Composite organic compound powder for medical use, method for producing same and suspension of same

Abstract

[Problem to be Solved] The purpose of present invention is to provide a medicine which has low contamination with a fine-pulverizing medium, is safe and has improved bioavailability. [Solution] A method for producing a composite organic compound powder for medical use is used which comprises: mixing a poorly water-soluble and crystalline organic compound powder, a physiologically acceptable salt, a physiologically acceptable polyol, and a carboxyvinyl polymer and fine-pulverizing the organic compound powder; and removing at least the salt and the polyol during or after fine-pulverizing.

1 - 16 . (canceled) 
     
     
         17 . A composite organic compound powder for medical use, comprising composite particles in which a lecithin is carried on the surface of particles of a poorly water-soluble organic compound, or composite particles in which the organic compound and the lecithin form a composite at a nano level, and having an average particle diameter of 400 nm or less as calculated in terms of volume. 
     
     
         18 . The composite organic compound powder for medical use according to  claim 17 , wherein the organic compound is one or more selected from the group consisting of fenofibrate, felbinac, pranlukast hydrate, miconazole, fluticasone propionate, indomethacin, amphotericin B, aciclovir, nifedipine, nicardipine, nimodipine, dipyridamole, disopyramide, prazosin hydrochloride, prednisolone, cortisone acetate, dexamethasone, betamethasone, beclometasone dipropionate, budesonide, fluocinolone acetonide, naproxen, ketoprofen, 7-(3,5-dimethoxy-4-hydroxycinnamoylamino)-3-octyloxy-4-hydroxy-1-methyl-2(1H)-quinolinone, phenyloin, phenacemide, ethotoin, primidone, diazepam, nitrazepam, clonazepam, digitoxin, spironolactone, triamterene, chlorthalidone, polythiazide, benzthiazide, griseofulvin, nalidixic acid, chloramphenicol, chlorzoxazine, phenprobamate, mequitazine, bisbentiamine, mitomycin C, bicalutamide, paclitaxel, ubenimex, dacarbazine, fluconazole, rifampicin, triamcinolone acetonide, clemastine fumarate, zafirlukast, dihydrocholesterol, β-carotene, propyl gallate, cinnamic acid, saccharin, folic acid, and maltol. 
     
     
         19 . The composite organic compound powder for medical use according to  claim 18 , wherein the powder is a powder of at least any one of amphotericin B, aciclovir and indomethacin having an average particle diameter of 50 to 250 nm. 
     
     
         20 . A suspension in which the composite organic compound powder for medical use according to  claim 17  is dispersed. 
     
     
         21 - 22 . (canceled) 
     
     
         23 . A suspension in which the composite organic compound powder for medical use according to  claim 18  is dispersed. 
     
     
         24 . A suspension in which the composite organic compound powder for medical use according to  claim 19  is dispersed. 
     
     
         25 . The composite organic compound powder for medical use according to  claim 17 , wherein the powder further has a carboxyvinyl polymer on the surface of the lecithin or the organic compound particles. 
     
     
         26 . The composite organic compound powder for medical use according to  claim 25 , wherein the organic compound is one or more selected from the group consisting of fenofibrate, felbinac, pranlukast hydrate, miconazole, fluticasone propionate and indomethacin. 
     
     
         27 . A suspension in which the composite organic compound powder for medical use according to  claim 25  is dispersed. 
     
     
         28 . A suspension in which the composite organic compound powder for medical use according to  claim 26  is dispersed. 
     
     
         29 . A method for producing a composite organic compound powder for medical use, comprising:
 mixing a poorly water-soluble organic compound powder, a physiologically acceptable salt, and a physiologically acceptable polyol and fine-pulverizing the organic compound powder;   adding a lecithin during and/or after the fine-pulverizing; and   removing at least the salt and the polyol after fine-pulverizing.   
     
     
         30 . The method for producing a composite organic compound powder for medical use according to  claim 29 , wherein the organic compound is one or more selected from the group consisting of fenofibrate, felbinac, pranlukast hydrate, miconazole, fluticasone propionate, indomethacin, amphotericin B, aciclovir, nifedipine, nicardipine, nimodipine, dipyridamole, disopyramide, prazosin hydrochloride, prednisolone, cortisone acetate, dexamethasone, betamethasone, beclometasone dipropionate, budesonide, fluocinolone acetonide, naproxen, ketoprofen, 7-(3,5-dimethoxy-4-hydroxycinnamoylamino)-3-octyloxy-4-hydroxy-1-methyl-2(1H)-quinolinone, phenyloin, phenacemide, ethotoin, primidone, diazepam, nitrazepam, clonazepam, digitoxin, spironolactone, triamterene, chlorthalidone, polythiazide, benzthiazide, griseofulvin, nalidixic acid, chloramphenicol, chlorzoxazine, phenprobamate, mequitazine, bisbentiamine, mitomycin C, bicalutamide, paclitaxel, ubenimex, dacarbazine, fluconazole, rifampicin, triamcinolone acetonide, clemastine fumarate, zafirlukast, dihydrocholesterol, β-carotene, propyl gallate, cinnamic acid, saccharin, folic acid, and maltol. 
     
     
         31 . The method for producing a composite organic compound powder for medical use according to  claim 29 , wherein the salt is one or more selected from the group consisting of sodium chloride, potassium chloride, ammonium chloride, sodium sulfate, magnesium sulfate, potassium sulfate, calcium sulfate, sodium malate, sodium citrate, disodium citrate, sodium dihydrogen citrate, potassium dihydrogen citrate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, and dipotassium hydrogen phosphate. 
     
     
         32 . The method for producing a composite organic compound powder for medical use according to  claim 30 , wherein the salt is one or more selected from the group consisting of sodium chloride, potassium chloride, ammonium chloride, sodium sulfate, magnesium sulfate, potassium sulfate, calcium sulfate, sodium malate, sodium citrate, disodium citrate, sodium dihydrogen citrate, potassium dihydrogen citrate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, and dipotassium hydrogen phosphate. 
     
     
         33 . The method for producing a composite organic compound powder for medical use according to  claim 29 , wherein the polyol is glycerin, propylene glycol, or polyethylene glycol. 
     
     
         34 . The method for producing a composite organic compound powder for medical use according to  claim 30 , wherein the polyol is glycerin, propylene glycol, or polyethylene glycol. 
     
     
         35 . The method for producing a composite organic compound powder for medical use according to  claim 29 , wherein the salt is sodium chloride and the polyol is glycerin. 
     
     
         36 . The method for producing a composite organic compound powder for medical use according to  claim 30 , wherein the salt is sodium chloride and the polyol is glycerin. 
     
     
         37 . The method for producing a composite organic compound powder for medical use according to  claim 29 , further comprising the step of adding a carboxyvinyl polymer during the fine-pulverizing. 
     
     
         38 . The method for producing a composite organic compound powder for medical use according to  claim 30 , further comprising the step of adding a carboxyvinyl polymer during the fine-pulverizing. 
     
     
         39 . The method for producing a composite organic compound powder for medical use according to  claim 37 , wherein the organic compound is one or more selected from the group consisting of fenofibrate, felbinac, pranlukast hydrate, miconazole, fluticasone propionate and indomethacin. 
     
     
         40 . The method for producing a composite organic compound powder for medical use according to  claim 38 , wherein the organic compound is one or more selected from the group consisting of fenofibrate, felbinac, pranlukast hydrate, miconazole, fluticasone propionate and indomethacin.