Formulations and methods for vascular permeability-related diseases or conditions
A vascular permeability and permeability technology is applied in the field of preparations for diseases or conditions related to vascular permeability, and can solve the problems of intractable pulmonary hypertension and low survival rate.
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0282] Example 1 Anti-permeability effect of rapamycin in the hamster cheek pouch model using VEGF
[0283] The hamster cheek pouch model was used to study the anti-permeability effects of rapamycin. In this model, tracer molecules are injected intravenously into hamsters, followed by various combinations of VEGF (permeability enhancer of hamster buccal pouch microcirculation), rapamycin (test compound), and various controls Administration to hamsters to determine their effect on VEGF-induced permeability. The levels of the tracer were determined by imaging using computer-aided digital image analysis. A higher integrated light intensity indicates a higher degree of transparency.
[0284] This protocol directly mimics the material and methods in Aramoto et al., Vascularendothelial growth factor stimulates differential signaling pathways in the in vivo microcirculation, Am J Physiolr Heart & Circ Physiol. 287: H1590-H1598, (2004) (“Aramoto 2004”) part; and has the following c...
Embodiment 2
[0307] Example 2 Anti-permeability effect of rapamycin in the hamster cheek pouch model using PAF
[0308] Analysis of the anti-permeabilization effect of rapamycin in response to platelet-activating factor (PAF). Use PAF (1-O-alkyl-2-acetyl-sn-3-glycero-phosphocholine; Sigma Chemical Co., St.Louis, MO) instead of VEGF to carry out the protocol of Example 1, the difference is Apply PAF topically through the side port to obtain 10 in the hamster cheek pouch compartment -7 M concentration. 0.5 mg / kg of RAPAMUNE was administered intraperitoneally 1 day before topical application of PAF and again 1 hour before topical application of PAF. A negative control of vehicle only and a positive control of (vehicle+PAF) were also used. There were 3 animals per treatment group.
[0309] Permeability data are shown in figure 2 middle. In figure legends, "R" refers to rapamycin treatment. PAF treatment resulted in significantly higher permeability levels than vehicle controls. Treatm...
Embodiment 3
[0311] Example 3 Effect of Rapamycin on Arteriole Diameter
[0312] The diameter of the arteriole measured using the MetaMorph imaging system was taken as the width of the epi-illuminated blood column. Two or three arterioles with a diameter of 20 to 30 μm were studied per animal. Baseline diameter measurements were normalized to a value of 1. For each vessel, the test diameter is expressed as a ratio of the baseline diameter (relative lumen diameter). To compare diameters before and after agonist application, diameters were measured at the same location in the target arteriole.
[0313] Arterial vasodilation data are shown in image 3 and Figure 4 middle. exist image 3 In each treatment group there were 3 animals. As noted in the legend to the figures, "R excipient" refers to the excipient of rapamycin. VEGF treatment resulted in a significant increase in relative lumen diameter compared to vehicle treatment. Vehicle pretreatment with rapamycin did not cause any si...
PUM
| Property | Measurement | Unit |
|---|---|---|
| diameter | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More