Cationic polymers for antimicrobial applications and delivery of bioactive materials

• US 9,974,303 B2
• Filed: 04/05/2014
• Issued: 05/22/2018
• Est. Priority Date: 03/31/2011
• Status: Active Grant

• Current Assignee: Agency For Science Technology and Research, International Business Machines Corporation
• Original Assignee: Agency For Science Technology and Research, International Business Machines Corporation
• Inventors: Coady, Daniel J., Engler, Amanda C., Fukushima, Kazuki, Hedrick, James L., Tan, Jeremy P. K., Yang, Yi Yan
• Primary Examiner(s): WORSHAM, JESSICA N
• Application Number:
  US14/246,045
• Publication Number:
  US 20140220093A1
• Time in Patent Office: 1,508 Days
• Field of Search: None
• CPC Class Codes: A01N 2300/00 Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48
• CPC Class Codes: A01N 25/10 Macromolecular compounds
• CPC Class Codes: A01N 33/12 Quaternary ammonium compounds
• CPC Class Codes: A01N 37/44 containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
• CPC Class Codes: A61K 48/0041 the non-active part being polymeric
• CPC Class Codes: C08G 83/004 After treatment of dendrimers
• CPC Class Codes: C12N 15/88 using microencapsulation, e.g. using amphiphile liposome vesicle

Abstract

A cationic star polymer is disclosed of the general formula (1):

wherein w′ is a positive number greater than or equal to 3, I′ is a dendritic polyester core covalently linked to w′ independent peripheral linear cationic polymer chains P′. Each of the chains P′ comprises a cationic repeat unit comprising i) a backbone functional group selected from the group consisting of aliphatic carbonates, aliphatic esters, aliphatic carbamates, aliphatic ureas, aliphatic thiocarbamates, aliphatic dithiocarbonates, and combinations thereof, and ii) a side chain comprising a quaternary amine group. The quaternary amine group comprises a divalent methylene group directly covalently linked to i) a positive charged nitrogen and ii) an aromatic ring.

Claims

1. A cationic star polymer of formula (1):

2. The cationic star polymer of claim 1, wherein I′

is G′

;

3. The cationic star polymer of claim 1, wherein I′

is G″

;

4. The cationic star polymer of claim 1, wherein I′

is G′

″

;

5. The cationic star polymer of claim 1, wherein each P′

is a diblock copolymer chain comprising a polyester block and a polycarbonate block, wherein the polyester block comprises i) a first end group linked to an end group of the polycarbonate block and ii) a second end group linked to I′

.

6. The cationic star polymer of claim 1, wherein the cationic star polymer is biocompatible and/or enzymatically biodegradable.

7. A method of forming the cationic star polymer of claim 1, comprising:

forming a mixture containing i) an organocatalyst, ii) an optional accelerator, iii) a solvent, iv) a dendritic polyester initiator comprising 3 or more peripheral nucleophilic initiator groups for ring opening polymerization (ROP), wherein the ester repeat units of the initiator are carboxylic ester repeat units of aliphatic alcohols, and the initiator is free of carboxylic esters of phenolic alcohols, and v) a cyclic carbonate monomer comprising a pendant electrophilic group capable of reacting with a tertiary amine to form a quaternary amine;

agitating the mixture, thereby forming an electrophilic polymer by ROP;

optionally endcapping the electrophilic polymer, thereby forming an endcapped electrophilic polymer; and

treating the electrophilic polymer and/or the endcapped electrophilic polymer with the tertiary amine, thereby forming the cationic star polymer.

8. The method of claim 7, wherein each P′

is a diblock copolymer chain.

9. The method of claim 7, wherein the initiator is selected from the group consisting of G-1(OH)₈, G-2(OH)₁₆, and G-3(OH)₃₂.

10. The method of claim 7, wherein the tertiary amine is selected from the group consisting of trimethylamine (TMA), TMEDA, and combinations thereof.

11. The method of claim 7, wherein the initiator is G-3(OH)₃₂ and the tertiary amine is trimethylamine (TMA).

12. The method of claim 7, wherein the initiator is G-1(OH)₈ and the tertiary amine is TMEDA.

13. The method of claim 7, wherein each P′

is a diblock copolymer chain comprising a polyester block and a polycarbonate block, wherein the polycarbonate block consists essentially of a homopolymer of cationic repeat unit selected from the group consisting of

15. A method of killing a microbe comprising contacting the microbe with the cationic star polymer of claim 1.

16. An injectable composition comprising an aqueous mixture of the cationic star polymer of claim 1.

17. A method of treating a cell comprising contacting the cell with a composition comprising i) the cationic star polymer of claim 1 and ii) a gene and/or a drug.

18. An article, comprising the cationic star polymer of claim 1 disposed on a surface of a medical device.

19. The article of claim 18, wherein the medical device is selected from the group consisting of swabs, catheters, sutures, stents, bedpans, gloves, facial masks, absorbent pads, absorbent garments, internal absorbent devices, insertable mechanical devices, wound dressings, and surgical instruments.

14. A cationic star polymer comprising:

3 or more independent peripheral monovalent linear cationic polymer chains P′

, wherein each of the chains P′

is covalently linked to a respective one of the ester repeat units of a dendritic polyester core I′

, and wherein each of the chains P′

independently comprises a cationic repeat unit of the general formula (11);

20. A cationic star polymer comprising i) a dendritic polyester core I′

comprising carboxylic ester repeat units of aliphatic alcohols, wherein I′

is free of carboxylic esters of phenolic alcohols, and I′

comprises three or more peripheral ester repeat units and ii) 3 or more independent monovalent cationic polymer chains P′

, wherein each of the peripheral ester repeat units is linked to a respective end unit of one of the polymer chains P′

, each of the polymer chains P′

independently comprises a homopolymer of a cationic repeat unit selected from the group consisting of

21. A cationic star polymer, comprising:

a multivalent hydrophobic dendritic polyester core I′

comprising carboxylic ester repeat units of aliphatic alcohols, wherein I′

is free of carboxylic esters of phenolic alcohols, and I′

comprises 3 or more peripheral ester repeat units covalently linked to respective independent peripheral monovalent cationic polymer chains P′

,

each of the polymer chains P′

independently comprises a cationic repeat unit comprising i) an aliphatic carbonate backbone functional group and ii) a side chain comprising a quaternary amine group, and

the quaternary amine group comprises a divalent methylene group directly covalently linked to i) a positive charged nitrogen and ii) an aromatic ring.