skilled in the art (comprising oral liquid, injection, capsule, tablet, granule, microcapsule etc.) with conventional formulation method.
Advantage of the present invention is to provide the Pterostilbene that progressive chronic glomerulus disease is had to definite improvement and therapeutical effect to prepare medicament (health product or medicine), for preventing and treat progressive chronic glomerulus disease.The present invention has 3 significantly progressive and advantages: 1, definite ingredients (Pterostilbene); 2, with clearly defined objective (renal glomerular disease); 3, regulating action clear and definite (obviously improving and therapeutical effect).
The present invention utilizes animal model in biochemical function and histiocyte level, scientifically to evaluate and proved definite improvement and the therapeutical effect of Pterostilbene to chronic glomerulus disease.
Pterostilbene involved in the present invention does not make significant difference to normal control animal chronic glomerulus disease association index, has good safety.
Essence for a better understanding of the present invention, illustrates its application in preparation prevention and treatment chronic glomerulus disease medicament by the pharmacological evaluation with Pterostilbene and result below.
Four, brief description of the drawings:
Fig. 1: PAS coloration result (fructose causes Glomerular lesions rat model)
The left figure of upper row: normal control; In upper row, scheme: normal control+Pterostilbene; The right figure of upper row: normal control+pioglitazone;
The left figure of lower row: fructose model; In lower row, scheme: fructose model+Pterostilbene; The right figure of lower row: fructose model+pioglitazone.
Fig. 2: transmission electron microscope results (fructose causes Glomerular lesions rat model)
The left figure of upper row: normal control; In upper row, scheme: normal control+Pterostilbene; The right figure of upper row: normal control+pioglitazone;
The left figure of lower row: fructose model; In lower row, scheme: fructose model+Pterostilbene; The right figure of lower row: fructose model+pioglitazone.
Five, detailed description of the invention: following examples are only as the use of further setting forth invention, can not be used for limiting the present invention.
Embodiment 1: the improve therapeutical effect of Pterostilbene to fructose rat model Glomerular lesions.
Laboratory animal: SD rat, 200-220 gram, male.
Medicine preparation: selecting Pterostilbene content is the tablet of prevention or the treatment for renal glomerular disease of 40mg/ sheet, ultrasonic being scattered in normal saline, for gastric infusion, dosage is 40mg/kg.
Experimental apparatus: High speed refrigerated centrifuge, histotome, microplate reader, optical microscope, transmission electron microscope etc.
Experimental technique:
1, the foundation of model: animal conformed after 1 week, was divided at random model group and normal group, 30 every group.Fructose rat model modeling: drinking water gives 10% fructose soln; Normal group gives tap water, 70 days modeling cycles.
2, after modeling 4 weeks, model group and normal group are set up respectively Pterostilbene and pioglitazone administration group, 10 every group.Every day, gavage gave Pterostilbene (40mg/kg) and pioglitazone (4mg/kg).This medicine continues 6 weeks, and during administration, animal pattern continues to give 10% fructose soln.
3, collect blood urine specimen, for detection of biochemical indicator: serum creatinine, blood urea nitrogen level and urinaryalbumin and urine creatine ratio.
4, on sacrifice of animal ice platform, separate renal tissue, be divided into 2 parts, fix through formaldehyde and glutaraldehyde respectively, conventional section.Under optical microscope (PAS dyeing) and transmission electron microscope, observe respectively the change of glomerule tectology.
Experimental result:
A: renal function biochemical indicator
+++p<0.001 and normal+normal saline group comparison;
*p<0.01,
* *p<0.001 and the comparison of fructose model+normal saline group
Fructose rat model serum creatinine, blood urea nitrogen level and urinaryalbumin and urine creatine ratio are all significantly higher than normal rats, and wherein serum creatinine and blood urea nitrogen level raise, and illustrate that fructose rat model filtration capacity of the kidney declines; Urinaryalbumin and urine creatine ratio raise and point out fructose rat model kidney filtration barrier to be damaged; Above-mentioned two kinds of renal function filtering function obstacles all illustrate the infringement of fructose Renal Glomeruli In Rats generating function.Pterostilbene can be alleviated the glomerular function damage that fructose causes significantly, and its effect exceedes positive control medicine pioglitazone, and intact animal gives Pterostilbene and These parameters all do not found to significant change.
B: nephridial tissue structure infringement
As shown in Figure 1: om observation presents obvious positive reaction to model group Renal Glomeruli In Rats PAS dyeing, prompting fructose Renal Glomeruli In Rats matrix secreted; Pterostilbene administration can effectively improve the glomerular mesangium substrate hypertrophy of fructose induction; With respect to normal control animal, Pterostilbene administration treated animal glomerular mesangium has no significant change.
As shown in Figure 2: transmission electron microscope observing merges and becomes flat to model group podocyte podocytic process, partial fusion, disappearance, glomerular basement membrane (GBM) thickens; Model administration group can effectively alleviate above-mentioned podocyte and GBM pathologic changes; With respect to normal control animal, Pterostilbene administration treated animal glomerular podocyte has no significant change.
Show by renal function index and organizational structure testing result; Pterostilbene has obvious protection improvement effect for fructose rat model glomerular function and structural damage; its effectiveness and pioglitazone are suitable, and its effect is mainly reflected in the protection for glomerular podocyte and film function.Pterostilbene administration does not make significant difference for intact animal's glomerular function and structure, illustrates that it is for the prevention of renal glomerular disease or the safety of therapeutic agent.
Embodiment 2:
According to conventional formulation method, add water and appropriate solubilizing agent (PEG400) to dissolve Pterostilbene, subpackage, sterilizing, being prepared into Pterostilbene content is renal glomerular disease prevention or the treatment oral liquid of 20mg/ml;
By Pterostilbene, according to conventional formulation method, soft capsule material selection gelatin and sorbitol, be prepared into Pterostilbene content and be renal glomerular disease prevention or the treatment capsule of 20mg/ grain;
Pterostilbene, according to conventional formulation method, is added to excipient cyclodextrin, and mix homogeneously, granulates, tabletting, and being prepared into Pterostilbene content is renal glomerular disease prevention and the treatment tablet of 20mg/ sheet.
Claims (2)
1. the application of Pterostilbene in preparation prevention and treatment glomerular podocyte medicine.
2. the application of Pterostilbene in preparation prevention and treatment membranous nephropathy medicine.
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| CN110075094A (en) * | 2019-02-27 | 2019-08-02 | 延边大学 | Pterostilbene is preparing the application in drug or health care product |
| CN110179773A (en) * | 2019-07-04 | 2019-08-30 | 合肥师范学院 | Dendrophnol prevents and treats the application in Chronic glomerular disease drug in preparation |
| CN113101295A (en) * | 2020-03-20 | 2021-07-13 | 上海疆云医疗健康科技有限公司 | Use of stilbene analogues in the treatment of diabetic renal disease |
| CN114533786A (en) * | 2020-11-25 | 2022-05-27 | 昆药集团股份有限公司 | New application of Quzhazhigan |
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