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 suitable for administration to a human subject comprising a mixture of isomerically-purified hydroxypropyl β-cyclodextrin molecules wherein 80% to 100% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 2-O-position, 3-O position, or a combination thereof.
2 . The composition of claim 1 , wherein the composition has an average degree of substitution from 4.00 to 8.00.
3 . The composition of claim 2 , wherein the composition has an average degree of substitution from 4.00 to 6.00.
4 . The composition of claim 3 , wherein the composition has an average degree of substitution from 4.00 to 5.00.
5 . The composition of claim 1 , wherein 80% to 85% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 2-O-position, 3-O position, or a combination thereof.
6 . The composition of claim 1 , wherein 85% to 90% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 2-O-position, 3-0 position, or a combination thereof.
7 . The composition of claim 1 , wherein 90% to 95% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 2-O-position, 3-O position, or a combination thereof.
8 . The composition of claim 1 , wherein 95% to 100% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 2-O-position, 3-O position, or a combination thereof.
9 . The composition of claim 1 , wherein 90% to 100% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 2-O-position, 3-O position, or a combination thereof.
10 . The composition of claim 1 , wherein 0% to 20% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 6-O-position.
11 . The composition of claim 1 , wherein 0% to 10% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 6-O-position.
12 . The composition of claim 1 , wherein 0% of the hydroxypropyl-β-cyclodextrin subunits are substituted at the 6-O-position.
13 . The composition of claim 1 , wherein the composition has a pH from about 6.0 to about 8.0.
14 . The composition of claim 1 , further comprising no more than 10 ppb of propylene glycol.
15 . The composition of claim 1 , further comprising no more than 1 ppm of propylene oxide.
16 . The composition of claim 1 , further comprising about 0 ppm to about 10 ppm of chloride.
17 . The composition of claim 1 , wherein the composition is suitable for administration to a human subject in need thereof.
18 . The composition of claim 1 , wherein the composition comprises endotoxins in no more than 1.0 EU/g β-cyclodextrin mixture.
19 . A method for treating liver disease, cardiovascular disease, familial hypercholesterolemia, or cholesterol deposits in a subject in need thereof comprising administering a therapeutically effective amount of the composition of claim 1 to the subject.
20 . The method of claim 19 , wherein the method comprises reducing the size or amount of circulating cholesterol crystals.
21 . The method of claim 20 , wherein the size of the cholesterol crystals is reduced by at least about 10%.
22 . The method of claim 20 , wherein the size of the cholesterol crystals is reduced by at least about 30%.
23 . The method of claim 20 , wherein the size of the cholesterol crystals is reduced by at least about 50%.
24 . The method of claim 19 , wherein therapeutically effective amount of the composition is from about 50 mg/kg to about 8,000 mg/kg.
25 . The method of claim 19 , wherein the composition is administered via an intrathecal, intravenous, oral, or intracerebroventricular route.
26 . The method of claim 19 , wherein the subject is human.