Methods of treating and preventing gastrointestinal motility disorders using aminosterols
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Publication Number
US-10975116-B2
Publication Date
2021-04-13
Expiration Date
Abstract
This invention relates to methods of stimulating the activity of the human and animal enteric nervous system. The method comprises orally administering an aminoserol, such as squalamine, a naturally occurring aminosterol isolated from Squalus acanthias, or derivatives thereof, to a subject in need.
Core Innovation
The invention provides an oral method of treating a gastrointestinal motility disorder in a subject in need thereof by orally administering a composition comprising at least one aminosterol, or a pharmaceutically acceptable salt or derivative thereof, in an amount sufficient to produce a beneficial effect. The disorders are selected from chronic idiopathic constipation, Irritable bowel syndrome, Opioid-induced constipation, and Inflammatory Bowel Disease.
The invention describes an Aminosterol-Induced GI Response characterized as time-sequenced changes in GI function, including a secretory/watery phase and later multi-day quieting or motility changes. The response is linked to activation of enterocyte/enteric neuron-related pathways and to effects involving VIP-related fluid and relaxation effects.
It is further described as involving direct stimulation of colonic intrinsic primary afferent neurons (IPANs). The description also includes aminosterol formulations and derivatives, including pharmaceutically acceptable salts and derivatives, and concepts for improving biodistribution and metabolic stability using medicinal-chemistry modifications and charge-related features.
Claims Coverage
The independent claim is directed to an orally administered aminosterol composition for treating selected gastrointestinal motility disorders. The claim coverage centers on a defined set of aminosterols, or pharmaceutically acceptable salt/derivatives, and selects the disorder group, with dependent coverage adding quantitative exposure and dosing features and specifying biological targets and response-linked effects.
Oral aminosterol treatment of selected GI motility disorders
A method of treating a gastrointestinal motility disorder in a subject in need thereof, comprising orally administering to the subject a composition comprising a pharmaceutically acceptable grade of at least one aminosterol, or a pharmaceutically acceptable salt or derivative thereof, in an amount sufficient to produce a beneficial effect, wherein the disorder or condition is selected from chronic idiopathic constipation, Irritable bowel syndrome, Opioid-induced constipation, and Inflammatory Bowel Disease.
Effective daily dosing range for oral aminosterol
The method includes using an effective daily dosing amount of about 0.1 to about 20 mg/kg body weight.
Low blood-stream exposure within a time window
The method includes detecting that, after oral administration, less than about 10 ng/mL of the administered aminosterol is present in the blood stream of the subject within about 1 to about 12 hours.
Increased colonic motility after aminosterol administration
After administering at least one aminosterol to a subject, colonic motility is increased.
Stimulation of intrinsic primary afferent neurons (IPANs) in the colon
The effective amount produces a beneficial effect to stimulate intrinsic primary afferent neurons (IPANs) in the colon of the subject.
Sequential administration of an additional active agent
In a dependent method, an additional active agent is administered separately and sequentially.
Overall, the claim set covers orally administering a pharmaceutically acceptable grade aminosterol, or salt/derivative, to treat a defined set of GI motility disorders, with dependent features specifying an effective daily dosing range, low blood-stream exposure within a defined time window, increased colonic motility, stimulation of colonic intrinsic primary afferent neurons (IPANs), and possible sequential administration of an additional active agent.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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