| 摘要 |
595984 The present disclosure relates to methods for producing particles of a biologically active material using dry milling processes as well as compositions comprising such materials, medicaments produced using said biologically active materials in particulate form and/or compositions, and to methods of treatment of an animal, including man, using a therapeutically effective amount of said biologically active materials administered by way of said medicaments. The method comprises the steps of: Dry milling a solid biologically active material, a facilitating agent and a millable grinding matrix selected from: lactose anhydrous, lactose monohydrate and mannitol, in a mill comprising a plurality of milling bodies, for a time period sufficient to produce particles of the biologically active material dispersed in an at least partially milled grinding material, Wherein the average particle size, determined on a particle number basis, is equal to or less than 2000 nm, or Wherein the particles have a median particle size, determined on a particle volume basis, equal or less than 2000 nm, and Wherein the total combined amount of biologically active material and grinding matrix in the mill at any given time is selected from the group consisting of: 1 kg, 2kg, 5 kg, 10 kg, 20 kg, 30 kg, 50 kg, 75 kg, 100 kg, 150 kg, 200 kg, 500 kg, 1000 kg, 1500kg and 2000 kg. Bioactive materials used in the method may include: cyclosporin A, progesterone, celecoxib, cilostazol, ciprofloxacin, 2,4-dichlorophenoxyacetic acid, anthraquinone, creatine monohydrate, glyphosate, halusulfuron, mancozeb, metsulfuron, salbutamol, sulphur, tribenuran and estradiol Facilitating agents used in the method may include surfactants such as: sodium lauryl sulfate, sodium docusate, sodium deoxycholate, Nlauroylsarcosine sodium salt, benzalkonium chloride, cetylpyridinium chloride, cetylpyridinium bromide, benzethonium chloride, PEG 40 stearate, PEG 100 stearate, poloxamer 188, Brji 72, Brji 700, Brji 78, Brji 76, Cremophor EL, Cremophor RH-40, Dehscofix920, Kollidon 25, Kraftsperse 1251, Lecithin, Poloxamer 407, polyethyleneglycol 3000, polyethyleneglycol, 8000, polyvinylpyrrolidone, sodium dodecylbenzenesulphonic acid, sodium octadecyl sulphate, sodium pentane sulphonate, soluplus HS15, Teric305, Tersperse 2700, Terwet 1221, Terwet 3785, Tween 80 and polysorbate 61. |
