Pharmaceutical composition and uses thereof

a technology of pharmaceutical compositions and compositions, applied in the field of pharmaceutical compositions, can solve the problems of abnormal elongation of the eye, untreatable blindness, and non-treatable pathologic changes of high myopia patients, and achieve the effect of reducing one or more chondrogenic proteins and reducing scleral chondrogenesis

Inactive Publication Date: 2016-03-10
KAOHSIUNG CHANG GUNG MEMORIAL HOSPITAL +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006]Pharmaceutical compositions comprising two anti-chondrogenesis agents are provided herein. The pharmaceutical compositions are effective in treating myopia, reducing one or more chondrogenic proteins and reducing scleral chondrogenesis.

Problems solved by technology

Maculopathy of high myopia has become the leading cause of cataract, glaucoma, retinal detachment, myopic retinal degeneration, visual impairment, and untreatable blindness.
These therapies, however, do not address the abnormal elongation of the eye and thus do not treat pathologic changes of high myopia patients.

Method used

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  • Pharmaceutical composition and uses thereof
  • Pharmaceutical composition and uses thereof
  • Pharmaceutical composition and uses thereof

Examples

Experimental program
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Effect test

example 1

SSPC Morphology Change After TGF-β Treatment

[0074]An in vitro study of the SSPC morphology change after TGF-β treatment was performed. SSPC was incubated with TGF-β2 treatment (0.1-10 ng / ml) for 24 hrs as previously described. Microscopy study shows without TGF-β2 treatment or at a low concentration of TGF-β2 treatment (0.1 ng / ml), many SSPCs had thin spindle shape and showed a widened phenotype. In addition, the cytoskeleton filaments of SSPCs were not prominent. After exposing to a higher concentration of TGF-β2 (1 to 10 ng / ml), SSPCs became broad with prominent cytoskeletal filaments. Immunofluorescence microscopy showed an increased number of α-SMA positive SSPCs (with prominent intracellular α-SMA filament staining) after treatment with 10 ng / ml of TGF-β2.

example 2

Effect of TGF-β Treatment on α-SMA and Col2 Expression

[0075]An in vitro study of the effect of TGF-β treatment on α-SMA and Col2 expression was performed using SSPC and 3-D pellets of SSPCs. SSPCs and 3-D pellets of SSPC were treated with various concentrations of TGF-β2, as previously described.

[0076]Total mRNA was analyzed to determine whether there was any alteration in α-SMA and Col2 gene expression after 0.1 to 10 ng / ml of TGF-β2 treatment for 24 hrs. FIG. 2 shows there is a statistically significant increase in α-SMA and Col2 gene expressions after TGF-β2 treatment using quantitative Real Time-PCR analysis, in a dose dependent manner (p<0.0001 and =0.011 respectively).

[0077]SSPC pellets were cultured in control medium and medium containing 10 ng / ml of TGF-β2 (TM-pellets) for 4 weeks. Histological analysis showed that most SSPC were located in the midperipheral and peripheral area which surrounded the central matrix tissue in TM-pellets. Immunohistochemical analysis showed Col2...

example 3

The Expression of Col2 and α-SMA in Sclera of FDM Mice

[0078]An in vivo study evaluating the expression of Col2 and α-SMA in the sclera was evaluated using FDM Mice. FDM was induced in the right eye of the mouse as described previously and the left eye served as a control. The differences between the two eyes of each mouse in axial length was not significant at the beginning (p=0.378). By Day 21, form deprived eyes had myopia with an axial length of 3055±39 μm which was significantly longer than the contralateral control eyes (3015±40 μm, p<0.001)

[0079]FIG. 3 shows after 21 days of visual deprivation, the expressions of Col2 and α-SMA were higher in the sclera of FDM eyes using western blot analysis. FIGS. 3A and 3B show the expressions of Col2 and α-SMA in FDM eyes were significantly higher than contralateral control eyes in the same mouse (P=0.021 for Col2 and (p=0.042 for α-SMA). Immunostaining shows Col2 expression was higher in the scleral region of the FDM eyes than in the cont...

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Abstract

Pharmaceutical compositions containing a combination of anti-chondrogenesis agents are disclosed. Methods of reducing scleral chondrogensis, reducing one or more ocular chondrogenic proteins, reducing inflammation induced chondrogensis and treating myopia by administering an effective amount of one or more anti-chondrogensis agents are also provided. The pharmaceutical compositions are useful for treating myopia.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Application No. 61 / 819,709, filed on 6 May 2013, the entire disclosure of which is incorporated herein by reference.TECHNOLOGY FIELD[0002]The present invention relates to pharmaceutical compositions and methods for the treating myopia, inhibiting ocular chondrogenic protein, scleral chondrogenesis and inflammation induced chondrogenesis.BACKGROUND OF THE INVENTION[0003]Myopia is due to progressive elongation of the eye and stretching of the ocular tissues. It is an important public health issue, as it affects approximately 25% of the LS, population, and as high as 80% of the population in some Asian countries. Maculopathy of high myopia has become the leading cause of cataract, glaucoma, retinal detachment, myopic retinal degeneration, visual impairment, and untreatable blindness.[0004]Optical and laser surgical corrective techniques have been used to alter the refractive state of the myopic eye...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/196A61K31/46A61K31/407
CPCA61K31/46A61K31/196A61K31/407A61K45/06A61K31/165A61K31/192A61K31/405A61P19/00A61P27/02A61P27/10A61P29/00A61P43/00A61P9/00A61K2300/00
Inventor WU, PEI-CHANGTSAI, CHIA-LINGCHEN, CHUEH-TAN
Owner KAOHSIUNG CHANG GUNG MEMORIAL HOSPITAL
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