Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11213496-B2
Publication Date
2022-01-04
Expiration Date
Abstract
The disclosure provides a method for systemic delivery of a therapeutically effective amount of epinephrine to a subject comprising orally administering dipivefrin or a dipivefrin salt to the subject. The disclosure also includes a method of treatment of a disease amenable to treatment by in vivo delivery of systemic epinephrine comprising administering dipivefrin or a dipivefrin salt to a subject in need of in vivo delivery of systemic epinephrine. The disease can be a respiratory disorder, anaphylaxis, cancer, or a microbial infection. The disclosure also includes dipivefrin or dipivefrin HCl orally dissolving tablets.
Core Innovation
The disclosure describes systemic delivery of epinephrine by orally administering dipivefrin or a pharmaceutically acceptable salt to a subject, where the epinephrine is produced by in vivo biotransformation after oral administration. The disclosure positions dipivefrin as an epinephrine prodrug that overcomes barriers to oral epinephrine delivery and provides systemic epinephrine exposure.
The background addresses barriers to oral epinephrine delivery, including monamine oxidase and catechol-O-methyltransferase activity in the GI/liver, which are described as preventing effective oral delivery of epinephrine. The document includes pharmacokinetic comparisons and tolerability observations supporting oral systemic epinephrine delivery.
The disclosure provides documented preclinical and efficacy support for treating epinephrine-responsive conditions using oral dipivefrin formulations, including influenza and MRSA microbial infections. In the anaphylaxis treatment context, the disclosure describes orally dissolving and orally disintegrating tablet formulations that produce epinephrine exposure patterns comparable to standard IM epinephrine.
Claims Coverage
The provided material includes four independent claims, each directed to oral administration of dipivefrin or L-dipivefrin hydrochloride for systemic epinephrine delivery or for treating an epinephrine-responsive condition, with additional claim limitations focused on anaphylaxis and epinephrine pharmacokinetic performance.
Orally administer dipivefrin for systemic delivery of epinephrine
A method for systemic delivery of a therapeutically effective amount of epinephrine to a subject, comprising orally administering dipivefrin or a pharmaceutically acceptable salt thereof to the subject, where the subject is a human or dog.
Orally administer dipivefrin oral dosage form for epinephrine-responsive condition treatment
A method for treating a condition responsive to epinephrine in a subject comprising administering, as an oral dosage form, a therapeutically effective amount of dipivefrin or a pharmaceutically acceptable salt thereof to the subject, where the subject is a human or dog.
Orally administer L-dipivefrin hydrochloride with epinephrine PK constraints for anaphylaxis
A method of treating anaphylaxis comprising orally administering not more than 63.5 mg L-dipivefrin hydrochloride to provide an epinephrine T_max of less than 45 minutes and an epinephrine plasma C_max of 0.1 to 50 ng/mL in the subject, where the subject is a human or dog.
Administer L-dipivefrin hydrochloride oral dosage form for anaphylaxis
A method for treating anaphylaxis comprising administering, as an oral dosage form, a therapeutically effective amount of L-dipivefrin hydrochloride to the subject, where the subject is a human or dog.
Across the independent claims, the core coverage is oral administration of dipivefrin or L-dipivefrin hydrochloride to achieve systemic epinephrine for epinephrine-responsive treatment, with anaphylaxis embodiments specifically using L-dipivefrin hydrochloride. One independent anaphylaxis claim includes quantitative epinephrine pharmacokinetic constraints, while another focuses on administering a therapeutically effective oral dosage form of L-dipivefrin hydrochloride.
Stated Advantages
Oral dipivefrin can safely and rapidly provide systemic epinephrine via in vivo biotransformation.
Preclinical results indicate improved tolerability of oral dipivefrin compared with IM epinephrine, including lower acute toxicity markers.
Oral dipivefrin formulations can inhibit melanoma growth and extend survival in mice.
Oral dipivefrin reduces influenza-related illness and weight loss.
Oral dipivefrin shows antibacterial activity in an MRSA peritonitis-sepsis model.
Orally dissolving tablets can produce epinephrine exposure patterns comparable to standard IM epinephrine for anaphylaxis treatment.
Documented Applications
Treatment of anaphylaxis in a subject (human or dog) using orally administered dipivefrin or L-dipivefrin hydrochloride oral dosage forms, including orally dissolving or orally disintegrating tablet formulations.
Treatment of conditions responsive to epinephrine, including use cases connected to cancer and microbial infections.
Anticancer activity including inhibition of B16-F10 melanoma growth and extended survival in mice.
Treatment of viral infection including influenza infection, described with reduced influenza-related illness and weight loss.
Treatment of microbial infection including MRSA, with antibacterial activity described in an MRSA peritonitis-sepsis model.
Interested in licensing this patent?