US6589548B1
Expired / Lapsed
US
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Controlled drug delivery system using the conjugation of drug to biodegradable polyester
Assignee: Mogam Biotechnology Research Institute
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Filing: 1999-05-14
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Granted: 2003-07-08
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Expires: 2019-05-14
Abstract
Abstract The present invention relates to a molecular sustained controlled release system constructed by the conjugation of molecules to be released with biodegradable polyester polymer via covalent bond and method for preparation thereof. In accordance with the present invention, the system may be formulated into microspheres, nanoparticles, or films. The molecular release rate from the above system can be regulated to be proportional to the chemical degradation rate of the biodegradable polyester polymers, resulting in near zero order kinetics profile of release without showing a burst effect, Moreover, a high loading efficiency of hydrophilic drugs can be achieved.
Inventors
- 👤 Jong Eun Oh
- 👤 Keon Hyoung Lee
- 👤 Tae Gwan Park
- 👤 Yoon Sung Nam
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 10:13
CPC Classifications
B; B82; B82Y; B82Y5/00; A; A61; A61K; A61K9/00; A61K9/48; A61K47/00; A61K47/50; A61K47/69; A61K47/6921; A61K47/6927; A61K47/6929; A61K47/6931; A61K47/6935; A61K47/6937
Claims Analysis
Total Claims: 6
Claim 1
Independent Claim
120 words
A method for manufacturing a sustained controlled release system wherein a drug molecule to be released is directly conjugated to a biodegradable polyester polymer via a covalent bond, comprising the steps of: 1) forming an activated polymer solution by activating a biodegradable polyester polymer by mixing with coupling agents selected from the group consisting of bis(2-oxo-3-oxazolydinyl)phosphonic chloride (BOP—Cl), bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBroP), benzotriazol-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBOP), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU), dicyclohexyl carbodiimide, disuccinimidyl carbonate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimde (DIPC), 2-(1H-benzotrioxazolyl)-1,1,3,3-tetramethyl-uronium tetrafluoroborate (TBTU), 2-(5-norboren)-2,3-dicarboxyimido)-1,1,3,3-tetramethyluronium tetrafluoroborate (TNTU), para-nitrophenylchloroformate, and O-(N-succinimidyl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TSTU), bases, and optionally additives; 2) directly conjugating a drug molecule with said polymer by adding said drug molecule to the activated polymer solution of step 1, and 3) purifying the polymer-molecule conjugate resulting from step 2.
Claim 2
Independent Claim
120 words
A method for manufacturing a sustained controlled release system wherein a drug molecule to be released is directly conjugated to a biodegradable polyester polymer via a covalent bond, comprising the steps of: 1) forming an activated polymer solution by activating a biodegradable polyester polymer by mixing with coupling agents selected from the group consisting of bis(2-oxo-3-oxazolydinyl)phosphonic chloride (BOP—Cl), bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBroP), benzotriazol-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBOP), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU), dicyclohexyl carbodiimide, disuccinimidyl carbonate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimde (DIPC), 2-(1H-benzotrioxazolyl)-1,1,3,3-tetramethyl-uronium tetrafluoroborate (TBTU), 2-(5-norboren)-2,3-dicarboxyimido)-1,1,3,3-tetramethyluronium tetrafluoroborate (TNTU), para-nitrophenylchloroformate, and O-(N-succinimidyl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TSTU), bases, and optionally additives; 2) directly conjugating a drug molecule with said polymer by adding said drug molecule to the activated polymer solution of step 1, and 3) purifying the polymer-molecule conjugate resulting from step 2.
Claim 3
Dependent Claim
28 words
The method of claim 1 , wherein the base of step 1 is selected from the group consisting of triethylamine, N-methylmorpholine, pyridine, 1,8-diazabicyclo[5,4,0]-undec-7-ene, N,N-dimethyl aminopyridine, and N,N-diisopropyl ethylamine.
Claim 4
Dependent Claim
23 words
The method of claim 1 , wherein the additives of step 1 are selected from the group consisting of hydroxybenzotriazole, pentafluorophenol and N-hydroxy-5-norboren-endo-2,3-dicarboximide.
Claim 5
Independent Claim
131 words
A method of preparing a sustained controlled release system wherein a drug molecule to be released is directly conjugated to a biodegradable polyester polymer via a covalent bond, comprising the steps of: 1) forming an activated drug molecule solution by activating a drug molecule by mixing with coupling agents selected from the group consisting of bis(2-oxo-3-oxazolydinyl)phosphonic chloride (BOP—Cl), bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBroP), benzotriazol-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBOP), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU), dicyclohexyl carbodiimide, disuccinimidyl carbonate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC), bis(2-oxo-3-oxazolydinyl)phosphin, diisopropyl carbodiimide (DIPC), 2-(1H-benzotrioxazolyl)-1,1,3,3-tetramethyl-uronium tetrafluoroborate (TBTU), 2-(5-norboren)-2,3-dicarboxyimido)-1,1,3,3-tetramethyluronium tetrafluoroborate (TNTU), para-nitrophenylchloroformate, and O-(N-succinimidyl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TSTU), bases, and optionally, additives; 2) directly conjugating the activated drug molecules resulting from step 1) with a biodegradable polyester polymer by adding a polymer to said activated drug molecule solution of step 1 and 3) purifying the polymer-molecule conjugate resulting from step 2.
Claim 6
Independent Claim
131 words
A method of preparing a sustained controlled release system wherein a drug molecule to be released is directly conjugated to a biodegradable polyester polymer via a covalent bond, comprising the steps of: 1) forming an activated drug molecule solution by activating a drug molecule by mixing with coupling agents selected from the group consisting of bis(2-oxo-3-oxazolydinyl)phosphonic chloride (BOP—Cl), bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBroP), benzotriazol-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBOP), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU), dicyclohexyl carbodiimide, disuccinimidyl carbonate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC), bis(2-oxo-3-oxazolydinyl)phosphin, diisopropyl carbodiimide (DIPC), 2-(1H-benzotrioxazolyl)-1,1,3,3-tetramethyl-uronium tetrafluoroborate (TBTU), 2-(5-norboren)-2,3-dicarboxyimido)-1,1,3,3-tetramethyluronium tetrafluoroborate (TNTU), para-nitrophenylchloroformate, and O-(N-succinimidyl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TSTU), bases, and optionally, additives; 2) directly conjugating the activated drug molecules resulting from step 1) with a biodegradable polyester polymer by adding a polymer to said activated drug molecule solution of step 1 and 3) purifying the polymer-molecule conjugate resulting from step 2.
References Cited (Backward Citations)
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