Pharmaceutical compositions of conjugates formed from polymer derivatives having particular atom arrangements
View Patent ↗Pharmaceutical compositions of conjugates are provided. The conjugates can be prepared by (among other ways) conjugating a pharmacologically active agent with a polymeric reagent that has a particular arrangement of atoms. Related methods, preparations, and so forth are also provided.
1. A pharmaceutical preparation comprising
(i) a conjugate of the following structure,
wherein:
POLY 1 is a poly(alkylene glycol);
POLY 2 is a poly(alkylene glycol);
(a) is 0, 1, 2 or 3;
(b) is 0, 1, 2 or 3;
(e) is 0, 1, 2 or 3;
(f′) is 0, 1, 2 or 3;
(g′) is 0, 1, 2 or 3;
(h) is 0, 1, 2 or 3;
(j) is 0 to 20;
each R 1 is independently H or an organic radical selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl and substituted aryl;
X 1 , when present, is a first spacer moiety;
X 2 , when present, is a second spacer moiety;
X 5 , when present, is a fifth spacer moiety;
X 6 , when present, is a sixth spacer moiety;
X 7 , when present, is a seventh spacer moiety;
X 8 , when present, is an eighth spacer moiety;
R 5 is a branching moiety selected from the group consisting of
wherein (p) is 1-10 and (q) is 1-10; and
Active Agent is a residue of a pharmacologically active agent; and
(ii) a pharmaceutically acceptable excipient.
2. The pharmaceutical preparation of claim 1 , wherein each R 1 is H.
3. The pharmaceutical preparation of claim 1 , wherein each poly(alkylene glycol) is a poly(ethylene glycol).
4. The pharmaceutical preparation of claim 3 , wherein each poly(ethylene glycol) is terminally capped with methoxy.
5. The pharmaceutical preparation of claim 4 , wherein each poly(ethylene glycol) has a molecular weight of from about 100 Daltons to about 100,000 Daltons.
6. The pharmaceutical preparation of claim 5 , wherein each poly(ethylene glycol) has a molecular weight of from about 1,000 Daltons to about 60,000 Daltons.
7. The pharmaceutical preparation of claim 6 , wherein each poly(ethylene glycol) has a molecular weight of from about 2,000 Daltons to about 50,000 Daltons.
8. The pharmaceutical preparation conjugate of claim 1 , wherein the conjugate has the following structure:
when the branching moiety R 5 is
and,
wherein:
(n) is 2 to 4000;
(g′) is 0, 1, 2 or 3;
(h) is 0, 1, 2 or 3;
(j) is 0 to 20
(p) is 1;
(q) is 1; and
Active Agent is a residue of a pharmacologically active agent.
9. The pharmaceutical preparation of claim 1 , wherein the conjugate has the following structure:
wherein:
(n) is 2 to 4000;
(g′) is 0, 1, 2 or 3;
(c) is 1 to 10;
each R 2 is H or an organic radical selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl and substituted aryl;
each R 3 is H or an organic radical selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl and substituted aryl;
(j) is 0 to 20; and
Active Agent is a residue of a pharmacologically active agent.
10. The pharmaceutical preparation of claim 1 , wherein the conjugate has the following structure:
wherein:
(n) is 2 to 4000;
(g′) is 0, 1, 2 or 3;
(c) is 1 to 10;
each R 2 is H or an organic radical selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl and substituted aryl;
each R 3 is H or an organic radical selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl and substituted aryl;
(j) is 0 to 20; and
Active Agent is a residue of a pharmacologically active agent.
11. The pharmaceutical preparation of claim 1 , wherein the conjugate has the following structure:
wherein:
(n) is 2 to 4000; and
Active Agent is a residue of a pharmacologically active agent.
12. The pharmaceutical preparation of claim 1 , wherein the pharmacologically active agent is selected from the group consisting of erythropoietin, granulocyte-colony stimulating factor, interferon-α, human growth hormone, interferon-β, follicle stimulating hormone, Factor VIII, B-domain deleted Factor VIII, desmopressin and amdoxivir.
13. The pharmaceutical preparation of claim 1 , wherein each R 1 is an organic radical and is selected from the the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl and substituted aryl.