COMPLEXING AGENTS FOR COMPOSITIONS CONTAINING INCLUSION COMPLEXES
The invention provides a composition containing particulate composite of a polymer and a therapeutic agent. The composition also contains a complexing agent. The polymer interacts with the complexing agent in a host-guest or a guest-host interaction to form an inclusion complex. A therapeutic composition of the invention may be used to deliver the therapeutic agent and to treat various disorders. Both the polymer of the particulate composite and the complexing agent may be used to introduce functionality into the therapeutic composition. The invention also relates to a method of preparing a composition. The method combines a therapeutic agent, a polymer having host or guest functionality, and a complexing agent having guest or host functionality to form the therapeutic composition. The complexing agent forms an inclusion complex with the polymer. The invention also relates to a method of delivering a therapeutic agent. According to the method, a therapeutically effective amount of a therapeutic composition of the invention is administered to a mammal (e.g. person or animal) in recognized need of the therapeutic. Also disclosed are compounds having the formula:
1 . A compound of the formula:
wherein
J is —NH—, —C(═O)NH—CH 2 ) d —, —NH—C(═O)—(CH 2 ) d —, —CH 2 SS—, —C(═O)O—(CH 2 ) e —O—P(═O)(O—(CH 2 ) c —Y)O—,
a peptide or polypeptide residue, or
—NH—(C═O)—CH(R 1 )—NH—(C═O)—CH(R 1 )—NH—;
Y is an additional host/guest functionality;
R 1 is —(CH 2 ) a —CO 2 H, an ester or salt thereof; or —(CH 2 ) a —CONH 2 ;
PEG is —O(CH 2 CH 2 O) z —, where z varies from 2 to 500;
L is H, —NH 2 , —NH—(C═O)—(CH 2 ) e —(C═O)—CH 2 —, —S(═O) 2 —HC═CH 2 —, —SS—, —C(═O)O—, or a carbohydrate residue;
a is 0 or 1;
b is 0 or 1;
d ranges from 0 to 6;
e ranges from 1 to 6;
n ranges from 0 to 6;
y is 0 or 1; and
x is 0 or 1.
2 . The compound of claim 1 , wherein the host/guest is selected from the group of adamantyl, naphthyl, cholesterol, cyclodextrin, and mixtures thereof.
3 . A compound of the formula:
wherein
J is —NH—, —C(═O)NH—(CH 2 ) d —, —NH—C(═O)—(CH 2 ) d —, —CH 2 SS—, —C(═O)O—(CH 2 ) e —O—P(═O)(O—(CH 2 ) e —Y)O—,
a peptide or polypeptide residue, or
—NH—(C═O)—CH(R 1 )—NH—(C═O)—CH(R 1 )—NH—;
Y is an additional host/guest functionality;
R 1 is —(CH 2 ) a —CO 2 H, an ester or salt thereof; or —(CH 2 ) a —CONH 2 ;
PEG is —O(CH 2 CH 2 O) z —, where z varies from 2 to 500;
L is H, —NH 2 , —NH—(C═O)—(CH 2 ) e —(C═O)—CH 2 —, —S(═O) 2 —HC═CH 2 —, —SS—, —C(═O)O—, or a carbohydrate residue;
a is 0 or 1;
b is 0 or 1;
d ranges from 0 to 6;
e ranges from 1 to 6;
n ranges from 0 to 6;
q ranges from 1 to 5;
w ranges from 1 to 5;
y is 0 or 1;
x is 0 or 1; and
z ranges from 1 to 5.
4 . The compound of claim 3 , wherein the host/guest is selected from the group of adamantyl, naphthyl, cholesterol, cyclodextrin, and mixtures thereof.
5 . A composition comprising a particulate composite of a cyclodextrin containing polymer and a therapeutic agent and an inclusion complex of said cyclodextrin polymer and a complexing agent comprising an inclusion guest is a compound of claim 1 .
6 . The composition of claim 5 , wherein said therapeutic agent is selected from the group consisting of an antibiotic, a steroid, a polynucleotide, small molecule pharmaceutical, a virus, a plasmid, a peptide, a peptide fragment, a chelating agent, a biologically active macromolecule, and mixtures thereof.
7 . The composition of claim 6 , wherein said therapeutic agent is a polynucleotide.
8 . A composition comprising a particulate composite of a cyclodextrin containing polymer and a therapeutic agent and an inclusion complex of said cyclodextrin polymer and a complexing agent comprising an inclusion guest is a compound of claim 3 .
9 . The composition of claim 8 , wherein said therapeutic agent is selected from the group consisting of an antibiotic, a steroid, a polynucleotide, small molecule pharmaceutical, a virus, a plasmid, a peptide, a peptide fragment, a chelating agent, a biologically active macromolecule, and mixtures thereof.
10 . The composition of claim 9 , wherein said therapeutic agent is a polynucleotide.
11 . A method of preparing a therapeutic composition, the method comprising:
combining a therapeutic agent; a polymer having host or guest functionality; and a complexing agent having guest or host functionality, wherein the complexing agent forms an inclusion complex with the polymer, to thereby form the therapeutic composition.
12 . A method of treating a subject, the method comprising administering a therapeutically effective amount of a therapeutic composition, wherein the therapeutic composition comprises a polymer having host or guest functionality; and a complexing agent having guest or host functionality, wherein the complexing agent forms an inclusion complex with the polymer, to thereby treat the subject.
13 . The method of claim 11 , wherein said therapeutic agent is selected from the group consisting of an antibiotic, a steroid, a polynucleotide, small molecule pharmaceutical, a virus, a plasmid, a peptide, a peptide fragment, a chelating agent, a biologically active macromolecule, and mixtures thereof.
14 . The method of claim 12 , wherein said therapeutic agent is selected from the group consisting of an antibiotic, a steroid, a polynucleotide, small molecule pharmaceutical, a virus, a plasmid, a peptide, a peptide fragment, a chelating agent, a biologically active macromolecule, and mixtures thereof.