Use of penetrant for preparation of medicament for treatment of ocular disorders

A technology of penetrants and uses, applied in the field of penetrants, can solve problems such as high cost of surgical intervention

Pending Publication Date: 2022-05-27
SINGAPORE HEALTH SERVICES PTE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Furthermore, current surgical interventions are costly, require the effort and time of a trained corneal surgeon, and most importantly require high-quality donor corneal tissue

Method used

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  • Use of penetrant for preparation of medicament for treatment of ocular disorders
  • Use of penetrant for preparation of medicament for treatment of ocular disorders
  • Use of penetrant for preparation of medicament for treatment of ocular disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Example 1: Inhibitory effect of osmotic agents on amyloid fibrillation

[0066] In the present study, a 23 amino acid long peptide from the fourth FAS1 domain of TGFBIp (TGFBIp611-633c.623G>R) with a rapidly forming amyloid fibril-forming substitution G623→R (EPVAEPDIMATNRVVHVITNVLQ) was used. Peptides were dissolved (0.6 mg / ml) in PBS and allowed to form amyloid fibrils in 50 ml Falcon tubes with and without the addition of osmotic agents in a shaking incubator at 37°C and 180 rpm. To study the effect of osmotic agents on amyloid fibrillation kinetics, the model peptide TGFBIp 611-633 G623R was treated with 200 mM betaine, raffinose, sarcosine and taurine (Sigma-Aldrich Inc., MO, USA), respectively, and its chemical structure is shown in figure 1 Treatment in 50 ml Falcon tubes for 24 hours (h), 48 hours and 72 hours, respectively, is indicated. TGFBIp incubated with PBS 611-633 The G623R peptide was used as a control.

[0067] Thioflavin T (ThT) assay:

[0068] P...

Embodiment 2

[0090] Example 2: Effect of osmotic agents on deaggregation of preformed amyloid fibrils

[0091] In vitro amyloid fibrillation:

[0092] TGFBIp 611-633 The G623R peptide was incubated in PBS for 24 hours to allow the formation of homogeneous amyloid fibrils. Then for TGFBIp 611-633 G623R peptide solutions were subjected to circular dichroism spectroscopy to confirm the formation of amyloid fibrils. The results showed an absorption minimum of about 218 nm and an absorption maximum of about 195 nm, which is very typical of the β-sheet rich secondary structure of amyloid fibrils. This indicates that the peptide forms amyloid fibrils within 24 hours.

[0093] Thioflavin T (ThT) assay:

[0094] Peptide solutions containing pre-formed amyloid fibrils were treated with 200 mM betaine, raffinose, sarcosine and taurine each in 50 ml Falcon tubes for 24 hours (h), 48 hours and 72 hours, respectively. A solution of preformed amyloid fibrils incubated with PBS was used as a control...

Embodiment 3

[0109] Example 3: Synergistic effect of taurine and sarcosine on amyloid fibrillation inhibition and preformed amyloid fibril deaggregation To investigate the effect of taurine and sarcosine on amyloid fibrillation inhibition The synergistic effect of the model peptide TGFBIp 611-633 G623R was treated with 100 mM taurine and 100 mM sarcosine (Sigma-Aldrich Inc., MO, USA) in 50 ml Falcon tubes for 24 hours (h), 48 hours and 72 hours, respectively, and the results were as follows Figure 9 shown. To investigate the synergistic effect of taurine and sarcosine on the deaggregation of preformed amyloid fibrils, the model peptide TGFBIp 611- 633 Pre-formed amyloid fibrils of G623R were treated with 100 mM taurine and 100 mM sarcosine (Sigma-Aldrich Inc., MO, USA) in 50 ml Falcon tubes for 24 hours (h), 48 hours and 72 hours, respectively, which The result is as Figure 10 shown.

[0110] Thioflavin T (ThT) fluorescence assay, circular dichroism (CD) assay, and ThT fluorescence ...

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Abstract

The invention provides an application of a penetrant in preparation of a medicine for treating protein aggregation related disorders, and particularly provides an application of a penetrant in preparation of a medicine for treating TGFBI corneal dystrophy. The penetrant is selected from betaine, raffinose, sarcosine, taurine and / or any pharmaceutically acceptable derivative thereof.

Description

technical field [0001] The present disclosure generally relates to the use of osmotic agents in the manufacture of a medicament for the treatment of protein aggregation-related disorders, and in particular to the use of an osmotic agent in the manufacture of a medicament for the treatment of TGFBI corneal dystrophy. Background technique [0002] The cornea is a highly transparent and avascular tissue that forms the front of the ocular surface. The human cornea has five distinct layers, namely: epithelium, Bowman's membrane, stroma, Descemet's membrane, and endothelium. Maintaining corneal transparency is critical for vision. The diameter of collagen fibers in each layer of the cornea is highly uniform, and the distance between fibers is also highly uniform, which is a necessary prerequisite for corneal transparency. Any defect or deformation of the above components will affect vision. [0003] Corneal dystrophies are a class of bilateral, symmetric, and heterogeneous gene...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/205A61K31/702A61K31/195A61K31/185A61P27/02
CPCA61K31/205A61K31/702A61P27/02A61K31/185A61K45/06A61K31/198A61K9/0048A61K9/08A61K2300/00A61K31/145
Inventor J·S·梅塔拉克什米纳拉亚南·R阿南达拉克什米·文卡特拉曼
Owner SINGAPORE HEALTH SERVICES PTE
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