U.S. patent application number 14/150124 was filed with the patent office on 2014-07-17 for antimicrobial crosslinked polymers containing biomass derived materials.
This patent application is currently assigned to E I DU PONT DE NEMOURS AND COMPANY. The applicant listed for this patent is E I DU PONT DE NEMOURS AND COMPANY. Invention is credited to MARK ALLEN ANDREWS, Henry Keith Chenault, Garret D. Figuly.
Application Number | 20140200314 14/150124 |
Document ID | / |
Family ID | 34910815 |
Filed Date | 2014-07-17 |
United States Patent
Application |
20140200314 |
Kind Code |
A1 |
ANDREWS; MARK ALLEN ; et
al. |
July 17, 2014 |
ANTIMICROBIAL CROSSLINKED POLYMERS CONTAINING BIOMASS DERIVED
MATERIALS
Abstract
Novel, crosslinked polymers using biomass derived materials,
such as aldaric acids and derivatives, are provided. The polymers
can be used as hydrogels and in antimicrobial compositions.
Inventors: |
ANDREWS; MARK ALLEN;
(Wilmington, DE) ; Figuly; Garret D.; (Wilmington,
DE) ; Chenault; Henry Keith; (Hockessin, DE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
E I DU PONT DE NEMOURS AND COMPANY |
Wilmington |
DE |
US |
|
|
Assignee: |
E I DU PONT DE NEMOURS AND
COMPANY
Wilmington
DE
|
Family ID: |
34910815 |
Appl. No.: |
14/150124 |
Filed: |
January 8, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11064191 |
Feb 23, 2005 |
8519058 |
|
|
14150124 |
|
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Current U.S.
Class: |
525/328.2 |
Current CPC
Class: |
A01N 37/36 20130101;
C08K 5/11 20130101; A61K 8/8111 20130101; A61L 15/225 20130101;
A61K 8/736 20130101; C08F 126/02 20130101; C08L 89/06 20130101;
C08F 26/02 20130101; A61K 8/042 20130101; C08G 73/02 20130101; A61Q
19/10 20130101; C08B 37/00 20130101; C08G 73/0206 20130101; A61L
27/22 20130101; C08K 3/015 20180101; C08L 39/02 20130101; A61K 8/84
20130101; A01N 37/18 20130101; A01N 43/08 20130101; C08B 37/003
20130101; A61Q 17/005 20130101; C08K 5/1535 20130101; C08F 8/00
20130101; A61L 2/16 20130101; A61Q 5/12 20130101; C08L 5/02
20130101; A61K 31/785 20130101; A61K 31/722 20130101; A61K 38/08
20130101; C08F 120/06 20130101; A61P 31/04 20180101 |
Class at
Publication: |
525/328.2 |
International
Class: |
A01N 43/08 20060101
A01N043/08 |
Claims
1. An antimicrobial composition comprising: an antimicrobial agent
which is a crosslinked polymer, the crosslinked polymer comprising:
A) a linear, branched or cyclic polymeric backbone comprising
repeat units that comprise one or more groups selected from:
hydrocarbylene groups selected from one or more aliphatic,
aromatic, linear, branched, or cyclic groups; heteroatoms; and
carbonyl groups; and B) one or more crosslinking units that include
at least one aldaroyl structural unit of Formula I: ##STR00019##
where n is 1-6; wherein the hydrocarbylene groups and heteroatoms
of the repeat units are optionally substituted with substituents
that comprise one or more of C.sub.1-C.sub.30 hydrocarbylene
groups, heteroatoms, and carbonyl carbon groups, and wherein the
hydrocarbylene groups of the substituents are aliphatic or
aromatic, linear, branched, or cyclic, or combinations thereof.
2. The antimicrobial composition of claim 1 wherein the polymeric
backbone of the crosslinked polymer comprises optionally
substituted --NZ--, --N+ZZ'--, --O--, --C(.dbd.O)NZ--,
--C(.dbd.O)O--, --C(.dbd.O)--, --OC(.dbd.O)O--, --OC(.dbd.O)NZ--,
--NHC(.dbd.O)NZ--, or --SiZZ'O-- linkages, wherein Z and Z' are
independently hydrogen, alkyl, substituted alkyl, aryl, or
substituted aryl.
3. The antimicrobial composition of claim 1 wherein the
substituents on the hydrocarbylene groups and heteroatoms of the
repeat units of the crosslinked polymer comprise one or more of:
--X, --O(Z), --N(ZZ'), --N+(ZZ'Z''), --C(.dbd.O)OZ, --C(.dbd.O)X,
--C(.dbd.O)NZZ', --C.dbd.N.dbd.O, --O--, --N(Z), --N+(ZZ')--,
--C(.dbd.O)N(Z)--, --C(.dbd.O)O--, --C(.dbd.O)--, --OC(.dbd.O)O--,
--OC(.dbd.O)N(Z)--, --N(Z)C(.dbd.O)N(Z')--,
--C(.dbd.O)NH(CH.sub.2)pNH2, --Si(ZZ')O--, --(OCH2CH2)mOH, or
--(OSi(ZZ'))nOH, and salts thereof, wherein X is a halogen, Z, Z',
and Z'' are independently hydrogen or C1-C22 alkyl, substituted
alkyl, aryl, or substituted aryl, and wherein m is 1 to 50, n is 1
to 100, and p is 1 to 12.
4. The antimicrobial composition of claim 3 wherein the repeat
units of the crosslinked polymer comprise aliphatic hydrocarbylene
groups having substituents comprising one or more of
C.sub.1-C.sub.22 aminoalkyl groups, --C(.dbd.O)OZ, --C(.dbd.O)X,
--C(.dbd.O)NZZ', or --C(.dbd.O)NH(CH.sub.2).sub.pNH.sub.2, and
salts thereof.
5. The antimicrobial composition of claim 1 wherein at least one
repeat unit of the crosslinked polymer is an azahydrocarbylene or
salt thereof, comprising a nitrogen atom having one or more
terminal aminoalkyl groups or salts thereof as substituents.
6. The antimicrobial composition of claim 1 wherein at least one
repeat unit of the crosslinked polymer contains one or more
substituents comprising one or more of C1-C22 aminoalkyl groups,
optionally substituted with alkyl or aldaroyl groups, or a salt
thereof.
7. The antimicrobial composition of claim 1 wherein the crosslinked
polymer is a derivative of polyallylamine, polyallylamine
hydrochloride, branched polyethyleneimine, branched
polyethyleneimine hydrochloride, poly(acryloyl chloride),
poly(methacryloyl chloride),
poly[N-(.quadrature.-aminoalkyl)acrylamide], polyglycosamine,
carboxymethylchitosan, chitosan, chitosan hydrochloride, or a
derivative or salt thereof.
8. The antimicrobial composition of claim 1 wherein the aldaroyl
moiety in the crosslinking unit is glucaroyl, galactaroyl,
mannaroyl, xylaroyl, or tartaroyl.
9. The antimicrobial composition of claim 1 wherein the
crosslinking unit comprises one or more groups selected from groups
having Formulae II, III, IV, and V ##STR00020## wherein Q is --O--
or --NH--, or a salt thereof, and R.sub.1, R.sub.2, R.sub.3 and
R.sub.4 are aliphatic or aromatic hydrocarbylene groups, linear,
branched or cyclic, optionally substituted, and optionally
containing --O--, --Si(ZZ')O--, --(C.dbd.O)-- or --NZ-- linkages,
where Z and Z' are independently hydrogen, alkyl, substituted
alkyl, alkaryl, substituted alkaryl, aryl, or substituted aryl; and
wherein the group having Formulae II, III, IV, or V is directly
attached to the polymer backbone.
10. The crosslinked polymer of claim 9 wherein: R.sub.1 is
--[(CH.sub.2).sub.0-22]--,
--(CH.sub.2).sub.aC.sub.6H.sub.10(CH.sub.2).sub.b--,
--(CH.sub.2CH.sub.2NH).sub.1-22CH.sub.2CH.sub.2--,
--[(CH.sub.2CH(Z')O).sub.1-22(CH.sub.2).sub.2-3]-- wherein Z' is H
or CH.sub.3, --C(O)NH(CH.sub.2).sub.2-22--, or
--(CH.sub.2).sub.a(C.sub.6H.sub.4)(CH.sub.2).sub.b--, wherein a=0-6
and b=0-6; R.sub.2 is --[(CH.sub.2).sub.1-21]--, --CH(CH.sub.3)--,
--CH(isopropyl)-, --CH(isobutyl)-,
--CH(CH(CH.sub.3)CH.sub.2CH.sub.3)--, --CH(CH.sub.2OH)--,
--CH(CH.sub.2CH.sub.2SCH.sub.3)--, --CH(CH(OH)CH.sub.3)--,
--CH(CH.sub.2C.sub.6H.sub.5)--, --CH(CH.sub.2C.sub.6H.sub.4OH)--,
--CH(CH.sub.2CONH.sub.2)--, or --CH(CH.sub.2CH.sub.2CONH.sub.2)--;
R.sub.3 is --[(CH.sub.2).sub.2-22]--,
--[(CH.sub.2).sub.0-6(C.sub.6H.sub.10)(CH.sub.2).sub.0-6]--,
--[(CH.sub.2).sub.0-6C.sub.6H.sub.4(CH.sub.2).sub.0-6]--,
--[CH.sub.2CH.sub.2(OCH.sub.2CH.sub.2).sub.1-21]--,
--[CH.sub.2CH(CH.sub.3)[OCH.sub.2CH(CH.sub.3CH)].sub.1-21]--,
--(CH.sub.2CH.sub.2NH).sub.1-22CH.sub.2CH.sub.2--,
--[CH.sub.2CH(CH.sub.3)[OCH.sub.2CH(CH.sub.3)].sub.x(OCH.sub.2CH.sub.2).s-
ub.y[OCH.sub.2CH(CH.sub.3)].sub.z]-- wherein x+y+z=2-50,
--[CH.sub.2CH.sub.2(OCH.sub.2CH.sub.2).sub.x[OCH.sub.2CH(CH.sub.3)].sub.y-
(OCH.sub.2CH.sub.2).sub.z]-- wherein x+y+z=2-50,
--[CH(CH.sub.3)CH.sub.2O].sub.xCH.sub.2C(Z')(CH.sub.2[OCH.sub.2CH(CH.sub.-
3)].sub.y--)CH.sub.2[OCH.sub.2CH(CH.sub.3)].sub.z-- wherein
x+y+z=2-10 and Z' is H, methyl or ethyl,
--[CH(CH.sub.3)CH.sub.2O].sub.xCH.sub.2CH([OCH.sub.2CH(CH.sub.3)].sub.y)C-
H.sub.2[OCH.sub.2CH(CH.sub.3)].sub.z-- wherein x+y+z=3-100, or
--CH.sub.2CH.sub.2CH.sub.2CH.sub.2[CH(NH.sub.2)CONHCH.sub.2CH.sub.2CH.sub-
.2CH.sub.2].sub.0-10CH(COYR)-- or salts thereof, wherein Y is O or
NH, and R is a C.sub.1-C.sub.22 optionally substituted alkyl, aryl,
or alkaryl; and R.sub.4 is --C(.dbd.O)--,
--C.sub.6H.sub.4CH.sub.2--,
--(CH.sub.2).sub.1-22Y'CH.sub.2CH(OH)CH.sub.2--, or
--(CH.sub.2).sub.1-22Y'C(O)CH(OH)CH.sub.2--, wherein Y' is O or
NH.
11. The antimicrobial composition of claim 1 wherein about 0.1% to
about 100% of the polymer backbone repeat units are connected to a
crosslinking unit.
12. The antimicrobial composition of claim 11 wherein about 1% to
about 30% of the polymer backbone repeat units are connected to a
crosslinking unit.
13. An antimicrobial composition comprising: an emulsifying agent
which is a crosslinked polymer prepared by a process comprising the
step of contacting a crosslinking agent with a substrate polymer to
form a crosslinked polymer; wherein the crosslinking agent has
Formula VI, VII or VIII: ##STR00021## wherein L and L'
independently contain a suitable functional group, and n=1-6,
m=0-4, and p=1-4; and the substrate polymer comprises: A) a linear,
branched or cyclic polymeric backbone comprising repeat units that
comprise one or more of hydrocarbylene groups, heteroatoms, and
carbonyl carbon groups; wherein the hydrocarbylene are aliphatic or
aromatic, linear, branched, or cyclic, or combinations thereof; and
wherein the hydrocarbylene groups and heteroatoms of the repeat
units are optionally substituted with substituents that comprise
one or more of C.sub.1-C.sub.30 hydrocarbylene groups, heteroatoms,
and carbonyl carbon groups, wherein the hydrocarbylene groups of
the substituents are aliphatic or aromatic, linear, branched, or
cyclic, or combinations thereof; and B) reactive pendant groups
attached to the polymeric backbone, the pendant groups being of the
formula -G or --R-G, wherein G is a nucleophile or electrophile;
wherein R is independently linear, cyclic, or branched alkylene,
arylene, or alkarylene groups of 1-22 carbon atoms, optionally
substituted with alkyl, aryl, hydroxy, amino, carbonyl, ester,
amide, alkoxy, nitrile or halogen, and optionally containing --O--,
--Si(ZZ')O--, --(C.dbd.O)-- or --NZ-- linkages, where Z and Z' are
independently hydrogen, alkyl, substituted alkyl, alkaryl,
substituted alkaryl, aryl, or substituted aryl.
14. The antimicrobial composition of claim 13 wherein the suitable
functional group of the crosslinked polymer is derived from an
amine, hydroxyl, carboxylic acid, ester, urethane, urea, amide, or
isocyanate; and G is an epoxide, isocyanate, benzylic halide,
amine, acid halide, ester, or amide.
15. The antimicrobial composition of claim 13 wherein L and L' are
independently selected from --Y--R, wherein Y is O, NH, or S and R
is alkyl, substituted alkyl, alkaryl, substituted alkaryl, aryl, or
substituted aryl.
16. The antimicrobial composition of claim 13 wherein L and L' are
independently selected from optionally substituted --NHR'', --OH,
and --C(.dbd.O)OR''; and G is selected from --NH.sub.2,
--C(.dbd.O)Cl, --C(.dbd.O)OR'', or --C(.dbd.O)NH--R''--NH.sub.2,
wherein R'' is independently hydrogen or an optionally substituted
hydrocarbyl or hydrocarbylene, and wherein n=2-4, m=0-1, and
p=2-3.
17. The antimicrobial composition of claim 13 wherein less than
100% of the reactive pendant groups are derivatized to be
substantially unreactive to the crosslinking agent, wherein the
derivatization is performed either before, during or after contact
of the crosslinker with the polymer substrate.
18. The antimicrobial composition of claim 13 wherein the reactive
pendant groups are derivatized before the contacting of the
crosslinker with the polymer substrate.
19. The antimicrobial composition of claim 13 wherein the reactive
pendant groups are derivatized to contain an optionally substituted
aliphatic carbon chain with optional --(NZ)--, and --O-- linkages,
where Z is hydrogen, optionally substituted alkyl or optionally
substituted aryl.
20. The antimicrobial composition of claim 13 wherein the reactive
pendant groups are derivatized to contain a linear or branched
alkyl group of 1-22 carbon atoms, optionally substituted with --O--
linkages, and optionally substituted with --NH.sub.2, halogen,
hydroxyl, or carbonyl groups, or salt thereof.
21. The antimicrobial composition of claim 13 wherein G is
--NH.sub.2 and the reactive pendant groups are derivatized with a
C.sub.1-C.sub.22 alkyl group.
22. The antimicrobial composition of claim 13 wherein up to about
50% of the reactive pendent groups are derivatized.
23. The antimicrobial composition of claim 13 wherein up to about
20% of the reactive pendent groups are derivatized.
24. The antimicrobial composition of claim 13 wherein the polymeric
backbone comprises at least one selected from: --NZ--,
--N.sup.+ZZ'--, --O--, --C(.dbd.O)NZ--, --C(.dbd.O)O--,
--C(.dbd.O)--, --OC(.dbd.O)O--, --OC(.dbd.O)NZ--,
--NHC(.dbd.O)NZ--, or --SiZZ'O-- linkages, where Z and Z' are
independently hydrogen, alkyl, substituted alkyl, aryl, and
substituted aryl.
25. The antimicrobial composition of claim 13 wherein the repeat
units of the substrate polymer comprise aliphatic hydrocarbylene
groups with one or more substituents comprising one or more of
aminoalkyl groups, --C(.dbd.O)OZ, --C(.dbd.O)X, --C(.dbd.O)NZZ', or
--C(.dbd.O)NH(CH.sub.2).sub.nNH.sub.2, or salts thereof, where X is
halogen, Z and Z' are independently hydrogen, C.sub.1-C.sub.22
alkyl, substituted alkyl, aryl, or substituted aryl, and
n=1-12.
26. The antimicrobial composition of claim 13 wherein substituents
on the repeat units are one or more of --X, --O(Z), --N(ZZ'),
--N.sup.+(ZZ'Z''), --C(.dbd.O)OZ, --C(.dbd.O)X, --C(.dbd.O)NZZ',
--C.dbd.N.dbd.O, --O--, --N(Z)--, --N.sup.+(ZZ')--,
--C(.dbd.O)N(Z)--, --C(.dbd.O)O--, --C(.dbd.O)--, --OC(.dbd.O)O--,
--OC(.dbd.O)N(Z)--, --N(Z)C(.dbd.O)N(Z')--,
--C(.dbd.O)NH(CH.sub.2).sub.pNH.sub.2, --Si(ZZ')O--,
--(OCH.sub.2CH.sub.2).sub.mOH, or --(OSi(ZZ')).sub.nOH, or salts
thereof, wherein X is a halogen, Z, Z', and Z'' are independently
hydrogen or C.sub.1-C.sub.22 optionally substituted alkyl or aryl,
and wherein m is 1 to 50, n is 1 to 100, and p is 1 to 12.
27. The antimicrobial composition of claim 13 wherein the repeat
units contain substituents comprising one or more of
C.sub.1-C.sub.22 aminoalkyl groups, optionally substituted with
alkyl or aldaroyl groups, or salts thereof.
28. The antimicrobial composition of claim 13 wherein at least one
repeat unit is an azahydrocarbylene or salt thereof, comprising a
nitrogen atom having one or more terminal aminoalkyl groups or
salts thereof as substituents.
29. The antimicrobial composition of claim 13 wherein the substrate
polymer comprises polyallylamine, polyallylamine hydrochloride,
branched polyethyleneimine, branched polyethyleneimine
hydrochloride, poly(acryloyl chloride), poly(methacryloyl
chloride), poly[N-(.omega.-aminoalkyl)acrylamide], polyglycosamine,
carboxymethylchitosan, chitosan, chitosan hydrochloride, or a
derivative or salt thereof.
30. The antimicrobial composition of claim 13 wherein the
crosslinking agent is derived from an aldaric acid, aldarolactone,
aldarodilactone, aldarolactone ester, aldaric acid monoester,
aldaric acid diester, or aldaramide, or salts thereof.
31. The antimicrobial composition of claim 13 wherein the
crosslinking agent is derived from glucaric acid, galactaric acid,
mannaric acid, xylaric acid or tartaric acid.
32. The antimicrobial composition of claim 13 wherein the
crosslinking agent is of the Formulae IX, X, XI, XII: ##STR00022##
wherein A1 is independently selected from: ##STR00023## and salts
thereof; and A2 is selected from --NH--R.sub.5--NH--
--NH--R.sub.5--O-- and --O--R.sub.5--O-- and salts thereof; wherein
R.sub.5 and R.sub.7 are independently aliphatic or aromatic
hydrocarbylene groups, linear or cyclic, optionally substituted
with alkyl, aryl, hydroxy, amino, carbonyl, carboxyl, ester, amide,
alkoxy, nitrile or halogen, or slats thereof, and optionally
containing --O--, --Si(ZZ')O--, --(C.dbd.O)-- or --NZ-- linkages,
where Z and Z' are independently hydrogen, alkyl, substituted
alkyl, alkaryl, substituted alkaryl, aryl, or substituted aryl; and
R.sub.6 is hydrogen or a 1-22 carbon alkyl group.
33. The antimicrobial composition of claim 32 wherein R.sub.5 and
R.sub.7 are independently optionally substituted aliphatic carbon
chains with optional --(NZ)-- or --O-- linkages, wherein Z is
hydrogen, optionally substituted alkyl or optionally substituted
aryl.
34. The antimicrobial composition of claim 32 wherein R.sub.5 and
R.sub.7 are independently linear, cyclic, or branched alkylene
groups of 1-10 carbon atoms, optionally substituted with --O--
linkages, and optionally substituted with --NH.sub.2 groups, or
salts thereof.
35. The antimicrobial composition of claim 32 wherein R.sub.7 is
--[(CH.sub.2).sub.1-21]--; --CH(CH.sub.3)--; --CH(isopropyl)-;
--CH(isobutyl)-; --CH(CH(CH.sub.3)CH.sub.2CH.sub.3)--;
--CH(CH.sub.2OH)--; --CH(CH.sub.2CH.sub.2SCH.sub.3)--;
--CH(CH(OH)CH.sub.3)--; --CH(CH.sub.2C.sub.6H.sub.5)--;
--CH(CH.sub.2C.sub.6H.sub.4OH)--; --CH(CH.sub.2CONH.sub.2)--; or
--CH(CH.sub.2CH.sub.2CONH.sub.2)--; and R.sub.5 is
--[(CH.sub.2).sub.2-22]--;
--[(CH.sub.2).sub.0-6(C.sub.6H.sub.10)(CH.sub.2).sub.0-6]--;
--[(CH.sub.2).sub.0-6C.sub.6H.sub.4(CH.sub.2).sub.0-6]--;
--[CH.sub.2CH.sub.2(OCH.sub.2CH.sub.2).sub.1-21]--;
--[CH.sub.2CH(CH.sub.3)[OCH.sub.2CH(CH.sub.3)].sub.1-21]--;
--(CH.sub.2CH.sub.2NH).sub.1-22CH.sub.2CH.sub.2--;
--[CH.sub.2CH(CH.sub.3)[OCH.sub.2CH(CH.sub.3)].sub.x(OCH.sub.2CH.sub.2).s-
ub.y[OCH.sub.2CH(CH.sub.3)].sub.z]-- wherein x+y+z=2-50;
--[CH.sub.2CH.sub.2(OCH.sub.2CH.sub.2).sub.x[OCH.sub.2CH(CH.sub.3)].sub.y-
(OCH.sub.2CH.sub.2).sub.z]-- wherein x+y+z=2-50;
--[CH(CH.sub.3)CH.sub.2O].sub.xCH.sub.2C(Z')(CH.sub.2[OCH.sub.2CH(CH.sub.-
3)].sub.y--)CH.sub.2[OCH.sub.2CH(CH.sub.3)].sub.z-- wherein
x+y+z=2-10 and Z' is H, methyl or ethyl;
--[CH(CH.sub.3)CH.sub.2O].sub.xCH.sub.2CH([OCH.sub.2CH(CH.sub.3)].sub.y---
)CH.sub.2[OCH.sub.2CH(CH.sub.3)].sub.z-- wherein x+y+z=3-100; or
--CH.sub.2CH.sub.2CH.sub.2CH.sub.2[CH(NH.sub.2)CONHCH.sub.2CH.sub.2CH.sub-
.2CH.sub.2].sub.0-10CH(COYR)--, or salts thereof, wherein Y is O or
NH, and R is a C.sub.1-C.sub.22 optionally substituted alkyl, aryl,
or alkaryl.
36. The antimicrobial composition of claim 32 wherein about 0.0005
to about 0.5 molar equivalents of crosslinking agent are used per
reactive pendant group.
37. The antimicrobial composition of claim 32 wherein from about
0.005 to about 0.5 molar equivalents of crosslinking agent are used
per reactive pendant group.
38. The antimicrobial composition of claim 32 wherein 0.01 to 0.25
molar equivalents of the reactive pendant groups are derivatized.
Description
[0001] This application is a Divisional of U.S. application Ser.
No. 11/064,191, now granted, filed on Feb. 23, 2005.
FIELD OF INVENTION
[0002] The invention is directed to the preparation of novel,
crosslinked polymers using biomass derived materials, such as
aldaric acids and derivatives. These polymers can be used as
hydrogels.
BACKGROUND
[0003] The concept of using biomass-derived materials to produce
other useful products has been explored since man first used plant
materials and animal fur to make clothing and tools. Biomass
derived materials have also been used for centuries as adhesives,
solvents, lighting materials, fuels, inks/paints/coatings,
colorants, perfumes and medicines. Recently, people have begun to
explore the possibility of using "refined biomass" as starting
materials for chemical conversions leading to novel high
value-in-use products. Over the past two decades, the cost of
renewable biomass materials has decreased to a point where many are
competitive with those derived from petroleum. In addition, many
materials that cannot be produced simply from petroleum feedstocks
are potentially available from biomass or refined biomass. Many of
these unique, highly functionalized, molecules would be expected to
yield products unlike any produced by current chemical processes.
"Refined biomass" is purified chemical compounds derived from the
first or second round of plant biomass processing. Examples of such
materials include cellulose, sucrose, glucose, fructose, sorbitol,
erythritol, and various vegetable oils.
[0004] A particularly useful class of refined biomass is that of
aldaric acids. Aldaric acids, also known as saccharic acids, are
diacids derived from naturally occurring sugars. When aldoses are
exposed to strong oxidizing agents, such as nitric acid, both the
aldehydic carbon atom and the carbon bearing the primary hydroxyl
group are oxidized to carboxyl groups. An attractive feature of
these aldaric acids includes the use of very inexpensive sugar
based feedstocks, which provide low raw material costs and
ultimately could provide low polymer costs if the proper oxidation
processes are found. Also, the high functional density of these
aldaric acids provide unique, high value opportunities, which are
completely unattainable at a reasonable cost from petroleum based
feedstocks.
[0005] Hydrogels (hydrated gel) are polymers that contain
water-swellable, three-dimensional networks of macromolecules held
together by covalent or noncovalent (e.g., ionic or hydrogen
bonded) crosslinks. Upon placement in an aqueous environment, these
networks swell to the extent allowed by the degree of crosslinking.
They are used in many fields such as medical applications, personal
care formulations, coatings, and surfactants.
[0006] U.S. Pat. No. 5,496,545 discloses crosslinked polyallylamine
and polyethyleneimine. The crosslinking agents disclosed include
epichlorohydrin, diepoxides, diisocyanates,
.alpha.,.omega.-dihaloalkanes, diacrylates, bisacrylamides,
succinyl chloride, and dimethyl succinate. The present invention
provides new crosslinked polymers that can function as hydrogels.
The polymers comprise crosslinking moieties that can be derived
from biomass sources.
SUMMARY OF THE INVENTION
[0007] One aspect of the present invention is a crosslinked polymer
comprising:
[0008] a linear, branched or cyclic polymeric backbone comprising
repeat units that comprise one or more of each of: hydrocarbylene
groups, heteroatoms, and carbonyl carbon groups; wherein the
hydrocarbylene groups are aliphatic or aromatic, linear, branched,
or cyclic, and can include combinations of aliphatic, aromatic,
linear, branched and/or cyclic hydrocarbylene groups; and
[0009] one or more crosslinking units containing at least one
aldaroyl structural unit of Formula I:
##STR00001## [0010] where n is 1-6.
[0011] The hydrocarbylene groups and heteroatoms of the repeat
units are optionally substituted with substituents that comprise
one or more of C.sub.1-C.sub.30 hydrocarbylene groups, heteroatoms,
and carbonyl carbon groups, wherein the hydrocarbylene groups of
the substituents are aliphatic or aromatic, linear, branched, or
cyclic, or combinations thereof.
[0012] Preferably the crosslinking units are one or more of
Formulae II, III, IV, and V:
##STR00002##
[0013] wherein Q is --O-- or --NH--, or salts thereof, and R.sub.1,
R.sub.2, R.sub.3 and R.sub.4 are aliphatic or aromatic
hydrocarbylene groups, linear, branched or cyclic, optionally
substituted, and optionally containing --O--, --Si(ZZ')O--,
--(C.dbd.O)-- or --NZ-- linkages, where Z and Z' are independently
hydrogen, alkyl, substituted alkyl, alkaryl, substituted alkaryl,
aryl, or substituted aryl;
[0014] and wherein Formulae II, III, IV, and V are directly
attached to the polymer backbone.
[0015] Another aspect of the present invention is a crosslinked
polymer prepared by a process comprising contacting a crosslinking
agent with a substrate polymer to form a crosslinked polymer,
wherein the crosslinking agent is one or more of Formulae VI, VII
and VIII:
##STR00003##
[0016] wherein L and L' independently contain a suitable functional
group, and n=1-6, m=0-4, and p=1-4;
[0017] and the substrate polymer comprises:
[0018] a linear, branched or cyclic polymeric backbone comprised of
repeat units that comprise one or more of hydrocarbylene groups,
heteroatoms, and carbonyl carbon groups [0019] wherein the
hydrocarbylene groups are aliphatic or aromatic, linear, branched,
or cyclic, or combinations thereof; and
[0020] reactive pendant groups attached to the polymeric backbone,
the pendant groups being of the formula -G or --R-G. [0021] wherein
G is a nucleophile or electrophile; [0022] wherein R is
independently linear, cyclic, or branched alkylene, arylene, or
alkarylene groups of 1-22 carbon atoms, optionally substituted with
alkyl, aryl, hydroxy, amino, carbonyl, ester, amide, alkoxy,
nitrile or halogen, and optionally containing --O--, --Si(ZZ')O--,
--(C.dbd.O)-- or --NZ-- linkages, where Z and Z' are independently
hydrogen, alkyl, substituted alkyl, alkaryl, substituted alkaryl,
aryl, or substituted aryl. The hydrocarbylene groups and
heteroatoms of the repeat units are optionally substituted with
substituents that comprise one or more of C.sub.1-C.sub.30
hydrocarbylene groups, heteroatoms, and carbonyl carbon groups. The
hydrocarbylene groups of the substituents can be aliphatic or
aromatic, linear, branched, or cyclic, or combinations thereof.
Preferably, L and L' are derived from an amine, hydroxyl,
carboxylic acid, ester, urethane, urea, amide, or isocyanate; and G
is an epoxide, isocyanate, benzylic halide, amine, acid halide,
ester, or amide. Also preferably L and L' are selected from
optionally substituted --NHR'', --OR'', and
hydrocarbylene-C(.dbd.O)OR'' and G is selected from --NH.sub.2,
--C(.dbd.O)Cl, --C(.dbd.O)OR'', or --C(.dbd.O)NH--R''--NH.sub.2;
wherein R'' is independently an optionally substituted hydrocarbyl
or hydrocarbylene, and wherein n=2-4, m=0-1, and p=2-3. The
optional substituents on R'' can be any heteroatom-containing group
that does not participate directly in reactions between the
substrate polymer and the crosslinking agent; i.e., the substituent
is preferably not displaced during such reaction and does not form
a covalent bond with the substrate polymer. Groups attached to the
polymer by reaction with G can contain aza (--NZ--) or ether
(--O--) linkages (e.g., G can be PEGylated). In one embodiment of
the process, less than 100% of the reactive pendant groups are
derivatized such that the derivatized pendant groups are
substantially unreactive to the crosslinking agent. "Substantially
unreactive", as used herein, means having a rate of reaction, e.g.,
with the crosslinking agent, of about 20% or less of the rate of
reaction of an underivatized pendant group under the same
conditions. The derivatization can be performed before, during or
after contact of the crosslinking group with the polymer substrate.
Preferably, the reactive pendant groups are derivatized to contain
an optionally substituted aliphatic carbon chain with optional
--(NZ)--, and --O-- linkages, where Z is hydrogen, optionally
substituted alkyl or optionally substituted aryl.
[0023] In another embodiment, the crosslinking agent is derived
from an aldaric acid, aldarolactone, aldarodilactone, aldarolactone
ester, aldaric acid monoester, aldaric acid diester, or aldaramide,
or salts thereof, and the substrate polymer comprises
polyallylamine, polyallylamine hydrochloride, branched
polyethyleneimine, branched polyethyleneimine hydrochloride,
poly(acryloyl chloride), poly(methacryloyl chloride),
poly[N-(.omega.-aminoalkyl)acrylamide], polyglycosamine,
carboxymethylchitosan, chitosan, chitosan hydrochloride, or
derivatives or salts thereof. By "derived from" is meant that the
crosslinking agent can be produced from a starting compound in
about six or fewer chemical reaction steps, and retains an aldaric
structure --C(.dbd.OXCHOR).sub.nC(.dbd.O)-- wherein R is H or a
carbon-containing group such as alkyl.
[0024] Preferably the crosslinking agent is one or more of the
Formulae IX, X, XI, and XII:
##STR00004##
[0025] wherein A1 is selected from:
##STR00005##
and salts thereof;
[0026] and A2 is selected from
--NH--R.sub.5--NH--
--NH--R--O--
and
--O--R--O--
and salts thereof;
[0027] wherein R.sub.5 and R.sub.7 are independently aliphatic or
aromatic hydrocarbylene groups, linear, branched or cyclic,
optionally substituted, and optionally containing --O--,
--Si(ZZ')O--, --(C.dbd.O)-- or --NZ-- linkages, where Z and Z' are
independently hydrogen, alkyl, substituted alkyl, alkaryl,
substituted alkaryl, aryl, or substituted aryl; and R.sub.6 is
hydrogen or a 1-22 carbon alkyl group.
[0028] The polymers and processes can be used to form compositions,
emulsifiers, thickeners, and personal care products comprising the
polymers. Examples of personal care products that can be made from
the polymers include skin and hair conditioners. In some
embodiments, the polymers or products made therefrom are
antimicrobial.
[0029] Other aspects of the invention include a method of cleaning
and smoothing human skin and a method of conditioning hair
comprising the application of an effective amount of the polymers
of the invention. Also included are methods for killing,
inhibiting, or preventing the growth of at least one microbe, the
method comprising contacting the microbe with an effective amount
of a crosslinked polymer according to the invention, a method of
reducing microbial population on a surface comprising contacting a
surface with an effective amount of the crosslinked polymer for a
time sufficient to reduce the microbial population on the surface,
an antimicrobial substrate comprising a crosslinked polymer
according to the invention that is bound to or incorporated into
the substrate, and articles comprising such antimicrobial
substrates.
[0030] These and other aspects of the present invention will be
apparent to one skilled in the art, in view of the following
description and the appended claims.
DETAILED DESCRIPTION
[0031] The following definitions may be used for the interpretation
of the present specification and the claims:
[0032] By hydrocarbyl is meant a straight chain, branched or cyclic
arrangement of carbon atoms connected by single, double, or triple
carbon-to-carbon bonds, and substituted accordingly with hydrogen
atoms. Hydrocarbyl groups can be aliphatic and/or aromatic.
Examples of hydrocarbyl groups include methyl, ethyl, propyl,
isopropyl, butyl, isobutyl, t-butyl, cyclopropyl, cyclobutyl,
cyclopentyl, methylcyclopentyl, cyclohexyl, methylcyclohexyl,
benzyl, phenyl, o-toluyl, m-toluyl, p-toluyl, xylyl, vinyl, allyl,
butenyl, cyclohexenyl, cyclooctenyl, cyclooctadienyl, and butynyl.
Examples of substituted hydrocarbyl groups include toluyl,
chlorobenzyl. --(CH.sub.2)--O--(CH.sub.2)--, fluoroethyl,
p-(CH.sub.3S)C.sub.6H.sub.5, 2-methoxypropyl, and
(CH.sub.3).sub.3SiCH.sub.2.
[0033] "Alkyl" means a saturated hydrocarbyl group. Examples of
alkyl groups include methyl, ethyl, propyl, isopropyl, butyl,
s-butyl, isobutyl, pentyl, neopentyl, hexyl, heptyl, isoheptyl,
2-ethyihexyl, cyclohexyl and octyl.
[0034] "Aryl" means a group defined as a monovalent radical formed
conceptually by removal of a hydrogen atom from a hydrocarbon that
is structurally composed entirely of one or more benzene rings.
Examples of aryl groups include benzene, biphenyl, terphenyl,
naphthalene, phenyl naphthalene, and naphthylbenzene.
[0035] "Alkaryl" means an alkylated aryl group; that is, an aryl
group as defined above that is substituted with an alkyl group.
[0036] By "hydrocarbylene," "alkylene," "arylene," or "alkarylene"
is meant the divalent form of the corresponding group.
[0037] "Substituted" means that a group contains one or more
substituent groups, or "substituents," that do not cause the
compound to be unstable or unsuitable for the use or reaction
intended. Unless otherwise specified herein, when a group is stated
to be "substituted" or "optionally substituted," substituent groups
that can be present include carboxyl, carboxamido (including
primary, secondary or tertiary carboxamido), acylamino,
alkoxycarbonylamino, sulfonylamino, cyano, alkoxy, alkoxycarbonyl,
acyloxy, fluoro, chloro, bromo, iodo, amino (including primary,
secondary and tertiary amino), hydroxy, alkenyl, oxo, imino,
hydroxyimino, hydrocarbyloxyimino, wherein the hydrocarbyl group
can be aliphatic, aryl or a combination of the two,
trihydrocarbylsilyl, wherein each hydrocarbyl group can be
independently alkyl or aryl, trihydrocarbylsiloxy, wherein each
hydrocarbyl group can be independently alkyl or aryl, nitro,
nitroso, hydrocarbylthio, wherein the hydrocarbyl group can be
aliphatic, aryl or a combination of the two, hydrocarbylsulfonyl,
wherein the hydrocarbyl group can be aliphatic, aryl or a
combination of the two, hydrocarbylsulfinyl, wherein the
hydrocarbyl group can be aliphatic, aryl or a combination of the
two, hydrocarbyloxysulfonyl, wherein the hydrocarbyl group can be
aliphatic, aryl or a combination of the two, sulfonamido (including
primary, secondary and tertiary sulfonamido), sulfonyl,
dihydrocarbylphosphino, wherein each hydrocarbyl group can be
independently alkyl or aryl, dihydrocarbyloxyphosphino, wherein
each hydrocarbyl group can be independently alkyl or aryl,
hydrocarbylphosphonyl, wherein the hydrocarbyl group can be
aliphatic, aryl or a combination of the two,
hydrocarbyloxyphosphonyl, wherein the hydrocarbyl group can be
aliphatic, aryl or a combination of the two, phosphonamido
(including primary, secondary and tertiary phosphonamido), and
salts of the aforementioned.
[0038] The present invention is directed to a crosslinked polymer
comprising a polymeric backbone and one or more crosslinking units
containing at least one aldaroyl unit.
[0039] The polymer comprises:
[0040] A) a linear, branched or cyclic polymeric backbone
comprising repeat units that comprise one or more groups selected
from hydrocarbylene groups, heteroatoms, and carbonyl carbon
groups, wherein the hydrocarbylene groups are aliphatic or
aromatic, linear, branched, or cyclic, or combinations thereof;
and
[0041] B) one or more crosslinking units containing at least one
aldaroyl structural unit of Formula I:
##STR00006## [0042] where n is 1-6.
[0043] The hydrocarbylene groups and heteroatoms of the repeat
units are optionally substituted with substituents that comprise
one or more of C.sub.1-C.sub.30 hydrocarbylene groups, heteroatoms,
and carbonyl carbon groups, wherein the hydrocarbylene groups of
the substituents are aliphatic or aromatic, linear, branched, or
cyclic, or combinations thereof.
[0044] The crosslinker shown in Formula I is attached to the
polymer backbone via the available valences at either end of the
structural unit. They are attached either directly with no other
atoms between the structure of Formula I and the backbone of the
polymer, or indirectly with other atoms or structural groups
between Formula I and the polymer backbone. For example, in one
embodiment shown below, the crosslinking unit (in which n=4) is
indirectly attached to the polyethylene backbone via the
--NH--CH.sub.2--C(.dbd.O)--NH--CH.sub.2-- structural unit:
##STR00007##
[0045] Aldaric acids are diacids derived from naturally occurring
sugars. When aldoses are exposed to strong oxidizing agents, such
as nitric acid, both the aldehydic carbon atom and the carbon
bearing the primary hydroxyl group are oxidized to carboxyl groups.
This family of diacids is known as aldaric acids (or saccharic
acids). An aldarolactone has one carboxylic acid lactonized; the
aldarodilactone has both lactonized. As illustration, the aldaric
acid derivatives starting from D-glucose are shown below.
##STR00008##
[0046] Any stereoisomer or mixture of stereoisomers can be used in
the compositions and processes disclosed herein. The aldaric acid
derivative can be glucaric acid or galactaric acid, or their
derivatives such as, for example, glucarolactone, glucarodilactone,
galactarolactone, and dimethyl galactarate.
[0047] The polymeric backbone can contain --NZ--, --N.sup.+ZZ'--,
--O--, --C(.dbd.O)NZ--, --C(.dbd.O)O--, --C(.dbd.O)--,
--OC(.dbd.O)O--, --OC(.dbd.O)NZ--, --NZC(.dbd.O)NZ'--, or
--SiZZ'O--linkages, where Z and Z' are independently hydrogen,
alkyl, substituted alkyl, aryl, or substituted aryl. Substituents
on the repeat units contain one or more of --X, --O(Z), --N(ZZ'),
--N.sup.+(ZZ'Z''), --C(.dbd.O)OZ, --C(.dbd.O)X, --C(.dbd.O)NZZ',
--C.dbd.N.dbd.O, --O--, --N(Z)--, --N.sup.+(ZZ')--,
--C(.dbd.O)N(Z)--, --C(.dbd.O)O--, --C(.dbd.O)--, --OC(.dbd.O)O--,
--OC(.dbd.O)N(Z)--, --N(Z)C(.dbd.O)N(Z')--,
--C(.dbd.O)NH(CH.sub.2).sub.pNH.sub.2, --Si(ZZ')O--,
--(OCH.sub.2CH.sub.2).sub.mOH, or --(OSi(ZZ')).sub.nOH, or salts
thereof, wherein X is a halogen, Z, Z', and Z'' are independently
hydrogen or C.sub.1-C.sub.22 optionally substituted alkyl or aryl,
and wherein m is 1 to 50, n is 1 to 100, and p is 1 to 12.
[0048] The repeat units of the crosslinked polymer preferably
comprise aliphatic hydrocarbylene groups with substituents
comprising one or more of aminoalkyl groups, --C(.dbd.O)OZ,
--C(.dbd.O)X, --C(.dbd.O)NZZ', or
--C(.dbd.O)NH(CH.sub.2).sub.pNH.sub.2, or salts thereof. The repeat
units are also preferably azahydrocarbylenes or salts thereof, with
one or more terminal aminoalkyl groups or salts thereof as
substituents on the nitrogen of the azahydrocarbylene repeat unit.
Also preferably the repeat units contain substituents comprising
one or more of C.sub.1-C.sub.22 aminoalkyl groups, optionally
substituted with alkyl or aldaroyl groups or salts thereof. The
aldaroyl moiety in the crosslinking unit is preferably glucaroyl,
galactaroyl, mannaroyl, xylaroyl, or tartaroyl.
[0049] In one embodiment, the crosslinked polymer is a derivative
of polyallylamine, polyallylamine hydrochloride, branched
polyethyleneimine, branched polyethyleneimine hydrochloride,
poly(acryloyl chloride), poly(methacryloyl chloride),
poly[N-(.omega.-aminoalkyl)acrylamide], polyglycosamine,
carboxymethylchitosan, chitosan, chitosan hydrochloride, or a
derivative or salt thereof. For example, polymers having amine
groups can have some of the amine groups alkylated, acylated,
sulfonated, or reacted to form imines or aminals. Also, they can be
in one or more salt forms or partial salt forms, e.g.,
polyallyamine hydrochloride can be converted to its
p-toluenesulfonic acid or acetic acid salt. Polymers with acyl
chloride groups can be partially reacted with a monofunctional
alcohol or amine to form ester or amide side chains. Such
derivatives retain the backbone structure and preferably some of
the reactive side chain structure as the original polymer from
which the derivative is derived. The crosslinked polymer can
additionally comprise one or more of the crosslinking units of
Formulae II, III, IV, or V:
##STR00009##
[0050] wherein Q is --O-- or --NH--, or a salt thereof, and
R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are aliphatic or aromatic
hydrocarbylene groups, linear, branched or cyclic, optionally
substituted, and optionally containing --O--, --Si(ZZ')O--,
--(C.dbd.O)-- or --NZ-- linkages, where Z and Z' are independently
hydrogen, alkyl, substituted alkyl, alkaryl, substituted alkaryl,
aryl, or substituted aryl.
[0051] The crosslinking units shown by Formulae II, III, IV, and V
are directly attached to the polymer backbone via the available
valences at either end of the structural units.
[0052] Preferably, R.sub.1 is --[(CH.sub.2).sub.0-22]--,
--(CH.sub.2).sub.aC.sub.6H.sub.10(CH.sub.2).sub.b--,
--(CH.sub.2CH.sub.2NH).sub.1-22CH.sub.2CH.sub.2--,
--[(CH.sub.2CH(Z')O).sub.1-22(CH.sub.2).sub.2-3]-- wherein Z' is H
or CH.sub.3, --C(O)NH(CH.sub.2).sub.2-22--, or
--(CH.sub.2).sub.a(C.sub.6H.sub.4)(CH.sub.2).sub.b--, wherein a=0-6
and b=0-6;
[0053] R.sub.2 is --[(CH.sub.2).sub.1-21]--, --CH(CH.sub.3)--,
--CH(isopropyl)-, --CH(isobutyl)-,
--CH(CH(CH.sub.3)CH.sub.2CH.sub.3)--, --CH(CH.sub.2OH)--,
--CH(CH.sub.2CH.sub.2SCH.sub.3)--, --CH(CH(OH)CH.sub.3)--,
--CH(CH.sub.2C.sub.6H.sub.5)--, --CH(CH.sub.2C.sub.6H.sub.4OH)--,
--CH(CH.sub.2CONH.sub.2)--, or
--CH(CH.sub.2CH.sub.2CONH.sub.2)--;
[0054] R.sub.3 is --[(CH.sub.2).sub.2-22]--,
--[(CH.sub.2).sub.0-6(C.sub.6H.sub.10)(CH.sub.2).sub.0-6]--,
--[(CH.sub.2).sub.0-6C.sub.6H.sub.4(CH.sub.2).sub.0-6]--,
--[CH.sub.2CH.sub.2(OCH.sub.2CH.sub.2).sub.1-21]--,
--[CH.sub.2CH(CH.sub.3)[OCH.sub.2CH(CH.sub.3)].sub.1-21]--,
--(CH.sub.2CH.sub.2NH).sub.1-22CH.sub.2CH.sub.2--,
--[CH.sub.2CH(CH.sub.3)[CH.sub.2CH(CH.sub.3)].sub.x(OCH.sub.2CH.sub.2).su-
b.y[OCH.sub.2CH(CH.sub.3)].sub.z]-- wherein x+y+z=2-50,
--[CH.sub.2CH.sub.2(OCH.sub.2CH.sub.2).sub.x[OCH.sub.2CH(CH.sub.3)].sub.y-
(OCH.sub.2CH.sub.2)]-- wherein x+y+z=2-50,
--[CH(CH.sub.3)CH.sub.2O].sub.xCH.sub.2C(Z')(CH.sub.2[OCH.sub.2CH(CH.sub.-
3)].sub.y)CH.sub.2[OCH.sub.2CH(CH.sub.3)].sub.z-- wherein
x+y+z=2-10 and Z' is H, methyl or ethyl,
--[CH(CH.sub.3)CH.sub.2O].sub.xCH.sub.2CH([OCH.sub.2CH(CH.sub.3)].sub.y---
)CH.sub.2[OCH.sub.2CH(CH.sub.3)].sub.z-- wherein x+y+z=3-100, or
--CH.sub.2CH.sub.2CH.sub.2CH.sub.2[CH(NH.sub.2)CONHCH.sub.2CH.sub.2CH.sub-
.2CH.sub.2].sub.0-10CH(COYR)-- or salts thereof, wherein Y is O or
NH, and R is a C.sub.1-C.sub.22 optionally substituted alkyl, aryl,
or alkaryl; and
[0055] R.sub.4 is --C(.dbd.O)--, --C.sub.6H.sub.4CH.sub.2--,
--(CH.sub.2).sub.1-22Y'CH.sub.2CH(OH)CH.sub.2--, or
--(CH.sub.2).sub.1-22Y'C(O)CH(OH)CH.sub.2--, wherein Y' is O or
NH.
[0056] The R.sub.3 moieties,
--[CH(CH.sub.3)CH.sub.2O].sub.xCH.sub.2C(Z')(CH.sub.2[OCH.sub.2CH(CH.sub.-
3)].sub.y--)CH.sub.2[OCH.sub.2CH(CH)].sub.z-- and
--[CH(CH.sub.3)CH.sub.2O].sub.xCH.sub.2CH([OCH.sub.2CH(CH.sub.3)].sub.y)C-
H.sub.2[OCH.sub.2CH(CH.sub.3)].sub.z--, are trivalent and therefore
can react to form crosslinked structures. Other polyalkylene,
polyalkyleneoxide, and polyalkylenearyl structures can be
trivalent, tetravalent, or higher multivalent. Therefore, when
R.sub.3 is multivalent, the polymer of the instant invention can
exist in a multivalent crosslinked structure with the empty
valences on the polyalkyleneoxide being endcapped by available
functionalities such as amines.
[0057] Preferably about 0.1% to about 100% of the polymer backbone
repeat units are connected to a crosslinking unit. More preferably
about 1% to about 30% of the polymer backbone repeat units are
connected to a crosslinking unit.
[0058] Also provided according to the invention are crosslinked
polymers prepared by a process comprising contacting a crosslinking
agent with a substrate polymer to form a crosslinked polymer,
wherein the crosslinking agent is one or more of Formulae VI, VII
and VIII:
##STR00010##
[0059] and n=1-6, m=0-4, and p=1-4. Preferably n=2-4, m=0-1, and
p=2-3.
[0060] The substrate polymer used in the instant process comprises
a linear, branched or cyclic polymeric backbone. The backbone
contains repeat units that comprise one or more of hydrocarbylene
groups, heteroatoms, and carbonyl carbon groups. The hydrocarbylene
groups are aliphatic or aromatic, linear, branched, or cyclic, or
combinations thereof. The hydrocarbylene groups and heteroatoms of
the repeat units are optionally substituted with substituents that
comprise one or more of C.sub.1-C.sub.30 hydrocarbylene groups,
heteroatoms, and carbonyl carbon groups, wherein the hydrocarbylene
groups of the substituents are aliphatic or aromatic, linear,
branched, or cyclic, or combinations thereof.
[0061] The polymeric backbone used in the process can contain
--NZ--, --N.sup.+ZZ'--, --O--, --C(.dbd.O)NZ--, --C(.dbd.O)O--,
--C(.dbd.O)--, --OC(.dbd.O)O--, --OC(.dbd.O)NZ--,
--NZC(.dbd.O)NZ'--, or --SiZZ'O-- linkages, where Z and Z' are
independently hydrogen, alkyl, substituted alkyl, aryl, or
substituted aryl.
[0062] The substituents on the repeat units are preferably one or
more of --X, --O(Z), --N(ZZ'), --N.sup.+(ZZ'Z''), --C(.dbd.O)OZ,
--C(.dbd.O)X, --C(.dbd.O)NZZ', --C.dbd.N.dbd.O, --O--, --N(Z)--,
--N.sup.+(ZZ')--, --C(.dbd.O)N(Z)--, --C(.dbd.O)O--, --C(.dbd.O)--,
--OC(.dbd.O)O--, --(OCH.sub.2CH.sub.2).sub.mOH, or
--(OSi(ZZ')).sub.nOH, or salts thereof, where X is a halogen, Z,
Z', and Z'' are independently hydrogen, C.sub.1-C.sub.22 optionally
substituted alkyl, or C.sub.1-C.sub.22 optionally substituted aryl,
and where m is 1 to 50, n is 1 to 100, and p is 1 to 12. More
preferably, the substituents comprise one or more of
C.sub.1-C.sub.22 aminoalkyl groups, optionally substituted with
alkyl or aldaroyl, or a salt thereof. The repeat units preferably
comprise aliphatic hydrocarbylene groups with substituents
comprising one or more of aminoalkyl groups, --C(.dbd.O)OZ,
--C(.dbd.O)X, --C(.dbd.O)NZZ', or
--C(.dbd.O)NH(CH.sub.2).sub.nNH.sub.2, or salts thereof, where X is
halogen, Z and Z' are independently hydrogen, C.sub.1-C.sub.22
alkyl, substituted alkyl, aryl, or substituted aryl, and
n=1-12.
[0063] The repeat unit can be an azahydrocarbylene or salt thereof
with one or more terminal amino groups or salts thereof as
substituents on the N of the azahydrocarbylene repeat unit.
[0064] The substrate polymer can also comprise polyallylamine,
polyallylamine hydrochloride, branched polyethyleneimine, branched
polyethyleneimine hydrochloride, poly(acryloyl chloride),
poly(methacryloyl chloride),
poly[N-(.omega.-aminoalkyl)acrylamide], polyglycosamine,
carboxymethylchitosan, chitosan, chitosan hydrochloride, or
derivatives or salts thereof.
[0065] Attached to the polymeric backbone are reactive pendant
groups of the formula -G or --R-G; where G is a nucleophile or
electrophile; and where R is independently linear, cyclic, or
branched alkylene, arylene, or alkarylene groups of 1-22 carbon
atoms, optionally substituted with alkyl, aryl, hydroxy, amino,
carbonyl, ester, amide, alkoxy, nitrile or halogen, and optionally
containing --O--, --Si(ZZ')O--, --(C.dbd.O)-- or --NZ-- linkages,
where Z and Z' are independently hydrogen, alkyl, substituted
alkyl, alkaryl, substituted alkaryl, aryl, or substituted aryl.
[0066] The terms, "electrophile" and "nucleophile," are well known
to those skilled in the art, and can be broadly defined as reactive
chemical moieties that act as electron acceptors or electron donors
respectively. Preferably, G is an epoxide, isocyanate, benzylic
halide, amine, acid halide, ester, or amide; more preferably G is
--NH.sub.2, --C(.dbd.O)Cl, --C(.dbd.O)OR'' or
--C(.dbd.O)NH--R''--NH.sub.2 wherein R'' is independently hydrogen
or an optionally substituted hydrocarbyl or hydrocarbylene. Most
preferably G is --NH.sub.2.
[0067] L and L' are defined as containing a suitable functional
group. A suitable functional group is herein defined as a
functional group that readily forms a covalent bond with the
reactive pendant group. The functional group employed depends upon
the synthetic method used to make the crosslinked polymer. The
functional group can contain heteroatoms such as O, N, S, and/or
can be derived from a functional group such as an amine, hydroxyl,
carboxylic acid, ester, urethane, urea, amide, or isocyanate.
Particularly useful functional groups are those that contain a
--NH-- group, a --C(.dbd.O)O-- group, a --O-- group, or salts
thereof. Preferably, the suitable functional group is derived from
an amine, hydroxyl, carboxylic acid, ester, urethane, urea, amide,
or isocyanate. More preferably L and L' are independently selected
from --Y--R, wherein Y is O, NH, or S and R is alkyl, substituted
alkyl, alkaryl, substituted alkaryl, aryl, or substituted aryl.
Also more preferably L and L' are independently selected from
optionally substituted --NHR'', --OR'', and
hydrocarbylene-C(.dbd.O)OR''; wherein R'' is an optionally
substituted hydrocarbylene, and wherein n=2-4, m=0-1, and
p=2-3.
[0068] As illustration, a crosslinker that is capped with a
carboxylic acid as the suitable functional group would be expected
to react readily with available amine pendant groups on the
polymeric backbone. A crosslinker end-capped with a hydroxyl group
or an amine as a functional group would not be expected to react
with the pendant amine functionality of the polymeric backbone.
However, if the subject polymer backbone had a carboxylic acid or
an isocyanate as pendant functionality, then a crosslinker capped
with an amine or a hydroxyl functional group could react with the
pendant group of the polymeric backbone.
[0069] In another embodiment, less than 100%, preferably up to
about 50%, and more preferably up to about 20% of the reactive
pendant groups are derivatized so that they are unreactive to the
crosslinking agent. The derivatization can be performed by
contacting the reactive pendant groups with a derivatizing reagent
before, during or after contact of the crosslinker with the
substrate polymer. Preferably, the reactive pendant groups are
derivatized before the contact of the crosslinker with the polymer
substrate. The reactive pendant groups can be derivatized to
contain an optionally substituted aliphatic carbon chain with
optional --(NZ)--, and --O-- linkages, where Z is hydrogen,
optionally substituted alkyl or optionally substituted aryl.
Preferably, the reactive pendant groups are derivatized to contain
a linear or branched alkyl group of 1-22 carbon atoms, optionally
substituted with --O-- linkages, and optionally substituted with
--NH.sub.2, halogen, hydroxyl, or carbonyl groups, or salts
thereof, more preferably a C.sub.1-C.sub.22 alkyl group, most
preferably a C.sub.2-C.sub.18 unsubstituted alkyl group.
[0070] The crosslinking agent can be derived from an aldaric acid,
aldarolactone, aldarodilactone, aldarolactone ester, aldaric acid
monoester, aldaric acid diester, or aldaramides, or salts thereof.
Preferably the crosslinking agent is derived from glucaric acid,
galactaric acid, mannaric acid, xylaric acid or tartaric acid.
[0071] In another embodiment, the crosslinking agent is of the
Formulae IX, X, XI, XII:
##STR00011##
[0072] wherein A1 is selected from:
##STR00012##
and salts thereof; and A2 is selected from
--NH--R.sub.5--NH--
--NH--R.sub.5--O--
and
--O--R.sub.5--O--
[0073] and salts thereof. R.sub.5 and R.sub.7 are independently
aliphatic or aromatic hydrocarbylene groups, linear, branched or
cyclic, optionally substituted with alkyl, aryl, hydroxy, amino,
carbonyl, carboxyl, ester, amide, alkoxy, nitrile or halogen, or
slats thereof, and optionally containing --O--, --Si(ZZ')O--,
--(C.dbd.O)-- or --NZ-- linkages, where Z and Z' are independently
hydrogen, alkyl, substituted alkyl, alkaryl, substituted alkaryl,
aryl, or substituted aryl; and R.sub.6 is hydrogen or a 1-22 carbon
alkyl group.
[0074] Preferably, R.sub.5 and R.sub.7 are independently optionally
substituted aliphatic carbon chains with optional --(NZ)-- or --O--
linkages, wherein Z is hydrogen, optionally substituted alkyl or
optionally substituted aryl. More preferably, R.sub.5 and R.sub.7
are independently linear, cyclic, or branched alkylene groups of
1-10 carbon atoms, optionally substituted with --O-linkages, and
optionally substituted with --NH.sub.2 groups, or salts
thereof.
[0075] Also preferably, R.sub.7 is --[(CH.sub.2).sub.1-21]--,
--CH(CH.sub.3)--, --CH(isopropyl)-, --CH(isobutyl)-,
--CH(CH(CH.sub.3)CH.sub.2CH.sub.3)--, --CH(CH.sub.2OH)--,
--CH(CH.sub.2CH.sub.2SCH.sub.3)--, --CH(CH(OH)CH.sub.3)--,
--CH(CH.sub.2C.sub.6H.sub.5)--, --CH(CH.sub.2C.sub.6H.sub.4OH)--,
--CH(CH.sub.2CONH.sub.2)--, or
--CH(CH.sub.2CH.sub.2CONH.sub.2)--;
[0076] and
[0077] R.sub.5 is --[(CH.sub.2).sub.2-22]--,
--[(CH.sub.2).sub.0-6(C.sub.6H.sub.10)(CH.sub.2).sub.0-6]--,
--[(CH.sub.2).sub.0-6C.sub.6H.sub.4(CH.sub.2).sub.0-6]--,
--[CH.sub.2CH.sub.2(OCH.sub.2CH.sub.2).sub.1-21]--,
--[CH.sub.2CH(CH.sub.3)[OCH.sub.2CH(CH.sub.3)].sub.1-21]--,
--(CH.sub.2CH.sub.2NH).sub.1-22CH.sub.2CH.sub.2--,
--[CH.sub.2CH(CH.sub.3)[OCH.sub.2CH(CH.sub.3)].sub.x(OCH.sub.2CH.sub.2).s-
ub.y[OCH.sub.2CH(CH.sub.3)].sub.z]-- wherein x+y+z=2-50,
--[CH.sub.2CH.sub.2(OCH.sub.2CH.sub.2).sub.x[OCH.sub.2CH(CH.sub.3)].sub.y-
(OCH.sub.2CH.sub.2).sub.z]-- wherein x+y+z=2-50,
--[CH(CH.sub.3)CH.sub.2O].sub.xCH.sub.2C(Z')(CH.sub.2[OCH.sub.2CH(CH.sub.-
3)].sub.y--)CH.sub.2[OCH.sub.2CH(CH.sub.3)].sub.z-- wherein
x+y+z=2-10 and Z' is H, methyl or ethyl,
--[CH(CH.sub.3)CH.sub.2O].sub.xCH.sub.2CH([OCH.sub.2CH(CH.sub.3)].sub.y---
)CH.sub.2[OCH.sub.2CH(CH.sub.3)].sub.z-- wherein x+y+z=3-100, or
--CH.sub.2CH.sub.2CH.sub.2CH.sub.2[CH(NH.sub.2)CONHCH.sub.2CH.sub.2CH.sub-
.2CH.sub.2].sub.0-10CH(COYR)-- or salts thereof, wherein Y is O or
NH, and R is a C.sub.1-C.sub.22 optionally substituted alkyl, aryl,
or alkaryl.
[0078] Examples of polyoxaalkyleneamines that can be used include
to those based on Jeffamine.RTM. polyether amines (Huntsman LLC,
Salt Lake City, Utah). Examples of polytetramethylene glycols that
can be used include those based on Terethane.RTM.
polytetramethyleneetherglycol (E. I. DuPont de Nemours, Wilmington,
Del.).
[0079] In some embodiments, about 0.0005 to about 0.5 molar
equivalents of crosslinking agent per reactive pendant group can be
used in the process. Preferably, from about 0.005 to about 0.5
molar equivalents of crosslinking agent are used per reactive
pendant group, and more preferably about 0.01 to 0.25 molar
equivalents per reactive pendant group.
[0080] The processes can be run at any suitable temperature but
preferably at about 20.degree. C. to about 100.degree. C. The
processes can be carried out in a polymer melt, but are preferably
carried out in the presence of a solvent. The choice of solvent is
not critical provided the solvent is not detrimental to reactant or
product. Preferred solvents include water, dimethylformamide,
dimethylformamide LiCl, dimethylacetamide, dimethylacetamide LiCl,
ethanol, and methanol.
[0081] The polymers disclosed herein are suitable for use as
hydrogels. Hydrogels (hydrated gels) are herein defined as
materials that absorb large quantities of liquid, i.e., greater
than 2 mass equivalents of liquid. They are usually
water-swellable, three-dimensional networks of macromolecules held
together by covalent or noncovalent crosslinks. When placed in
aqueous solution, the networks swell to the extent allowed by the
degree of crosslinking.
[0082] Hydrogels are useful in many applications, such as medical
products, personal care formulations, exfoliants, humectants,
surfactants, thickeners, anti-irritants, antimicrobials,
lubricants, emulsifiers, delivery agents, coatings, and
surfactants. In some embodiments the hydrogels are conducting. The
polymers can be modified to introduce a wide range of properties to
make them more suitable in such applications. Additionally,
divalent crosslinking agents as disclosed herein can be used as
water-soluble chain extenders for polyurethanes, and hydroxylated
block or comb copolymers made with the processes described herein
can be used as pigment dispersants. When used as co-polymers or
modifiers to other polymeric materials, the polymers can impart
moisture wicking improvements, dyeability, and/or flame resistance
to the other materials.
[0083] As used herein, the term "antimicrobial" means killing, or
preventing or inhibiting the growth of, microorganisms, including
bacteria and fungi. "Growth inhibition" means reduced rate of
growth of a population of microorganisms. "Growth prevention" means
that growth is stopped.
[0084] Polymers described herein are also suitable for use in
cosmetic products.
[0085] Also provided are methods for cleaning and/or smoothing
human skin comprising the application of an effective amount of the
polymers described herein, and methods of conditioning hair
comprising the application of an effective amount of the polymers
described herein.
[0086] As used herein, "cosmetic products" are products intended
for increasing the appeal, visually and/or olfactorily, of the
human body. Likewise, "personal care products" are products
intended for cleaning, smoothing or otherwise improving the health,
feel, or well-being of the outside of the human body. These
definitions of cosmetic and personal care products at least
partially overlap since many products provide functions in both
categories. Examples of cosmetic products are: perfumes and like
products known as "eau de toilette" and "eau de parfum," hand and
body lotions, skin tonics, shaving products, bath and shower
products, deodorant and antiperspirant products, hair care products
such as shampoos and hair conditioners, and mouth and dental care
products. Such products are well known in the art. Thus, examples
of skin care products are described in "Harry's Cosmeticology," R.
G. Harry, 6.sup.th edition, Leonard Hill Books (1973), Chapters
5-13, 18 and 35; examples of deodorants and antiperspirants are
described in C. Fox, cosmetics and Toiletries 100 (December 1985),
pp 27-41; examples of hair care products are described "Harry's
Cosmeticololgy," vide supra, chapters 25-27; examples of dental
care products are described in M. Pader, Oral Hygiene: Products and
Practice, Marcel Dekker, New York (1988).
[0087] For use in the personal care field, the polymers can be
modified to enhance moisture retention, lubricity, static control,
curl retention, sheen, and/or "body" in hair-care related products.
For skin care products could the polymers can be used to make
exfoliants (for example, as .alpha.-hydroxy acid replacements),
humectants, surfactants, thickeners, anti-irritants,
antimicrobials, lubricants, emulsifiers, and delivery agents. The
polymers can be used to make topical antimicrobial substances or
barriers, or as additives to inhibit microbial growth in a separate
formulation, or may impart residual antimicrobial activity. Such
residual antimicrobial activity can be imparted to a surface, for
example, by depositing the polymer onto the surface or by
covalently or otherwise attaching the polymer to the surface.
Examples of surfaces to which the polymers can be applied include
steel, and plastic, although substantially any surface can be
treated by application of the polymers. Antimicrobial products
containing the polymers can be applied to animal skin, including
human skin.
[0088] Skin conditioning agents as herein defined include
astringents, which tighten skin; exfoliants, which remove exterior
skin cells: emollients, which help maintain a smooth, soft, pliable
feel and appearance; humectants, which increase the water content
of the top layer of skin; occlusives, which retard evaporation of
water from the skin's surface; and miscellaneous compounds that
enhance the feel and/or appearance of dry or damaged skin or reduce
flaking and restore suppleness. Skin conditioning agents are well
known in the art, and are disclosed, for example, in Green et al.
WO 0107009, and are available commercially from various sources.
Examples of skin conditioning agents include alpha-hydroxy acids,
beta-hydroxy acids, polyols, hyaluronic acid, D,L-panthenol,
polysalicylates, vitamin A palmitate, vitamin E acetate, glycerin,
sorbitol, silicones, silicone derivatives, lanolin, natural oils,
and triglyceride esters.
[0089] The skin care, hair care, and hair coloring compositions
made from the polymers can also contain one or more conventional
cosmetic or dermatological additives or adjuvants, such as, for
example, fillers, surfactants, thixotropic agents, antioxidants,
preserving agents, dyes, pigments, fragrances, thickeners,
vitamins, hormones, moisturizers, UV absorbing sunscreens, wetting
agents, cationic, anionic, nonionic or amphoteric polymers, and
hair coloring active substances. Such adjuvants are well known in
the field of cosmetics and are disclosed, for example, in "Harry's
Cosmeticology." 8.sup.th edition, Martin Rieger, ed., Chemical
Publishing, New York (2000).
[0090] The polymers can also function as surface disinfectants, or
as ingredients in a formulation designed to function as a surface
disinfectant.
[0091] For use in medical applications, the polymers can act as
coatings that retain moisture, lubricate, conduct electricity,
facilitate sustained release of therapeutic agents, absorb
undesirable materials that accumulate in the area of an implant, or
act as local antimicrobial agents. The materials of the current
invention can be used as components of polymeric medical adhesives
(or anti-adhesives), as monomeric crosslinkers, and as components
of adhesives that can be deactivated to prevent bandages from
creating or enlarging sores on chronically bandaged areas. In the
area of medical devices, the polymers can be used as biocompatible
agents to attach antimicrobial, anti-inflammatory, or
anti-proliferative agents to the surface of catheters, stents, or
other medical implants. Sustained release can be accomplished by
slow diffusion of at least one biologically active agent out of the
polymeric hydrogel matrix. Sustained release can further be
facilitated by slow hydrolysis of the crosslink bonds.
[0092] In agriculture, uses for the polymers include use as seed
coatings, microencapsulating agents (for lower toxicity, slow
release, and/or chemical stability), surface tension modifying
agents (to improve spreadability or wash-off resistance), or to
improve water solubility of non-soluble active ingredients.
EXAMPLES
[0093] Unless otherwise stated, in the Examples, the abbreviations
used have the following meanings:
TABLE-US-00001 Abbreviation Ingredient Name 1BrC16
1-bromohexadecane 4,9-DODDA 4,9-dioxa-1,12-dodecanediamine 9DA
1,9-diaminononane DMG dimethyl galactarate GA D-glucaric acid GDL
D-glucaro-1,4:6,3-dilactone HMDA 1,6-hexanediamine JEFF Jeffamine
.RTM. JEFF EDR-148 Jeffamine .RTM.
(H.sub.2NCH.sub.2CH.sub.2OCH.sub.2CH.sub.2OCH.sub.2CH.sub.2NH.sub.2)
JEFF EDR-192 Jeffamine .RTM.
(H.sub.2NCH.sub.2CH.sub.2(OCH.sub.2CH.sub.2).sub.3NH.sub.2) JEFF
T5000 Jeffamine .RTM. polyethertriamine JEFF T403 Jeffamine .RTM.
polypropyleneoxytriamine PAlAmHCl polyallylamine HCl (obtained from
Polysciences, Inc., Warrington, PA)
ANALYSES
[0094] Unless otherwise specified, the analyses were performed as
follows.
Inherent Viscosity (.eta..sub.inh)
[0095] Inherent viscosities were generally run as 0.5% solutions in
either hexafluoroisopropanol (HFIP) or m-cresol at 30.degree.
C.
Differential Scanning Calorimetry (DSC) and Thermogravimetric
Analysis (TGA)
[0096] DSC and TGA studies of all polymers were conducted on 5-10
mg samples run at 10.degree. C./min under nitrogen. Sample
temperatures spanned ranges beginning as low as -100.degree. C. to
as high as 300.degree. C., depending on polymer character and
stability. Samples were generally cooled after the first heat cycle
and a second heat cycle was then conducted. Generally, polymer DSC
results reported are second heat results to eliminate artifacts of
thermal history variations.
Swell Factor
[0097] Into a pre-dried, tared, 150 mL coarse fritted filter funnel
was added about 1 g of polymer. The stem of the funnel was sealed
with a rubber stopper. The funnel was placed on a filter flask and
about 100 mL of distilled water at about 22.degree. C. is added to
the funnel. The contents were stirred, if necessary, to fully
disperse the water and polymer. The contents were then left
undisturbed for 15 minutes. The rubber stopper was then removed
from the stem of the funnel, and suction was applied to the funnel
for 5 minutes. The stem and underside of the funnel were then
rinsed with ethanol to remove any remaining water droplets and
suction was then continued for an additional 5 minutes. Any
remaining water droplets were wiped off the funnel with a paper
towel. The funnel and contents were then weighed to determine the
weight of water retained by the polymer.
Swell factor = ( total wt . of wet polymer + funnel ) - ( total wt
. of dry polymer + funnel ) wt . of dry polymer = ( wet wt . - dry
wt . ) dry wt . = g water retained g polymer ##EQU00001##
Solubility
[0098] Solubilities were generally determined using 0.01 g of test
material in 10 mL of test solvent. The vials containing the samples
were constantly agitated via a shaker tray at room temperature for
anywhere between 24 hours and 4 weeks. Solubility was determined by
visual inspection to determine sample homogeneity. Any variance in
density gradient, or refractive index was taken as indicating
insolubility. Samples deemed to be insoluble were shaken at room
temperature for at least 1 week, and in many cases were shaken for
2 weeks or more. A wide range of common solvent types was generally
used to allow a broad range of polarity and solvent parameters to
come into play.
Film Properties
[0099] Film properties were determined on 0.25 inch.times.2 inch
samples cut from larger films spread onto glass with a blade
applicator. Generally, films had thicknesses of 5 mil or less. Film
properties reported represent an average of at least five
measurements for each sample.
[0100] The reactions depicted in the following Examples are meant
to be illustrative only and not representative of exact
structures.
Examples 1-28
[0101] Polymers were prepared by first dissolving polyallylamine
hydrochloride of .about.60,000 molecular weight in water. To that
solution was added enough sodium hydroxide to just neutralize the
equivalent amount of ammonium hydrochloride functions as would be
used by the added GDL. To the partially neutralized polyallylamine
hydrochloride was added a water solution of GDL at room
temperature. The reaction was substantially over in a matter of
minutes. A representative polymerization with GDL is shown
below.
[0102] The crosslinking was performed using various compounds as
described below in a representative reaction with GDL. When another
compound was used in the in the crosslinking reaction along with
the GDL, such as 9DA, they were both added simultaneously. Into a
250-mL 3-necked round bottom flask equipped with a heating mantle,
reflux condenser, nitrogen inlet, and overhead stirrer was added 20
mL of water, 2.80 g (0.030 equivalent, 60,000 MW) of polyallylamine
HCl, and 0.26 g (0.0066 mol) of sodium hydroxide. This mixture was
stirred at room temperature until a homogeneous solution was
achieved (.about.10 minutes). At this point, a homogeneous solution
prepared from 10 mL of water and 0.57 g (0.0033 mol) of GDL was
slowly poured at room temperature into the solution containing the
polyallylamine HCl. Within 1 to 2 minutes, gel had formed. The gel
was then allowed to stir for .about.2 hours at room temperature,
after which time it was removed from the flask. The gel was then
washed 3 times with 100 mL aliquots of methanol followed by THF.
The gel was then dried in a vacuum oven at 80.degree. C. to yield
2.79 g (89.1%) of a granular white hydrogel polymer. The results
are shown in Table 1. The % crosslinking shown in Table 1 is a
theoretical calculation of the % of total amine nitrogens (from the
polyallylamine hydrochloride) tied up in the crosslinking process
with the aldaric acid. The calculation was based on the total
weight of polyallylamine hydrochloride used (molar equivalents of
allylamine) and the total molar equivalents of the GDL added to the
process. Total final crosslinking was not measured but is assumed
since the polymer gelled and became insoluble, although NMR
indicated that conversion was less than 100%.
[0103] When only 5-15% of the ammonium groups were allowed to react
with GDL, a very viscous water solution resulted that could be cast
into a film. The resulting films were brittle, but less so than the
starting polyallylamine hydrochloride homopolymer. As more ammonium
groups reacted with GDL, gels eventually formed. Highly swellable
hydrogels (with swell ratios as high as 90) were readily formed
when .about.22% of the ammonium hydrochloride equivalents were
neutralized and GDL was added in an equivalent amount (.about.11%
since both ends of the molecule are assumed to react). The gels
were optically clear and colorless. The data in Tables 1 and 2 show
some of the properties that can be obtained in the polymers by
varying the ingredients used in making them.
TABLE-US-00002 TABLE 1 Solvent/ % Ex. Composition Catalyst Media
Color Yield Inh Visc Inh Sol. Polym. Character Swell 1 PAlAmHCl/GDL
(10:1) - 20% triethylamine Water white -- insol HFIP Powder 4.72
crosslinking 2 PAlAmHCl/GDL (8:1) - 25% triethylamine Water white
-- insol HFIP powder - very brittle 12.27 crosslinking film 3
PAlAmHCl/GDL (8.7:1) - 23% triethylamine Water white -- insol HFIP
powder - poor film 80.73 crosslinking 4 PAlAmHCl/GDL (5:1) - 40%
triethylamine Water off white 90.1 insol HFIP Powder 48
crosslinking 5 PAlAmHCl/GDL (9.1:1) - 22% triethylamine Water white
-- insol HFIP powder - very brittle 28.1 crosslinking film 6
PAlAmHCl/GDL (9.1:1) - 22% sodium Water white 89.1 insol HFIP
Powder 89.5 crosslinking hydroxide 7 PAlAmHCl/GDL (9.1:1) - 22%
calcium Water white 84.7 insol HFIP Powder 88.5 crosslinking
hydroxide 8 PAlAmHCl/GDL (9.1:1) - 22% calcium Water white -- insol
HFIP powder - poor film, 6.36 crosslinking hydroxide very brittle 9
PAlAmHCl/GDL (9.1:1) - 22% calcium Water white -- insol HFIP powder
- poor film, sol. in crosslinking hydroxide very brittle water 10
PAlAmHCl/(GDL/JEFF EDR- sodium Water white 68.1 insol water powder
- brittle, 71.3 148 (2:1)) - 20% crosslinking hydroxide clear film
11 PAlAmHCl/(GDL/JEFF EDR- sodium Water white 92.9 insol water
powder - brittle, 49 192 (2:1)) - 20% crosslinking hydroxide clear
film 12 PAlAmHCl/(GDL/JEFF T5000 sodium water/ white 40 insol water
Powder 40.1 (3:1)) - 10% crosslinking hydroxide ethanol 13
PAlAmHCl/(GDL/JEFF T5000 sodium water/ white 31.9 insol water
Powder 8.04 (3:1)) - 20% crosslinking hydroxide ethanol 14
PAlAmHCl/(GDL/JEFF T5000 sodium water/ white 28.4 insol water
powder - poor film sol. in (3:1)) - 5% crosslinking hydroxide
ethanol water 15 PAlAmHCl/(GDL/JEFF T5000 sodium water/ white --
insol water powder - poor, sol. in (3:1)) - 1% crosslinking
hydroxide ethanol clear, brittle film water 16 PAlAmHCl/(GDL/JEFF
T5000 sodium water/ white 61.6 insol water powder - very poor 11
(3:1)) - 3% crosslinking hydroxide ethanol film 17
PAlAmHCl/(GDL/JEFF T403 sodium Water white 69.4 insol water powder
- poor, sol. in (3:1)) - 3% crosslinking hydroxide brittle film
water 18 PAlAmHCl/(GDL/JEFF T403 sodium Water white 74.2 insol
water powder - poor, very sol. in (3:1)) - 5% crosslinking
hydroxide brittle film water 19 PAlAmHCl/(GDL/JEFF T403 sodium
Water white 83.9 insol water powder - poor, 83.8 (3:1)) - 20%
crosslinking hydroxide brittle film 20 PAlAmHCl/(GDL/4,9-DODDA
sodium Water white 77.4 insol water powder - clear film, 78.6
(2:1)) - 20% crosslinking hydroxide slightly flexible, fair 21
PAlAmHCl/(GDL/4,9-DODDA sodium Water light 77.2 insol water powder
- very poor 26.7 (2:1)) - 25% crosslinking hydroxide yellow film 22
PAlAmHCl/(GDL/(9DA/4,9- sodium water white 60 -- -- Powder 31.1
DODDA) (2:0.5:0.5)) - 20% hydroxide crosslinking 23
PAlAmHCl/(GDL/9DA (2:1)) - sodium Water white 63.6 -- -- Powder
23.7 20% crosslinking hydroxide 24 PAlAmHCl/(GDL/9DA (2:1)) -
sodium Water white -- -- -- powder - fair film, 75.2 15%
crosslinking hydroxide slightly flexible 25 PAlAmHCl/(GDL/4,9-
sodium Water tan -- -- -- powder--poor, brittle 48.5 DODDA/9DA
(2/0.5/0.5)) - hydroxide film 15% crosslinking 26
PAlAmHCl/(GDL/4,9-DODDA sodium Water tan -- -- -- powder - poor
film 2 (1.33:1)) hydroxide 27 PAlAmHCl/(GDL/9DA sodium Water off
white -- -- -- powder - poor film 1.29 (1.33:1)) hydroxide 28
PAlAmHCl/(GDL/9DA (2:1)) - sodium Water light 82.9 -- -- Powder
0.65 100% crosslinking hydroxide yellow
TABLE-US-00003 TABLE 2 Ex. Composition Tg 1 (C.) Tg 2 (C.) Tg 3
(C.) Tm 1 (C.) .DELTA.H (J/g) Tm 2 (C.) d H (J/g) Tm 3 (C.) d H
(J/g) 1 PAlAmHCl/GDL (10:1) - -- -- -- 180.9 -- -- -- -- -- 20%
crosslinking 2 PAlAmHCl/GDL (8:1) - 25% -- -- -- 190.97 -- -- -- --
-- crosslinking 3 PAlAmHCl/GDL (8.7:1) - -- -- -- 191.23 7.544 --
-- -- -- 23% crosslinking 4 PAlAmHCl/GDL (5:1) - 40% -- -- --
192.38 17.99 -- -- -- -- crosslinking 5 PAlAmHCl/GDL (9.1:1) - --
-- -- 196.63 5.076 -- -- -- -- 22% crosslinking 6 PAlAmHCl/GDL
(9.1:1) - -- -- -- 196.75 5.318 -- -- -- -- 22% crosslinking 7
PAlAmHCl/GDL (9.1:1) - -- -- -- 251.32 15.99 -- -- -- -- 22%
crosslinking 8 PAlAmHCl/GDL (9.1:1) - -- -- -- 202.61 7.165 -- --
-- -- 22% crosslinking 9 PAlAmHCl/GDL (9.1:1) - -- -- -- 165.56
1.245 -- -- -- -- 22% crosslinking 10 PAlAmHCl/(GDL/JEFF -- -- --
187 5.99 248.04 6.291 -- -- EDR-148 (2:1)) - 20% crosslinking 11
PAlAmHCl/(GDL/JEFF -- -- -- -- -- -- -- -- -- EDR-192 (2:1)) - 20%
crosslinking 12 PAlAmHCl/(GDL/JEFF -- -- -- 188.45 1.008 251.86
4.542 -- -- T5000 (3:1)) - 10% crosslinking 13 PAlAmHCl/(GDL/JEFF
-- -- -- 251.88 7.862 -- -- -- -- T5000 (3:1)) - 20% crosslinking
14 PAlAmHCl/(GDL/JEFF -- -- -- 220.09 2.666 -- -- -- -- T5000
(3:1)) - 5% crosslinking 15 PAlAmHCl/(GDL/JEFF 204.2 -- -- -- -- --
-- -- -- T5000 (3:1)) - 1% crosslinking 16 PAlAmHCl/(GDL/JEFF 102.6
215.5 -- -- -- -- -- -- -- T5000 (3:1)) - 3% crosslinking 17
PAlAmHCl/(GDL/JEFF 224.4 -- -- -- -- -- -- -- -- T403 (3:1)) - 3%
crosslinking 18 PAlAmHCl/(GDL/JEFF 170 232.3 -- -- -- -- -- -- --
T403 (3:1)) - 5% crosslinking 19 PAlAmHCl/(GDL/JEFF 175.7 227.5 --
-- -- -- -- -- -- T403 (3:1)) - 20% crosslinking 20
PAlAmHCl/(GDL/4,9- 168.8 234.4 204.7 1.281 -- -- -- -- DODDA (2:1))
- 20% crosslinking 21 PAlAmHCl/(GDL/4,9- 171 209.5 247.6 -- -- --
-- -- -- DODDA (2:1)) - 25% crosslinking 22 PAlAmHCl/(GDL/(9DA/4,9-
174.4 -- -- -- -- -- -- -- -- DODDA) (2:0.5:0.5)) - 20%
crosslinking 23 PAlAmHCl/(GDL/9DA 174.9 -- -- -- -- -- -- -- --
(2:1)) - 20% crosslinking 24 PAlAmHCl/(GDL/9DA 168.7 -- -- -- -- --
-- -- -- (2:1)) - 15% crosslinking 25 PAlAmHCl/(GDL/4,9- 142.5
174.2 -- 224.28 0.261 -- -- -- -- DODDA/9DA (2/0.5/0.5)) - 15%
crosslinking 26 PAlAmHCl/(GDL/4,9- 45 216.6 -- 103.33 177.97 23.69
188.41 16.3 DODDA (1.33:1)) 27 PAlAmHCl/(GDL/9DA 75.94 -- -- 152.48
12.17 165.25 31.69 195.55 9.072 (1.33:1)) 28 PAlAmHCl/(GDL/9DA
(2:1)) - -- -- -- 167.03 4.206 190.61 14.02 -- -- 100%
crosslinking
TABLE-US-00004 TABLE 3 Tc 1 d H Tc 2 d H Tdec Sol. Sol. Sol. Sol.
Sol. Sol. Sol. Ex. Composition (C.) (J/g) (C.) (J/g) (C.) H2O MeOH
Toluene DMSO DMAC THF CH2CL2 1 PAlAmHCl/GDL (10:1) - -- -- -- --
200 sol. insol. insol. insol. insol. insol. insol. 20% crosslinking
2 PAlAmHCl/GDL (8:1) - 25% -- -- -- -- 200 insol. insol. insol.
insol. insol. insol. insol. crosslinking 3 PAlAmHCl/GDL (8.7:1) -
-- -- -- -- 225 insol. insol. insol. insol. insol. insol. insol.
23% crosslinking 4 PAlAmHCl/GDL (5:1) - 40% -- -- -- -- 225 insol.
insol. insol. insol. insol. insol. insol. crosslinking 5
PAlAmHCl/GDL (9.1:1) - -- -- -- -- 200 insol. insol. insol. insol.
insol. insol. insol. 22% crosslinking 6 PAlAmHCl/GDL (9.1:1) - --
-- -- -- 225 insol. insol. insol. insol. insol. insol. insol. 22%
crosslinking 7 PAlAmHCl/GDL (9.1:1) - -- -- -- -- 220 insol. insol.
insol. insol. insol. insol. insol. 22% crosslinking 8 PAlAmHCl/GDL
(9.1:1) - -- -- -- -- 210 insol. insol. insol. insol. insol. insol.
insol. 22% crosslinking 9 PAlAmHCl/GDL (9.1:1) - -- -- -- -- 210
sol. insol. insol. insol. insol. insol. insol. 22% crosslinking 10
PAlAmHCl/(GDL/JEFF -- -- -- -- 210 -- -- -- -- -- -- -- EDR-148
(2:1)) - 20% crosslinking 11 PAlAmHCl/(GDL/JEFF 223.41 9.953 -- --
210 insol. insol. insol. insol. insol. insol. insol. EDR-192 (2:1))
- 20% crosslinking 12 PAlAmHCl/(GDL/JEFF -- -- -- -- 200 insol.
insol. insol. insol. insol. insol. insol. T5000 (3:1)) - 10%
crosslinking 13 PAlAmHCl/(GDL/JEFF -- -- -- -- 210 insol. insol.
insol. insol. insol. insol. insol. T5000 (3:1)) - 20% crosslinking
14 PAlAmHCl/(GDL/JEFF -- -- -- -- 225 insol. insol. insol. insol.
insol. insol. insol. T5000 (3:1)) - 5% crosslinking 15
PAlAmHCl/(GDL/JEFF -- -- -- -- 250 sol. insol. insol. insol. insol.
insol. insol. T5000 (3:1)) - 1% crosslinking 16 PAlAmHCl/(GDL/JEFF
-- -- -- -- 235 insol. insol. insol. insol. insol. insol. insol.
T5000 (3:1)) - 3% crosslinking 17 PAlAmHCl/(GDL/JEFF -- -- -- --
240 sol. insol. insol. insol. insol. insol. insol. T403 (3:1)) - 3%
crosslinking 18 PAlAmHCl/(GDL/JEFF -- -- -- -- 240 sol. insol.
insol. insol. insol. insol. insol. T403 (3:1)) - 5% crosslinking 19
PAlAmHCl/(GDL/JEFF -- -- -- -- 225 insol. insol. insol. insol.
insol. insol. insol. T403 (3:1)) - 20% crosslinking 20
PAlAmHCl/(GDL/4,9- -- -- -- -- 200 insol. insol. insol. insol.
insol. insol. insol. DODDA (2:1)) - 20% crosslinking 21
PAlAmHCl/(GDL/4,9- 284.77 1.116 -- -- 200 insol. insol. insol.
insol. insol. insol. insol. DODDA (2:1)) - 25% crosslinking 22
PAlAmHCl/(GDL/(9DA/4,9- -- -- -- -- 225 insol. insol. insol. insol.
insol. insol. insol. DODDA) (2:0.5:0.5)) - 20% crosslinking 23
PAlAmHCl/(GDL/9DA -- -- -- -- 225 insol. insol. insol. insol.
insol. insol. insol. (2:1)) - 20% crosslinking 24 PAlAmHCl/(GDL/9DA
-- -- -- -- 225 insol. insol. insol. insol. insol. insol. insol.
(2:1)) - 15% crosslinking 25 PAlAmHCl/(GDL/4,9- -- -- -- -- 175
insol. insol. insol. insol. insol. insol. insol. DODDA/9DA
(2/0.5/0.5)) - 15% crosslinking 26 PAlAmHCl/(GDL/4,9- -- -- -- --
150 insol. insol. insol. insol. insol. insol. insol. DODDA
(1.33:1)) 27 PAlAmHCl/(GDL/9DA -- -- -- -- 150 insol. insol. insol.
insol. insol. insol. insol. (1.33:1)) 28 PAlAmHCl/(GDL/9DA -- -- --
-- 150 -- -- -- -- -- -- -- (2:1)) - 100% crosslinking
Example 29
Synthesis of Modified Polyallylamine Crosslinked with GDL
[0104] Into a 2000-mL 3-necked flask equipped with a heating
mantle, reflux condenser, nitrogen inlet, and overhead stirrer was
added 525 mL of water, 70 g of polyallylamine hydrochloride (0.749
mole equivalent of amine), and 2.24 g (0.056 mol) of sodium
hydroxide. After these ingredients dissolved. 17.08 g (0.056 mol)
of 1-bromohexadecane was added. The reaction mixture was heated at
reflux for 5 hours. Afterward, the reaction mixture was cooled to
room temperature and stirred overnight. An additional 5.60 g (0.140
mol) of sodium hydroxide was added to the mixture. After the sodium
hydroxide dissolved, 12.18 g (0.070 mol) of GDL dissolved in 175 mL
of water was added to the reaction mixture. Almost immediately a
gel formed. The gelled mixture was then gently heated at 50.degree.
C. for about 7 hours. The gel was filtered, washed 3.times. with
methanol, and then washed 3.times. with THF. It was then put into a
vacuum oven set at 80.degree. C. for at 24 hours to dry the
polymer. The pale yellow polymer (58.85 g, 60.5%) exhibited a swell
ratio of 7.9.
Example 30A
Synthesis of Polyallylamine Crosslinked with Diethyl Tartrate
[0105] The preparation was conducted under nitrogen atmosphere with
oven-dried glassware. Polyallylamine hydrochloride (MW ca. 60,000,
0.876 g, 9.36 mmol) was weighed into a 20-mL scintillation vial
equipped with a magnetic stirbar, and water (2 mL) was added.
Dropwise addition of an aqueous solution (1.0 mL) of sodium
hydroxide (0.113 g, 2.83 mmol) to the solution resulted in a
viscous solution. A solution of diethyl L-tartrate (0.240 mL, 1.40
mmol) in water (1.0 mL) was added and the resulting solution was
stirred at ambient temperatures for 38 hours. The gelled reaction
mixture was washed with methanol (160 mL) to remove sodium
chloride. Vacuum-drying gave a white solid (0.86 g, 93% yield) that
exhibited a swell ratio of 112.6 (determined after swollen gel was
subjected to 6 hours of dynamic suction followed by .about.28 hours
of static suction).
Example 30B
Synthesis of Polyallylamine Crosslinked with Diethyl Tartrate
[0106] Poly(allylamine hydrochloride), M.sub.w 60,000 (42.04 g,
0.4493 mole of amine groups) was dissolved overnight in 155 mL of
water in a 3-neck 500-mL round-bottom flask equipped with a
magnetic stir bar. A solution of 5.392 g (0.1348 mole) of sodium
hydroxide in 25 mL of water was added dropwise over a period of 10
minutes, using 2 mL of water to complete the transfer. To the
resulting pale yellow syrup was added with stirring a solution of
13.897 g (67.40 mmoles) of diethyl L-tartrate in 10 mL of water,
using 2 mL of water to complete the transfer. The reaction was
allowed to proceed for 4 days, during which the mixture gelled and
the magnetic stir bar seized. The reaction mixture was combined
with 250 mL of methanol to precipitate out the product. The
resulting gummy solid was separated from the liquid and triturated
in a blender with 8 successive 250-mL portions of methanol,
decanting the methanol each time. The resulting solid was ground
and dried under vacuum to give 38.47 g (86% yield) of hydrogel that
exhibited a swell factor of 224.
Example 31
Synthesis of Polyallylamine Crosslinked with GDL
##STR00013##
[0108] The preparation was conducted in a drybox with oven-dried
glassware. Polyallylamine hydrochloride (MW ca. 60,000, 6.88 g,
73.5 mmol) was weighed into a 500-mL round-bottom flask equipped
with a magnetic stirbar. Methanol (285 mL) was added and the
solution was treated with neat triethylamine (12.3 mL, 88.3 mmol)
followed by dropwise addition of a solution of GDL (0.13 g, 0.74
mmol) in methanol (10 mL). The resulting solution was stirred at
ambient temperature for four days. Most of the reaction solvent was
decanted, and the remaining reaction mixture was filtered and
vacuum-dried to give a white solid (1.00 g, 23% yield) that
exhibited a swell ratio of 22.8. When the swell test was repeated,
allowing 19 hours for the gel to swell followed by 2 hours of
dynamic suction and 9 hours of static suction, the swell ratio was
22.4. After 14 hours' exposure to ambient atmosphere, the sample
retained 19.9 times its own weight in water.
Example 32A
Synthesis of Polyallylamine Crosslinked with
N,N'-Bis(ethoxycarbonylmethyl)-D-glucaramide
##STR00014##
[0110] Preparation was conducted in a drybox with oven-dried
glassware. Polyallylamine hydrochloride (MW ca. 60,000, 6.55 g,
70.0 mmol) was weighed into a 500-mL round-bottom flask equipped
with a magnetic stirbar. Methanol (270 mL) was added and the
solution was treated with neat triethylamine (11.7 mL, 84.0 mmol)
followed by a slurry of
N,N'-bis(methoxycarbonylmethyl)-D-glucaramide (0.25 g, 0.69 mmol)
in methanol (20 mL). The resulting solution was stirred at ambient
temperature for four days. The reaction solvent was removed under
vacuum, and the oily solid was washed repeatedly with methanol (180
mL). Addition of pentane (50 mL) to a methanol slurry (ca. 20 mL
volume) produced a solid that was filtered and then vacuum-dried to
give a white solid (2.39 g, 57% yield) that exhibited a swell ratio
(after 29 minutes of suction) of 62.8. When the swell test was
repeated, allowing 16 hours for the gel to swell followed by 34
minutes of suction, the swell ratio was 118.9. After 23 hours'
exposure to ambient atmosphere, the sample retained 108.6 times its
own weight in water.
Example 32B
Synthesis of Polyallylamine Crosslinked with
N,N'-Bis(ethoxycarbonylmethyl)-D-glucaramide
[0111] To 23.03 g (0.2463 mole of amine groups) of poly(allylamine
hydrochloride), M.sub.w 60,000, in 950 mL of dry methanol in a 2-L
round-bottom flask under nitrogen were added 41.2 mL (0.296 mole)
of triethylamine over 30 minutes. A slurry of
N,N'-bis(ethoxycarbonylmethyl)-D-glucaramide in a total of 65 mL of
dry methanol was then added. The mixture was stirred at ambient
temperature for 5 days and then concentrated under reduced pressure
to about 150 mL. The resulting solid was separated from the
methanol, washed repeatedly with methanol and then dried under
vacuum to give 12.92 g (88% yield) of hydrogel that exhibited a
swell factor of 125.
Example 33
##STR00015##
[0113] Polyallylamine hydrochloride (MW ca. 60,000, 2.84 g, 30.4
mmol) was weighed into 100-mL round-bottom flask equipped with a
magnetic stirbar. Water (16 mL) was added and the solution was
treated with an aqueous (4 mL) solution of sodium hydroxide (0.27
g, 6.67 mmol) followed by a solution of GDL (0.58 g. 3.34 mmol) in
water (10 mL). The reaction solution was stirred overnight at
ambient temperature resulting in a gel-like mixture. The gel was
washed with four 50-mL portions of methanol and then vacuum-dried
to give a white solid (2.26 g, 69% yield) that exhibited a swell
ratio (after 2 hours of suction) of 186.5. After 3 additional days'
exposure to static suction, the sample retained 67.9 times its own
weight in water. When the swell test was repeated with the same
sample, allowing 5 hours for the gel to swell followed by 2 hours
of dynamic suction and 24 hours of static suction, the swell ratio
was 206.0. After 3 and 8 days' additional exposure to static
suction, the sample retained 173.8 and 65.5 times its own weight in
water, respectively.
Example 34
##STR00016##
[0115] Preparation was conducted under nitrogen atmosphere with
oven-dried glassware. Polyallylamine hydrochloride (MW ca. 60,000,
1.01 g, 10.8 mmol) was weighed into a 20-mL scintillation vial
equipped with a magnetic stirbar, and water (2 mL) was added.
Dropwise addition to the slurry of an aqueous solution (1.0 mL) of
sodium hydroxide (0.033 g, 0.83 mmol) resulted in a viscous
solution. A solution of
N,N'-bis(methoxycarbonylmethyl)-D-glucaramide (0.14 g, 0.41 mmol)
in water (1.5 mL) was added, and the resulting solution was stirred
at ambient temperature for 45 hours. Solvent was removed under
vacuum from the gelled reaction mixture, and the solid was washed
with methanol (125 mL) to remove sodium chloride. Vacuum-drying
gave a white solid (0.98 g, 89% yield) that exhibited a swell ratio
(after 5 minutes of dynamic suction and 45 minutes of static
suction) of 105.8. After 2 days' exposure to ambient atmosphere,
the sample retained 96.5 times its own weight in water. When the
swell test was repeated with the same sample, allowing 4.5 hours
for the gel to swell followed by 5 hours of dynamic suction and
hours of static suction, the swell ratio was 197.6. After 6 days'
exposure to ambient atmosphere, the sample retained 167.8 times its
own weight in water.
Example 35
##STR00017##
[0117] Polyethylenimine (M.sub.n=ca. 10,000, M.sub.w=ca. 25,000,
Aldrich 408727, 0.74 g, 17.2 mmol) was weighed into a 20-mL
scintillation vial equipped with a magnetic stirbar, and methanol
(4.5 mL) was added. Concentrated hydrochloric acid (0.72 mL, 8.65
mmol) was added to the reaction solution dropwise over ca. one
minute and the mixture was stirred at ambient temperature for 3
hours. A solution of GDL (0.15 g, 0.862 mmol) in methanol (1 mL)
was added dropwise over ca. one minute to the reaction solution.
The reaction mixture began to gel after 3 hours, but stirring was
continued for 24 hours. The solvent was removed under vacuum and
the solid was vacuum-dried to give a yellow solid (ca. 0.2 g) that
exhibited a swell ratio (after 1 hour of static suction) of 24.1.
After 5 days' exposure to ambient atmosphere, the sample retained
9.2 times its own weight in water. When the swell test was repeated
with the same sample, allowing 7.5 hours for the gel to swell
followed by 35 minutes of dynamic suction, the swell ratio was
36.6. After 1 day's exposure to ambient atmosphere, the sample
retained 34.2 times its own weight in water.
Example 36
##STR00018##
[0119] Polyethylenimine (M.sub.n=ca. 10,000, M.sub.w=ca. 25,000,
Aldrich 408727, 0.67 g, 15.6 mmol) was weighed into a 20-mL
scintillation vial equipped with a magnetic stirbar, and water (2.5
mL) was added. Concentrated hydrochloric acid (0.65 mL) was added
dropwise to the solution followed by solid
N,N'-bis(methoxycarbonylmethyl)-D-glucaramide (0.14 g, 0.39 mmol)
and water (1 mL). The reaction solution was stirred for 5 days at
ambient temperature. The solvent was then removed under vacuum, and
the solid was vacuum-dried to give a colorless solid that exhibited
a swell ratio (after 50 minutes of dynamic suction and 15 minutes
of static suction) of 17.6. When the swell test was repeated with
the same sample, allowing 15 hours for the gel to swell followed by
2.25 hours of suction, the swell ratio was 25.5. After five days'
exposure to ambient atmosphere, the sample retained 22.8 times its
own weight in water.
Example 37
Biocidal Activity of Crosslinked Hydrogels
[0120] Antimicrobial activity was determined by a standard
micro-shake flask test. Bacterial cultures were inoculated into TSB
(Trypticase Soy Broth) and incubated at 37.degree. C. overnight for
20+/-2 hours. The following day, the concentration of bacteria was
adjusted to .about.1.0.times.10.sup.5 cfu/mL (cfu=colony forming
unit) by dilution with 0.6 mM phosphate buffer. Diluted bacterial
culture (2.5 mL) was then transferred into culture plate wells
containing 2.5 mL of hydrogel (.about.50 mg of solid dispersed in
2.5 mL of 0.6 mM phosphate buffer) or just 2.5 mL of 0.6 mM
phosphate buffer (control). The culture plates were incubated at
room temperature on a platform shaker with constant shaking motion.
Three 100-.mu.L aliquots were periodically removed from each well
and serially diluted with 0.6 mM phosphate buffer. Undiluted and
diluted samples from each well were plated onto duplicate TSA
(trypticase soy agar) plates, and incubated at 37.degree. C. for
20.+-.2 hrs. After incubation, the number of bacterial colonies on
each plate was counted using a Q-count instrument or equivalent
counting method. The colony count was averaged and normalized by
correcting for the dilution factor and reported as the number of
colony forming units (cfu) per mL. Log reduction (log
rd.times.n)=(mean log.sub.10 density of microbes in flasks of
untreated control samples)-(mean log.sub.10 density of microbes in
flasks of treated samples).
[0121] Microbes tested were Escherichia coli, Pseudomonas
aeruginosa, Stapphylococcus aureus, and Candida albicans.
[0122] Three hydrogel samples were tested for antimicrobial
activity: Sample A was prepared as in Example 29. Sample B was
prepared in the manner of Example 30A. Sample C was prepared as in
Example 31. Results are in Table 4.
TABLE-US-00005 TABLE 4 Biocidal Activity of Crosslinked Hydrogels
sample inoculum A B C hydrogel, (control) log log log log log log
microbe t, h wt % log cfu cfu rdxn cfu rdxn cfu rdxn E. coli 4 1.0
4.86 1.37 3.49 0.00 4.86 0.00 4.86 0.50 4.86 1.73 3.13 0.00 4.86
0.00 4.86 0.25 4.86 1.70 3.16 0.00 4.86 0.00 4.86 0.10 4.86 2.22
2.64 0.00 4.86 0.00 4.86 24 1.0 4.86 0.00 4.86 0.50 4.86 0.00 4.86
0.25 4.86 0.00 4.86 0.10 4.86 0.00 4.86 P. aeruginosa 4 1.0 4.86
0.00 4.86 0.00 4.86 0.00 4.86 0.50 4.86 0.00 4.86 0.00 4.86 0.00
4.86 0.25 4.86 0.00 4.86 0.00 4.86 0.00 4.86 0.10 4.86 0.00 4.86
0.00 4.86 0.00 4.86 S. aureus 4 1.0 4.66 3.94 0.72 0.00 4.66 0.00
4.66 0.50 4.66 3.92 0.74 0.00 4.66 0.00 4.66 0.25 4.66 3.51 1.15
0.00 4.66 0.00 4.66 0.10 4.66 3.47 1.19 0.00 4.66 0.00 4.66 24 1.0
4.66 2.40 2.26 0.50 4.66 1.37 3.29 0.25 4.66 1.18 3.49 0.10 4.66
1.67 2.99 C. albicans 4 1.0 5.09 0.00 5.09 0.00 5.09 0.00 5.09 0.50
5.09 0.00 5.09 0.00 5.09 0.00 5.09 0.25 5.09 0.00 5.09 0.00 5.09
0.00 5.09 0.10 5.09 1.92 3.17 0.00 5.09 0.00 5.09
Example 38
Emulsion Prepared Using Hydrogel Prepared from Polyallylamine HCl.
GDL, and Jeffamine.RTM. EDR-192
[0123] A crosslinked hydrogel was prepared in the following manner:
28.0 g (0.30 equiv of polyallylamine hydrochloride was dissolved in
200 mL of water along with 2.4 g (0.06 mol) of sodium hydroxide. To
that solution was added a solution of 5.2 g (0.030 mol) of GDL and
2.9 g (0.015 mol) of Jeffamine.RTM. EDR-192 dissolved in 100 mL of
water. The mixture was then heated to 50.degree. C. Within 1 hour,
a gelled product had formed. The gel was left to "cure" overnight
at room temperature. It was then filtered and washed 3 times with
MeOH/THF. The remaining polymer was then dried in a vacuum oven at
80.degree. C. to yield 20.63 g (61%) of a white granular material.
The polymer exhibited a swell ratio of 81.
[0124] An emulsion was prepared using 2.0 g of the polymer prepared
above, 17.0 g of octyl palmitate, and 148 mL of water. These
ingredients were added to a 250-mL beaker and emulsified using a
Silverson Lab Mixer equipped with a rotor-stator square-holed blade
running at 5,000 rpm for 5 min. A thick, creamy white emulsion was
prepared. After 8 months' storage in a jar at room temperature,
separation of the emulsion was negligible.
Example 39
Preparation of Crosslinked Polymer using Poly(methacryloyl
chloride), GDL, and Ethylenediamine
[0125] Into a 250-mL 3-necked round-bottom flask equipped with a
heating mantle, reflux condenser, nitrogen inlet, and overhead
stirrer was added a 25 mL of dioxane containing 6.25 g (0.598
equivalent) of poly(methacryloyl chloride) (Polysciences, Inc.,
Warrington, Pa.). To this solution was added 3.5 g (0.0150 mol) of
N,N'-bis(2-aminoethyl)-D-glucaramide (prepared by reacting 10
equivalents of ethylenediamine with GDL in DMAC at 50.degree. C.
and isolating the product as a white precipitate). The mixture was
stirred and heated at 50.degree. C. over a period of 21 hours.
During this time, a slight color change from brown to yellow was
noted; however, it did not appear that the diaminodiamide was ever
fully solubilized in the dioxane solvent. The resulting product was
poured into THF, filtered, and washed 3 times with THF to yield
2.65 g (27%) of a light tan solid material; Tg.sub.1 49.67.degree.
C.; Tg.sub.2 64.14.degree. C.; T.sub.dec 175.degree. C.--onset;
.eta..sub.inh (HFIP) insol.
Example 40
Synthesis of Chitosan Crosslinked with GDL
[0126] Chitosan (Primex TM-656, MW ca. 79,000. 95% deacetylated,
0.79 g, 4.90 mmol) was weighed into a 20-mL scintillation vial
equipped with a magnetic stirbar. Water (11.5 mL) was added, and
the mixture was stirred for 15 minutes at ambient temperature. A
solution of hydrochloric acid (37%, 0.29 mL, 3.45 mmol) in water
(1.5 mL) was added dropwise, and the resulting viscous light yellow
mixture was stirred for 15 minutes at ambient temperature. A
freshly prepared solution of GDL (0.09 g, 5.40 mmol) in water (1.5
mL) was added dropwise, and the reaction mixture was stirred for 38
hours at ambient temperature, resulting in a tan-colored
homogeneous gel-like mixture. Approximately 5 mL of the solvent was
removed under vacuum and the reaction mixture was transferred to a
round-bottom flask with 15 mL of tetrahydrofuran. The resulting
precipitate was washed with four 30-mL portions of tetrahydrofuran
then vacuum-dried to give a white solid (0.75 g) that had a swell
ratio of 3.
Example 41
Hard Surface Disinfection by Crosslinked Hydrogels
[0127] Tests were performed by Consumer Product Testing Company,
Fairfield, N.J. following Association of Official Analytical
Chemists (AOAC) Use Dilution test methods 955.14 and 955.15.
[0128] Hydrogel A was prepared by reacting poly(allylamine
hydrochloride), M.sub.w 60,000, with 0.15 mole equivalent (relative
to amine groups) of diethyl L-tartrate according to Example 30B to
give a polymer nominally having 30% of its amine groups
crosslinked. Hydrogel B was prepared by reacting poly(allylamine
hydrochloride), M.sub.w 60,000, with 0.01 mole equivalent (relative
to amine groups) of N,N'-bis(ethoxycarbonylmethyl)-D-glucaramide
according to Example 32B to give a polymer nominally having 2% of
its amine groups crosslinked. Each hydrogel was dispersed in
deionized water, hydrogel A at 0.5 wt % (w/v) and hydrogel B at 1
wt % (w/v).
[0129] Type 304 stainless steel penicylinders (8 mm OD, 6 mm ID, 10
mm L) were soaked overnight in 1 N sodium hydroxide, washed with
water until the rinse water was neutral to phenolphthalein, and
autoclaved in 0.1% w/v aqueous asparagine solution. The sterile
penicylinders were drained and transferred aseptically into a
48-hour culture broth (1 mL per cylinder) of Staphylococcus aureus
(ATCC#6538) or Salmonella choleraesuis (ATCC#10708). After being
immersed in culture broth for 15 minutes, the penicylinders were
drained and transferred by sterile hook into a sterile glass petri
dish lined with sterile filter paper so that the cylinders stood on
end without touching one another. The penicylinders were dried at
37.degree. C. for 40 minutes.
[0130] For each hydrogel tested, 10 penicylinders inoculated with a
given test organism were immersed individually for 10 minutes at
20.degree. C. in 10 mL of aqueous hydrogel dispersion. Each
penicylinder was then removed from the hydrogel dispersion,
drained, and deposited into a primary culture tube containing 10 mL
of Letheen broth and incubated at 37.degree. C. After 30 minutes,
each penicylinder was transferred into secondary culture tube
containing 10 mL of Letheen broth, and both primary and secondary
culture tubes were incubated at 37.degree. C. for 48 hours, after
which they were examined for microbial growth as evidenced by
turbidity.
[0131] Neutralization of each antimicrobial hydrogel by double
serial subculture was shown to be effective by inoculating tubes
showing no growth with low levels of test organism. Viability of
test organisms was demonstrated by incubating inoculated
penicylinders in deionized water instead of a hydrogel
suspension.
[0132] Results in Table 5 demonstrate that hydrogel B is
bactericidal against Staphylococcus aureus. While it is also active
against Salmonella choleraesuis, hydrogel B does not completely
eradicate viable Salmonella choleraesuis under the conditions
employed.
TABLE-US-00006 TABLE 5 Use Dilution Test Results. Number of
Penicylinders Showing Residual Microbial Activity after 10-Minute
Exposure to Hydrogel test organism Staphylococcus aureus Salmonella
choleraesuis hydrogel.sup.a wt %.sup.b primary Secondary primary
secondary A 0.5 10/10 10/10 10/10 10/10 B 1.0 0/10 0/10 3/10 3/10
.sup.aSee text of Example 41 for descriptions of hydrogels A and B.
.sup.bLoading of hydrogel (w/v) in aqueous dispersion.
Example 42
Preservation of a Skin Cream by a Crosslinked Hydrogel
[0133] Skin creams were formulated by mixing ingredients in the
amounts listed in Table 6. The crosslinked hydrogel used was made
according to Example 30B. Ingredients of Phase 1 were combined and
heated to 77.degree. C.
[0134] Ingredients of Phase 2 were combined and heated to
77.degree. C. While Phase 1 was kept at 77.degree. C. and
vigorously agitated by an overhead stirrer, Phase 2 was added to
Phase 1. After 15 minutes of vigorous agitation at 77.degree. C.,
triethanolamine was added to the mixture. After the mixture had
been vigorously agitated at 77.degree. C. for an additional 15 to
25 minutes, external heating was discontinued, and the vigorously
agitated mixture was allowed to cool. When the temperature of the
mixture reached 37 to 38.degree. C., Dow Corning 200.RTM. fluid
dimethicone was added, the speed of agitation was reduced, and the
mixture was allowed to cool to room temperature.
TABLE-US-00007 TABLE 6 Skin Cream Formulations formulation
Ingredient A (control) B Phase 1 deionized water 70.0 g 69.3 g
crosslinked hydrogel 0.0 g 1.0 g Phase 2
Octamethylcyclotetrasiloxane 20.0 g 19.8 g Abil .RTM. EM-90 cetyl
dimethicone copolyol 2.0 g 2.0 g Stepan TAB-2 .RTM. 3.0 g 3.0 g
Phase 3 Triethanolamine 2.4 g 2.4 g Dow Corning 200 .RTM. fluid
dimethicone 2.5 g 2.5 g
[0135] Ten grams of each skin cream formulation were supplemented
with 500 .mu.L of trypticase soy broth, mixed in by hand, to
promote bacterial growth. Each skin cream sample was then
inoculated with 100 .mu.L of a 1:10 dilution of an overnight
culture of Pseudomonas aeruginosa and 100 .mu.L of a 1:10 dilution
of an overnight culture of Staphylococcus aureus, yielding a
bacterial load of approximately 1.times.10.sup.6 cfu/g for each
organism (cfu=colony forming unit). Periodically, each inoculated
skin cream was sampled with a 10-.mu.L loop, which was then
streaked onto a trypticase soy agar (TSA) plate. Plates were
incubated at 37.degree. C. for 24 hours and then examined for
bacterial growth.
[0136] Results in Table 7 show that bacteria persisted in the
unpreserved control sample, A, but not in the sample containing
crosslinked hydrogel, B.
TABLE-US-00008 TABLE 7 Bacterial Growth Observed After Streaking on
TSA Plates skin cream formulation time, days A (control) B 0 heavy
heavy 0.25 heavy heavy 1 heavy 10-100 cfu 7 moderate-heavy none
Example 42A
Preservation of a Skin Cream by a Crosslinked Hydrogel
[0137] Microbiological tests were performed by Consumer Product
Testing Company, Fairfield, N.J. according to the United States
Pharmacopoeia (USP), 24.sup.th Edition, <51> Antimicrobial
Effectiveness Testing.
[0138] Hydrogel A was prepared by reacting poly(allylamine
hydrochloride), M.sub.w 60,000, with 0.15 mole equivalent (relative
to amine groups) of diethyl L-tartrate according to Example 30B to
give a polymer nominally having 30% of its amine groups
crosslinked. Hydrogel B was prepared by reacting poly(allylamine
hydrochloride), M.sub.w 60,000, with 0.01 mole equivalent (relative
to amine groups) of N,N'-bis(ethoxycarbonylmethyl)-D-glucaramide
according to Example 32B to give a polymer nominally having 2% of
its amine groups crosslinked.
[0139] Skin creams were formulated by mixing ingredients in the
amounts listed in Table 8. Ingredients of Phase 1 were combined and
heated to 77.degree. C. Ingredients of Phase 2 were combined and
heated to 77.degree. C. While Phase 1 was kept at 77.degree. C. and
vigorously agitated by an overhead stirrer, Phase 2 was added to
Phase 1. After 15 minutes of vigorous agitation at 77.degree. C.,
triethanolamine was added to the mixture. After the mixture had
been vigorously agitated at 77.degree. C. for an additional 15 to
25 minutes, external heating was discontinued, and the vigorously
agitated mixture was allowed to cool. When the temperature of the
mixture reached 37 to 38.degree. C., Dow Corning 200.RTM. fluid
dimethicone was added, the speed of agitation was reduced, and the
mixture was allowed to cool to room temperature.
TABLE-US-00009 TABLE 8 Skin Cream Formulations formulation
ingredient 1 (control) 2 3 Phase 1 deionized water 350.5 g 346.5 g
207.9 g crosslinked hydrogel A -- 5.0 g -- crosslinked hydrogel B
-- -- 3.0 g Phase 2 octamethylcyclotetrasiloxane 100.0 g 99.0 g
59.4 g Abil .RTM. EM-90 cetyl dimethicone 10.0 g 10.0 g 6.0 g
copolyol Stepan TAB-2 .RTM. 15.0 g 15.0 g 9.0 g Phase 3
triethanolamine 12.0 g 12.0 g 7.2 g Dow Corning 200 .RTM. fluid
12.5 g 12.5 g 7.5 g dimethicone
[0140] The microbial tests described below were performed by
Consumer Product Testing Company, Fairfield, N.J. Twenty-gram
portions of each skin cream formulation were aseptically
transferred into sterile glass containers and inoculated with 100
.mu.L of a 1.times.10.sup.8 cfu/mL culture of Staphylococcus aureus
(ATCC#6538), Escherichia coli (ATCC#8739), Pseudomonas aeruginosa
(ATCC#9027), Candida albicans (ATCC#10231) or Aspergillus niger
(ATCC#16404), yielding a microbial load between 1.times.10.sup.5
and 1.times.10.sup.6 cfu/g. Inoculated samples were incubated at 20
to 25.degree. C. protected from light. Periodically, samples of
each inoculated skin cream were serially diluted tenfold, and
microbial counts were determined by the pour plate method, using
trypticase soy agar (TSA) plates incubated at 20 to 25.degree. C.
for 3 days for bacteria and Sabouraud dextrose agar (SDA) plates
incubated at 20 to 25.degree. C. for 5 days for the fungi.
[0141] Results in Table 9 demonstrate that the hydrogels increase
the rate of kill of gram positive (S. aureus) and gram negative (E.
coli, P. aeruginosa) bacteria and yeast (C. albicans) in a skin
cream formulation. No activity against mold (A. niger) was
demonstrated by the two hydrogel compositions tested.
TABLE-US-00010 TABLE 9 Log (CFU/g) for Microorganisms in Skin Cream
Formulations test microorganism S. aureus E. coli P. aeruginosa C.
albicans A. niger skin cream formulation day 1 2 3 1 2 3 1 2 3 1 2
3 1 2 3 0 5.91 5.91 5.91 6.04 6.04 6.04 5.99 5.99 5.99 5.96 5.96
5.96 5.79 5.79 5.79 7 3.34 <1 <1 3.88 2.57 2.46 3.70 2.15
2.60 3.56 2.28 2.08 5.08 5.20 5.04 14 2.70 <1 <1 2.15 <1
<1 1.00 <1 2.43 2.67 <1 <1 5.04 5.18 4.98 28 <1
<1 <1 <1 <1 <1 <1 <1 <1 2.66 <1 <1
3.45 4.15 4.58
Example 43
Human Repeat Insult Patch Test of Crosslinked Hydrogels
[0142] Hydrogel A was prepared by reacting poly(allylamine
hydrochloride), M.sub.w 60,000, with 0.15 mole equivalent (relative
to amine groups) of diethyl L-tartrate according to Example 30B to
give a polymer nominally having 30% of its amine groups
crosslinked. Hydrogel B was prepared by reacting poly(allylamine
hydrochloride), M.sub.w 60,000, with 0.01 mole equivalent (relative
to amine groups) of N,N'-bis(ethoxycarbonylmethyl)-D-glucaramide
according to Example 32B to give a polymer nominally having 2% of
its amine groups crosslinked. Each hydrogel was dispersed in
deionized water, hydrogel A at 0.5 wt % (w/v) and hydrogel B at 0.8
wt % (w/v).
[0143] The Repeat Insult Patch Test was performed by Consumer
Product Testing Company, Fairfield, N.J. The fifty-two subjects
completing this test included 12 men, age 32 to 68 years, and 40
women, age 22 to 79 years. Subjects had no visible skin disease,
were in good health, were not pregnant or nursing, were not under a
doctor's care or taking medication that would influence the outcome
of the study, and had not used a topical or systemic steroid or
antihistamine for at least seven days prior to beginning the
study.
[0144] Approximately 0.2 mL of each hydrogel dispersion, or an
amount sufficient to cover the contact surface, was applied to the
3/4''.times.3/4'' absorbent pad of an adhesive dressing. The
dressing was then applied to a marked spot between the scapulae of
each subject, thus forming an occlusive patch. Patches were applied
to the same site three times a week (typically, Monday, Wednesday,
and Friday) for three consecutive weeks (total of 9 applications).
Each patch was removed after 24 hours of contact. The site of
application was examined and scored upon removal of the first patch
and again 24 hours after removal of the first patch. Thereafter,
the site of application was examined and scored 24 or 48 hours
after the removal of each patch, usually just before application of
the subsequent patch. Thus, the application site on each subject
was examined 10 times during the Induction Phase. Approximately 2
weeks after application of the final Induction patch, a Challenge
patch was applied to a virgin site adjacent to the original site,
following the same procedure as described above. The patch was
removed 24 hours after application, and the site was examined and
scored. The Challenge site was examined and scored again 48 hours
after removal of the Challenge patch.
[0145] Each time an Induction or Challenge site was examined, it
was scored according to the following scale: 0=no visible skin
reaction, +=barely perceptible or spotty erythema, 1=mild erythema
covering most of the test site, 2=moderate erythema with possible
presence of mild edema, 3=marked erythema with possible edema, and
4=severe erythema with possible edema, vesiculation, bullae or
ulceration. For both materials tested, all scores (10 Induction and
2 Challenge for each of 52 subjects) were 0. In addition, 5
subjects who began the study but discontinued for various reasons
not related to the test materials generated scores of only 0 as
well. Thus, hydrogel A and hydrogel B showed no dermal irritation
or allergic contact sensitization.
Example 44
Speed of Kill of Crosslinked Hydrogels
[0146] Hydrogel A was prepared by reacting poly(allylamine
hydrochloride), M.sub.w 60,000, with 0.01 mole equivalent (relative
to amine groups) of N,N'-bis(ethoxycarbonylmethyl)-D-glucaramide
according to Example 32A to give a polymer nominally having 2% of
its amine groups crosslinked. Hydrogel B was prepared by reacting
poly(allylamine hydrochloride), M.sub.w 60,000, with 0.15 mole
equivalent (relative to amine groups) of diethyl L-tartrate
according to Example 30A to give a polymer nominally having 30% of
its amine groups crosslinked. Hydrogel C was prepared by reacting
poly(allylamine hydrochloride), M.sub.w 60,000, with 0.25 mole
equivalent (relative to amine groups) of diethyl L-tartrate
according to Example 30, except using 0.900 g of poly(allylamine
hydrochloride), 0.192 g of sodium hydroxide, and 0.412 mL of
diethyl L-tartrate and allowing the reaction to proceed for 88
hours before washing with methanol, to give a polymer nominally
having 50% of its amine groups crosslinked.
[0147] For each hydrogel, an exposure of E. coli to a 100 ppm
loading was effected by dispersing 5 mg of hydrogel in 25 mL of 0.6
mM phosphate buffer, stirring overnight, and then adding 25 mL of a
culture broth (.about.1.0.times.10.sup.5 cfu/mL) of Escherichia
coli ATCC#25922. After 15, 30, 60, 120, 180, and 240 minutes,
aliquots of the test mixture were removed and serially diluted 1:10
with TSB in a 96-well microtiter plate. After incubating overnight
at 37.degree. C., each plate was scored for microbial growth using
a Most Probable Number (MPN) protocol, and log reduction calculated
as (mean log.sub.10 density of microbes in untreated control
samples)-(mean log.sub.10 MPN density of microbes in treated
samples).
[0148] Exposure of E. coli to a 10 ppm loading of each hydrogel was
effected similarly except using 1 mg of hydrogel in 50 mL of buffer
and adding 50 mL of a culture broth (.about.1.0.times.10.sup.5
cfu/mL) of Escherichia coli ATCC#25922.
[0149] Results in Table 10 show that all three hydrogels eliminate
viable E. coli when present at 100 ppm. At 10 ppm loading, it
becomes more apparent that the speed of kill of hydrogel A is
faster than that of hydrogel B, which is faster than that of
hydrogel C.
TABLE-US-00011 TABLE 10 Speed of Kill of E. coli #25922 by
Crosslinked Hydrogels log reduction of cfu/mL t, hydrogel A.sup.a
hydrogel B.sup.a hydrogel C.sup.a minutes 100 ppm 10 ppm 100 ppm 10
ppm 100 ppm 10 ppm 15 5.40 3.09 2.39 1.69 2.39 0.99 30 5.40 5.36
2.39 2.78 3.48 1.69 60 5.40 5.40 3.23 2.78 3.48 1.83 120 5.40 5.40
5.40 3.95 5.36 2.08 180 5.40 5.40 5.40 3.79 5.40 3.09 240 5.40 5.40
5.40 5.40 5.40 2.78 .sup.aSee text of Example 44 for descriptions
of hydrogels A, B, and C.
* * * * *