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Publication Number
US-11173209-B2
Publication Date
2021-11-16
Expiration Date
Abstract
The present invention provides compositions and methods and for increasing the bioavailability of therapeutic agents in a subject. The compositions include at least one alkyl glycoside and at least one therapeutic agent, wherein the alkylglycoside has an alkyl chain length from about 10 to about 16 carbon atoms.
Core Innovation
The invention relates to a method of treating a condition ameliorated by epinephrine in a subject. The method comprises intranasally administering to the subject in need thereof an aqueous composition consisting of epinephrine, an alkylglycoside, and inactive excipients, formulated for intranasal delivery.
The alkylglycoside includes an alkyl chain including between 8 to 20 carbons and is present at a concentration between about 0.001% and 10.0% (w/v). The disclosed alkylglycoside options include undecyl maltoside, dodecyl maltoside, tridecyl maltoside, tetradecyl maltoside, sucrose mono-dodecanoate, sucrose mono-tridecanoate, and sucrose mono-tetradecanoate. Additional formulation parameters described include benzalkonium chloride, EDTA, or a combination thereof, and a composition pH range of about 2.0 to 5.0.
The composition provides an epinephrine Cmax in the subject that is about 2-fold or greater compared to administration without alkylglycoside. The document also describes dose-dependent oral/solid and mucosal delivery compositions, enteric or pH-soluble polymer coatings, and surfactants comprising alkyl glycosides and saccharide alkyl esters for stabilizing drugs, increasing bioavailability, and reducing bioavailability variance.
For mucosal administration, the document reports intranasal, ocular, buccal/oral cavity, and CSF routes, including examples of improved pharmacokinetics and antiviral/antibacterial activity. Non-irritancy of the nasal mucosa is also discussed for repeated nasal dosing, and buccal dosage forms are described as fast-dispersing and lyophilized with attenuation of first-pass effects.
Claims Coverage
The document provides one independent claim. It focuses on intranasal administration of an aqueous epinephrine composition containing a defined alkylglycoside and inactive excipients, with numeric constraints on alkyl chain length and alkylglycoside concentration, and dependent constraints including specific alkylglycoside selections, concentration narrowing, Cmax comparison, pH, and excipient selection.
Intranasal epinephrine-alkylglycoside aqueous composition for treating epinephrine-ameliorated condition
A method of treating a condition ameliorated by epinephrine by intranasally administering an aqueous intranasal composition consisting of epinephrine, an alkylglycoside, and inactive excipients formulated for intranasal delivery.
Defined alkylglycoside alkyl chain length and concentration in aqueous intranasal formulation
The alkylglycoside has an alkyl chain including between 8 to 20 carbons and the alkylglycoside concentration is between about 0.001% and 10.0% (w/v).
Select alkylglycoside candidates within the alkylglycoside definition
The alkylglycoside is selected from undecyl maltoside, dodecyl maltoside, tridecyl maltoside, tetradecyl maltoside, sucrose mono-dodecanoate, sucrose mono-tridecanoate, and sucrose mono-tetradecanoate.
Constrain alkylglycoside concentration to a narrower w/v range
The alkylglycoside concentration is between about 0.05% and 0.5% (w/v).
Achieve epinephrine Cmax at least about 2-fold versus without alkylglycoside
The composition provides an epinephrine Cmax in the subject that is about 2-fold or greater compared to administration without alkylglycoside.
Formulate the composition within a defined pH range
The composition has a pH of about 2.0 to 5.0.
Use specified inactive excipients
The inactive excipients are chosen from benzalkonium chloride, EDTA, or a combination of both.
Claim coverage centers on a single independent method claim for intranasal delivery of an aqueous epinephrine composition comprising an alkylglycoside with an 8 to 20 carbon alkyl chain and a defined 0.001% to 10.0% (w/v) concentration, with dependent claims further narrowing to specific alkylglycoside selections, a 0.05% to 0.5% concentration range, a Cmax performance comparison, a pH range, and specific inactive excipients.
Stated Advantages
Provides an epinephrine Cmax in the subject that is about 2-fold or greater compared to administration without alkylglycoside.
Increases bioavailability while reducing bioavailability variance.
Increases pharmacokinetic performance, including higher Cmax and/or faster Tmax.
Reduces first-pass metabolism by enabling systemic absorption via routes such as intranasal, ocular, buccal/oral cavity, and CSF.
Provides antiviral/antibacterial activity as reported in the document.
Non-irritant nasal mucosa findings with repeated nasal dosing.
Documented Applications
Intranasal treatment of a condition ameliorated by epinephrine in a subject using an aqueous intranasal composition containing epinephrine and an alkylglycoside.
Intranasal, ocular, buccal/oral cavity, and CSF delivery routes for systemic absorption of drugs and peptides as described in the document.
Buccal delivery using fast-dispersing and lyophilized buccal dosage forms with alkylsaccharide-containing porous networks, with reported attenuation of first-pass effect.
Examples of drug-specific applications explicitly mentioned include insulin, calcitonin (MIACALCIN), exenatide/exendin-4, glucagon, antisense oligonucleotide in primates with tetradecyl-beta-D-maltoside, sumatriptan nasal with dodecyl maltoside, and additional named drug classes including opioids/triptans and protease/peptidase inhibitors.
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