A kind of sirolimus nano-suspension and preparation method thereof

A nano-suspension, sirolimus technology, which is applied in pharmaceutical formulations, medical preparations with inactive ingredients, and medical preparations containing active ingredients, etc., can solve the problems of high equipment requirements, easy metal residues, and high costs , to achieve the effect of good dispersion stability, low ethanol content and uniform particle size

Active Publication Date: 2019-06-28
NKD PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For drug nanosuspensions, the preparation methods mainly include grinding method, high-pressure homogenization method and liquid phase precipitation method. The first two methods use physical methods to break large particles of raw materials into nanoparticles, which are time-consuming and expensive. High, easy metal residues, high requirements for equipment, etc., and the anti-solvent recrystallization method is a physical and chemical method. First, the drug is dissolved in a water-miscible solvent, and then mixed with an aqueous solution. By controlling the relevant conditions, it can be The nano-suspension is prepared, the whole process is simple and fast, and can be produced continuously, but there is also the problem of adding organic solvents, which makes the nano-suspension require further follow-up treatment to remove the organic solvent, resulting in cumbersome preparation steps and a sharp increase in production costs. Scale-up and continuous preparation

Method used

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  • A kind of sirolimus nano-suspension and preparation method thereof
  • A kind of sirolimus nano-suspension and preparation method thereof
  • A kind of sirolimus nano-suspension and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0079] Embodiment 1: Preparation of low concentration sirolimus nanosuspension (0.5mg / mL)

[0080]

[0081] Dissolve the sirolimus bulk drug in 40 mL of ethanol at room temperature, and filter through a 0.22 μm filter membrane to obtain a sirolimus solution. Then dissolve polyethylene glycol 4000, Tween 80, methylcellulose, sucrose and sodium benzoate in 2000 mL of water at room temperature, add water to make up to 2624 mL, and filter through a 0.22 μm filter membrane to obtain an aqueous solution of excipients. Finally, the sirolimus solution was poured into the auxiliary material aqueous solution, and the stirring paddle was stirred at 500 rpm for one minute to obtain the sirolimus nanosuspension. The average particle size is 249nm as tested by a nanometer particle size analyzer.

Embodiment 2

[0082] Embodiment 2: the preparation of high concentration sirolimus nanosuspension (3mg / mL)

[0083]

[0084] Sirolimus raw material and methylparaben were dissolved in 80 mL of ethanol at room temperature, and filtered through a 0.22 μm filter membrane to obtain a sirolimus solution. Then, dissolve povidone K30, sodium alginate, hydroxypropyl methylcellulose and sorbitol in 2500 mL of water at room temperature, add water to make up to 3120 mL of water, and filter through a 0.22 μm filter membrane to obtain an aqueous solution of excipients. Finally, pour the sirolimus solution into the auxiliary material aqueous solution, and stir for one minute with a high-speed homogenizer at 10,000 rpm to obtain the sirolimus nanosuspension. The average particle size is 363nm as tested by a nanometer particle size analyzer. Embodiment 3: Preparation of medium concentration sirolimus nanosuspension (2mg / mL)

Embodiment 3

[0084] Sirolimus raw material and methylparaben were dissolved in 80 mL of ethanol at room temperature, and filtered through a 0.22 μm filter membrane to obtain a sirolimus solution. Then, dissolve povidone K30, sodium alginate, hydroxypropyl methylcellulose and sorbitol in 2500 mL of water at room temperature, add water to make up to 3120 mL of water, and filter through a 0.22 μm filter membrane to obtain an aqueous solution of excipients. Finally, pour the sirolimus solution into the auxiliary material aqueous solution, and stir for one minute with a high-speed homogenizer at 10,000 rpm to obtain the sirolimus nanosuspension. The average particle size is 363nm as tested by a nanometer particle size analyzer. Embodiment 3: Preparation of medium concentration sirolimus nanosuspension (2mg / mL)

[0085]

[0086]

[0087] Dissolve the sirolimus bulk drug in 40 mL of ethanol at room temperature, and filter through a 0.22 μm filter membrane to obtain a sirolimus solution. T...

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Abstract

The invention relates to sirolimus nano suspension and a preparation method thereof. The nano suspension comprises active component sirolimus, surfactant, a suspending agent, a sweetening agent, preservatives, ethanol and water, wherein the average particle size of the sirolimus nano particles is smaller than 400 nanometers, the concentration of the sirolimus nano particles is 0.5-3mg/mL, and the volume content of the ethanol is 1.5-2.5%. The preparation method adopts an anti-solvent recrystallization method and includes: a sirolimus-ethanol solution is added into an auxiliary aqueous solution, and fierce mixing is performed to obtain the nano suspension. The nano suspension has the advantages that the ethanol in the nano suspension needs not to be removed, the nano suspension can be directly used for finished-production filling, and the nano suspension is suitable for being taken by children.

Description

technical field [0001] The invention relates to a pharmaceutical preparation, in particular to a nano-suspension of an immunosuppressive drug sirolimus and a preparation method thereof, belonging to the field of pharmaceuticals. Background technique [0002] Sirolimus is a novel potent lipophilic triene nitrogen-containing macrolide antibiotic immunosuppressant. As a third-generation immunosuppressant, its effective anti-proliferation effect on peripheral blood mononuclear cells is 50-500 times stronger than that of cyclosporine. Due to its low nephrotoxicity, it was first launched in the United States in October 1999 as an anti-rejection drug for kidney transplantation. At the same time, sirolimus also has analgesic, antifungal, anti-inflammatory and anti-tumor effects. [0003] The commercially available sirolimus preparation abroad has two kinds of oral liquid and nano crystal tablet, and wherein oral liquid is with Phosal50PG (phosphatidylcholine, PEG, monoglyceride, d...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/10A61K31/436A61K47/12A61K47/10A61K47/32A61K47/20A61P37/02A61P19/02A61P3/10A61P9/00A61P9/10A61P37/06
CPCA61K9/0053A61K9/10A61K31/436A61K47/10A61K47/12A61K47/20A61K47/32
Inventor 陶秀梅张志兵
Owner NKD PHARMA CO LTD
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