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Publication Number
US-10238646-B2
Publication Date
2019-03-26
Expiration Date
Abstract
The present invention relates to methods for treating pruritus with anti-pruritic compositions.
Core Innovation
A method of treating prurigo nodularis is provided, wherein an anti-pruritus agent is orally administered to a human subject in need thereof, and the anti-pruritus agent is nalbuphine or a pharmaceutically acceptable salt or ester. The disclosure emphasizes oral extended-release or sustained-release nalbuphine dosage forms designed to achieve target pharmacokinetic exposure and a prolonged anti-pruritic effect.
The document describes sustained-release oral formulations, including multilayer tablet architectures and bi-layer (ER/IR) tablets, together with release profile and plateau region concepts. A mechanism for prolonged effect is also discussed using enterohepatic recirculation of nalbuphine conjugates, including glucuronide conjugates, and reference to UDP-glucuronyl transferase is included.
Pharmacokinetic targets and regimen selection are described in terms of Cmax, AUC(0-τ), AUCtau, and Cmin, with clinical trial therapeutic-effect criteria and pharmacokinetic evaluation versus immediate-release oral solution control. Formulation details are described for sustained-release delivery systems using hydrophilic polymers and gums such as xanthan and locust bean gum, along with diluents such as mannitol and optional cationic cross-linkers such as calcium sulfate, and a Phase I pharmacokinetic comparison is reported for sustained-release and immediate-release oral forms.
Claims Coverage
The independent claim covers an oral nalbuphine-based method for treating prurigo nodularis. Across the independent claim and its refinements, the inventive features include extended-release oral dosage form characteristics, pharmacokinetic exposure constraints, specific dosing and titration regimens, and a specified nalbuphine hydrochloride formulation with defined excipients.
Oral nalbuphine treatment of prurigo nodularis
A method of treating prurigo nodularis comprising orally administering an effective amount of an anti-pruritus agent to a human subject in need of such treatment, wherein the anti-pruritus agent is nalbuphine or a pharmaceutically acceptable salt or ester thereof.
Extended-release oral dosing with mean Cmax ranges
The method is practiced using an extended-release oral dosage form of an anti-pruritus agent such that administration results in a subject having a mean Cmax within specified ranges.
Exposure targeting by mean AUCtau range
The method further specifies that administration results in the subject having a mean AUCtau from about 100 ng·hr/mL to about 300 ng·hr/mL.
Specific twice-daily dosing regimen
The method includes carrying out by administering an anti-pruritus agent at a dose of about 180 mg twice daily.
Initial dose and titration to an effective dose
The method is carried out by starting with an initial oral dose of about 15 mg to about 30 mg twice daily and then titrating to an effective dose.
Nalbuphine hydrochloride formulation with defined excipients
The method includes administering the anti-pruritus agent in a formulation comprising nalbuphine hydrochloride, mannitol, hydroxypropyl cellulose, locust bean gum, xanthan gum, calcium sulfate dihydrate and magnesium stearate.
The claim set centers on orally treating prurigo nodularis using nalbuphine or a pharmaceutically acceptable salt or ester and refines this by requiring or targeting extended-release or sustained-release oral exposure characteristics, and by specifying example dosing and titration regimens and a defined nalbuphine hydrochloride-containing sustained-release formulation with listed excipients.
Stated Advantages
Prolonged anti-pruritic effect, including more than about 8–12 hours and in some cases up to 24 hours.
Oral extended/sustained-release dosing designed to achieve target pharmacokinetic exposure (mean Cmax and AUC ranges).
Multilayer tablet designs are provided for sustained-release delivery with a prolonged effect.
Documented Applications
Treatment of prurigo nodularis in a human subject by orally administering nalbuphine or a pharmaceutically acceptable salt or ester.
Anti-pruritus treatment discussed across pruritic conditions including prurigo nodularis and uremic pruritus/renal impairment.
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