CN102512677A - Application of guanylate cyclase inhibitor to preparation of medicament for inhibiting myopia - Google Patents
Application of guanylate cyclase inhibitor to preparation of medicament for inhibiting myopia Download PDFInfo
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- CN102512677A CN102512677A CN2011103992630A CN201110399263A CN102512677A CN 102512677 A CN102512677 A CN 102512677A CN 2011103992630 A CN2011103992630 A CN 2011103992630A CN 201110399263 A CN201110399263 A CN 201110399263A CN 102512677 A CN102512677 A CN 102512677A
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- myopia
- guanylate cyclase
- cyclase inhibitor
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Abstract
The invention relates to a preparation method of a medicament for delaying and inhibiting myopia, in particular to the application of a guanylate cyclase inhibitor for the preparation of a medicament for inhibiting myopia. The guanylate cyclase inhibitor serves as the myopia-inhibiting medicament to reduce the content of cGMP (guanosine-3',5'-cyclized-phosphate, cyclic guanosine monophosphate) and then, can inhibit the formation of animal experimental myopia.
Description
Technical field
The present invention relates to a kind of method for preparing that delays, suppresses the medicine of myopia, particularly utilize the guanylate cyclase inhibitor to reduce the application of cGMP (guanosine-3', 5'-cyclisation one phosphoric acid, cyclic guanosine monophosphate) level in suppressing near-sighted medicine.
Background technology
95% human myopia all is excessively to prolong and utmost point portion's sclera remarkable attenuation in back is a principal character with axis oculi.Human and mammiferous scleral tissue mainly is made up of cell component (is main with fibroblast) and extracellular matrix, and extracellular matrix is secreted by the sclera cell.In the myopia progression process, the cell component in the sclera is accepted the input of the upper reaches (retina or maincenter) signal, and the adjustment extracellular matrix constitutes; Comprise synthetic the minimizing and the degraded acceleration, finally cause the sclera attenuation, bio-mechanical property changes; Cause that finally axis oculi excessively prolongs, myopia forms.The pathological change of the sclera particularly attenuation of back utmost point portion sclera possibly be the key link that myopia forms.
The extracellular matrix main component is collagen fiber, accounts for 90% of sclera dry weight, and is wherein the highest with I Collagen Type VI content.In normal mammalian and people's eye sclera, collagenous fiber bundle is the unordered state that interweaves, thereby has kept the opaqueness of sclera.In addition, the collagen fiber diameter appears by thin to thick graded from inside to outside, and showing as episcleral layer is main with the collagen fiber of particle size, and internal layer is main with the collagen fiber in thin footpath then.The formation of this sclera holostrome of bibliographical information collagen fiber diameter gradient is relevant with the tolerant pressure effect to wall of eyeball of ophthalmic.Zooperal result finds that after high myopia took place, the sclera collagen content reduced (mainly being I, III, V-type), sclera attenuation; Significant change has also taken place in the arrangement of collagen fiber.Collagen fiber are the layer structure of ordered arrangement by the unordered state-transition that interweaves, and sclera holostrome collagen diameter Gradient distribution disappears.
Except structural variation, a series of biochemistry has also taken place in the sclera changed.Dan Baijutang is a kind of glycoprotein that extensively exists in the sclera, forms the regulatory factor that it is considered to the collagen fiber assembling and arranges by core protein and the secondary chain of glycosaminoglycans.In experimental myopia, Dan Baijutang is synthetic to reduce the degraded increase, and the prolongation degree of vitreous chamber is negative correlation in the synthetic ratio of back utmost point portion sclera Dan Baijutang and the near-sighted forming process.In addition, matrix metalloproteinase family (MMPs) in the extracellular matrix and TIMP (TIMPs) regulate and control the process that sclera is reinvented jointly.MMPs promotes the degraded of collagen and other extracellular matrix components, and TIMPs then can suppress this effect of MMPs, and the balance of two kinds of strength is very important for the normal condition of keeping sclera.Find all that in kinds of experiments property myopia studies the mRNA level of experimental eye MMP-2 obviously raises to branch hole, and recover normal gradually in myopia its level of convalescent period.Opposite, the TIMP-3 level reduces when myopia and raises to some extent in convalescent period.
More than research all show sclera possibly be the secreted extracellular matrix composition of most important target tissue in the development of myopia process, particularly sclera cell variation with myopia incidence and development closely bound up.CGMP (guanosine-3', 5'-cyclisation one phosphoric acid, cyclic guanosine monophosphate) is the second message,second messenger who extensively exists in the cell; Through activating guanylate cyclase (Guanylate cyclase with the link coupled G albumen of receptor; GC), catalysis GTP generates cGMP, the further activated protein kinase G of cGMP (protein kinase G; PKG) or cyclic nucleotide ion channel etc., bring into play corresponding physiological function.Discover that cGMP all has its Growth and Differentiation of inhibition and the excretory effect of extracellular matrix to polytype fibroblast.(2008) such as Peng Li are discovered at myocardial cell; The activation energy of ANP/cGMP/PKG signal pathway is disturbed TGF-β 1 inductive pSmad3 nuclear translocation, thereby suppresses the expression of 1 inductive myofibroblast proliferation and differentiation of TGF-β and extracellular matrix molecule.In addition, secretion and collagen that the activation of discovery such as Yi-Chiang Hsu (2007) NO/cGMP path can suppress scar tissue fibroblast TGF-β 1 synthesize, thereby suppress the hyperplasia of cicatrix.And the relevant report that cGMP level and myopia take place seldom; In the Cavia porcellus except the present form deprivation property myopia of (2007) Crinis Carbonisatus such as Jie Wu; Thereafter NOS and cGMP concentration raise in the utmost point portion sclera, infer the cGMP level variation maybe certain be got in touch with the existence of myopia.Do not find to raise or reduce the effect of cGMP but up to the present still have to myopia.
Summary of the invention
The object of the present invention is to provide a kind of method that suppresses near-sighted medicine for preparing.
For realizing above-mentioned purpose, the technical scheme that the present invention adopts is: the guanylate cyclase inhibitor that reduces the cGMP level suppresses the application in the near-sighted medicine in preparation.
As preferred version, said guanylate cyclase inhibitor adopts NS-2028.
The invention has the beneficial effects as follows:, can delay, suppress myopia effectively through reducing the effect of ophthalmic cGMP.
Description of drawings
Accompanying drawing 1 is experimental eye and offside refraction of eye degree differential chart.
Accompanying drawing 2 is experimental eye and offside camera vitrea bulbi degree of depth differential chart.
Accompanying drawing 3 is experimental eyes and to branch hole axiallength differential chart.
In the accompanying drawing, " difference " refers to the difference of experimental eye and offside refraction of eye degree or axis oculi parameter; " * " representes P < 0.05; " * * " representes P < 0.01.
The specific embodiment
Laboratory animal be 3 the week age Britain plant trichroism undercoat Cavia porcellus.Adopt the face shield method to carry out 2 weeks of simple eye form deprivation (FDM), give the injection of form deprivation eye variable concentrations guanylate cyclase inhibitor (GCI) NS-2028 1ml ball week simultaneously every day.Animal is divided into 4 groups at random: and the form deprivation matched group (FDM+non-injection), form deprivation+solvent control group (FDM+vehicle), form deprivation+drug group (FDM+0.1 μ M NS-2028 group and FDM+ 1 μ M NS-2028 group).Medicine is injected in 9 of every mornings to carry out, and injects for 2 weeks continuously, then will not any processing to branch hole.In Mus ages 3 (before the experiment), 4,5 weeks, use infrared eccentric photorefractor to measure diopter, keratometer measurement corneal curvature, the ultra axis oculi parameter of measuring of A.
The result finds the form deprivation eye of administration group, and its vitreous chamber and axis oculi prolong degree and dioptric myopic degree all less than form deprivation group and solvent control group merely, compares with solvent control group to have statistical significance.Therefore, ball week injection guanylate cyclase inhibitor (ACI) NS-2028 can suppress the formation of Cavia porcellus form deprivation property myopia.
Can be found out that by Fig. 1 Mus is during 5 weeks of age, simple form deprivation group and form deprivation injection solvent group form myopia amount zero difference, explain that injection and solvent do not have influence to form deprivation.Administration forms the myopia amount all less than group of solvents for two groups, explains that guanylate cyclase inhibitor NS-2028 can suppress the formation of form deprivation property myopia.
Can be found out that by Fig. 2 Mus is during 5 weeks of age, simple form deprivation group and form deprivation injection solvent group vitreous chamber prolong zero difference, explain that injection and solvent do not have influence to form deprivation.Two groups of vitreous chambers of administration prolong all less than group of solvents, explain that guanylate cyclase inhibitor NS-2028 can suppress the prolongation of form deprivation vitreous chamber.
Can be found out that by Fig. 3 Mus is during 5 weeks of age, simple form deprivation group and form deprivation injection solvent group axis oculi prolong zero difference, explain that injection and solvent do not have influence to form deprivation.Two groups of axis oculi of administration prolong all less than group of solvents, explain that guanylate cyclase inhibitor NS-2028 can suppress the prolongation of axis oculi behind the form deprivation.
Claims (2)
1. the guanylate cyclase inhibitor that reduces the cGMP level suppresses the application in the near-sighted medicine in preparation.
2. guanylate cyclase inhibitor according to claim 1 suppresses the application in the near-sighted medicine in preparation, and it is characterized in that: the model of said guanylate cyclase inhibitor is NS-2028.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2011103992630A CN102512677A (en) | 2011-12-06 | 2011-12-06 | Application of guanylate cyclase inhibitor to preparation of medicament for inhibiting myopia |
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| CN2011103992630A CN102512677A (en) | 2011-12-06 | 2011-12-06 | Application of guanylate cyclase inhibitor to preparation of medicament for inhibiting myopia |
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| CN102512677A true CN102512677A (en) | 2012-06-27 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1179979A (en) * | 1996-10-03 | 1998-04-29 | 株式会社Lg化学 | Ophithalmic formulation for treating myopia comprising dopamine agonist and cyclodextrin |
| WO2005046660A1 (en) * | 2003-11-13 | 2005-05-26 | Cell Center Cologne Gmbh | MODULATING SUBSTANCES OF THE NITRIC OXID (NO) - CYCLIC GUANOSINE - 3’,5’- MONOPHOSPHATE (cGMP) SIGNALING PATHWAY FOR THE TREATMENT OF DENTAL DISORDERS |
| CN102078614A (en) * | 2010-12-27 | 2011-06-01 | 温州医学院眼视光研究院 | Method for inhibiting shortsightedness and application of adenylate cyclase inhibitor as medicament for inhibiting shortsightedness |
-
2011
- 2011-12-06 CN CN2011103992630A patent/CN102512677A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1179979A (en) * | 1996-10-03 | 1998-04-29 | 株式会社Lg化学 | Ophithalmic formulation for treating myopia comprising dopamine agonist and cyclodextrin |
| WO2005046660A1 (en) * | 2003-11-13 | 2005-05-26 | Cell Center Cologne Gmbh | MODULATING SUBSTANCES OF THE NITRIC OXID (NO) - CYCLIC GUANOSINE - 3’,5’- MONOPHOSPHATE (cGMP) SIGNALING PATHWAY FOR THE TREATMENT OF DENTAL DISORDERS |
| CN102078614A (en) * | 2010-12-27 | 2011-06-01 | 温州医学院眼视光研究院 | Method for inhibiting shortsightedness and application of adenylate cyclase inhibitor as medicament for inhibiting shortsightedness |
Non-Patent Citations (1)
| Title |
|---|
| 文丹等: "近视豚鼠视网膜超微结构改变及环磷酸鸟苷的表达", 《中南大学学报( 医学版)》 * |
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Application publication date: 20120627 |