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    • 60. 发明申请
    • Delivery of nucleic acid-like compounds
    • US20040037874A1
    • 2004-02-26
    • US10439856
    • 2003-05-15
    • Keelung HongWei-Wen ZhengDaryl C. DrummondDmitri B. KirpotinMark Eamon Hayes
    • A61K009/127A61K048/00
    • A61K9/1272A61K9/127A61K9/1271A61K31/711A61K48/0025A61K48/0041A61K48/0091
    • A process for preparing a microparticulate complex is provided. The process comprises (a) combining a particle-forming component (nullPFCnull) and a nucleic acid-like component (nullNACnull) in a monophasic composition comprising water and a water-miscible, organic solvent to form a mixture wherein the PFC and the NAC are independently molecularly or micellarly soluble in the aqueous/organic solvent system, and (b) reducing the amount of the organic solvent in the mixture. This effects formation of the microparticulate complex of the NAC and the PFC. Also provided is a microparticulate complex that comprises a particle-forming component complexed to a nucleic acid-like component forming an approximately spherical particle, wherein the particle-forming component encloses an interior of the particle containing the nucleic acid-like component and the so-enclosed interior volume has less than about 50% (preferably less than 20%) of the volume containing free water. Also disclosed composition comprising water and particles of the microparticulate complex. According to the invention a nucleic acid-like component is delivered to a cell by (a) contacting the cell with a composition comprising water and the microparticulate complex, and (b) maintaining the contact for a time sufficient to allow the nucleic acid-based moiety to enter the cell. A therapeutic nucleic acid-like component is delivered into a patient in need thereof by administering a composition comprising water and particles of the microparticulate complex. Also disclosed is a charge-changing composition represented by the formula A-X-B, wherein X represents a chemical bond capable of irreversible dissociation in reaction to a factor in a physiological or bioprocess environment; A represents a molecular moiety that upon dissociation of the bond X produces a ionically charged product; and B represents a molecular moiety, which upon the dissociation of bond X, separates from the composition leaving the remaining ionically charged product more positive than that of A-X-B itself.