IP Library Granted Patent US 7,553,918
Granted Patent B2
US 7,553,918 · App. 10/510,371 · Granted Jun 30, 2009

pH-sensitive polymer

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Quick Facts
Patent No.
US 7,553,918
App. No.
10/510,371
Granted
Jun 30, 2009
Kind
B2
Abstract

The invention relates to a pH-sensitive polymer which is a (meth)acrylate copolymer composed of 20 to 65% by weight acrylic and/or methacrylic acid units and 80 to 35% by weight units of C 1 - to C 18 -alkyl esters of (meth)acrylic acid, characterized in that it has a molecular weight in the range from 1 000 to 50 000 g/mol, and brings about at least 60% haemolysis at pH 5.5, and less than 5% haemolysis at pH 7.4, in a concentration of 150 μg/ml in a cytotoxicity test with human red blood cells. The invention further relates to the use of the pH-sensitive polymer as carrier for pharmaceutically effective biomolecules or active pharmaceutical ingredients and as ingredient of corresponding dosage forms.

Claims (38)

1. A pH-sensitive polymer comprising:

25 to 65% by weight of methacrylic acid units, and

60 to 35% by weight of units of ethyl acrylate;

wherein the pH-sensitive polymer has a molecular weight in the range from 1,000 to 50,000 g/mol,

and

brings about at least 60% haemolysis at pH 5.5, and less than 5% haemolysis at pH 7.4, at a concentration of 150 μg/ml in a cytotoxicity test with human red blood cells.

2. The pH-sensitive polymer according to claim 1 ,

wherein the pH-sensitive polymer comprises:

40 to 60% by weight of methacrylic acid units and

60 to 40% by weight of ethyl acrylate units.

3. The pH-sensitive polymer according to claim 1 ,

wherein the pH-sensitive polymer comprises

30 to 50% by weight of methacrylic acid units,

and

35 to 50% by weight of ethyl acrylate units.

4. The pH-sensitive polymer according to claim 1 ,

wherein the pH-sensitive polymer essentially consists of:

50 wt. % methacrylic acid and 50 wt. % ethylacrylate; or

30 wt. % methacrylic acid, 35 wt. % ethylacrylate, and 35 wt. % methylacrylate.

5. The pH-sensitive polymer according to claim 1 ,

wherein the pH-sensitive polymer does not contain transition metal complexes.

6. The pH-sensitive polymer according to claim 1 , which brings about in a MTT test with the macrophage-like cell type J774A.1 (ATCC TIB-67) a percentage value of cell survival of at least 25% when the concentration of pH-sensitive polymer is 0.03125 mg/ml.

7. The pH-sensitive polymer according to claim 6 , which brings about in a LDH test with the macrophage-like cell type J774A.1 (ATCC TIB-67) a LDH release value of not more than 40% when the concentration of pH-sensitive polymer is 0.03125 mg/ml.

8. A pH-sensitive polymer according to claim 1 , further comprising a pharmaceutically effective natural or synthetic biomolecule or an active pharmaceutical ingredient.

9. The pH-sensitive polymer according to claim 8 , wherein the pH-sensitive polymer is coupled to a conformation-altering agent.

10. The pH-sensitive polymer according to claim 8 , wherein the pH-sensitive polymer is a constituent of a complex crosslinked via nucleic acids after chemical modification.

11. A process for preparing a pH-sensitive polymer according to claim 1 , the process comprising:

free-radically polymerizing 25 to 65% by weight of methacrylic acid monomer units with 60 to 35% by weight of monomer units of ethylacrylate in the presence of polymerization initiators and molecular weight regulators by block polymerization, bead polymerization, emulsion polymerization, group transfer polymerization (GTP), or atom transfer radical polymerization (ATRP) to form the polymer, and optionally:

discharging the polymer,

dissolving the polymer,

purifying the polymer and/or

drying the polymer.

12. The process according to claim 11 , wherein the molecular weight regulator is dodecyl mercaptan and/or 2-ethylhexyl thioglycolate.

13. The pH-sensitive polymer of claim 1 which is produced by free radical polymerization of said monomers in the presence of a polymerization initiator and molecular weight regulator by block, bead or emulsion polymerization.

14. The pH-sensitive polymer of claim 1 which is not produced by catalytic chain polymerization (CCT), group transfer polymerization (GTP) or by atom transfer radical polymerization (ATRP).

15. A pH-sensitive polymer according to claim 1 , wherein said pH-sensitive polymer is produced by polymerizing methacrylic acid and ethylacrylate in the presence of a molecular weight regulator which incorporates on a terminal of said polymer.

16. The pH-sensitive polymer of claim 15 , which is produced by polymerizing a monomer mixture of methacrylic acid and ethylacrylate in the presence of 5 to 15% of n-dodecyl mercaptan by weight based on the weight of the monomer mixture.

17. The pH-sensitive polymer of claim 15 , which is produced by polymerizing a monomer mixture of methacrylic acid and ethylacrylate in the presence of 5 to 10% of 2-ethylhexyl thioglycolate by weight based on the weight of the monomer mixture.

Assignments (6)
CHANGE OF NAME Recorded Feb 11, 2020
From: EVONIK ROEHM GMBH
To: ROEHM GMBH
Reel/Frame 051893/0671 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 11, 2020
From: ROEHM GMBH
To: EVONIK DEGUSSA GMBH
Reel/Frame 051893/0727 →
CHANGE OF NAME Recorded Feb 11, 2020
From: EVONIK DEGUSSA GMBH
To: EVONIK OPERATIONS GMBH
Reel/Frame 051894/0001 →
CHANGE OF ENTITY Recorded Feb 25, 2010
From: ROHM GMBH & CO. KG
To: ROHM GMBH
Reel/Frame 023998/0760 →
CHANGE OF NAME Recorded Feb 25, 2010
From: ROHM GMBH
To: EVONIK ROHM GMBH
Reel/Frame 023998/0789 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 1, 2005
From: PETEREIT, HANS-ULRICH; MEIER, CHRISTIAN; SCHULTES, KLAUS; YESSINE, MARIE-ANDREE; LEROUX, JEAN-CHRISTOPHE
To: ROEHM GMBH & CO. KG; UNIVERSITE DE MONTREAL
Reel/Frame 016223/0986 →