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 wherein 60% to 100% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 2-O-position and the composition has an average degree of substitution from 4.00 to 8.00.
2 . The composition of claim 1 , wherein the composition has an average degree of substitution from 4.00 to 6.00.
3 . The composition of claim 2 , wherein the composition has an average degree of substitution from 4.00 to 5.00.
4 . The composition of claim 1 , wherein 80% to 100% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 2-O-position.
5 . The composition of claim 1 , wherein 90% to 100% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 2-O-position.
6 . The composition of claim 1 , wherein 0% to 10% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 6-O-position.
7 . The composition of claim 1 , wherein 0% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 6-O-position.
8 . The composition of claim 1 , wherein the composition has a pH from about 6.0 to about 8.0.
9 . The composition of claim 1 , further comprising no more than 10 ppb of propylene glycol as measured by HPLC.
10 . The composition of claim 1 , further comprising no more than 1 ppm of propylene oxide.
11 . The composition of claim 1 , further comprising about 0 ppm to about 10 ppm of chloride.
12 . The composition of claim 1 , wherein the composition is suitable for administration to a human subject in need thereof.
13 . The composition of claim 1 , wherein the composition comprises endotoxins in no more than 1.0 EU/g β-cyclodextrin mixture.
14 . A method for reducing the size or amount of circulating cholesterol crystals in the blood, serum, or plasma of a subject in need thereof comprising administering a therapeutically effective amount of the composition of claim 1 to the subject.
15 . The method of claim 14 , wherein the size of the cholesterol crystals is reduced by at least about 10%.
16 . The method of claim 14 , wherein the size of the cholesterol crystals is reduced by at least about 30%.
17 . The method of claim 14 , wherein the size of the cholesterol crystals is reduced by at least about 50%.
18 . The method of claim 14 , wherein the amount of the cholesterol crystals is reduced by at least about 10%.
19 . The method of claim 14 , wherein the amount of the cholesterol crystals is reduced by at least about 30%.
20 . The method of claim 14 , wherein the amount of the cholesterol crystals is reduced by at least about 50%.
21 . The method of claim 14 , wherein therapeutically effective amount of the composition is from about 50 mg/kg to about 8,000 mg/kg.
22 . The method of claim 14 , wherein the composition is administered via an intrathecal, intravenous, oral, or intracerebroventricular route.
23 . The method of claim 14 , wherein the subject is human.