Drug-containing sustained release microparticle, process for producing the same and preparation containing the microparticle

Abstract

Sustained release microparticles suitable for various types of drugs, or drug-containing sustained release microparticles capable of sustained release of drugs over a period of three days or more and capable of inhibiting initial burst release; a process for producing the same; and preparations containing the microparticles are disclosed. The drug-containing sustained release microparticles comprise a drug other than human growth hormone and a porous apatite derivative, and optionally include a water-soluble bivalent metal compound. The drug-containing sustained release microparticles can be produced by dispersing under agitation microparticles of a porous apatite derivative in an aqueous solution containing a drug so that the aqueous solution infiltrates into the porous apatite derivative; optionally adding an aqueous solution containing a water-soluble bivalent metal compound that may infiltrate into the porous apatite derivative; further adding additives such as a stabilizer to the mixture; and effecting lyophilization or vacuum drying.

1 . Drug-containing sustained release microparticles characterized by comprising a drug other than human growth hormone and a porous apatite derivative.  
   
   
       2 . Drug-containing sustained release microparticles characterized by comprising a drug other than human growth hormone, a porous apatite derivative and a water-soluble bivalent metal compound.  
   
   
       3 . The drug-containing sustained release microparticles according to  claim 1 , characterized in that the porous apatite derivative is a porous apatite derivative in which a portion of calcium as a constituent of hydroxyapatite is substituted with zinc during production.  
   
   
       4 . The drug-containing sustained release microparticles according to  claim 3 , characterized in that the porous apatite derivative has a zinc substitution rate or zinc content rate of 0.1 to 2.0.  
   
   
       5 . The drug-containing sustained release microparticles according to  claim 2 , characterized in that the water-soluble bivalent metal compound is a zinc compound.  
   
   
       6 . The drug-containing sustained release microparticles according to  claim 5 , characterized in that the water-soluble bivalent metal compound is zinc chloride or zinc acetate.  
   
   
       7 . A preparation for parenteral administration characterized by comprising, drug-containing sustained release microparticles according to  claim 1 .  
   
   
       8 . The preparation according to  claim 7 , characterized in that the preparation for parenteral administration is either a subcutaneous injection or an intramuscular injection.  
   
   
       9 . A process for producing drug-containing sustained release microparticles characterized by comprising: dispersing under agitation microparticles of a porous apatite derivative in an aqueous solution containing a drug so that the aqueous solution infiltrates into the porous apatite derivative; adding thereto an aqueous solution containing a water-soluble bivalent metal compound so that the water-soluble bivalent metal compound infiltrates into the porous apatite derivative; further adding an additive such as a stabilizer to the mixture; and effecting lyophilization or vacuum-drying.  
   
   
       10 . The production process according to  claim 9 , characterized in that the porous apatite derivative is a porous apatite derivative in which a portion of calcium as a constituent of hydroxyapatite is substituted with zinc during production.  
   
   
       11 . The production process according to  claim 10 , characterized in that the porous apatite derivative has a zinc substitution rate or zinc content rate of 0.1 to 2.0  
   
   
       12 . The process according to  claim 9 , characterized in that the water-soluble bivalent metal compound is zinc chloride or zinc acetate.