Abstract: Described herein are passive nasal respiratory devices, in particular, passive nasal respiratory devices configured to achieve positive end-expiratory pressure (PEEP) in a subject wearing the device. PEEP devices may have a threshold pressure for opening during expiration. These devices may include a flap valve that opens on inhalation nested with a spring valve that opens when exhalation pressure exceeds a predetermined threshold. The device may be configured to be comfortably worn by a sleeping subject.

Abstract: Devices for altering the flow of air in a respiratory cavity such as the nostrils of the nose. These methods and devices may be useful for affecting a physiologic benefit in patients suffering from a variety of medical disorders, including snoring and sleep apnea. The devices are typically removable devices that may be placed in both nostrils to increase resistance to airflow within the respiratory cavity. Resistance to expiration may be selectively increased relative to inspiration. The nasal devices may also increases patency of the nares. Any of these devices may be configured to achieve positive end-expiratory pressure (PEEP) in a subject wearing the device.

Abstract: Described herein are passive nasal respiratory devices, in particular, passive nasal respiratory devices configured to achieve positive end-expiratory pressure (PEEP) in a subject wearing the device. PEEP devices may have a threshold pressure for opening during expiration. These devices may include a flap valve that opens on inhalation nested with a spring valve that opens when exhalation pressure exceeds a predetermined threshold. The device may be configured to be comfortably worn by a sleeping subject.

Abstract: Described herein are nasal respiratory devices, in particular, nasal respiratory devices configured to achieve positive end-expiratory pressure (PEEP) in a subject wearing the device. PEEP devices may have a threshold pressure for opening during expiration. In some variations, these devices have a threshold pressure for closing during expiration.

Abstract: Described herein are nasal devices. In particular, layered nasal respiratory devices are described. Layered nasal device may include a layered airflow resistor that is configured to resist airflow in a first direction more than airflow in a second direction and that includes a flap valve adjacent to a flap valve limiting layer and an adhesive holdfast layer that is configured to secure the layered airflow resistor in communication with the subject's nasal cavity. Methods of using and methods of assembling layered nasal device are also described.

Abstract: Described herein are nasal devices, including nasal devices formed in layers having four or fewer layers. In some variations, the nasal devices include a single integrated layer from which the flap of the airflow resistor is formed as well as the base of the holdfast region. The nasal devices may include a single aligner or rim body on the side of the device facing the subject. The aligner may protect the airflow resistor, and may help center or position the nasal device. In some variations, these nasal devices may include a noise-reduction feature. Also described herein are systems, devices and methods for determining if a passive nasal respiratory device having an airflow resistor configured to inhibit exhalation more than inhalation has been worn by a subject, and thereby confirming compliance.

Abstract: The invention provides a crystalline 1,2-ethanedisulfonic acid salt of biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-5-methoxyphenylcarbamoyl)ethyl]piperidin-4-yl ester or a solvate thereof. This invention also provides pharmaceutical compositions comprising such a salt or prepared using such a salt; processes and intermediates for preparing such a salt; and methods of using such a salt to treat a pulmonary disorder.

Abstract: The invention provides a process of preparing an intermediate useful in the synthesis of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester, and a process of preparing a crystalline freebase of the ester.

Abstract: The invention is directed to compounds of formula I: wherein Ar, r, R3, X, and R5-7 are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds of formula I have AT1 receptor antagonist activity and neprilysin inhibition activity. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and a process and intermediates for preparing such compounds.

Abstract: In one aspect, the invention relates to compounds of formula I: where X, Y, R1, R2, R3, R4, R4, and n are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds of formula I are serotonin reuptake inhibitors. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

Abstract: The invention provides crystalline forms of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester, and pharmaceutically acceptable solvates thereof. The crystalline form can be a freebase, or a salt such as a diphosphate, monosulfate or dioxalate salt. The invention also provides pharmaceutical compositions comprising these crystalline compounds or prepared using these compounds; processes and intermediates for preparing the crystalline compounds; and methods of using these compounds to treat a pulmonary disorder.

Abstract: Methods, apparatus, and kits for enhancing breathing in patients suffering from chronic pulmonary obstructive disease are described. The methods and apparatus rely on increasing flow resistance to expiration in a manner which mimics “pursed lip” breathing which has been found to benefit patients suffering from this disease. In a first example, a device is implanted in a trachea or bronchial passage to increase flow resistance, preferably selectively increase resistance to expiration relative to inspiration. In a second embodiment, a mouthpiece is provided, again to increase resistance to expiration, preferably with a lesser increase in flow resistance to inspiration. In a third embodiment, the patient's trachea or bronchial passage is modified by the application of energy in order to partially close the lumen therethrough.

Abstract: The invention provides 3-carboxypropyl-aminotetralin compounds of formula (I): wherein R1, R2, R3, R4, R5, and R6 are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.

Abstract: The invention relates to crystalline oxalate salts of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]-methyl}phenylcarbamoyl)butyl]methylcarbamoyl}ethyl)piperidin-4-yl ester. This invention also relates to compositions containing such a crystalline oxalate salt; methods of using such a crystalline oxalate salt to, for example, treat a pulmonary disorder; and to processes for preparing such a crystalline oxalate salt.

Abstract: In one aspect, the invention relates to compounds having the formula: where R1-R6, a, b, and Z are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

Abstract: In one aspect, the invention relates to compounds having the formula: where R1, R2, R3, a, R4, R5, and R6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

Abstract: In one aspect, the invention relates to compounds having the formula: wherein: Ar, Z, R3, R4 and R5 are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have AT1 receptor antagonist activity and neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

Abstract: The invention is directed to compounds having the formula: wherein: Ar, r, R2-3, X, and R5-7 are as defined in the specification, and pharmaceutically acceptable salts thereof. These compounds have AT1 receptor antagonist activity and neprilysin inhibition activity. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

Abstract: The invention provides novel 8-azabicyclo[3.2.1]octane compounds of formula (I): wherein R1, R2, R3, A, and G are defined in the specification, or a pharmaceutically-acceptable salt or solvate thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.

Abstract: The invention provides crystalline hydrochloride salts of (S)-3-[(S)-2-methanesulfonyl-1-(4-trifluoromethylphenoxy)ethyl]pyrrolidine. This invention also provides pharmaceutical compositions comprising the crystalline salts, processes and intermediates for preparing the crystalline salts, and methods of using the crystalline salts to treat diseases.