COMPOSITIONS OF HYDROXYPROPYL-BETA-CYCLODEXTRIN AND METHODS OF PURIFYING THE SAME
The present disclosure relates to compositions comprising mixtures of hydroxypropyl-β-cyclodextrin, wherein the compositions may be isomerically purified. The disclosure also relates to methods of isomerically purifying a mixture of hydroxypropyl-β-cyclodextrins.
1 . A composition comprising a mixture of isomerically-purified hydroxypropyl β-cyclodextrin molecules comprising:
about 6% to about 12% β-cyclodextrin substituted with eight hydroxypropyl groups (“DS-8”);
about 18% to about 24% β-cyclodextrin substituted with nine hydroxypropyl groups (“DS-9”);
about 24% to about 30% β-cyclodextrin substituted with ten hydroxypropyl groups (“DS-10”);
about 10% to about 16% β-cyclodextrin substituted with eleven hydroxypropyl groups (“DS-11”);
about 4% to about 10% β-cyclodextrin substituted with thirteen hydroxypropyl groups (“DS-13”); and
about 0% to about 6% β-cyclodextrin substituted with fourteen hydroxypropyl groups (“DS-14”).
2 . The composition of claim 1 , wherein the mixture further comprises less than 1% β-cyclodextrin substituted with five hydroxypropyl groups (“DS-5”).
3 . The composition of claim 1 , wherein the composition further comprises less than 1% β-cyclodextrin substituted with four hydroxypropyl groups (“DS-4”).
4 . The composition of claim 1 , wherein the composition further comprises less than 1% β-cyclodextrin substituted with three hydroxypropyl groups (“DS-3”).
5 . The composition of claim 1 , wherein the mixture further comprises less than 0.05% unsubstituted beta-cyclodextrin (“DS-0”) and less than 0.05% β-cyclodextrin substituted with one hydroxypropyl group (“DS-1f”).
6 . The composition of claim 1 , wherein the composition further comprises no more than 10 ppb of propylene glycol as measured by HPLC.
7 . The composition of claim 1 , wherein the composition comprises no more than 1 ppm propylene oxide.
8 . The composition of claim 1 , wherein the composition comprises between 0 and 10 ppm chloride.
9 . The composition of claim 1 , wherein at least 50% of the hydroxypropyl substitutions in the hydroxypropyl-β-cyclodextrin molecules are located at the 2-O-position of the hydroxypropyl-β-cyclodextrin molecules.
10 . The composition of claim 1 , wherein 0% to 20% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 6-O-position.
11 . A composition comprising a mixture of isomerically-purified hydroxypropyl β-cyclodextrin molecules comprising:
β-cyclodextrin substituted with seven hydroxypropyl groups (“DS-7”);
β-cyclodextrin substituted with eight hydroxypropyl groups (“DS-8”);
β-cyclodextrin substituted with nine hydroxypropyl groups (“DS-9”);
β-cyclodextrin substituted with ten hydroxypropyl groups (“DS-10”);
β-cyclodextrin substituted with eleven hydroxypropyl groups (“DS-11”);
β-cyclodextrin substituted with thirteen hydroxypropyl groups (“DS-13”); and
β-cyclodextrin substituted with fourteen hydroxypropyl groups (“DS-14”),
wherein the mixture of isomerically-purified hydroxypropyl β-cyclodextrin molecules has an average degree of substitution of about 9 to about 10.
12 . The composition of claim 11 , wherein the mixture further comprises less than 1% β-cyclodextrin substituted with five hydroxypropyl groups (“DS-5”).
13 . The composition of claim 11 , wherein the composition further comprises less than 1% β-cyclodextrin substituted with four hydroxypropyl groups (“DS-4”).
14 . The composition of claim 11 , wherein the composition further comprises less than 1% β-cyclodextrin substituted with three hydroxypropyl groups (“DS-3”).
15 . The composition of claim 11 , wherein the mixture further comprises less than 0.05% unsubstituted beta-cyclodextrin (“DS-0”) and less than 0.05% β-cyclodextrin substituted with one hydroxypropyl group (“DS-1”).
16 . The composition of claim 11 , wherein the composition further comprises no more than 10 ppb of propylene glycol as measured by HPLC.
17 . The composition of claim 11 , wherein the composition comprises no more than 1 ppm propylene oxide.
18 . The composition of claim 11 , wherein the composition comprises between 0 and 10 ppm chloride.
19 . The composition of claim 11 , wherein at least 50% of the hydroxypropyl substitutions in the hydroxypropyl-β-cyclodextrin molecules are located at the 2-O-position of the hydroxypropyl-β-cyclodextrin molecules.
20 . The composition of claim 11 , wherein 0% to 20% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 6-O-position.
21 . A composition comprising a mixture of isomerically-purified hydroxypropyl β-cyclodextrin molecules comprising:
β-cyclodextrin substituted with six hydroxypropyl groups (“DS-6”);
β-cyclodextrin substituted with seven hydroxypropyl groups (“DS-7”);
β-cyclodextrin substituted with eight hydroxypropyl groups (“DS-8”);
β-cyclodextrin substituted with nine hydroxypropyl groups (“DS-9”);
β-cyclodextrin substituted with ten hydroxypropyl groups (“DS-10”);
β-cyclodextrin substituted with eleven hydroxypropyl groups (“DS-11”);
β-cyclodextrin substituted with thirteen hydroxypropyl groups (“DS-13”); and
β-cyclodextrin substituted with fourteen hydroxypropyl groups (“DS-14”),
wherein the mixture of isomerically-purified hydroxypropyl β-cyclodextrin molecules has an average degree of substitution of about 7.5 to about 8.5.
22 . The composition of claim 21 , wherein the mixture further comprises less than 1% β-cyclodextrin substituted with five hydroxypropyl groups (“DS-5”).
23 . The composition of claim 21 , wherein the composition further comprises less than 1% β-cyclodextrin substituted with four hydroxypropyl groups (“DS-4”).
24 . The composition of claim 21 , wherein the composition further comprises less than 1% β-cyclodextrin substituted with three hydroxypropyl groups (“DS-3”).
25 . The composition of claim 21 , wherein the mixture further comprises less than 0.05% unsubstituted beta-cyclodextrin (“DS-0”) and less than 0.05% β-cyclodextrin substituted with one hydroxypropyl group (“DS-1”).
26 . The composition of claim 21 , wherein the composition further comprises no more than 10 ppb of propylene glycol as measured by HPLC.
27 . The composition of claim 21 , wherein the composition comprises no more than 1 ppm propylene oxide.
28 . The composition of claim 21 , wherein the composition comprises between 0 and 10 ppm chloride.
29 . The composition of claim 21 , wherein at least 50% of the hydroxypropyl substitutions in the hydroxypropyl-β-cyclodextrin molecules are located at the 2-O-position of the hydroxypropyl-β-cyclodextrin molecules.
30 . The composition of claim 21 , wherein 0% to 20% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 6-O-position.