Method for producing preparation containing bioactive substance

Abstract

A method for producing a preparation containing a bioactive substance, characterized in that it comprises forming a solid material containing the bioactive substance and a polymer, and contacting the solid material with a high pressure gas. The method allows the production of a preparation which is suppressed in excessive initial release of the bioactive substance immediately after the administration thereof, is capable of releasing a predetermined amount of the bioactive substance over a long period of time, and is extremely reduced in the deterioration of the bioactive substance and in the amount of a residual organic solvent.

1 . A method for producing a preparation containing a peptidic bioactive substance, which comprises forming a solid material containing the bioactive substance and a polymer, and contacting the solid material with high-pressure gas.  
   
   
       2 . The method according to  claim 1 , wherein the peptidic bioactive substance is that being unstable to heat or solvents.  
   
   
       3 . The method according to  claim 1 , wherein the peptidic bioactive substance has a molecular weight of about 2,000 to about 500,000.  
   
   
       4 . The method according to  claim 1 , wherein the peptidic bioactive substance has a molecular weight of about 5,000 to about 500,000.  
   
   
       5 . The method according to  claim 4 , wherein the peptidic bioactive substance is human growth hormone.  
   
   
       6 - 11 . (canceled)  
   
   
       12 . The method according to  claim 1 , wherein the polymer is biodegradable.  
   
   
       13 . The method according to  claim 12 , wherein the biodegradable polymer is a homopolymer or a copolymer of α-hydroxycarboxylic acids, or a mixture thereof.  
   
   
       14 . The method according to  claim 13 , wherein the biodegradable polymer is a homopolymer or a copolymer of lactic acid/glycolic acid having a composition ratio of lactic acid/glycolic acid of about 100/0 to about 40/60 mol %.  
   
   
       15 . The method according to  claim 13 , wherein the biodegradable polymer is a homopolymer of lactic acid.  
   
   
       16 . The method according to  claim 12 , wherein the weight-average molecular weight of the biodegradable polymer is about 3,000 to about 50,000.  
   
   
       17 . The method according to  claim 1 , wherein the solid material is contacted with high-pressure gas at a temperature range of about +20° C. to about −60° C. based on the glass transition temperature of the polymer.  
   
   
       18 . The method according to  claim 17 , wherein the solid material is contacted with high-pressure gas at a temperature range of about +0° C. to about −40° C. based on the glass transition temperature of the polymer.  
   
   
       19 . The method according to  claim 1 , wherein the period for contacting the solid material with high-pressure gas is about 5 minutes to about 48 hours.  
   
   
       20 . The method according to  claim 19 , wherein the period for contacting the solid material with high-pressure gas is about 10 minutes to about 12 hours.  
   
   
       21 . The method according to  claim 1 , wherein the high-pressure gas is inert to the peptidic bioactive substance and polymer.  
   
   
       22 . The method according to  claim 21 , wherein the high-pressure gas is carbon dioxide.  
   
   
       23 . The method according to  claim 1 , wherein the pressure of the high-pressure gas is about 1 MPa to about 7 Mpa.  
   
   
       24 . The method according to  claim 23 , wherein the pressure of the high-pressure gas is about 1 MPa to about 4 Mpa.  
   
   
       25 . The method according to  claim 1 , wherein the preparation is sustained-release microcapsules.  
   
   
       26 . The method according to  claim 25 , wherein the sustained-release microcapsules are obtained by in-water drying method.  
   
   
       27 . A preparation obtained by the method according to  claim 1 .  
   
   
       28 . Sustained-release microcapsules obtained by the method according to  claim 25 .  
   
   
       29 . An injectable preparation containing the sustained-release microcapsules according to  claim 28 .  
   
   
       30 . A method for suppressing the initial release of a peptidic bioactive substance, which comprises forming a solid material containing said bioactive substance and a polymer, and contacting the solid material with high-pressure gas.  
   
   
       31 . A method for suppressing the denaturation of a peptidic bioactive substance, which comprises forming a solid material containing said bioactive substance and a polymer, and contacting the solid material with high-pressure gas.