Jun.28,2007  20  US 2007/0148124 Al  polymers of the present invention are tailored with a smaller  number of strong hydrophobic groups like naphthyl or a  larger number of less hydrophobic groups like phenyl. One  skilled in the art possesses the ability to strike the above  balance between hydrophobicity, solubility and dissociation  properties by manipulating the parameters of the modifica› tion and degree of substitution to arrive at the desired  performance.  [0192]  The modifications, according to the present inven› tion, are not limited to reactions with anhydrides but include  any substitution of R at any of the hydroxyl groups in the  cellulosic backbone.  It  is thus highly desirable to have  modified polymers bearing one or more hydrophobic groups  such as phenyl and the like.  It  has been demonstrated by the  present invention that such balance could be made in the  case ofHPMCT at a range of trimellityl substitution of about  0.25 to about 0.7 per glucose unit. This balance and subse› quent biological activity can be duplicated with other modi› fiers by changing conditions and level of substitution. There› fore, it is understood to one skilled in the art that the scope  of the invention is not limited to the discrete formulae or  examples in the specification.  [0193]  For acrylic-based polymers, a similar balance  between hydrophobicity, solubility and dissociation is  effected to affect the biological function needed to suppress  infectivity or STD transmission. For example, in MVE/MA› like polymers, desired functional groups may be incorpo› rated into the polymer either by selectively substituting the  R  $^{5 }$group of the viny 1 co-monomer used, or by mixing under  the proper conditions the resulting anhydride with the appro› priate R---0 H-bearing intermediates as shown in Scheme 1.  It  is thus feasible using a variety of strategies to incorporate  moieties such as those shown in Table 1 into the acrylic› based polymer. For the purpose of the present invention, it  is preferable to have a molecularly dispersed polymer that  remains dissociated in the pH range from about 3 to about  14, and possesses a level of hydrophobicity that would be  optimal for blocking infectivity with STD causing agents.  Further, introduction of sulfate or sulfonate groups, or other  groups with low pKa values brings favorable solubility and  dissociation parameters to very low pH levels ( e.g.  ~  1.0).  One skilled in the art can readily ascertain the suitable  reaction conditions to achieve the latter result.  [0194]  It  is yet another embodiment of the present inven› tion to include both strong and weak acid groups in the  polymer or copolymer, either cellulosic- or acrylic-based  such as those described in the instant specification. Weak  acid groups include carboxylic groups having low pKa  values as given in Table 1. Strong acid groups include  sulfate, sulfonate, or others with low pKa values in the range  of 1.0 or below. Resulting molecules possessing the prop› erties given in polymers such as HPMCT or acrylic equiva› lents and including strong acid groups such as sulfate and  sulfonates will operate by more than one mechanism to  prevent infectivity and transmission of STDs. For example,  the presence of sulfate groups in a polymeric molecule is  known to strongly bind to the V3 loop of HIV-1 gp 120  (Este, J. A., Schols, D., De Vreese, K., Cherepanov, P.,  Witvrouw, M., Pannecouque, C., Debyser, Z., Desmyter, J.,  Rando, R. F., and De Clercq, E., "Human immunodeficiency  virus glycoprotein gp120 as the primary target for the  antiviral action of ARI 77 (Zintevir)."Mol.  Pharm.  53:340- 345 (1998)), and thus the addition of sulfate or sulfonate  groups to the cellulose molecules of Formula I or acrylic  molecules of Formula II, such as in a molecule like HPMCT,  will expand the spectrum of activity by conferring to the new  molecule the ability to act via multiple distinct mechanisms.  An example of a sulfate or sulfonated moiety in the cellulose  backbone is illustrated by the substitution of, but not limited  to, the anhydride of 2-sulfobenzoic acid, as shown in Table  1. The incorporation a sulfate or sulfonated moiety into a  cellulose backbone along with carboxylic acid groups is  readily apparent to one skilled in the art, e.g., the polymer  backbone is substituted by, but not limited to the anhydride  of 4-sulfo-1,8-naphthalic acid, as shown in Table 1. Further› more, the position of the sulfate or sulfonate groups on the  ring structures can be varied to adjust performance of the  resulting polymer.  [0195]  In one aspect, of the present invention, R1, R 2 , R 3 ,  and R 4  in Formula I or R 5  in Formula II is an aliphatic or  aromatic moiety containing more than one carboxylic acid  groups such that once covalently attached to the polymer,  copolymer, or oligomer backbone the resultant compound  remains molecularly dispersed and mostly dissociated in  solution at a range of pH from about 3 to about 14, and more  preferably from about pH 3 to about pH 5;  [0196]  In another aspect, the oligomer or polymer in  Formula I is hydroxylpropyl methyl cellulose (HPMC)› based.  [0197]  In another aspect, the oligomer or polymer in  Formula I is cellulose acetate based.  [0198]  In another aspect, one of R1, R 2 , R 3 , and R 4  in  Formula I is derived from the reaction with trimellitic  anhydride, and the resultant molecule is hydroxypropyl  methylcellulose trimellitate, abbreviated HPMCT, which  can remain molecularly dispersed and mostly dissociated in  solution at pH ranging from about 3 to about 14.  [0199]  In another aspect, R1, R 2 , R 3 , and R 4  in Formula I  is derived from the reaction with a mixture of maleic  anhydride and acetic acid, and the resultant molecule is  hydroxypropyl methylcellulose acetate maleate, abbreviated  HPMC-AM, which can remain molecularly dispersed and  mostly dissociated in solution at pH ranging from about 3 to  about 14.  [0200]  In another aspect R1, R 2 , R 3 , and R 4  in Formula I  is derived from the reaction with a mixture of2-sulfobenzoic  acid cyclic anhydride and acetic acid, and the resultant  molecule is hydroxypropyl methylcellulose acetate sul› fobenzoate, and can remain molecularly dispersed and  mostly dissociated in solution at pH ranging from about 3 to  about 14.  [0201]  In another aspect R1, R 2 , R 3 , and R 4  in Formula I  is derived from the reaction with a mixture of trimellitic  anhydride and acetic acid, and the resultant molecule is  cellulose acetate trimellitate, abbreviated CAT, which is  molecularly dispersed and mostly dissociated in solution at  pH ranging from about 3 to about 14.  [0202]  In another aspect R1, R2, R 3 , and R 4  in Formula I  is derived from reaction with a mixture of 2-sulfobenzoic  acid cyclic anhydride and acetic acid, and the resultant  molecule is  cellulose acetate sulfobenzoate, which is  molecularly dispersed and mostly dissociated in solution at  pH ranging from about 3 to about 14. 