Polysulfate of cyclodextrin derivative and process for preparing the same

Claim 2

The compound according to claim 1, in which R is a group of the formula: -OSO₂R¹, and R¹ is a mesityl group.

Claim 3

The compound according to claim 1, in which R is a group of the formula: -SR², and R² is a C₁₋₂₀ alkyl group; a C₁₋₄ alkyl having 1 to 3 substituents selected from a phenyl group, a halogeno-substituted phenyl group and a C₁₋₄ alkoxy-substituted phenyl group; a phenyl group; a halogeno-substituted phenyl group; a C₁₋₄ alkyl-substituted phenyl group; a C₁₋₄ alkoxy-substituted phenyl group; a dihydroxy-substituted pyrimidinyl group or a purinyl group.

Claim 4

The compound according to claim 1, in which R is a group of the formula: and R³ and R⁴ are a C₁₋₄ alkyl group; a hydroxy-substituted C₁₋₄ alkyl group; an amino-substituted C₁₋₄ alkyl group; a C₃₋₈ cycloalkyl group; a phenyl group; a halogeno-substituted phenyl group; a C₁₋₄ alkyl-substituted phenyl group; a C₁₋₄ alkoxy-substituted phenyl group; a phenyl-substituted C₁₋₄ alkyl group; a C₁₋₄ alkoxyphenyl-substituted C₁₋₄ alkyl group; and the other is a hydrogen atom or a C₁₋₄ alkyl group; or both may be combined at their ends to form a C₁₋₄ alkylene group.

Claim 5

The compound according to claim 1, in which R is a group of the formula: -NHSO₂R⁵, and R⁵ is a C₁₋₂₀ alkyl group; a phenyl group; a halogeno-substituted phenyl group; a C₁₋₄ alkyl-substituted phenyl group; a C₁₋₄ alkoxy-substituted phenyl group; a naphthyl group; a thienyl group; a C₁₋₄ alkyl-substituted isooxazolyl group or a C₁₋₄ alkyl-substituted thiazolyl group.

Claim 6

The compound according to claim 1, in which R is a group of the formula: and R⁶ is C₁₋₂₀ alkyl group; a phenyl gorup; a hydroxy-substituted phenyl group; a C₁₋₄ alkyl-substituted phenyl group; a C₁₋₄ alkoxy-substituted phenyl group; a phenyl-substituted C₁₋₄ alkyl group; a thienyl group or a pyrenylcarbonyl-substituted C₁₋₄ alkyl group and R⁷ is a hydrogen atom; a C₂₋₅ alkanoylamino-substituted C₁₋₄ alkyl group or a benzoylamino-substituted C₁₋₄ alkyl group.

Claim 7

The compound according to Claim 3 or 6, which is a polysulfate of a α-cyclodextrin in which at least one of 6 D-gulcose units has been replaced by a unit represented by Formula (I), or a salt thereof.

Claim 8

The compound according to any one of Claim 2 through 6, which is a polysulfate of a β-cycrodextrin in which at least one of 7 D-glucose units has been replaced by a unit represented by Formula (I), or a salt thereof.

Claim 9

The compound according to Claim 3, which is a polysulfate of a γ-cycrodextrin in which at least one of 8 D-glucose units has been replaced by a unit represented by formula (I), or a salt thereof.

Claim 10

The compound according to claim 1, in which the number of the sulfate group in the molecule is 8 to 23.

Claim 11

The compound according to claim 1, in which R is a N-benzoyl-N-2-benzoylaminoethylamino group, an octadecanoylamino group, a hexanoylamino group, an octanoylamino group, a 1-pyrenylcarbonylpropanoylamino group, a 4-metoxyphenylamino group, a 2-naphthylsulfonyloxy group, an octylsulfonylamino group, a mesitylenesulfonyloxy group, a benzylthio group, a 4-chlorobenzylthio group, a 4-methoxybenzylthio group, a 4-methylphenylthio group, a 4-methoxyphenyl group or a purinylthio group.

Claim 12

A sulfate of a β-cyclodextrin in which one to 7 D-glucose units constituting β-cyclodextrin has been replaced by a unit represented by Formula (IV) wherein R¹ is a mesityl group, and 0 to 2 D-glucose units has been replaced by a unit represented by Formula (V) wherein R˝ is pyridinio group or a lower-alkylamino group.

Claim 13

A process for preparing a polysulfate of a cyclodextrin in which at least one of 6 to 8 D-glucose units constituting the cyclodextrin has been replaced by a unit represented by Formula(I): wherein R is a group represented by the formula: where R¹ represents mesityl group; R² represents an alkyl group; a lower alkyl group having 1 to 3 substituted or unsubstituted phenyl groups; a substituted or unsubstituted phenyl group or a nitrogen-containing heterocyclic group which may hve substitutent(s); one of R³ and R⁴ represeents a lower alkyl group; a hydroxy-substituted lower alkyl group; an amino-substituted lower alkyl group; a cycloalkyl group; a substituted or unsubstituted phenyl group or a substituted or unsubstituted phenyl-substituted lower alkyl group; and the other represents a hydrogen atom or a lower alkyl group, or both may be combined at their ends to form a lower alkylene group, R⁵ represents an alkyl group; a substituted or unsubstituted phenyl group; a naphthyl group; or a heterocyclic group containing one or two hetero atoms selected from nitrogen, oxygen and sulfur, which may have substituent(s); R⁶ represents an alkyl group; a substituted or unsubstituted phenyl group; a phenyl-substituted lower alkyl group; a sulfur-containing heterocyclic group; or a pyrenylcarbonyl-substituted lower alkyl group; and R⁷ represents a hydrogen atom; or a lower alkyl group substituted by a lower alkanoylamino group or a benzoylamino group, or a salt thereof, which comprises reacting a cyclodextrin derivative in which at least one of 6 to 8 D-glucose units constituting the cylclodextrin is replaced by the unit or units represented by the above Formula (I), with a sulfonating agent, and then converting the product into a salt, if desired.

Claim 14

A pharmaceutical composition which comprises a therapeutically effective amount of the compound claimed in claim 1 and a pharmaceutically acceptable carrier therefor.