Stabilized polymeric nanocapsules, dispersions comprising the nanocapsules, and methods for the treatment of bacterial biofilms

Patent metadata

Field	Value
Publication number	US-10493039-B2
Application number	US-201615757092-A
Country	US
Kind code	B2
Filing date	Aug 16, 2016
Priority date	Sep 3, 2015
Publication date	Dec 3, 2019
Grant date	Dec 3, 2019

Abstract

A nanocapsule includes a liquid hydrophobic care including an essential oil, and a shell encapsulating the core. The shell includes a copolymer having repeating units of Formula (I) and (II) wherein X, L 1 , R 1 , R 2 , y, and p are as described herein. A dispersion is also disclosed, wherein the dispersion includes a plurality of nanocapsules. The nanocapsules described herein are particularly useful for the treatment of bacterial biofilms.

First claim

The invention claimed is:

1. A nanocapsule comprising,
a liquid hydrophobic core comprising an essential oil; and
a shell encapsulating the core, the shell comprising a copolymer comprising repeating units of Formula (I) and (II)

wherein
X is independently at each occurrence —O—, —S—, —CH 2 —, —(CR 4 R 5 )—, or

 wherein R 4 and R 5 are independently at each occurrence a C 1-6 alkyl group and R 6 and R 7 are independently at each occurrence hydrogen or a C 1-6 alkyl group;
L 1 is independently at each occurrence a divalent group that is (—CH 2 —) z , wherein z is an integer from 1 to 10, a divalent a C 1-20 alkylene oxide group, or a divalent poly(C 1-6 alkylene oxide) group;
R 1 is independently at each occurrence hydrogen, a C 1-12 alkylene group, or a —C(═O)—O—(C 1-6 alkyl) group;
y is 2 or 3;
p is 0 or 1; and
R 2 is independently at each occurrence a C 1-12 alkylene group, a C 6-20 arylene group, a C 1-20 alkylene oxide group, a poly(C 1-6 alkylene oxide) group, or a zwitterionic group.

2. The nanocapsule of claim 1 , wherein the copolymer further comprises repeating units of Formula (III)

wherein
X is independently at each occurrence —O—, —S—, —CH 2 —, —(CR 4 R 5 )—, or

 wherein R 4 and R 5 are independently at each occurrence a C 1-6 alkyl group and R 6 and R 7 are independently at each occurrence hydrogen or a C 1-6 alkyl group;
L 2 is independently at each occurrence a divalent group that is (—CH 2 —) z , wherein z is an integer from 1 to 10, a divalent a C 1-20 alkylene oxide group, or a divalent poly(C 1-6 alkylene oxide) group;
R 3 is independently at each occurrence hydrogen, a C 1-12 alkylene group, or a —C(═O)—O—(C 1-6 alkyl) group;
a is 2 or 3; and
b is 0 or 1.

3. The nanocapsule of claim 1 , wherein the copolymer further comprises repeating units of Formula (IV).

4. The nanocapsule of claim 1 , wherein the copolymer further comprises repeating units of Formula (V)

wherein X is independently at each occurrence —O—, —S—, —CH 2 —, —(CR 4 R 5 )—, or

 wherein R 4 and R 5 are independently at each occurrence a C 1-6 alkyl group and R 6 and R 7 are independently at each occurrence hydrogen or a C 1-6 alkyl group;
R 2 is independently at each occurrence a C 1-12 alkylene group, a C 6-20 arylene group, a C 1-20 alkylene oxide group, a poly(C 1-6 alkylene oxide) group, or a zwitterionic group; and
L 3 is a divalent group that is (—CH 2 —) z , wherein z is an integer from 1 to 10.

5. The nanocapsule of claim 1 , wherein the core further comprises a hydrophobic anhydride-containing polymer in an amount of 0.01 to 15 weight percent, based on the weight of the core, wherein the hydrophobic anhydride-containing polymer comprising repeating units of Formula (VI)

wherein R 8 is independently at each occurrence a hydrogen, a C 1-20 alkyl group or a C 6-20 aryl group.

6. The nanocapsule of claim 5 , wherein at least a portion of the shell is crosslinked with the anhydride-containing polymer.

7. The nanocapsule of claim 1 , wherein the essential oil is selected from the group consisting of peppermint oil, oregano oil, thymol, menthol, methyl salicylate, eucalyptol, carvacrol, camphor, anethole, carvone, eugenol, isoeugenol, limonene, osimen, n-decyl alcohol, citronel, a-salpineol, methyl acetate, citronellyl acetate, methyl eugenol, cineol, linalool, ethyl linalaol, safrola vanillin, spearmint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, pimento oil, laurel oil, cedar leaf oil, clove oil, cilantro oil, coriander oil, or a combination thereof.

8. The nanocapsule of claim 2 , wherein the copolymer comprises
5 to 50 mole percent repeating units of Formula (I);
10 to 50 mole percent repeating units of Formula (II); and
25 to 45 mole percent repeating units of Formula (III);
wherein mole percent of each component is based on the total moles of the copolymer.

9. The nanocapsule of claim 1 , wherein
X is —O—;
L 1 is propylene;
R 1 is hydrogen;
y is 3;
p is 1; and
R 2 is a C 1-20 alkylene oxide group.

10. The nanocapsule of claim 1 , wherein R 2 is a group having the structure

wherein
n is 1, 2, 3, or 4; and
R 10 is hydrogen, methyl, or a C 1-6 alkylamino group.

11. The nanocapsule of claim 2 , wherein
R 3 is hydrogen;
L 2 is propylene;
a is 3; and
b is 1.

12. The nanocapsule of claim 1 , wherein the copolymer has a number average molecular weight of 3,000 to 100,000 Daltons.

13. The nanocapsule of claim 1 , comprising
90 to 99.9 weight percent of the core; and
0.1 to 10 weight percent of the shell;
wherein weight percent is based on the total weight of the nanocapsule.

14. The nanocapsule of claim 1 , wherein the nanocapsule comprises
1 to 10 weight percent, based on the weight of the nanocapsule, of the core comprising carvacrol oil; and
90 to 99 weight percent, based on the weight of the nanocapsule, of the shell comprising the copolymer, wherein
each occurrence of X is —O—;
each occurrence of L 1 is propylene;
each occurrence of R 1 is hydrogen;
each occurrence of y is 3;
each occurrence of p is 1;
each occurrence of R 2 is a group having the structure

wherein n is 4; and

the nanocapsule has a diameter of 1 to 100 nanometers.

15. The nanocapsule of claim 2 , wherein the nanocapsule comprises
1 to 10 weight percent, based on the weight of the nanocapsule, of the core comprising
85 to 99.99 weight percent, based on the weight of the core, of carvacrol oil; and
0.01 to 15 weight percent, based on the weight of the core, of the hydrophobic anhydride containing polymer comprising repeating units of Formula (VI)

wherein m is an integer from 1 to 16; and

90 to 99 weight percent, based on the weight of the nanocapsule, of the shell comprising the copolymer, wherein
each occurrence of X is —O—;
each occurrence of L 1 and L 2 are propylene;
each occurrence of R 1 is hydrogen;
each occurrence of y is 3;
each occurrence of p is 1;
each occurrence of R 2 is a group having the structure

wherein n is 4;

each occurrence of R 3 is hydrogen;
each occurrence of

Assignees

• Univ Massachusetts

Inventors

• Rotello Vincent M
• Landis Ryan Francis
• Gupta Akash
• Lee Yiwei

Classifications

• C08G2261/418

  Ring opening metathesis polymerisation [ROMP] · CPC title

• C08F32/02

  having no condensed rings · CPC title

• A61K9/5138 Primary

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• C08G61/08

  of carbocyclic compounds containing one or more carbon-to-carbon double bonds in the ring · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title