Synthesis and use of cationic steroids for anti-inflammatory drug therapy
The invention relates to compositions and methods for a one-step synthetic technique for making cationic steroid pharmaceutical compositions for use in treating inflammation and other diseases and disorders.
1. An amphiphilic steroid-polyamine dimeric molecule,
wherein the dimeric molecule comprises a cationic polyamine conjugated with a first and a second steroid,
wherein the polyamine comprises a first and a second primary amine,
wherein the first steroid is conjugated through its C-21 position to the first primary amine of the polyamine and the second steroid is conjugated through its C-21 position to the second primary amine of the polyamine, and
wherein the polyamine is selected from the group consisting of spermidine and spermine.
2. An amphiphilic dexamethasone-spermine dimeric molecule,
wherein the dimeric molecule comprises a spermine conjugated with a first and a second dexamethasone,
wherein the spermine comprises a first and a second primary amine, and
wherein the first dexamethasone is conjugated through its C-21 position to the first primary amine of the spermine and the second dexamethasone is conjugated through its C-21 position to the second primary amine of the spermine.
3. A pharmaceutical composition comprising an amphiphilic steroid-polyamine dimeric molecule and a lipid,
wherein the dimeric molecule comprises a cationic polyamine conjugated with a first and a second steroid,
wherein the polyamine comprises a first and a second primary amine,
wherein the first steroid is conjugated through its C-21 position to the first primary amine of the polyamine and the second steroid is conjugated through its C-21 position to the second primary amine of the polyamine, and
wherein the polyamine is selected from the group consisting of spermidine and spermine.
4. A pharmaceutical composition comprising an amphiphilic dexamethasone-spermine dimeric molecule and a lipid,
wherein the dimeric molecule comprises a spermine conjugated with a first and a second dexamethasone,
wherein the spermine comprises a first and a second primary amine, and
wherein the first dexamethasone is conjugated through its C-21 position to the first primary amine of the spermine and the second dexamethasone is conjugated through its C-21 position to the second primary amine of the spermine.
5. A composition comprising an amphiphilic steroid-polyamine dimeric molecule and a pharmaceutically acceptable carrier,
wherein said molecule is generated by a method comprising the steps of: contacting first and second steroids, a conjugating reagent, and a cationic polyamine comprising first and second primary amines, wherein said conjugating reagent conjugates said first primary amine of said polyamine to said first steroid through the C-21 position of said first steroid via the displacement of a leaving group and conjugates said second primary amine of said polyamine to said second steroid through the C-21 position of said second steroid via the displacement of a leaving group; and purifying said conjugated steroid-polyamine molecule, thereby producing a composition comprising said purified amphiphilic steroid-polyamine dimeric molecule,
wherein the polyamine is selected from the group consisting of spermidine and spermine.
6. A method of generating an amphiphilic steroid-polyamine dimeric molecule,
said method comprising the steps of: contacting first and second steroids, a conjugating reagent, and a cationic polyamine comprising first and second primary amines, wherein said conjugating reagent conjugates said first primary amine of said polyamine to said first steroid through the C-21 position of said first steroid via the displacement of a leaving group and conjugates said second primary amine of said polyamine to said second steroid through the C-21 position of said second steroid via the displacement of a leaving group, and purifying said conjugated, steroid-polyamine molecule, thereby generating said amphiphilic steroid-polyamine dimeric molecule,
wherein the polyamine is selected from the group consisting of spermidine and spermine.
7. A composition comprising an amphiphilic steroid-polyamine dimeric molecule, a lipid and a pharmaceutical acceptable carrier,
wherein said molecule is generated by a method comprising the steps of: contacting first and second steroids, a conjugating reagent, and a cationic polyamine comprising first and second primary amines, wherein said conjugating reagent conjugates said first primary amine of said polyamine to said first steroid through the C-21 position of said first steroid via the displacement of a leaving group and conjugates said second primary amine of said polyamine to said second steroid through the C-21 position of said second steroid via the displacement of a leaving group, and purifying said conjugated steroid-polyamine molecule,
wherein the polyamine is selected from the group consisting of spermidine and spermine.
8. A pharmaceutical composition comprising an amphiphilic steroid-polyamine dimeric molecule and a lipid, wherein the composition is prepared by a method comprising the steps of: contacting first and second steroids, a conjugating reagent, and a cationic polyamine comprising first and second primary amines, wherein said conjugating reagent conjugates said first primary amine of said polyamine to said first steroid through the C-21 position of said first steroid via the displacement of a leaving group and conjugates said second primary amine of said polyamine to said second steroid through the C-21 position of said second steroid via the displacement of a leaving group; purifying said conjugated steroid-polyamine molecule; and mixing said steroid-polyamine molecule with a lipid, thereby producing a cationic steroid pharmaceutical composition comprising an amphiphilic steroid-polyamine dimeric molecule and a lipid,
wherein the polyamine is selected from the group consisting of spermidine and spermine.
9. A kit comprising a cationic steroid pharmaceutical composition, an applicator, and an instructional material for the use thereof,
wherein the cationic steroid pharmaceutical composition comprises an amphiphilic steroid-polyamine dimeric molecule,
wherein the dimeric molecule comprises a cationic polyamine conjugated with a first and a second steroid, wherein the polyamine comprises a first and a second primary amine, wherein the first steroid is conjugated through its C-21 position to the first primary amine of the polyamine and the second steroid is conjugated through its C-21 position to the second primary amine of the polyamine, and
wherein the polyamine is selected from the group consisting of spermidine and spermine.
10. A kit comprising a cationic steroid pharmaceutical composition, an applicator, and an instructional material for the use thereof,
wherein said composition comprises an amphiphilic steroid-polyamine dimeric molecule, wherein said molecule is generated by a method comprising the steps of: contacting first and second steroids, a conjugating reagent, and a cationic polyamine comprising first and second primary amines, wherein said conjugating reagent conjugates said first primary amine of said polyamine to said first steroid through the C-21 position of said first steroid via the displacement of a leaving group and conjugates said second primary amine of said polyamine to said second steroid through the C-21 position of said second steroid via the displacement of a leaving group; and purifying said conjugated steroid-polyamine molecule,
wherein the polyamine is selected from the group consisting of spermidine and spermine.
11. The kit of claim 9 , wherein the cationic steroid pharmaceutical composition further comprises a lipid.
12. The kit of claim 11 , wherein the cationic steroid pharmaceutical composition further comprises dimethylsulfoxide.
13. A method of preparing a composition comprising a lipid and an amphiphilic steroid-polyamine dimeric molecule, the method comprising contacting first and second steroids, a conjugating reagent, and a polyamine comprising first and second primary amines, wherein said conjugating reagent conjugates said first primary amine of said polyamine to said first steroid through the C-21 position of said first steroid via the displacement of a leaving group and conjugates said second primary amine of said polyamine to said second steroid through the C-21 position of said second steroid via the displacement of a leaving group, purifying said conjugated steroid-polyamine molecule, and mixing said steroid-polyamine molecule with a lipid, thereby producing a composition comprising a lipid and an amphiphilic steroid-polyamine dimeric molecule, wherein the polyamine is selected from the group consisting of spermidine and spermine.
14. A method of preparing a composition comprising a lipid and an amphiphilic steroid-polyamine dimeric molecule, the method comprising contacting first and second steroids, dimethylsulfoxide, a conjugating reagent, and a polyamine comprising first and second primary amines, wherein said conjugating reagent conjugates said first primary amine of said polyamine to said first steroid through the C-21 position of said first steroid via the displacement of a leaving group and conjugates said second primary amine of said polyamine to said second steroid through the C-21 position of said second steroid via the displacement of a leaving group, purifying said conjugated steroid-polyamine molecule, and mixing said steroid-polyamine molecule with a lipid, thereby producing a composition comprising a lipid and an amphiphilic steroid-polyamine dimeric molecule, wherein the polyamine is selected from the group consisting of spermidine and spermine.