CN110179773A - Dendrophnol prevents and treats the application in Chronic glomerular disease drug in preparation - Google Patents
Dendrophnol prevents and treats the application in Chronic glomerular disease drug in preparation Download PDFInfo
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- CN110179773A CN110179773A CN201910598785.XA CN201910598785A CN110179773A CN 110179773 A CN110179773 A CN 110179773A CN 201910598785 A CN201910598785 A CN 201910598785A CN 110179773 A CN110179773 A CN 110179773A
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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
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
- A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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Abstract
The invention discloses a kind of dendrophnols to prevent and treat the application in Chronic glomerular disease drug in preparation.Animal test results show: dendrophnol has apparent prevention improvement result to methionine model mice glomerular function and organic lesion.Relevant auxiliary materials are equipped with using dendrophnol, can be made into the health care product or drug that specific aim prevents and treats renal glomerular disease with conventional formulation method.Above-mentioned health care product and drug can be used for including that metabolic syndrome is related to the disease of chronic glomerulus damage, delay and improve the related disease mesonephric glomerulus progressive course of disease.
Description
Technical field
The present invention relates to a kind of dendrophnols to prevent and treat the application in Chronic glomerular disease drug in preparation, is related to day
The new medical use of right active components of plants dendrophnol.
Background technique
Currently, dendrophnol (dendrophenol, CAS:108853-14-1), a kind of bibenzyl phenolic substance, are extracted from stone
The root of dry measure used in former times is one of effective medicinal components of dendrobium nobile.Have now been found that some evidences illustrate dendrobium nobile with various biological
Activity, including enhancing immunity of organisms, help gastric digestion, anti-cataract, adjust blood glucose, it is antitumor the effects of.By to stone
The discovery of dry measure used in former times phenol anti-cataract mechanism study, dendrophnol can be by inhibiting nitric oxide synthase type and its specific binding site
Activity to achieving the effect that anti-cataract.
Chronic renal disease (CKD) is the major disease for seriously threatening the health of our people, and illness rate is up to 11%.It is existing
Research shows that CKD and plasma homocysteine (HHcy) are in close relations.Homocysteine is the centre of Methionine metabolism
Product, metabolic disorder cause homotype semicystinol concentration investigating in blood to increase extremely, referred to as HHcy.Chinese HHcy incidence is very
Height is higher than westerner mainly due to folic acid insufficiency of intake in diet and mthfr gene 677TT site mutation rate.HHcy can pass through
The mechanism such as oxidative stress, inflammatory reaction and DNA hypomethylation promote the occurrence and development of kidney trouble.
For Chronic glomerular disease, sertoli cell (podocyte) lesion is highly important in its occurrence and development process
Pathology affair.Sertoli cell is the visceral layer epithelial cell on the outside of glomerular capillary basement membrane, because its endochylema is in basilar memebrane
Surface forms pseudo- Microfilament and gains the name.Slit membrane (split mernbrane) between podocytic process is the last of glomerular filtration
One of barrier, therefore Podocytes in Renal Tissue will lead to albuminuria appearance.With going deep into sertoli cell biological study, especially exist
It was found that sertoli cell has been considered as participating in various primary or secondary after some specific proteins molecules of sertoli cell expression
The key cells of renal glomerular disease progress.Primary sertoli cell disease often with minute lesion, focal segmental glomerulosclerosis and
The form of expression of membranous nephropathy and fall ill；And secondary sertoli cell disease is common in infection correlation, drug-associated, metal class medicine
Object correlation, autoimmune, cancer-related, kidney transplant correlation membranous nephropathy.
Not yet occur becoming the drug of specific aim target with glomerulopathy both at home and abroad at present, to inhibit or postponing the course of disease
Change to dialysis, the common medicament of clinic includes: steroid drugs, anticoagulant, immunosuppressor, angiotensin-ii-receptor
Antagonist class etc..Said medicine improvement result is limited, and side effect is obvious.
Summary of the invention
The technical problem to be solved by the present invention is to overcome the deficiencies of existing technologies, a kind of dendrophnol is provided and is prevented in preparation
With the application in treatment Chronic glomerular disease drug.
In order to solve the above-mentioned technical problem, the technical scheme is that dendrophnol prevents and treats chronic renal in preparation
Application in bead disease medicament.
Further, the Chronic glomerular disease is glomerular podocyte disease.
Further, the Chronic glomerular disease is IgA nephrosis.
Further, the Chronic glomerular disease is focal glomerulosclerosis.
Further, the Chronic glomerular disease is membranous nephropathy.
Further, the Chronic glomerular disease is membrano proliferative glomerulonephritis.
Further, oral solution or capsule or tablet or granule or micro-capsule is made in the auxiliary material that dendrophnol is equipped with corresponding dosage form
Agent uses.
After above-mentioned technical proposal, the present invention provides the Chronic glomerular diseases to progressive to have definite improve
Medicament (health care product or drug) is prepared with the dendrophnol of therapeutic effect, for preventing and treating the chronic glomerulus disease of progressive
Disease.
The present invention have the advantages that 3 apparent progress and: 1, definite ingredients (dendrophnol)；2, with clearly defined objective (glomerulus disease
Disease)；3, adjustment effect is clear (be obviously improved and therapeutic effect).
Detailed description of the invention
Fig. 1 is PAS coloration result (methionine causes Glomerular lesions mouse model)
The picture left above: normal control；Top right plot: dendrophnol control group；
Lower-left figure: methionine model；Bottom-right graph: methionine model+dendrophnol；
Fig. 2 is transmission electron microscope results (methionine causes Glomerular lesions mouse model)
The picture left above: normal control；Top right plot: dendrophnol control group；
Lower-left figure: methionine model；Bottom-right graph: methionine model+dendrophnol.
Specific embodiment
In order that the present invention can be more clearly and readily understood, right below according to specific embodiment and in conjunction with attached drawing
The present invention is described in further detail.
Embodiment 1: improvement therapeutic effect of the dendrophnol to methionine model mice Glomerular lesions.
Experimental animal: ApoE-/-Mouse, 5-7 weeks, male.
Drug is prepared: selecting dendrobium nobile phenol content is the tablet of prevention or the treatment for renal glomerular disease of 25mg/ piece, is surpassed
Sound is scattered in 0.5% sodium carboxymethylcellulose (CMC-Na), is used for gastric infusion, dosage 25mg/kg.
Laboratory apparatus: high speed freezing centrifuge, histotome, microplate reader, optical microscopy, transmission electron microscope
Deng.
Experimental method:
1, it is grouped and handles: after animal adapts to environment 1 week, being randomly divided into Normal group, dendrophnol control group, model
Group, dendrophnol group, every group 8.Each group gives normal diet, and main component is protein (24.4%), carbohydrate
(63.3%) and grease (12.3%).Model group 8 stomach-filling methionine (20mg/kg) every morning, at night 8 stomach-fillings are isometric
0.5%CMC-Na；Dendrophnol group 8 stomach-filling methionine (20mg/kg) every morning, 8 stomach-filling dendrophnol (25mg/ of evening
kg)；The daily stomach-filling same volume physiological saline of Normal group；Dendrophnol control group 8 isometric physiology of stomach-filling every morning
Salt water, 8 stomach-filling dendrophnols (25mg/kg) of evening.Administration time is identical as the disease model time is established, and is 16 weeks.
2, blood urine specimen is collected, for detecting biochemical indicator: serum creatinine, blood urea nitrogen level and urinary albumin and urine
Creatinine ratio.
3, animal puts to death and separates renal tissue on ice platform, is divided into 2 parts, fixes respectively through formaldehyde and glutaraldehyde, routinely cuts
Piece.The change of glomerulus tectology is observed under optical microscopy (PAS dyeing) and transmission electron microscope respectively.Experimental result:
A: renal function biochemical indicator
| Group | Serum creatinine (μm ol/L) | Blood urea nitrogen (mmol/L) | Urinary albumin (mg/mg Cr.) |
| Normal group | 5.61±0.41 | 3.78±0.50 | 18.82±5.97 |
| Dendrophnol control group | 7.56±2.01 | 4.75±0.75 | 17.52±2.11 |
| Model group | 52.66±5.61+++ | 21.58±1.14+++ | 74.60±20.02+ |
| Dendrophnol group | *15.12±0.89 | *9.78±1.72 | *25.61±7.99 |
+++P < 0.001 is compared with Normal group；**P<0.01,***P < 0.001 is compared with model group
Methionine model mice serum creatinine, blood urea nitrogen level and urinary albumin and urine creatinine ratio are all remarkably higher than normally
Group mouse, wherein serum creatinine and blood urea nitrogen level increase, and illustrate that methionine model mice filtration capacity of the kidney declines；Urinate white egg
It is white then to prompt methionine model mice kidney filtration barrier to be destroyed with the raising of urine creatinine ratio；Above two renal function filtration
Dysfunction illustrates that functional lesion occurs for methionine murine glomerular.Dendrophnol can be alleviated significantly caused by methionine
Glomerular function damage, and intact animal gives dendrophnol and does not then find significant change to These parameters.
B: nephridial tissue structure damage
As shown in Fig. 1: apparent positive reaction is presented to model group murine glomerular PAS dyeing in om observation, prompts
Methionine murine glomerular matrix secreted；Dendrophnol administration can effectively improve the glomerular mesangium base of methionine induction
Matter hyperplasia；Relative to Normal control animals, dendrophnol administration group animal glomerular mesangium has no significant change.
As shown in Fig. 2: transmission electron microscope observing to model group sertoli cell podocytic process, which merges, becomes flat, partial fusion, disappearance, kidney
Bead basilar memebrane (GBM) thickens；Model administration group can effectively mitigate above-mentioned sertoli cell and the variation of GBM pathologic；Relative to just
Normal control-animal, dendrophnol administration group animal glomerular podocyte have no significant change.
Show dendrophnol for methionine model mice glomerulus function by renal function index and institutional framework testing result
There can be apparent protection improvement result with structural damage, effect is mainly reflected in the guarantor for glomerular podocyte and film function
In shield.Dendrophnol administration does not make significant difference for intact animal glomerular function and structure, illustrates that it is used for renal glomerular disease
Prevention or the safety of therapeutic agent.
Comparison through this embodiment, it was demonstrated that the present invention utilizes animal model section on biochemical function and histocyte level
Ground is learned to evaluate and demonstrate exact improvement and therapeutic effect of the dendrophnol to Chronic glomerular disease.
Dendrophnol according to the present invention does not make significant difference to Normal control animals Chronic glomerular disease index of correlation, tool
There is good safety.
Embodiment 2:
By dendrophnol according to conventional preparation method, water is added and appropriate solubilizer (polyethylene glycol 400) dissolution, packing are gone out
Bacterium is prepared into renal glomerular disease prevention or treatment oral solution that dendrobium nobile phenol content is 20mg/ml；
By dendrophnol according to conventional preparation method, soft capsule material selection gelatin and sorbierite, it is prepared into dendrobium nobile phenol content
For 20mg/ renal glomerular disease preventions or treatment capsule；
By dendrophnol according to conventional preparation method, excipient cyclodextrin is added, is uniformly mixed, granulation, tabletting is prepared into stone
Dry measure used in former times phenol content is that tablet is used in the renal glomerular disease prevention and treatment of 20mg/ piece.
Particular embodiments described above, pair present invention solves the technical problem that, technical scheme and beneficial effects carry out
It is further described, it should be understood that the above is only a specific embodiment of the present invention, is not limited to this
Invention, all within the spirits and principles of the present invention, any modification, equivalent substitution, improvement and etc. done should be included in this hair
Within bright protection scope.
Claims (7)
1. dendrophnol prevents and treats the application in Chronic glomerular disease drug in preparation.
2. dendrophnol according to claim 1 prevents and treats the application in Chronic glomerular disease drug in preparation,
It is characterized in that,
The Chronic glomerular disease is glomerular podocyte disease.
3. dendrophnol according to claim 1 prevents and treats the application in Chronic glomerular disease drug in preparation,
It is characterized in that,
The Chronic glomerular disease is IgA nephrosis.
4. dendrophnol according to claim 1 prevents and treats the application in Chronic glomerular disease drug in preparation,
It is characterized in that,
The Chronic glomerular disease is focal glomerulosclerosis.
5. dendrophnol according to claim 1 prevents and treats the application in Chronic glomerular disease drug in preparation,
It is characterized in that,
The Chronic glomerular disease is membranous nephropathy.
6. dendrophnol according to claim 1 prevents and treats the application in Chronic glomerular disease drug in preparation,
It is characterized in that,
The Chronic glomerular disease is membrano proliferative glomerulonephritis.
7. dendrophnol according to claim 1 prevents and treats the application in Chronic glomerular disease drug in preparation,
It is characterized in that,
Oral solution or capsule or tablet or granule is made in the auxiliary material that dendrophnol is equipped with corresponding dosage form or microcapsules uses.
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| CN201910598785.XA CN110179773A (en) | 2019-07-04 | 2019-07-04 | Dendrophnol prevents and treats the application in Chronic glomerular disease drug in preparation |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114631564A (en) * | 2021-12-08 | 2022-06-17 | 合肥师范学院 | Blood sugar reducing yoghourt and preparation method thereof |
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| KR20130047458A (en) * | 2011-10-31 | 2013-05-08 | 한국과학기술연구원 | Composition for preventing, improving, or treating a disease controlled by ppar action |
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Patent Citations (4)
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| KR20130047458A (en) * | 2011-10-31 | 2013-05-08 | 한국과학기술연구원 | Composition for preventing, improving, or treating a disease controlled by ppar action |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114631564A (en) * | 2021-12-08 | 2022-06-17 | 合肥师范学院 | Blood sugar reducing yoghourt and preparation method thereof |
| CN114631564B (en) * | 2021-12-08 | 2023-11-21 | 合肥师范学院 | Sugar-reducing yoghourt and preparation method thereof |
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Application publication date: 20190830 |