2-alkylated-cyclodextrin derivatives: reversal agents for drug-induced neuromuscular block

1. A 2-alkylated-cyclodextrin derivative represented by formula I

wherein m is 0–7 and n is 1–8 and m+n=7 or 8;

R is (CH 2 ) p -phenylene-(CH 2 ) q , (C 1-6 )alkylene, or (CH 2 ) r —S—(C 1-4 )alkylene, of which each alkylene group may be substituted with 1–3 OH groups;

p and r are independently 1–4;

q is 0–4;

X is COOH, SO 2 OH, (CH 2 —CH 2 —O) s —H or OH;

s is 1–3; or

a pharmaceutically acceptable salt thereof; with the proviso that when m+n=7, n is 1 and X is OH, R cannot be 2-methyl-1,2-ethanediyl, 2,2-dimethyl-1,2-ethanediyl, 2-hydroxy-1,3-propanediyl or 2-hydroxy-2-methyl-1,3-propanediyl.

2. The 2-alkylated-cyclodextrin derivative according to claim 1 , wherein X is COOH.

3. The 2-alkylated-cyclodextrin derivative according to claim 1 , wherein X is COOH; m is 0; n is 8; and R is (CH 2 )p-phenylene-(CH 2 ) q ; p is 1 and q is 0.

4. A kit for providing neuromuscular block and its reversal, comprising:

(a) neuromuscular blocking agent, and

(b) a 2-alkylated-cyclodextrin derivative according to claim 1 .

5. The kit according to claim 4 , wherein the neuromuscular blocking agent is selected from the group consisting of rocuronium, vecuronium, pancuronium and rapacuronium.

6. The kit according to claim 5 , wherein the neuromuscular blocking agent is rocuronium.

7. A method for reversal of drug-induced neuromuscular block in a patient, comprising: parenterally administering to said patient in need thereof an effective amount of a 2-alkylated-cyclodextrin derivative according to claim 1 .

8. A pharmaceutical composition, comprising:

a 2-alkylated-cyclodextrin derivative represented by general formula I

wherein m is 0–7 and n is 1–8 and m+n=7 or 8;

R is (CH 2 ) p -phenylene-(CH 2 ) q , (C 1-6 )alkylene, or (CH 2 ) r —S—(C 1-4 )alkylene, of which each alkylene group may be substituted with 1–3 OH groups;

p and r are independently 1–4;

q is 0–4;

X is COOH, SO 2 OH, (CH 2 —CH 2 —O) s —H or OH;

s is 1–3; or

a pharmaceutically acceptable salt thereof, and pharmaceutically acceptable auxilliaries.