In the recent development of new medical drugs, combinatorial chemistry methods have been adopted in synthesizing candidate compounds. Combinatorial chemistry is the art of adopting combinations to synthesize a wide variety of compounds in a short time at one time. Compounds obtained by this method have a solubility problem in many cases. That is, in many cases, even if a compound is found to have excellent physiological activity in itself, if the compound has a property of being difficult to dissolve in water, development of the compound is abandoned. Even with compounds obtained by extraction from natural products, various organic syntheses are carried out and structural optimization is performed to improve solubility. Some medical drugs already on the market are also low in solubility. With such drugs, a drug absorption amount varies within an individual patient and varies among individuals, and this places a large burden in terms of control of levels in blood, etc. on both a physician using a drug and a patient on whom the drug is used.
Microparticle formulations have been received attention as a solution to the above problems. With a microparticle formulation, poorly soluble drug particles that are made no more than a micrometer in size are dispersed in water with stability. By using a microparticle formulation, a drug can be increased in absorption rate and amount in a living body. Reduction in variation of absorption amount within an individual patient and among individuals and increase in effective availability with respect to a dose can also be anticipated. Inventions of methods for manufacturing such microparticle formulations are disclosed in the following Patent documents 1 and 2.
With the invention disclosed in the Patent Document 1, ultrashort pulse laser light is irradiated on organic bulk crystals dispersed in a solvent to induce ablation by nonlinear absorption and thereby pulverize the organic bulk crystals into highly dispersed scattered matter, and the highly dispersed scattered matter is recovered by the solvent to obtain ultrafine microparticles of an organic compound. With the invention disclosed in the Patent Document 2, a solution is prepared by dispersing and dissolving a block copolymer, containing a hydrophilic segment and a hydrophobic segment, and a poorly water-soluble drug in a volatile organic solvent, the organic solvent is eliminated from the solution, and a residue obtained by elimination of the organic solvent is stirred and thereby uniformly dispersed in water at a temperature of no more than 30° C. to manufacture a formulation containing polymer micelles encapsulating the drug.    Patent Document 1: Japanese Published Unexamined Patent Application No. 2005-238342    Patent Document 2: Japanese Published Unexamined Patent Application No. 2003-342168
USPTO Backgrounds
USPTO Backgrounds