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US6004573A
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Biodegradable low molecular weight triblock poly(lactide-co-glycolide) polyethylene glycol copolymers having reverse thermal gelation properties
Assignee: KIM PHD SUNG WAN
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Filing: 1997-10-03
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Granted: 1999-12-21
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Expires: 2017-10-03
Abstract
Abstract A water soluble biodegradable ABA-type block copolymer made up of a major amount of hydrophobic poly(lactide-co-glycolide) copolymer A-blocks and a minor amount of a hydrophilic polyethylene glycol polymer B-block, having an overall average molecular weight of between about 3100 and 4500, possesses reverse thermal gelation properties. Effective concentrations of the block copolymer and a drug may be uniformly contained in an aqueous phase to form a drug delivery composition. At temperatures below the gelation temperature of the copolymer the composition is a liquid and at temperatures at or above the gelation temperature the composition is a gel or semi-solid. The gelation temperature is preferably at or below body temperature of a warm-blooded animal. The composition may be administered to a warm-blooded animal as a liquid by parenteral, ocular, topical, transdermal, vaginal, transurethral, rectal, nasal, oral, or aural delivery means and is a gel at body temperature. The composition may also be administered as a gel. The drug is released at a controlled rate from the gel which biodegrades into non-toxic products. The release rate of the drug may be adjusted by changing various parameters such as hydrophobic/hydrophilic component content, copolymer concentration, molecular weight and polydispersity of the block copolymer. Because the copolymer is amphiphilic it functions to increase the solubility and/or stability of drugs in the composition.
Inventors
- 👤 Ramesh C. Rathi
- 👤 Gaylen M. Zentner
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 18:50
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0019; A61K9/0024; A61K47/00; A61K47/30; A61K47/34; B; B82; B82Y; B82Y5/00; C; C08; C08G; C08G63/00; C08G63/66; C08G63/664; C08L; C08L71/00; C08L71/02
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
108 words
An aqueous biodegradable polymeric drug delivery composition possessing reverse thermal gelation properties comprised of an aqueous phase having uniformly contained therein: (a) an effective amount of a drug; and (b) a biodegradable ABA-type block copolymer of the formula: PLGA-PEG-PLGA where PLGA is a hydrophobic poly(lactide-co-glycolide) copolymer that comprises the A-blocks and PEG is a hydrophilic polyethylene glycol polymer that comprises the B-block, said block copolymer having an average molecular weight of between about 3100 and 4500 wherein, in the block copolymer, the PLGA A-blocks comprise about 51 to 83% by weight of said copolymer and the PEG B-block comprises about 17 to 49% by weight of said copolymer.
Claim 2
Dependent Claim
108 words
An aqueous biodegradable polymeric drug delivery composition possessing reverse thermal gelation properties comprised of an aqueous phase having uniformly contained therein: (a) an effective amount of a drug; and (b) a biodegradable ABA-type block copolymer of the formula: PLGA-PEG-PLGA where PLGA is a hydrophobic poly(lactide-co-glycolide) copolymer that comprises the A-blocks and PEG is a hydrophilic polyethylene glycol polymer that comprises the B-block, said block copolymer having an average molecular weight of between about 3100 and 4500 wherein, in the block copolymer, the PLGA A-blocks comprise about 51 to 83% by weight of said copolymer and the PEG B-block comprises about 17 to 49% by weight of said copolymer.
Claim 3
Dependent Claim
24 words
An aqueous polymeric composition according to claim 1 wherein the block copolymer content of said composition is between about 3 and 50% by weight.
Claim 4
Dependent Claim
31 words
An aqueous polymeric composition according to claim 2 wherein the PLGA copolymer A-block comprises between about 65 to 85 mole percent lactide and between about 15 and 35 mole percent glycolide.
Claim 5
Dependent Claim
38 words
An aqueous polymeric composition according to claim 3 wherein the block copolymer comprises between about 65 to 78% by weight of said hydrophobic PLGA A-blocks and between about 22 to 35% by weight of said hydrophilic PEG B-block.
Claim 6
Dependent Claim
23 words
An aqueous polymeric composition according to claim 4 wherein the block copolymer has an average molecular weight of between about 3500 and 4100.
Claim 7
Dependent Claim
16 words
An aqueous polymeric composition according to claim 3 wherein said drug is a polypeptide or protein.
Claim 8
Dependent Claim
114 words
An aqueous polymeric composition according to claim 6 wherein said polypeptide or protein is a member selected from the group consisting of oxytocin, vasopressin, adrenocorticotropic hormone, epidermal growth factor, platelet-derived growth factor (PDGF), prolactin, luliberin or luteinizing hormone releasing hormone, growth hormone, growth hormone releasing factor, insulin, somatostatin, glucagon, interleukin-2 (IL-2), interferon-α, interferon-β, interferon-γ, -; gastrin, tetragastrin, pentagastrin, urogastrone, secretin, calcitonin, enkephalins, endorphins, angiotensins, thyrotropin releasing hormone (TRH), tumor necrosis factor (TNF), nerve growth factor (NGF), granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), macrophage-colony stimulating factor (M-CSF), heparinase, bone morphogenic protein (BMP), hANP, glucagon-like peptide (GLP-1), interleukin-11 (IL-11), renin, bradykinin, bacitracins, polymyxins, colistins, tyrocidine, gramicidins, cyclosporins, enzymes, cytokines, monoclonal antibodies and vaccines.
Claim 9
Dependent Claim
23 words
An aqueous polymeric composition according to claim 13 wherein the drug content of said composition is between about 0.01 and 20% by weight.
Claim 10
Dependent Claim
18 words
An aqueous polymeric composition according to claim 9 wherein said drug is an anti-cancer or anti-cell proliferation agent.
Claim 11
Dependent Claim
34 words
An aqueous polymeric composition according to claim 9 wherein said drug is an anti-cancer agent selected from the group consisting of mitomycin, bleomycin, BCNU, carboplatin, doxorubicin, daunorubicin, methotrexate, paclitaxel, taxotere, actinomycin D, and camptothecin.
Claim 12
Dependent Claim
23 words
An aqueous polymeric composition according to claim 10 wherein the drug content of said composition is between about 0.01 and 20% by weight.
Claim 13
Independent Claim
161 words
A method for the administration of a drug to a warm blooded animal in a controlled release form which comprises: (1) providing an aqueous biodegradable polymeric drug delivery composition possessing reverse thermal gelation properties comprised of an aqueous phase having uniformly contained therein: (a) an effective amount of a drug; and (b) a biodegradable ABA-type block copolymer of the formula: PLGA-PEG-PLGA where PLGA is a hydrophobic poly(lactide-co-glycolide) copolymer that comprises the A-blocks and PEG is a hydrophilic polyethylene glycol polymer that comprises the B-block, said block copolymer having an average molecular weight of between about 3100 and 4500. (2) maintaining said composition as a liquid at a temperature below the gelation temperature of said block copolymer; and (3) administering said composition as a liquid to said warm blooded animal with the subsequent formation of a gel as the temperature of said composition is raised by the body temperature of said animal to be above the gelation temperature of said block polymer.
Claim 14
Independent Claim
161 words
A method for the administration of a drug to a warm blooded animal in a controlled release form which comprises: (1) providing an aqueous biodegradable polymeric drug delivery composition possessing reverse thermal gelation properties comprised of an aqueous phase having uniformly contained therein: (a) an effective amount of a drug; and (b) a biodegradable ABA-type block copolymer of the formula: PLGA-PEG-PLGA where PLGA is a hydrophobic poly(lactide-co-glycolide) copolymer that comprises the A-blocks and PEG is a hydrophilic polyethylene glycol polymer that comprises the B-block, said block copolymer having an average molecular weight of between about 3100 and 4500. (2) maintaining said composition as a liquid at a temperature below the gelation temperature of said block copolymer; and (3) administering said composition as a liquid to said warm blooded animal with the subsequent formation of a gel as the temperature of said composition is raised by the body temperature of said animal to be above the gelation temperature of said block polymer.
Claim 15
Dependent Claim
23 words
A method according to claim 12 wherein said administration is by parenteral, ocular, topical, transdermal, vaginal, transurethral, rectal, nasal, oral, or aural means.
Claim 16
Dependent Claim
22 words
A method according to claim 13 wherein the block copolymer content of said composition is between about 3 and 50% by weight.
Claim 17
Dependent Claim
41 words
A method according to claim 14 wherein, in the block copolymer of said composition, the PLGA A-blocks comprises about 51 to 83% by weight of said copolymer and the PEG B-block comprises about 17 to 49% by weight of said copolymer.
Claim 18
Dependent Claim
36 words
A method according to claim 15 wherein, in the block copolymer of said composition, the PLGA copolymer A-block comprises between about 65 to 85 mole percent lactide and between about 15 and 35 mole percent glycolide.
Claim 19
Dependent Claim
43 words
A method according to claim 16 wherein, in the block copolymer of said composition, the PLGA A-blocks comprises between about 65 to 78% by weight of said copolymer and the PEG B-Block comprises between about 22 to 35% by weight of said copolymer.
Claim 20
Dependent Claim
24 words
A method according to claim 15 wherein the block copolymer of said composition has an average molecular weight of between about 3500 and 4100.
Claim 21
Dependent Claim
15 words
A method according to claim 15 wherein said drug administered is a polypeptide or protein.
Claim 22
Dependent Claim
111 words
A method according to claim 19 wherein said polypeptide or protein is a member selected from the group consisting of oxytocin, vasopressin, adrenocorticotropic hormone, epidermal growth factor, platelet-derived growth factor (PDGF), prolactin, luliberin or luteinizing hormone releasing hormone, growth hormone, growth hormone releasing factor, insulin, somatostatin, glucagon, interleukin-2 (IL-2), interferon-α, interferon-β, interferon-γ, gastrin, tetragastrin, pentagastrin, urogastrone, secretin, calcitonin, enkephalins, endorphins, angiotensins, thyrotropin releasing hormone (TRH), tumor necrosis factor (TNF), nerve growth factor (NGF), granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), macrophage-colony stimulating factor (M-CSF), heparinase, bone morphogenic protein (BMP), hANP, glucagon-like peptide (GLP-1), interleukin-11 (IL-11), renin, bradykinin, bacitracins, polymyxins, colistins, tyrocidine, gramicidins, cyclosporins, enzymes, cytokines, monoclonal antibodies and vaccines.
Claim 23
Dependent Claim
21 words
A method according to claim 19 wherein the drug content of said composition is between about 0.01 and 20% by weight.
Claim 24
Dependent Claim
17 words
A method according to claim 15 wherein said drug administered is an anti-cancer or anti-cell proliferation agent.
Claim 25
Dependent Claim
32 words
A method according to claim 22 wherein said drug is an anti-cancer agent selected from the group consisting of mitomycin, bleomycin, BCNU, carboplatin, doxorubicin, daunorubicin, methotrexate, paclitaxel, taxotere, actinomycin D and camptothecin.
Claim 26
Dependent Claim
21 words
A method according to claim 22 wherein the drug content of said composition is between about 0.01 and 20% by weight.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2002-12-20 | 2003-06-21 | 2003-12-21 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2006-12-20 | 2007-06-21 | 2007-12-21 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2010-12-20 | 2011-06-21 | 2011-12-21 | $7700.00 | Window Closed / Lapsed |