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Drug delivery system for the treatment of vascular diseases

A drug delivery system and technology for vascular diseases, applied in the field of drug delivery systems for treating vascular diseases

Inactive Publication Date: 2011-12-28
ACADEMISCH MEDISCH CENT BIJ DE UNIV VAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] Since existing laser treatments are ineffective in about 60% of cases, the purpose of this case was to provide a way to improve the clearance rate

Method used

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  • Drug delivery system for the treatment of vascular diseases
  • Drug delivery system for the treatment of vascular diseases
  • Drug delivery system for the treatment of vascular diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0163] Preparation of the drug delivery system of the present invention.

[0164] Several possible combinations of drug delivery systems that can be used in SSPLT are in Figure 4 are displayed in . The formulation of the different liposomal delivery systems is described below.

[0165] 1. A heat-sensitive liposome encapsulating an antifibrinolytic agent (tranexamic acid).

[0166] 1,2-Dipalmitoyl-sn-glycerol-3-phosphatidylcholine (DPPC) and 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphatidylcholine (MPPC) are both derived from Avanti polar Butter (Alabaster, Alabama). The sodium salt of HEPES [4-hydroxyethylpiperazineethanesulfonic acid] was from Sigma Aldrich (St. Louis, MO). Tranexamic acid (4-(aminomethyl)cyclohexane-1-carboxylic acid, TA) was purchased from Fluka (Buchs, Switzerland). All other reagents were of analytical grade.

[0167] The large single-layer blastocyst prepared by extrusion technology was prepared from DPPC:MPPC at a molar ratio of 90:10. DPPC was ...

Embodiment 2

[0188] Features of the drug delivery system of the present invention

[0189] 1. Determination of the physicochemical characteristics of the drug delivery system

[0190] Physicochemical characterization of liposome size and polydispersity (measurement of particle size distribution) of liposome delivery systems was performed in equilibration buffer (10 mM HEPES, 0.88% (w / v) NaCl, pH=7.4, 0.291 kilograms of osmol / kg) after diluting, obtain with measurement photon correlation spectrum using single peak analysis (British Malvern instrument, Malvern laser particle size analyzer 3000) at 90 ° angle. The results for several alternative formulations are shown in Figure 8 .

[0191] The phase transition temperature of liposomes was measured by differential scanning calorimetry (MICROCAL, Northampton, MA) after diluting liposomes with equilibration buffer to a final lipid concentration of 3 mM. Equilibration buffer is used as a reference. The results for the two candidate formul...

Embodiment 3

[0217] Drug release of drug delivery system of the present invention

[0218] 1. Heat-induced release of tranexamic acid from polyethylene glycol thermosensitive liposomes

[0219] Quantification of the heat-induced release of tranexamic acid released from heat-sensitive large unilamellar blastocysts (LUVETs) prepared by the extrusion technique was determined by the formula DPPC:DSPE-PEG (96:4 molar ratio) and DPPC:MPPC:DSPE- PEG (86:10:4 molar ratio) was prepared.

[0220] Prior to heat treatment, gel-filtered LUVET suspensions were diluted ten-fold with equilibration buffer kept at 4 °C. 20 μL of gel-filtered LUVET suspension was diluted 50 times (n=3 per experiment) and the total intravascular TA concentration was measured by fluorescence spectroscopy (final dilution was 1250 times). The average overall TA concentration was used to calculate the percentage of TA molecules released.

[0221] After equilibrating for 5 minutes at 4°C, and before heat-induced drug release,...

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Abstract

The present invention relates to a drug delivery system for use in the treatment of vascular and vessel-related pathologies, comprising a drug delivery platform that comprises at least one compound capable of exerting an effect on the formation and / or maintenance of a thrombus in the vessel to be treated. The platform is preferably formed by liposomes that are sterically stabilized by grafting of poly(ethylene glycol) onto the liposome surface. The liposomes may further comprise photosensitizers and targeting molecules. The liposomes may be thermosensitive. The compound is suitably tranexamic acid. The drug delivery system is preferably used for the treatment of port wine stains.

Description

Technical field: [0001] The invention relates to a drug delivery system for treating vascular diseases, more specifically a drug delivery system for treating port-wine stains (port-wine stains) by selective photothermolysis. Background technique: [0002] Port-wine stains (hereinafter referred to as PWS) are congenital vascular lesions, which mainly manifest as dilation of capillaries in the papillary and middle reticular dermis and posterior capillaries (30-300 microns in diameter). These birthmarks occur in 0.3-0.5% of neonates and begin as flat pink spots that progress to red to purple hypertrophic lesions in direct proportion to patient age. Although its etiology remains unknown, the progressive hypertrophy of the lesion is thought to result from too low a density of nerves around the dilating vessels, leading to neurotrophic deficiency and tonic spasmodic modulation of the damaged vasculature. Increased perfusion pressure and age-related collagen degradation in the der...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K31/198A61K47/48
CPCA61K47/48823A61K41/0071A61K41/0028A61K9/1272A61K9/1271A61K47/6913A61P7/00A61P7/02A61P9/00
Inventor 麦克海洛
Owner ACADEMISCH MEDISCH CENT BIJ DE UNIV VAN
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