Vector delivery-based microbicides
A new class of anti-microbial agents and methods for preventing or reducing the risk of sexually transmitted infections and/or diseases is provided. Preferably, these anti-microbial agents are also contraceptive and, thus, also prevent or reduce the risk of unplanned pregnancies. The anti-microbial agents comprise a delivery vector having anti-microbial activity (and preferably contraceptive activity) coupled with a nitric oxide donor moiety.
1. An anti-microbial agent for reducing risk of transmitting a sexually transmitted disease, said anti-microbial agent comprising:
a covalent adduct of an H 2 SO 4 -modified mandelic acid and a nitric oxide donor,
the nitric oxide donor consisting of a nitric oxide donor moiety and a spacer;
the nitric oxide donor being covalently bonded through the spacer to a carbonyl carbon atom derived from a carboxyl of the H 2 SO 4 -modified mandelic acid wherein NO is released from the anti-microbial agent during use.
2. The anti-microbial agent as defined in claim 1 , wherein the NO-donor is selected from the group consisting of nitrate esters, furoxans, ketoximes, S-nitrosothiols, nitrosohydrazines, and hydroxylamides.
3. The anti-microbial agent as defined in claim 1 , wherein the NO-donor is a nitrate ester.
4. The anti-microbial agent as defined in claim 1 , wherein the antimicrobial agent is contained in an inert carrier.
5. The anti-microbial agent as defined in claim 3 , wherein the antimicrobial agent is contained in an inert carrier.
6. The anti-microbial agent as defined in claim 4 , wherein the antimicrobial agent is at a concentration greater than about 0.2 mg/g.
7. The anti-microbial agent as defined in claim 5 , wherein the antimicrobial agent is at a concentration greater than about 0.2 mg/g.
8. The anti-microbial agent as defined in claim 4 , wherein the antimicrobial agent is at a concentration of about 10 to 100 mg/g.
9. The anti-microbial agent as defined in claim 5 , wherein the antimicrobial agent is at a concentration of about 10 to 100 mg/g.
10. The anti-microbial agent as defined in claim 1 , wherein the H 2 SO 4 -modified mandelic acid is a fractionated H 2 SO 4 -modified mandelic acid having a narrower molecular weight range and a higher biological activity relative to the H 2 SO 4 -modified mandelic acid without fractionation.
11. The anti-microbial agent of claim 1 , wherein the covalent adduct of the H 2 SO 4 -modified mandelic acid and the nitric oxide donor is a compound having a structure:
wherein n is an average of 10 and the nitric oxide donor comprises a nitrate ester moiety; and
R at each monomer is independently H, —(CH 2 ) m —O—NO 2 wherein m is 2-6 or 1,3-nitrooxyphenyl.
12. The anti-microbial agent of claim 11 wherein the the R′s are each independently H or —(CH 2 ) 3 —O—NO 2 .
13. The anti-microbial agent of claim 11 wherein about 7% of the R′s are (CH 2 ) 3 —O—NO 2 and the remaining about 93% of the R′s are H.
14. The anti-microbial agent of claim 11 wherein about 23% of the R′s are (CH 2 ) 3 —O—NO 2 and the remaining about 77% of the R′s are H.