METHOD FOR ALTERING MORPHOLOGY OF BLOCK COPOLYMER
The invention provides a pharmaceutical formulation comprising drug-encapsulated polymer micelles formed from a block copolymer having a hydrophilic segment and hydrophobic segment, and has been subjected to high-pressure treatment. The invention also provides a treatment method for a block copolymer having a hydrophilic segment and a hydrophobic segment for formation of drug-encapsulated polymer micelles, the treatment method comprises a step of subjecting the block copolymer to high-pressure treatment.
1 . A treatment method for a block copolymer having a hydrophilic segment and a hydrophobic segment for formation of drug-encapsulated polymer micelles, the treatment method comprising subjecting the block copolymer to high-pressure treatment.
2 . The method according to claim 2 , wherein the high-pressure treatment is carried out by subjecting a solution containing the block copolymer to ultrahigh-pressure dispersion/emulsification.
3 . The method according to claim 2 , wherein the ultrahigh-pressure dispersion/emulsification is carried out with an ultrahigh-pressure homogenizer.
4 . The method according to claim 1 , wherein the pressure for the high-pressure treatment is 3,000 psi or higher.
5 . The method according to claim 4 , wherein the pressure for the high-pressure treatment is 20,000 MPa or higher.
6 . The method according to claim 1 , wherein the block copolymer which has a higher-order structure is subjected to high-pressure treatment to yield a polymer with the higher-order structure of the polymer destroyed.
7 . The method according to claim 1 , wherein the block copolymer which has a higher-order structure and is biocompatible is subjected to high-pressure treatment to yield a polymer with the higher-order structure of the polymer destroyed.
8 . The method according to claim 1 , wherein the hydrophobic segment is a polyamino acid derivative.
9 . The method according to claim 8 , wherein the polyamino acid derivative is a poly(aspartic acid) derivative.
10 . The method according to claim 9 , wherein the polyamino acid derivative is a poly(glutamic acid) derivative.
11 . The method according to claim 1 , wherein the hydrophobic segment is a biocompatible polymer or a biodegradable polymer.
12 . The method according to claim 1 , wherein the hydrophilic segment is polyethylene glycol or a derivative thereof.
13 . The method according to claim 1 , wherein the hydrophilic segment has 30-1000 repeating units and the hydrophobic segment has 10-100 repeating units.
14 . The method according to claim 1 , wherein the micelles have a Chi-square distribution of up to 6.3.
15 . The method according to claim 1 , wherein the micelles have a Chi-square distribution of up to 3.9.
16 . The method according to claim 1 , wherein the micelles have a Chi-square distribution of up to 2.2.
17 . The method according to claim 1 , wherein the micelles have a Chi-square distribution of up to 1.5.
18 . The method according to claim 1 , wherein the formed micelles are further characterized by having a single peak in view of the particular sizes measured by NICOMP 380 ZLS.
19 . The method according to claim 1 , further comprising subjecting the formed micelles to a filtration treatment.
20 . The method according to claim 16 , wherein the filtration treatment is performed by use of a 0.22 μm hydrophilic filter.