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.

What is claimed is: 
     
         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: 
   
       
         
           
           
               
               
           
         
         
           
             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 1 -C 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(═O)NZ—, —C(═O)O—, —C(═O)—, —OC(═O)O—, —OC(═O)NZ—, —NHC(═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(═O)OZ, —C(═O)X, —C(═O)NZZ′, —C═N═O, —O—, —N(Z), —N+(ZZ′)—, —C(═O)N(Z)—, —C(═O)O—, —C(═O)—, —OC(═O)O—, —OC(═O)N(Z)—, —N(Z)C(═O)N(Z′)—, —C(═O)NH(CH 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 1 -C 22  aminoalkyl groups, —C(═O)OZ, —C(═O)X, —C(═O)NZZ′, or —C(═O)NH(CH 2 ) p NH 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-(□-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 
       
         
           
           
               
               
           
         
         wherein Q is —O— or —NH—, or a salt thereof, and R 1 , R 2 , R 3  and R 4  are aliphatic or aromatic hydrocarbylene groups, linear, branched or cyclic, optionally substituted, and optionally containing —O—, —Si(ZZ′)O—, —(C═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 1  is —[(CH 2 ) 0-22 ]—, —(CH 2 ) a C 6 H 10 (CH 2 ) b —, —(CH 2 CH 2 NH) 1-22 CH 2 CH 2 —, —[(CH 2 CH(Z′)O) 1-22 (CH 2 ) 2-3 ]— wherein Z′ is H or CH 3 , —C(O)NH(CH 2 ) 2-22 —, or —(CH 2 ) a (C 6 H 4 )(CH 2 ) b —, wherein a=0-6 and b=0-6; 
 R 2  is —[(CH 2 ) 1-21 ]—, —CH(CH 3 )—, —CH(isopropyl)-, —CH(isobutyl)-, —CH(CH(CH 3 )CH 2 CH 3 )—, —CH(CH 2 OH)—, —CH(CH 2 CH 2 SCH 3 )—, —CH(CH(OH)CH 3 )—, —CH(CH 2 C 6 H 5 )—, —CH(CH 2 C 6 H 4 OH)—, —CH(CH 2 CONH 2 )—, or —CH(CH 2 CH 2 CONH 2 )—; 
 R 3  is —[(CH 2 ) 2-22 ]—, —[(CH 2 ) 0-6 (C 6 H 10 )(CH 2 ) 0-6 ]—, —[(CH 2 ) 0-6 C 6 H 4 (CH 2 ) 0-6 ]—, —[CH 2 CH 2 (OCH 2 CH 2 ) 1-21 ]—, —[CH 2 CH(CH 3 )[OCH 2 CH(CH 3 CH)] 1-21 ]—, —(CH 2 CH 2 NH) 1-22 CH 2 CH 2 —, —[CH 2 CH(CH 3 )[OCH 2 CH(CH 3 )] x (OCH 2 CH 2 ) y [OCH 2 CH(CH 3 )] z ]— wherein x+y+z=2-50, —[CH 2 CH 2 (OCH 2 CH 2 ) x [OCH 2 CH(CH 3 )] y (OCH 2 CH 2 ) z ]— wherein x+y+z=2-50, —[CH(CH 3 )CH 2 O] x CH 2 C(Z′)(CH 2 [OCH 2 CH(CH 3 )] y —)CH 2 [OCH 2 CH(CH 3 )] z — wherein x+y+z=2-10 and Z′ is H, methyl or ethyl, —[CH(CH 3 )CH 2 O] x CH 2 CH([OCH 2 CH(CH 3 )] y )CH 2 [OCH 2 CH(CH 3 )] z — 
 wherein x+y+z=3-100, or —CH 2 CH 2 CH 2 CH 2 [CH(NH 2 )CONHCH 2 CH 2 CH 2 CH 2 ] 0-10 CH(COYR)— or salts thereof, wherein Y is O or NH, and R is a C 1 -C 22  optionally substituted alkyl, aryl, or alkaryl; and 
 R 4  is —C(═O)—, —C 6 H 4 CH 2 —, —(CH 2 ) 1-22 Y′CH 2 CH(OH)CH 2 —, or —(CH 2 ) 1-22 Y′C(O)CH(OH)CH 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:   
       
         
           
           
               
               
           
         
         
           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 1 -C 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═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(═O)OR″; and G is selected from —NH 2 , —C(═O)Cl, —C(═O)OR″, or —C(═O)NH—R″—NH 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 2 , halogen, hydroxyl, or carbonyl groups, or salt thereof. 
     
     
         21 . The antimicrobial composition of  claim 13  wherein G is —NH 2  and the reactive pendant groups are derivatized with a C 1 -C 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 + ZZ′—, —O—, —C(═O)NZ—, —C(═O)O—, —C(═O)—, —OC(═O)O—, —OC(═O)NZ—, —NHC(═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(═O)OZ, —C(═O)X, —C(═O)NZZ′, or —C(═O)NH(CH 2 ) n NH 2 , or salts thereof, where X is halogen, Z and Z′ are independently hydrogen, C 1 -C 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 + (ZZ′Z″), —C(═O)OZ, —C(═O)X, —C(═O)NZZ′, —C═N═O, —O—, —N(Z)—, —N + (ZZ′)—, —C(═O)N(Z)—, —C(═O)O—, —C(═O)—, —OC(═O)O—, —OC(═O)N(Z)—, —N(Z)C(═O)N(Z′)—, —C(═O)NH(CH 2 ) p NH 2 , —Si(ZZ′)O—, —(OCH 2 CH 2 ) m OH, or —(OSi(ZZ′)) n OH, or salts thereof, wherein X is a halogen, Z, Z′, and Z″ are independently hydrogen or C 1 -C 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 1 -C 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-(ω-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: 
       
         
           
           
               
               
           
         
         wherein A1 is independently selected from: 
       
       
         
           
           
               
               
           
         
         and salts thereof; 
         and A2 is selected from
   —NH—R 5 —NH—
 
   —NH—R 5 —O—
 
   and 
   —O—R 5 —O—
 
 
       
       and salts thereof;
 wherein R 5  and R 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═O)— or —NZ— linkages, where Z and Z′ are independently hydrogen, alkyl, substituted alkyl, alkaryl, substituted alkaryl, aryl, or substituted aryl; and R 6  is hydrogen or a 1-22 carbon alkyl group. 
 
     
     
         33 . The antimicrobial composition of  claim 32  wherein R 5  and R 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 5  and R 7  are independently linear, cyclic, or branched alkylene groups of 1-10 carbon atoms, optionally substituted with —O— linkages, and optionally substituted with —NH 2  groups, or salts thereof. 
     
     
         35 . The antimicrobial composition of  claim 32  wherein R 7  is —[(CH 2 ) 1-21 ]—; —CH(CH 3 )—; —CH(isopropyl)-; —CH(isobutyl)-; —CH(CH(CH 3 )CH 2 CH 3 )—; —CH(CH 2 OH)—; —CH(CH 2 CH 2 SCH 3 )—; —CH(CH(OH)CH 3 )—; —CH(CH 2 C 6 H 5 )—; —CH(CH 2 C 6 H 4 OH)—; —CH(CH 2 CONH 2 )—; or —CH(CH 2 CH 2 CONH 2 )—;
 and 
 R 5  is —[(CH 2 ) 2-22 ]—; —[(CH 2 ) 0-6 (C 6 H 10 )(CH 2 ) 0-6 ]—; —[(CH 2 ) 0-6 C 6 H 4 (CH 2 ) 0-6 ]—; —[CH 2 CH 2 (OCH 2 CH 2 ) 1-21 ]—; —[CH 2 CH(CH 3 )[OCH 2 CH(CH 3 )] 1-21 ]—; —(CH 2 CH 2 NH) 1-22 CH 2 CH 2 —; —[CH 2 CH(CH 3 )[OCH 2 CH(CH 3 )] x (OCH 2 CH 2 ) y [OCH 2 CH(CH 3 )] z ]— wherein x+y+z=2-50; —[CH 2 CH 2 (OCH 2 CH 2 ) x [OCH 2 CH(CH 3 )] y (OCH 2 CH 2 ) z ]— wherein x+y+z=2-50; —[CH(CH 3 )CH 2 O] x CH 2 C(Z′)(CH 2 [OCH 2 CH(CH 3 )] y —)CH 2 [OCH 2 CH(CH 3 )] z — wherein x+y+z=2-10 and Z′ is H, methyl or ethyl; —[CH(CH 3 )CH 2 O] x CH 2 CH([OCH 2 CH(CH 3 )] y —)CH 2 [OCH 2 CH(CH 3 )] z — 
 wherein x+y+z=3-100; or —CH 2 CH 2 CH 2 CH 2 [CH(NH 2 )CONHCH 2 CH 2 CH 2 CH 2 ] 0-10 CH(COYR)—, or salts thereof, wherein Y is O or NH, and R is a C 1 -C 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.