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Drug-containing nanoparticles

By using nanoparticle technology to deliver pioglitazone to unstable plaques, the shortcomings of existing drug-eluting stents in preventing acute coronary syndromes are solved, achieving effective treatment of atherosclerotic diseases and reducing systemic side effects.

Inactive Publication Date: 2012-11-21
KYUSHU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, DES currently used in the world contain immunosuppressants (such as sirolimus) or anticancer agents (such as paclitaxel), and compared with conventional bare metal stents (BMS), although DES can inhibit restenosis, it has been reported that Its long-term prognosis shows a higher incidence of acute coronary syndrome (ACS), a more lethal pathology than BMS, and it has also been shown not to improve vital prognosis
[0003] Therefore, the reason is speculated that although acute coronary syndrome is mainly caused by rupture of atherosclerotic plaque (plaque rupture), it is a relatively mild to moderate lesion rather than severe narrowing lesion (which is usually target of PCI), however, DES using immunosuppressants or anticancer agents inhibits restenosis by inhibiting neointimal thickening by preventing smooth muscle cell growth, and its nonspecific cell proliferation inhibition prevents endothelial Regenerates and forms unstable plaques that become thrombi, increasing the incidence of ACS

Method used

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Examples

Experimental program
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Effect test

preparation example Construction

[0044] Although the preparation method of the nanoparticles of the present invention is not particularly limited as long as it can process pioglitazone or a salt thereof and a biocompatible polymer into particles having an average particle size of less than 1,000 nm, a spherical crystallization method can preferably be used (spherical crystallization method), which is a non-high shear force particle preparation method.

[0045] The spherical crystallization method is a method of designing spherical crystal particles by controlling the crystal formation / growth process at the final stage of compound synthesis, and processing the particles by directly controlling their properties. One of spherical crystallization methods is an emulsion solvent diffusion method (ESD method).

[0046] The ESD method is a technique for preparing nanospheres by the following principle. In this method, two kinds of solvents are used: a good solvent that can dissolve lactic acid-glycolic acid copolyme...

Embodiment 1

[0102] Preparation of PLGA nanoparticles containing pioglitazone

[0103] An aqueous solution of 0.5 wt% polyvinyl alcohol (Gosenol EG-05 (registered trademark), manufactured by The Nippon Synthetic Chemical Industry Co., Ltd.) was prepared and used as a poor solvent. Separately, lactic acid-glycolic acid copolymer (PLGA7520, lactic acid / glycolic acid=75 / 25, weight average molecular weight 20,000, Wako Pure Chemical Industries, Ltd.) (1 g) was dissolved in acetone (40 mL), and mixed with methanol ( 20 mL) of pioglitazone hydrochloride (40 mg), and this mixture was used as a polymer solution. At 40° C., the solution was added dropwise to the previously obtained poor solvent at 4 mL / min while stirring at 400 rpm to obtain a PLGA nanoparticle suspension containing pioglitazone. Under reduced pressure, acetone and methanol were evaporated for 1.5 hours, and the residue was freeze-dried to obtain pioglitazone-containing PLGA nanoparticle powder.

[0104] The obtained powder had g...

Embodiment 2

[0209] (1) Preparation of chitosan-modified PLGA nanoparticles comprising pioglitazone

[0210] PLGA (PLGA7520, lactic acid / glycolic acid=75 / 25, weight average molecular weight 20,000, manufactured by Wako Pure Chemical Industries, Ltd.) (2 g) was dissolved in acetone (20 mL), and pioglitazone dissolved in methanol (10 mL) was added Hydrochloride (100 mg) to give a polymer solution. This solution was added dropwise to an aqueous solution (50 mL) of 2 wt% polyvinyl alcohol (PVA, manufactured by KURARAY CO., LTD.) at a constant rate of 4 mL / min at 40°C while stirring. At this time, nano-sized emulsion droplets are prepared because of self-emulsification caused by turbulence generated on the surface of emulsion droplets by interdiffusion of acetone, methanol, and water. Thereafter, acetone and methanol were evaporated, and the obtained PLGA nanoparticle suspension was centrifuged (centrifugal acceleration 41000G, -20°C, 20min) to obtain a PLGA nanoparticle precipitate, which was...

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Abstract

The present invention relates to nanoparticles containing pioglitazone or a salt thereof and a biocompatible polymer, a pharmaceutical preparation containing the nanoparticles for the prophylaxis or treatment of arteriosclerotic diseases, and a stent carrying the nanoparticles. Using the nanoparticles of the present invention, rupture of arteriosclerotic plaque can be suppressed, and they are useful for the prophylaxis or treatment of arteriosclerotic diseases.

Description

technical field [0001] The present invention relates to nanoparticles comprising pioglitazone or a salt thereof, and pharmaceutical preparations and stents comprising the nanoparticles. Background of the invention [0002] With advances in coronary intervention (percutaneous coronary intervention; PCI) techniques including drug-eluting stents (DES), restenosis, which is usually a concern of PCI, has decreased. However, DES currently used in the world contain immunosuppressants (such as sirolimus) or anticancer agents (such as paclitaxel), and compared with conventional bare metal stents (BMS), although DES can inhibit restenosis, it has been reported that Its long-term prognosis shows a higher incidence of acute coronary syndrome (ACS), a more lethal pathology than BMS, and it has also been shown not to improve vital prognosis. [0003] Therefore, the reason is speculated that although acute coronary syndrome is mainly caused by rupture of atherosclerotic plaque (plaque rup...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/51A61L31/00A61K31/4439
CPCA61K9/5153A61K31/4439A61L2300/422A61L2400/12A61L31/16A61K9/5161A61P3/06A61P9/00A61P9/10A61P9/14
Owner KYUSHU UNIV