Analgesic preparation with nanocarriers and use thereof
Inventors
Fleige, Emanuel • MORÉ, Sam • Unbehauen, Michael • Haag, Rainer • Stein, Christoph • Machelska-Stein, Halina • Paulus, Florian
Assignees
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Publication Number
US-11253599-B2
Publication Date
2022-02-22
Expiration Date
Abstract
The invention relates to the field of analgesics. According to the invention, a kit or composition, particularly a pharmaceutical composition or a pharmaceutical kit, is provided, comprising a nanocarrier which is a hyperbranched polymer, such as a dendritic polymer or dendrimer, preferably having a molecular weight of 1,000-100,000 g/mol, and an analgesic which, when administered without nanocarrier, has both peripheral and central analgesic effect, preferably an opioid such as nalbuphine. According to the invention, the analgesic in this composition mainly or exclusively has a peripheral effect and thus reduces side effects triggered by the activation of central or intestinal opioid receptors. It is used for the treatment of peripheral pain and/or inflammation. The invention also relates to particularly suitable nanocarriers.
Core Innovation
The invention provides a pharmaceutical composition for selectively delivering an active agent to peripheral tissue of a patient. The composition includes a hydrophilic nanocarrier comprising a hyperbranched polymer selected from dendritic polymers and dendrimers forming a dendritic core, and an active agent that, when administered without the nanocarrier, has both peripheral action and action in the central nervous system. The composition is configured so it acts through the peripheral action of the active agent.
The invention reduces the effect of the active agent in the central nervous system in comparison to a corresponding composition without the nanocarrier. The hyperbranched polymer has a degree of branching of at least 25%, and the dendritic core comprises polyglycerol and has a molecular weight of 5-10 kDa. The composition includes no targeted release of the active agent via tissue-specific antigen or receptors.
The invention further includes use of the pharmaceutical composition for treating a disease or disease symptom comprising acute or chronic pain or inflammation in a subject in need thereof. In this context, the active ingredient is an analgesic, and the transfer of analgesics through the blood-brain-barrier is blocked by the nanocarriers. The analgesic is based on an opioid that has both peripheral action and central nervous system action when administered without the nanocarrier.
Claims Coverage
Two independent claims are identified, each covering a method that relies on a hydrophilic hyperbranched dendritic nanocarrier carrying an active agent that normally acts both peripherally and in the central nervous system. The inventive features focus on peripheral-action selectivity, reduced central nervous system effect, structural constraints on the hyperbranched polymer and polyglycerol dendritic core, and in one claim blocking of blood-brain-barrier transfer.
Selectively delivering an active agent to peripheral tissue using a hydrophilic hyperbranched dendritic nanocarrier
A pharmaceutical composition comprising a hydrophilic nanocarrier comprising a hyperbranched polymer selected from dendritic polymers and dendrimers forming a dendritic core, and the active agent which when administered without the nanocarrier has both peripheral action and action in the central nervous system; wherein the pharmaceutical composition acts through the peripheral action of the active agent.
Reducing central nervous system effect while avoiding targeted antigen or receptor release
The effect of the active agent is reduced in the central nervous system in comparison to a corresponding composition without nanocarrier; and there is no targeted release of the active agent via tissue-specific antigen or receptors.
Hyperbranched polymer degree of branching and polyglycerol dendritic core size
The hyperbranched polymer has a degree of branching of at least 25%; the dendritic core comprises polyglycerol and has a molecular weight of 5-10 kDa.
Treating acute or chronic pain or inflammation by blocking blood-brain-barrier transfer
A pharmaceutical composition comprising a hydrophilic nanocarrier comprising a hyperbranched polymer selected from dendritic polymers and dendrimers forming a dendritic core, and an active agent which when administered without nanocarrier has both peripheral action and action in the central nervous system; wherein the pharmaceutical composition acts through the peripheral action of the active agent; wherein the effect of the active agent is reduced in the central nervous system in comparison to a corresponding composition without nanocarrier; and wherein the transfer of analgesics through the blood-brain-barrier is blocked by the nanocarriers.
Analgesic use with specified hyperbranched polymer properties
The hyperbranched polymer has a degree of branching of at least 25%; the dendritic core comprises polyglycerol and has a molecular weight of 5-10 kDa; the active ingredient is an analgesic.
Across both independent claims, the inventive concept is selective peripheral action of an active agent delivered by a hydrophilic hyperbranched dendritic nanocarrier, combined with reduced central nervous system effect and, in the treatment claim, blocking transfer across the blood-brain-barrier, while meeting defined branching and polyglycerol dendritic core size constraints.
Stated Advantages
Reduced effect of the active agent in the central nervous system compared with a corresponding composition without nanocarrier.
Peripheral action of the active agent is maintained.
Reduced transfer of analgesics through the blood-brain-barrier by blocking blood-brain-barrier transfer.
Reduced adverse effects caused by activating opioid receptors in the central nervous system compared with a corresponding composition without a nanocarrier, including addiction, respiratory depression, nausea, sedation, constipation, neonatal depression, hallucinations, and depression-like symptoms.
Documented Applications
Treating a disease or disease symptom comprising acute or chronic pain or inflammation in a subject in need thereof.
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