Injectable compositions of nanoparticulate immunosuppressive compounds

A nanoparticle and composition technology, applied in the field of injectable nanoparticle compositions, can solve the problems not mentioned etc.

Inactive Publication Date: 2008-05-07
ELAN PHRMA INT LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The '684 patent also describes methods of preparing such nanoparticulate active agent compositions, but does not mention compositions containing tacrolimus in nanoparticulate form

Method used

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  • Injectable compositions of nanoparticulate immunosuppressive compounds
  • Injectable compositions of nanoparticulate immunosuppressive compounds
  • Injectable compositions of nanoparticulate immunosuppressive compounds

Examples

Experimental program
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Embodiment 1

[0211] The purpose of this example was to prepare a nanoparticulate tacrolimus formulation suitable as an injectable dosage form. Figure 1 shows a 100X optical micrograph of unmilled tacrolimus taken with phase optics.

[0212] 10% (w / w) tacrolimus (Camida LLC) water dispersion in NanoMill  0.01 (NanoMill Systems, King of Prussia, PA; see e.g. US Pat. No. 6,431,478) in a 10 ml grinding chamber with 500 micron PolyMill  Milling media (Dow Chemical, 89% media load) were co-milled. The mixture was milled for 60 minutes at a speed of 2500 rpm.

[0213] After milling, the particle size of the milled tacrolimus particles was measured in deionized distilled water using a Horiba LA910 particle size analyzer. The initial average milled tacrolimus particle size was 192 nm, D50 was 177 nm, and D90 was 278 nm, as shown in Table 1. Figure 2 shows a 100X optical micrograph of milled tacrolimus taken with phase optics. In a second measurement in distilled water after refrigerated at ...

Embodiment 2

[0217] The purpose of this example was to prepare a nanoparticulate tacrolimus formulation suitable as an injectable dosage form.

[0218] A 10% (w / w) aqueous dispersion of tacrolimus (Camida LLC) combined with 2% PVP K12 and 0.15% sodium deoxycholate was prepared in the NanoMill  0.01 (NanoMill Systems, King of Prussia, PA; see e.g. US Pat. No. 6,431,478) in a 10 ml grinding chamber with 500 micron PolyMill  Milling media (Dow Chemical, 89% media load) were co-milled. The mixture was milled for 150 minutes at a speed of 2500 rpm.

[0219] After milling, the particle size of the milled tacrolimus particles was measured in deionized distilled water using a Horiba LA910 particle size analyzer. The average milled tacrolimus particle size was 329 nm, with a D50 of 303 nm and a D90 of 466 nm. Figure 4 shows a 100X optical micrograph of milled tacrolimus taken with phase optics.

[0220] The results indicated that a stable nanoparticulate tacrolimus formulation was successfull...

Embodiment 3

[0222] The purpose of this example was to prepare a nanoparticulate tacrolimus formulation suitable as an injectable dosage form.

[0223] Combined with 3% (w / w) Pluronic  20% (w / w) tacrolimus (Camida LLC) aqueous dispersion of S630 and 0.05% (w / w) DOSS in NanoMill  0.01 (NanoMill Systems, King of Prussia, PA; see e.g. US Patent 6,431,478) in a 10 ml grinding chamber with 500 micron PolyMill  Milling media (Dow Chemical, 89% media load) were co-milled. The mixture was milled for 60 minutes at a speed of 2500 rpm. A 100X optical micrograph of milled tacrolimus taken with phase optics is shown in FIG. 5 .

[0224] After milling, the particle size of the milled tacrolimus particles was measured in deionized distilled water using a Horiba LA910 particle size analyzer. The initial average milled tacrolimus particle size was 171 nm, with a D50 of 163 nm and a D90 of 230 nm, as shown in Table 2 below. In a second measurement in distilled water after refrigerated at <15°C for ...

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Abstract

The present invention relates to an injectable nanoparticulate immunosuppressant composition for the formation of a subcutaneous or intramuscular depot. The invention is also directed to an injectable composition of nanoparticulate tacrolimus and / or sirolimus which eliminates the need to use polyoxyl 60 hydrogenated castor oil (HCO-60) and / or polysorbate 80 as a solubilizer. This invention further discloses a method of making an injectable nanoparticulate tacrolimus and / or sirolimus composition and is also directed to methods of treatment using the injectable nanoparticulate formulations comprising tacrolimus, sirolimus, or combination thereof for a subcutaneous or intramuscular depot for the prophylaxis of organ rejection and for the treatment of psoriasis or other immune diseases.

Description

technical field [0001] The present invention relates to injectable nanoparticle compositions comprising at least one immunosuppressive compound. In an exemplary embodiment, the present invention describes injectable compositions of nanoparticulate immunosuppressive compounds such as tacrolimus, sirolimus, or combinations thereof. technical background [0002] A. Background on Immunosuppressive Compounds [0003] Examples of immunosuppressive compounds include, but are not limited to, tacrolimus and sirolimus. [0004] 1. Background on tacrolimus [0005] Tacrolimus, or FK-506, is a macrolide immunosuppressant that is said to be 100 times more potent than cyclosporine. It is produced by fermentation of Streptomyces tsukubaensis, a monotype species of Streptomyces. Tacrolimus is described in US Patent 4,894,366 and EPO Publication No. 0184162, the entire contents of which are incorporated herein by reference. [0006] Tacrolimus with PROGRAF  (available from Fujisawa US...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K9/00A61K31/4745
CPCA61K9/0019A61K9/145A61K9/143A61K9/146A61K9/0024A61K31/4745A61P37/06A61K9/16B82Y5/00
Inventor G·利弗西奇S·詹金斯
Owner ELAN PHRMA INT LTD
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