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Method and composition for enhancing the delivery of Anti-platelet drugs for the treatment of acute stroke

a technology of anti-platelet drugs and compositions, applied in the direction of drug compositions, peptide/protein ingredients, extracellular fluid disorders, etc., can solve the problems of increasing the mortality rate of mice in the stroke model, the risk of death due to high degree of hemorrhage cannot be avoided, and the patient suffering from acute or chronic cerebrovascular diseases becomes a huge burden on the medical care system, so as to enhance the delivery of anti-platelet drugs, reduce the binding rate of plasma proteins

Inactive Publication Date: 2015-03-05
LIN JEN CHENG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention provides a method for delivering an anti-platelet drug to treat acute stroke using a composition that reduces the binding of plasma proteins. This allows for a lower dose of the drug to be used. The drug is a phosphodiesterase inhibitor and is delivered using a polymeric vehicle or liposome. The polymeric vehicle is made of a specific polymer and a specific solvent. The method involves forming a nanoparticle of the drug and vehicle that reduces the binding of plasma proteins. The polymeric vehicle is made of a specific polymer and a specific solvent. The technical effect is an improved delivery of the anti-platelet drug for the treatment of acute stroke.

Problems solved by technology

The technical problem addressed in this patent text is the development of a delivery system for an anti-platelet drug (dipyridamole) to treat acute stroke using a vehicle that can reduce the binding rate of plasma proteins. This system aims to improve the efficacy and safety of the drug while minimizing the risk of side effects.

Method used

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  • Method and composition for enhancing the delivery of Anti-platelet drugs for the treatment of acute stroke
  • Method and composition for enhancing the delivery of Anti-platelet drugs for the treatment of acute stroke
  • Method and composition for enhancing the delivery of Anti-platelet drugs for the treatment of acute stroke

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example

Example 1

Synthesis of the Nanoparticle Vehicle of (poly(lacitide-co-glycolide)-(ethylene glycol-(poly(lacitide-co-glycolide) (PLCA-PEG-PLGA) (PEP) Polymer and Dipyridamole

[0037]1.1 Synthesis of (poly(lacitide-co-glycolide))-(ethylene glycol)-(poly(lacitide-co-glycolide) (PLGA-PEG-PLGA)

[0038]As shown in reaction diagram I below, lactide (LA), glycolide (GA) and poly ethylene glycol) 2000 (PEG2000) monomers which were purchased from the Sigma (Steinheim, Germany) were added into a 250 mL flask, and the flask was sealed after nitrogen was introduced to the flask and heated while stirring in a 140° Coil bath. After the monomers were completely dissolved, 0.005 wt % of stannous octoate was added, and the mixture was heated and reacted while stirring for 8 hours and then static-cooled down. De-ionized water was added into the reactants and the mixture was stirred at 5° C. until the ingredients were complete dissolved to provide an aqueous solution. The solution was then heated to 70° C. ...

example 2

Analysis of the Inclusion Rate and Particle Size Distribution of the Nanoparticles of PLGA-PEG-PLGA High Molecular and Dipyridamole

[0044]High-performance liquid chromatography (HPLC) (fluorescence detector (Shimadzu, Japan)) was employed to analyze the Dipyridamole nanoparticles of the invention. The Dipyridamole nanoparticles were filtered with a 0.45 μm filter membrane to ensure that Dipyridamole is kept at a constant size so as to control the particle size that encapsulates the drug. The concentration of Dipyridamole before membrane filtration is designated as CTotal; the concentration of Dipyridamole after membrane filtration is designated as C. The formula for calculating the encapsulation rate (%) is C / CTotal×100%. The calculated encapsulation rate of the nanoparticles of PLGA-PEG-PLGA polymer and Dipyridamole is about 50%, wherein the content of Dipyridamole is about 2.0 mg / mL.

[0045]X Laser Particle Size Analyzer (Zetasizer, category no. 3000 HAS, Melven, UK) was employed to ...

example 3

Establishment of Ischemic Brain Occlusion Model

[0046]In order to simulate human brain stroke, an intravascular suture-occluded method was employed to establish a middle cerebral artery occlusion (MCAO) model in mice. Prior to experimentation, the body weights of the mice were measured and rectum temperatures were recorded. The mice were anesthetized with 4% halothane in 100% O2 followed by 0.5-1% halothane in 70% N2O and 30% O2 to maintain the anesthetized status. The mouse cerebral artery occlusion model is established according to the Tamura method (Focal cerebral ischemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb Blood Flow Metab. 1981;1(1):53-60. Tamura A, Graham D I, McCulloch J, Teasdale G M). The mouse was secured in prone position and an incision was introduced to the lateral of the head and neck portion by a scalpel to expose the right common carotid artery. The middle cerebral artery...

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Abstract

The invention provides a method for enhancing the delivery of an anti-platelet drug for the treatment of acute stroke, comprising delivering a composition comprising an anti-platelet drug and a vehicle that can reduce the binding rate of plasma proteins, so that the anti-platelet drug can achieve the effect of treating acute stroke at a low dose. By use of the neuro-protective efficacy of anti-platelet drug, the invention allows the drug to release slowly to the site of treatment by combining anti-platelet drugs with a vehicle that can reduce the binding rate of plasma proteins to effectively reduce the dose of the anti-platelet drug and consequently reduce the side effects such as hypotension caused by, administration of a high dose of the anti-platelet drugs. The invention also provides a pharmaceutical composition for enhancing treatment of acute stroke and a method for treating acute stroke using the pharmaceutical composition of the invention.

Description

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Claims

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Application Information

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Owner LIN JEN CHENG
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