Responsive microgel and methods related thereto

• US 20080003288A1
• Filed: 04/11/2007
• Published: 01/03/2008
• Est. Priority Date: 01/29/2002
• Status: Abandoned Application

• Current Assignee: Supratek Pharma, Inc.
• Original Assignee: Supratek Pharma, Inc.
• Inventors: Temchenko, Marina, Bromberg, Lev
• Application Number:
  US11/786,373
• Publication Number:
  US 20080003288A1
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 8/042 Gels
• CPC Class Codes: A61K 8/90 Block copolymers A61K8/89 takes precedence
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin

Abstract

A responsive microgel is provided which responds volumetrically and reversibly to a change in one or more aqueous conditions selected from the group consisting of (temperature, pH, and ionic conditions) comprised of an ionizable network of covalently cross-linked homopolymeric ionizable monomers wherein the ionizable network is covalently attached to an amphiphilic copolymer to form a plurality of ‘dangling chains’ and wherein the ‘dangling chains’ of amphiphilic copolymer form immobile micelle-like aggregates in aqueous solution. A responsive microgel is further provided that comprises at least one therapeutic entity and delivers a substantially linear and sustained release of the therapeutic entity under physiological conditions.

Claims

1-3. -3. (canceled)

4. A responsive microgel which comprises:

an ionizable network of covalently cross-linked homopolymeric ionizable monomers wherein the ionizable network is covalently attached to an amphiphilic copolymer to form a plurality of ‘

dangling chains’ and

wherein the ‘

dangling chains’

of amphiphilic copolymer form immobile aggregates in aqueous solution;

and at least one therapeutic entity.

5. A responsive microgel according to claim 4 which comprises a cationic therapeutic entity.

6. A responsive microgel according to claim 4 which comprises a hydrophobic therapeutic entity.

7. A responsive microgel according to claim 4 which comprises an amphiphilic therapeutic entity.

8. A responsive microgel according to claim 4 which delivers a substantially linear and sustained release of a hydrophobic or amphiphilic therapeutic entity under physiological conditions.

17. A method of administering at least one therapeutic entity to a patient comprising administering a responsive microgel according to claim 4.

18. A method of administering at least one therapeutic entity to a patient according to claim 17 comprising orally administering a responsive microgel.

19. A method of administering at least one therapeutic entity to a patient according to claim 17 selected from the group consisting of (hydrophobic entities, cationic entities, and amphiphilic entities).

20. A method of administering at least one therapeutic entity to a patient according to claim 17 selected from the group consisting of (a steroidal antiandrogen, a non steroidal antiandrogen, an estrogen, diethylstilbestrol, a conjugated estrogen, a selective estrogen receptor modulator (SERM), a taxane, a LHRH analog, substrates of ABC transporters such as P-glycoprotein;

MRP1-MRP9;

ABC half-transporters such as BCRP and other transporters that are involved into a limited drug transport across small intestinal epythlium, cerebral endothelium and other barrier tissues in the body, as well as substrates of metabolic enzyme isoforms without limitation, cytochrome P-450;

esterase;

epoxide hydrolase;

alcohol dehydrogenase;

aldehyde dehydroganase;

dihydropyrimidine dehydroganase;

NADPH-quinone oxidoreductase;

uridine 5′

-triphosphat glucoronosyltransferase;

sulfotransferase;

glutatione S-transferase;

N-acetiltransferase;

histamine methyltransferase;

catechol-o-methyl transferase;

thiopurine methyltransferase. This group of therapeutic agents include without limitation doxorubicin and other anthracyclines, mitoxantrone, mitomycin C, methotrexate, paclitaxel, docetaxel and other taxanes, topotecan and other camptotecines, cysplatin, carboplatin, oxaliplatin and other platinum complexes;

megesterol acetate and other steroids;

carvedilol and other beta-blocking agents;

azidothymidine, fludarabine and other nucleoside containing agents in their dephospho, mono-, di- and tri-phosphorylated forms;

vinblastine, vincristine and other vinka alkaloids;

etoposide and other podophilotoxins).

9-16. -16. (canceled)