Controlled release method for a pharmaceutical composition composed of chelating complex micelles
Inventors
Chen, Chia-Hung • Wang, Chau-Hui • Lin, John-Son • Chiu, Tieh-Hsiung • Chen, Jing-Yi • Liao, Pi-Hung • Su, Chia-Chi • Liao, Wei-Chuan
Assignees
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Publication Number
US-9597406-B2
Publication Date
2017-03-21
Expiration Date
Abstract
This invention provides the controlled-release method for a pharmaceutical composition comprising of metals in the drug carrier. The specific chelator is used to trigger the release of active pharmaceutical ingredients from chelating complex micelles. The drug release rate and half-life can also be controlled by manipulating the dosing sequence and the concentration of metal and specific chelator.
Core Innovation
The invention relates to a controlled-release method for manipulating drug release using chelating complex micelles formed via coordinate bonding. The chelating complex micelles comprise at least a drug molecule that donates lone pairs of electrons and a polymer ligand that donates an electron pair to a metal core, wherein the metal core is Fe, and a metal chelator that corresponds to the metal core is administered to manipulate the drug release.
The method further specifies a timing relationship between administering the chelating complex micelles and administering the metal chelator. In particular embodiments, the metal chelator is administered 10 minutes to 12 hours following administering the chelating complex micelles, or 10 minutes to 12 hours prior to administration of the chelating complex micelles, and deferoxamine is administered in a post-administration window of 0.1 to 24 hours.
In additional embodiments, the invention provides ways to start, stop, or prolong the drug release process by further administering a metal that is the same as the metal core of the chelating complex micelles. The metal is administered following administration of the metal chelator to stop or prolong the drug release process, providing controlled, tunable release behavior through the dosing sequence.
Claims Coverage
The provided excerpts contain five independent claims, each describing a controlled-release method based on chelating complex micelles formed via coordinate bonding and release manipulation by a corresponding metal chelator, with different timing constraints and, in one case, an additional same-metal administration step.
Coordinate-bonded Fe chelating complex micelles with corresponding chelator dosing
Administration of chelating complex micelles formed via coordinate bonding that comprise at least a drug molecule that donates lone pairs of electrons, a polymer ligand that donates an electron pair to a metal core which is Fe, and administration of a metal chelator that corresponds to the metal core.
Fe chelating complex micelles with deferoxamine post-administration timing window
Administration of chelating complex micelles containing ferrous ion and embedded drug, wherein the drug is amifostine, vancomycin, ciprofloxacin, doxorubicin, or epirubicin, followed by administration of deferoxamine 0.1 to 24 hours post administration of the chelating complex micelles.
Pre-administration corresponding chelator for coordinate-bonded Fe chelating complex micelles
Administration of chelating complex micelles formed via coordinate bonding comprising at least a drug molecule that donates lone pairs of electrons and a polymer ligand that donates an electron pair to a metal core which is Fe, and further administering a metal chelator that corresponds to the metal core, wherein the metal chelator is administered 10 minutes to 12 hours prior to administration of the chelating complex micelles.
Pre-administration corresponding same-metal to Fe chelating complex micelles
Administration of chelating complex micelles formed via coordinate bonding comprising at least a drug molecule that donates lone pairs of electrons and a polymer ligand that donates an electron pair to a metal core which is Fe, and further administering a metal that is the same as the metal core of the chelating complex micelles wherein the metal is administered 5 minutes to 180 minutes prior to administration of the chelating complex micelles.
Chelator followed by same-metal to stop or prolong drug release process
Administration of chelating complex micelles formed via coordinate bonding comprising at least a drug molecule that donates lone pairs of electrons and a polymer ligand that donates an electron pair to a metal core which is Fe, and further administering a metal chelator that corresponds to the metal core of the chelating complex micelles and a metal that is the same as the metal core of the chelating complex micelles, wherein the metal chelator is administered 10 mins to 12 hours post administration of the chelating complex micelles and the metal is administered following the administration of the metal chelator to stop or prolong the drug release process.
Across the independent claims, the inventive approach centers on coordinate-bonded chelating complex micelles with an Fe metal core and electron-pair/lone-pair donor components, followed by administration of a corresponding metal chelator, or in additional embodiments a same-metal step, with specified pre- or post-administration time windows to manipulate drug release, including stopping or prolonging the drug release process.
Stated Advantages
Tunable release rate/half-life via dosing sequence and chelator concentration.
Reduced toxicity/safety improvements from chelator use and metal cycling.
Documented Applications
The document describes experimentally supported controlled-release behavior using specific example drug cargos embedded in chelating complex micelles and release manipulation by corresponding metal chelators.
The document describes an approach consistent with pulsed or modulated drug release behavior based on chelator timing.
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