Temperature sensitive polymers

• US 7,425,581 B2
• Filed: 03/18/2004
• Issued: 09/16/2008
• Est. Priority Date: 07/30/1999
• Status: Expired due to Term

• Current Assignee: Cristal Delivery B.V.
• Original Assignee: Universiteit Utrecht
• Inventors: Van Steenbergen, Marinus Jacob, Soga, Osamu, Hennink, Wilhelmus Everardus, Van Nostrum, Cornelus Franciscus
• Primary Examiner(s): Hartley; Michael G.
• Assistant Examiner(s): Silverman; Eric E.
• Application Number:
  US10/804,302
• Publication Number:
  US 20040247670A1
• Time in Patent Office: 1,643 Days
• Field of Search: None
• US Class Current: 514/772.1
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/51 Nanocapsules; Nanoparticles; nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00
• CPC Class Codes: C08F 120/58 containing oxygen in addition to the carbonamido oxygen , e.g. N-methylolacrylamide, N-acryloyl morpholine
• CPC Class Codes: C08F 20/56 Acrylamide; Methacrylamide
• CPC Class Codes: C08F 20/58 containing oxygen in addition to the carbonamido oxygen , e.g. N-methylolacrylamide, N-acryloylmorpholine
• CPC Class Codes: C08F 220/54 Amides , e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
• CPC Class Codes: C08F 220/56 Acrylamide; Methacrylamide
• CPC Class Codes: C08F 220/58 containing oxygen in addition to the carbonamido oxygen , e.g. N-methylolacrylamide, N-(meth)acryloylmorpholine
• CPC Class Codes: C08F 293/005 using free radical "living" or "controlled" polymerisation, e.g. using a complexing agent
• CPC Class Codes: C08F 8/12 Hydrolysis
• CPC Class Codes: C08F 8/44 Preparation of metal salts or ammonium salts

Abstract

The present invention relates to compositions comprising polymers whose solubility characteristics can be changed by incubation and particularly poly (N-(2-hydroxypropyl)methacrylamide mono/di-lactate) interpolymers. Another aspect of this invention is the application of such temperature sensitive polymers as release systems of biologically active compounds. The polymers of the present invention, comprise monomers which have modifiable functionality. The functionality of the monomers can for example be modified by the presence of hydrolysable groups. The modification is effected by the incubation, leading to a change of the water solubility characteristics of the polymer. The polymers used in the present invention contain hydrolysable chemical groups. As a result the polymer'"'"'s solution characteristics, specifically its lower critical solution temperature (LCST), change upon incubation.

Claims

1. A controlled release system comprising a temperature sensitive polymer having a lower critical solution temperature (LCST) that changes during incubation in an aqueous medium wherein said temperature sensitive polymer consists of

(a) a homopolymer formed from monomers consisting of N-(2-hydroxypropyl) methyl acrylamide (lactate)_n where n is 1-10 and n is the same in the monomers that constitute said homopolymer, said homopolymer coupled to a hydrophilic block;

or

(b) an interpolymer formed from monomers consisting of N-(2-hydroxypropyl) methyl acrylamide (lactate)_n where n is 1-10 and n varies in the monomers that constitute the interpolymer, said interpolymer optionally coupled to a hydrophilic block; and

an active ingredient.

2. The controlled release system of claim 1, wherein the hydrophilic block comprises poly(ethyleneglycol).

3. The controlled release system of claim 2, wherein the system is in the form of a hydrogel or a micelle.

4. The controlled release system of claim 1 which is in the form of a hydrogel or micelle and wherein said temperature sensitive polymer contains said interpolymer wherein the value of n is varied.

5. The controlled release system of claim 4, wherein the interpolymer is coupled to a hydrophilic block.

6. The controlled release system of claim 5, wherein the hydrophilic block comprises poly(ethyleneglycol).

7. The controlled release system of claim 1 further comprising a homing device.

8. The controlled release system of claim 4 further comprising a homing device.