Solubilising polysaccharides substituted with dydrophilic and hydrophobic groups
View Patent ↗This invention relates to novel carbohydrate polymers with hydrophobic and hydrophilic side-groups suitable for solubilising, for example, hydrophobic drugs. The chain length of the carbohydrate polymeric backbone, and the type and number of the hydrophobic and hydrophilic side-groups are specifically chosen to improve the solubility properties of the carbohydrate polymers.
1. A solubilising carbohydrate polymer of average molecular weight of about 2-30 kD according to the following formula:
wherein m is 0.01% to 10.00%;
n is 0.01% to 99.98%;
p is 0.00% to 99.98%
X is any hydrophobic, linear, branched or cyclo form of an alkyl, alkenyl, alkynyl, aryl, amine, amide, alcohol or acyl group;
R′, R″, R′″ are independently any linear, branched or cyclo form of an alkyl, alkenyl, alkynyl, aryl, acyl group, a sugar substituent selected from glucose, galactose, fructose and muramic acid, or oligo polyoxa C 1 -C 3 alkylene units, optionally substituted with amine, amide or alcohol; and
R 1 , R 2 and R 3 are independently any linear, branched, or cyclo forms of any alkyl, alkenyl, alkynyl, aryl or acyl group.
2. A solubilising carbohydrate polymer according to claim 1 wherein the m, n and p units form any arrangement in the solubilising carbohydrate polymer.
3. A solubilising carbohydrate polymer according to claim 1 wherein the arrangement of the m, n and p units are random or in a block copolymer form.
4. A solubilising carbohydrate polymer according to claim 3 wherein the block copolymer is mnpmnpmnp.
5. A method of forming a solubilising carbohydrate polymer according to claim 1 wherein the method comprises;
depolymerising a carbohydrate polymer to form depolymerised carbohydrate;
reacting the depolymerised carbohydrate with a first reactive compound to form hydrophobic side-groups on the carbohydrate backbone and thus form hydrophobically substituted depolymerised carbohydrate; and
adding a second reactive compound to the hydrophobically substituted depolymerised carbohydrate to quaternarise an amine group and thereby form the solubilising carbohydrate polymer.
6. A method according to claim 5 wherein the carbohydrate polymer is selected from the following: glycol chitosans, dextrans, alginic acids, starches, dextran and guar gums.
7. A carbohydrate polymer according to claim 1 and a pharmaceutically acceptable carrier.
8. A carbohydrate polymer according to claim 7 wherein the ratio of carbohydrate polymer to pharmaceutical acceptable carrier ranges from 0.05 wt. % to 10 wt. %.
9. A pharmaceutical composition comprising a carbohydrate polymer according to claim 1 and a drug.
10. A pharmaceutical composition according to claim 9 wherein the drug is selected from any of the following: prednisolone; cyclosporine; oestradiol, testosterone, drugs with multicyclic ring structures which lack polar groups etoposide.
11. A method of dissolving poorly soluble drugs in a carbohydrate polymer wherein the solubilising carbohydrate polymer is as defined in claim 1 , whereby on dissolving a poorly soluble drug in the solubilising carbohydrate polymer a substantially clear solution is obtained.
12. A method according to claim 11 wherein the solubilising carbohydrate polymer is selected from any derivatives of the following: chitosans, dextrans, alginic acids, starches, dextran and guar gums.
13. A pharmaceutical composition according to claim 10 wherein the drug is paclitaxel.
14. A solubilising carbohydrate polymer according to claim 1 , wherein X is selected from any of the following linear or branched or cyclo groups: C 1 -C 30 ; C 8 -C 24 ; or C 12 -C 18 .
15. A solubilising carbohydrate polymer according to claim 1 , wherein X is CH 3 (CH 2 ) 14 CONH, or CH 3 (CH 2 ) 15 NH.
16. A solubilising carbohydrate polymer according to claim 1 , wherein R′, R″ and R″′ are independently any linear or branched or cyclo form of the following alkyl, alkenyl, alkynyl, aryl, or acyl groups: C 1 -C 30 ; C 1 -C 12 ; and C 1 -C 6 , optionally substituted with amine, amide or alcohol.
17. A solubilising carbohydrate polymer according to claim 1 , wherein R′, R″ and R′″ are C 1 -C 4 linear glycol based groups.
18. A solubilising carbohydrate polymer according to claim 1 , wherein R′, R″ and R′″ are any of the following sugar substituents: glucose, galactose, fructose and muramic acid.
19. A solubilising carbohydrate polymer according to claim 1 , wherein R′, R″ and R′″ are oligo polyoxa C 1 -C 3 alkylene units.
20. A solubilising carbohydrate polymer according to claim 1 , wherein all of R′, R″ and R′″ are CH 2 OCH 2 CH 2 OH or CH 2 CH 2 OH.