Cyclodextrin-based polymers for therapeutics delivery
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-047/48
C08B-037/16
A61K-009/51
A61P-035/00
출원번호
US-0572294
(2012-08-10)
등록번호
US-8680202
(2014-03-25)
발명자
/ 주소
Cheng, Jianjun
Davis, Mark E.
Khin, Kay T.
출원인 / 주소
Cerulean Pharma Inc.
대리인 / 주소
Lando & Anastasi LLP
인용정보
피인용 횟수 :
0인용 특허 :
107
초록▼
The present invention relates to novel compositions of therapeutic cyclodextrin containing polymeric compounds designed as a carrier for small molecule therapeutics delivery and pharmaceutical compositions thereof. These cyclodextrin-containing polymers improve drug stability and solubility, and red
The present invention relates to novel compositions of therapeutic cyclodextrin containing polymeric compounds designed as a carrier for small molecule therapeutics delivery and pharmaceutical compositions thereof. These cyclodextrin-containing polymers improve drug stability and solubility, and reduce toxicity of the small molecule therapeutic when used in vivo. Furthermore, by selecting from a variety of linker groups and targeting ligands the polymers present methods for controlled delivery of the therapeutic agents. The invention also relates to methods of treating subjects with the therapeutic compositions described herein. The invention further relates to methods for conducting pharmaceutical business comprising manufacturing, licensing, or distributing kits containing or relating to the polymeric compounds described herein.
대표청구항▼
1. A method of making a water soluble linear polymer camptothecin conjugate comprising: providing a water soluble linear polymer comprising cyclodextrin moieties and comonomers which do not contain cyclodextrin moieties (comonomers), wherein the cyclodextrin moieties and comonomers alternate in the
1. A method of making a water soluble linear polymer camptothecin conjugate comprising: providing a water soluble linear polymer comprising cyclodextrin moieties and comonomers which do not contain cyclodextrin moieties (comonomers), wherein the cyclodextrin moieties and comonomers alternate in the water soluble linear polymer and wherein the water soluble linear polymer comprises at least four cyclodextrin moieties and at least four comonomers; andcovalently attaching camptothecin moieties to the water soluble linear polymer, thereby making a water soluble linear polymer camptothecin conjugate, wherein the camptothecin moieties can be cleaved from the water soluble linear polymer conjugate under biological conditions to release the camptothecin moieties. 2. The method of claim 1, wherein each of the camptothecin moieties is attached to the water soluble linear polymer via a linker. 3. The method of claim 1, wherein the water soluble linear polymer is made by a process comprising: providing cyclodextrin moiety precursors,providing comonomer precursors, andcopolymerizing the cyclodextrin moiety precursors and the comonomer precursors to thereby make the water soluble linear polymer. 4. The method of claim 3, comprising providing cyclodextrin moiety precursors modified to bear one reactive site at each of exactly two positions, and reacting the cyclodextrin moiety precursors with the comonomer precursors having exactly two reactive moieties capable of forming a covalent bond with the reactive sites under polymerization conditions that promote reaction of the reactive sites with the reactive moieties to form covalent bonds between the comonomers and the cyclodextrin moieties, whereby the water soluble linear polymer comprising alternating units of a cyclodextrin moiety and a comonomer is produced. 5. The method of claim 1, wherein the camptothecin moieties make up at least 5%, by weight of the water soluble linear polymer conjugate. 6. The method of claim 5, wherein each of the comonomers comprises a polyethylene glycol of molecular weight 0.2 to 5 kDa and the cyclodextrin moiety comprises beta-cyclodextrin. 7. The method of claim 3, wherein each of the comonomer precursors is a compound containing two functional groups through which reaction and thus linkage of the cyclodextrin moieties is achieved. 8. The method of claim 7, wherein the two functional groups, which may be the same or different, terminal or internal, of each of the comonomer precursors comprise an amino acid, imidazole, hydroxyl, thio, acyl halide, —HC═CH—, —C≡C— group, or derivative thereof. 9. The method of claim 7, wherein the two functional groups are the same and are located at termini of each of the comonomer precursors. 10. The method of claim 1, wherein each of the comonomers contains one or more pendant groups with at least one functional group through which reaction and thus linkage of the camptothecin moieties is achieved. 11. The method of claim 10, wherein the functional groups, which may be the same or different, terminal or internal, of the one or more pendant groups comprise an amino acid, imidazole, hydroxyl, thiol, acyl halide, ethylene, ethyne group, or derivative thereof. 12. The method of claim 10, wherein the one or more pendant groups are a substituted or unsubstituted branched, cyclic or straight chain C1-C10 alkyl, or arylalkyl optionally containing one or more heteroatoms within the chains or rings. 13. The method of claim 1, wherein each of the cyclodextrin moieties comprises an alpha, beta, or gamma cyclodextrin moiety. 14. The method of claim 1, wherein administration of the water soluble linear polymer camptothecin conjugate to a patient results in release of camptothecin over a period of at least 6 hours. 15. The method of claim 1, wherein administration of the water soluble linear polymer camptothecin conjugate to a patient results in release of the camptothecin moieties over a period of 6 hours to a month. 16. The method of claim 1, wherein, upon administration of the water soluble linear polymer camptothecin conjugate to a patient the rate of the camptothecin moieties release is dependent primarily upon the rate of hydrolysis as opposed to enzymatic cleavage. 17. The method of claim 1, wherein the water soluble linear polymer camptothecin conjugate has a molecular weight of 10,000-500,000 amu. 18. The method of claim 1, wherein the cyclodextrin moieties make up at least about 2% of the polymer by weight. 19. The method of claim 1, wherein the cyclodextrin moieties make up at least about 5% of the polymer by weight. 20. The method of claim 1, wherein the cyclodextrin moieties make up at least about 10% of the polymer by weight. 21. The method of claim 1, wherein each of the comonomers comprises a group selected from the following: an alkylene chain,polysuccinic anhydride,poly-L-glutamic acid,poly(ethyleneimine),an oligosaccharide, oran amino acid chain. 22. The method of claim 1, wherein each of the comonomers comprises a polyethylene glycol chain. 23. The method of claim 1, wherein each of the comonomers comprises a group selected from the following: polyglycolic acid or a polylactic acid chain. 24. The method of claim 1, wherein each of the comonomers comprises a hydrocarbylene group wherein one or more methylene groups is optionally replaced by a group Y (provided that none of the Y groups are adjacent to each other), wherein each Y, independently for each occurrence, is selected from, substituted or unsubstituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl, or —O—, C(═X) (wherein X is NR1, O or S), —OC(O)—, —C(═O)O, —NR1—, —NR1CO—, —C(O)NR1—, —S(O)n— (wherein n is 0, 1, or 2), —OC(O)—NR1, —NR1—C(O)—NR1—, —NR1—C(NR1)—NR1—, and —B(OR1)—; and R1, independently for each occurrence, represents H or a lower alkyl. 25. The method of claim 1, wherein each of the cyclodextrin moieties comprises a beta cyclodextrin moiety. 26. The method of claim 2, wherein the linker comprises glycine, the comonomer comprises a polyethylene glycol, and the cyclodextrin moiety comprises beta-cyclodextrin. 27. A method of making a water soluble linear polymer having the following formula: wherein the group has a Mw of 0.2-5 kDa and n is at least 4, the method comprising: providing cyclodextrin moiety precursors of the following formula: providing comonomer precursors comprising the group having a Mw of 0.2-5 kDa; and copolymerizing the cyclodextrin moiety precursors and the comonomer precursors to thereby make the water soluble linear polymer. 28. The method of claim 27, wherein each of the comonomer precursors comprising the group has exactly two reactive moieties capable of forming a covalent bond with the cyclodextrin moiety precursors under polymerization conditions. 29. A method of making a water soluble linear polymer camptothecin conjugate having the following formula: wherein: the group has a Mw of 0.2 to 5 kDa and n is at least 4; each L is independently a linker or absent;each D is independently camptothecin or OH; the method comprising:providing cyclodextrin moiety precursors of the following formula: providing comonomer precursors of the following formula: copolymerizing the cyclodextrin moiety precursors and the comonomer precursors to provide the water soluble linear polymer; andcovalently attaching L-D moieties to the water soluble linear polymer, to provide the water soluble linear polymer camptothecin conjugate. 30. The method of claim 29, wherein the cyclodextrin moiety precursor has the following formula: 31. A method of making a water soluble linear polymer camptothecin conjugate, the method comprising: coupling a water soluble linear polymer of the following formula: wherein the group has a Mw of 0.2 to 5 kDa and n is at least 4, with a compound of the following formula: or a salt thereof,in the presence of a coupling agent, to provide the camptothecin polymer conjugate. 32. The method of claim 31, wherein the coupling agent is 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC).
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (107)
Ekwuribe Nnochiri ; Ramaswamy Muthukumar ; Rajagopalan Jayanthi Sethuraman, Amphiphilic drug-oligomer conjugates with hydroyzable lipophile components and methods for making and using the same.
Winkler, James L.; Fodor, Stephen P. A.; Buchko, Christopher J.; Ross, Debra A.; Aldwin, Lois; Modlin, Douglas N., Combinatorial strategies for polymer synthesis.
Low Philip Stewart (West Lafayette IN) Horn Mark Alan (Piscataway NJ) Heinstein Peter Frederick (West Lafayette IN), Composition and method for tumor imaging.
Curiel David T. (Chapel Hill NC) Birnstiel Max L. (Vienna ATX) Cotten Matthew (Vienna ATX) Wagner Ernst (Langenzersdorf ATX) Zatloukal Kurt (Vienna ATX) Plank Christian (Vienna ATX) Oberhauser Berndt, Composition for introducing nucleic acid complexes into higher eucaryotic cells.
Wolff, Jon A.; Hagstrom, James E.; Monahan, Sean D.; Budker, Vladimir; Rozema, David B.; Slattum, Paul M., Compositions and methods for drug delivery using amphiphile binding molecules.
Zemel Haya (Des Plaines IL) Koch Mark B. (Des Plaines IL) Rohrbach Ronald P. (Des Plaines IL), Crosslinked cyclodextrins supported on porous refractory inorganic oxides.
Weltrowski, Marek; Morcellet, Michel; Martel, Bernard, Cyclodextrin polymers and/or cyclodextrin derivatives with complexing properties and ion-exchange properties and method for the production thereof.
Soon-Shiong Patrick (Los Angeles CA) Desai Neil P. (Los Angeles CA) Sandford Paul A. (Los Angeles CA) Heintz Roswitha A. (Los Angeles CA) Sojomihardjo Soebianto (Pasadena CA), Gel compositions prepared from crosslinkable polysaccharides, polycations and/or lipids and uses therefor.
Pirrung Michael C. (Durham NC) Read J. Leighton (Palo Alto CA) Fodor Stephen P. A. (Palo Alto CA) Stryer Lubert (Stanford CA), Large scale photolithographic solid phase synthesis of an array of polymers.
Pirrung Michael C. (Durham NC) Read J. Leighton (Palo Alto CA) Fodor Stephen P. A. (Palo Alto CA) Stryer Lubert (Stanford CA), Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof.
Vgtle Friedrich (St. Augustin DEX) Dix Johannes P. (Bonn-Beuel DEX) Jaworek Dieter (Weilheim DEX), Ligands assayed by host molecules including cyclophanes, crown ethers, crypstands and podands.
Phillips Christopher P. (Brandamore PA) Snow Robert A. (West Chester PA), Lyophilized polyethylene oxide modified protein and polypeptide complexes with cyclodextrin.
Wahlig Helmut (Darmstadt DEX) Dingeldain Elvira (Dreieich DEX) Braun Dietrich (Darmstadt-Arheilgen DEX), Medicinally useful, shaped mass of collagen resorbable in the body.
Wahlig Helmut (Darmstadt DEX) Dingeldein Elvira (Dreieich DEX) Braun Dietrich (Darmstadt DEX), Medicinally useful, shaped mass of collagen resorbable in the body.
Rhett L. Affleck ; Doug Hobbs ; Ilya Feygin ; Gregory L. Kirk ; James A. Connelly ; Ning Zhao ; James P. Mueller ; Peter Kieselbach, Method and apparatus for controlled photoelution.
Wu George Y. (Bloomfield CT) Wu Catherine H. (Bloomfield CT), Method for the introduction of genes into mammalian cells by a soluble molecular complex comprising a receptor ligand an.
Toda Fumio (Ehime JPX) Tanaka Koichi (Matsuyama JPX) Nakata Tetsuya (Ibaraki JPX), Method of optically resolving a racemate or a diastereomeric mixture of glycidyl compound.
Davis,Mark E.; Gonzalez,Hector; Hwang,Suzie (Sue Jean), Method of preparing a supramolecular complex containing a therapeutic agent and a multi-dimensional polymer network.
Tsuchiyama Yukio (Yokohama JPX) Sato Michikatsu (Fujisawa JPX) Yagi Yoshiaki (Fujisawa JPX) Ishikura Tomoyuki (Chigasaki JPX), Partially methylated cyclodextrins and process for producing the same.
Casey Donald J. (Ridgefield CT) Huffman Kenneth R. (Stamford CT), Poly(glycolic acid)/poly(alkylene glycol) block copolymers and method of manufacturing the same.
Hyon Suong-Hyu (Uji JPX) Ikada Yoshita (Uji JPX), Polylactic acid type microspheres containing physiologically active substance and process for preparing the same.
DeLuca Patrick P. (Lexington KY) Kanke Motoko (Fukuyama JPX) Sato Toyomi (Tokyo CA JPX) Schroeder Hans G. (Encinitas CA), Porous microspheres for drug delivery and methods for making same.
Bachmann Frank (Freiburg DEX) Lohmann Dieter (Munchenstein CHX) Chabrecek Peter (Basel CHX), Unsaturated carbohydrate derivatives polymers thereof and their use.
Fodor Stephen P. A. (Palo Alto CA) Stryer Lubert (Stanford CA) Pirrung Michael C. (Durham NC) Read J. Leighton (Palo Alto CA), Very large scale immobilized polymer synthesis.
Szejtli Jzsef (Budapest HUX) Fenyvesi va (Budapest HUX) Zsadon Bla (Budapest HUX) Szilasi Mria (Budapest HUX) Dcsei Lajos (Budapest HUX), Water soluble cyclodextrin polymers substituted by ionic groups and process for the preparation thereof.
Nussstein Peter (Munich DEX) Staudinger Guenther (Munich DEX) Kreuzer Franz-Heinrich (Martinsried DEX) Schmitt-Sody Wolfgang (Wolfratshausen DEX), Water-insoluble cyclodextrin polymers and processes for their preparation.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.