Local administration-type pharmaceutical for improving dysphagia
Inventors
Kitamura, Koichi • Kondo, Maho • Shimoyama, Kiyoshi • Kurosawa, Toru
Assignees
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Publication Number
US-10052281-B2
Publication Date
2018-08-21
Expiration Date
Abstract
A dysphagia improving composition characterized in that a substance having an inhibitory action on an angiotensin converting enzyme, which is a degrading enzyme of substance P, is administered locally in a dosage not influencing blood pressure, and a pharmaceutical for improving dysphagia containing the composition.
Core Innovation
The invention relates to a dysphagia improving local administration pharmaceutical for treating a subject suffering from dysphagia or aspiration pneumonia. The drug comprises an angiotensin-converting enzyme (ACE) inhibitor having lisinopril as an active ingredient, and is administered locally to at least one site selected from an intraoral site, a pharyngolaryngeal site, and the respiratory tract. The local administration improves swallowing reflex and treats dysphagia without lowering blood pressure.
The underlying mechanism described is inhibition of the degradation of substance P at pharyngeal tissues by using an ACE inhibitor. In the disclosed dysphagia model, local administration of an ACE inhibitor increases swallowing-related responses in a dose-dependent manner. The improvement is suppressed by a substance P receptor antagonist (FK888), and FK888-induced swallowing impairment is prevented by prior administration of the ACE inhibitor.
The disclosure further states that local administration is superior to oral administration for early and sustained improvement of dysphagia. Comparative data are also described indicating that suppression of an angiotensin I-induced vasopressor response is not affected by the locally used low-dose/non-systemic formulations. This supports the stated advantage that the dysphagia improvement occurs without blood pressure influence.
Claims Coverage
The independent claim covers a local administration method for treating dysphagia and aspiration pneumonia using lisinopril as an ACE inhibitor, with a specific dosage range and a requirement of treating dysphagia without lowering blood pressure. The claim set includes four dependent inventive refinements that further specify formulation and administration mode, and add a comparative performance timing feature relative to oral administration.
Local administration of lisinopril to treat dysphagia or aspiration pneumonia without lowering blood pressure
Administering to the subject a dysphagia improving drug comprising lisinopril at a dosage ranging from 1.2ng/kg to 12 micro g/kg, wherein the drug is administered locally to at least one site selected from an intraoral site, a pharyngolaryngeal site, and the respiratory tract, and wherein the dosage treats dysphagia without lowering blood pressure.
Faster dysphagia treatment than oral administration
The method wherein the drug treats dysphagia within a shorter period compared to that observed with oral administration of the drug.
Spray, nebulizer, or direct application to pharyngeal mucosa
The drug is administered by spray, nebulizer or direct application to pharyngeal mucosa.
Liquid form administration
The drug is administered in a liquid form.
Fast-acting drug
The drug is fast-acting.
Overall, the claim coverage centers on locally administering an ACE inhibitor (lisinopril) in a specified dosage range to intraoral, pharyngolaryngeal, and/or respiratory tract sites to treat dysphagia without lowering blood pressure. Dependent claims further narrow the disclosure to liquid form, spray/nebulizer/direct application to pharyngeal mucosa, a fast-acting effect, and faster dysphagia treatment than oral administration.
Stated Advantages
Treats dysphagia without lowering blood pressure.
Improves swallowing reflex.
Suppresses swallowing impairment associated with substance P receptor signaling when used such that FK888 suppression is addressed.
Provides early and sustained improvement compared with oral administration.
Local administration avoids blood pressure influence, supported by angiotensin I-induced vasopressor response suppression not being affected by locally used low-dose/non-systemic formulations.
Documented Applications
Treatment of a subject suffering from dysphagia.
Treatment of a subject suffering from aspiration pneumonia.
Use in a guinea pig haloperidol-induced dysphagia model with swallowing-related response measurements.
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