Abstract: This invention provides methods useful in aiding in the diagnosis of Alzheimer's disease. The methods involve measuring the amount of amyloid-.beta. peptide (x-.gtoreq.41) in the cerebrospinal fluid of a patient. High levels of the peptide generally are inconsistent with a diagnosis of Alzheimer's. Low levels of the peptide are consistent with the disease and, with other tests, can provide a positive diagnosis.

Abstract: The present invention provides methods for identifying beta amyloid production inhibitors, wherein cells are cultured under conditions which result in secretion of a soluble fragment of beta amyloid precursor protein. The amino acid sequence of the fragment extends from the amino terminus of beta APP to the amino terminus of the beta amyloid peptide. The cultured cells are exposed to test compounds which cause a change in the secreted amount of the soluble fragment of beta APP which is determined.

Abstract: A proteolytic enzyme isolated from human tissue which exhibits a proteolytic activity to hydrolyze Met-Asp peptide bond in an amyloid-like substrate is disclosed. This enzyme has been designated "amyloidin" because it proteolytically cleaves a Met-Asp bond similar to the one present in the amyloid precursor protein to release a fragment having the mature Asp terminus of the .beta.-amyloid peptide. Antibodies to the amyloidin protease are also provided. Methods to isolate and purify the amyloidin protease are provided, as well as assays to screen for inhibitors of the amyloidin protease. Also disclosed is the gene encoding the protease and methods for expression of the protease by recombinant DNA means.

Abstract: A dosage form is provided for administering a drug of the formula ##STR1## to a patient to produce an anxiolytic benefit in the patient.

Abstract: A dosage form is disclosed comprising a wall surrounding a compartment, which comprises a first composition comprising a carboxymethylcellulose and a second composition comprising a higher molecular weight carboxymethylcellulose. The first composition comprises a dosage amount of drug that delivers from the dosage form at a controlled rate over time.

Abstract: An osmotic system is disclosed for delivering a beneficial agent formulation to an environment of use. The osmotic system comprises (a) an outside semipermeable wall, (b) a middle osmotically active layer, (c) a capsule comprising a beneficial agent, and (d) a passageway for dispensing the beneficial agent from the osmotic system.

Abstract: A delivery system is disclosed for delivering a beneficial agent to an animal. The delivery system comprises a wall that surrounds a lumen, said wall comprising a composition that limits the passage of fluid into the system and a composition that permits the passage of fluid into the system. The lumen comprises a beneficial agent and an expandable member. The delivery system comprises an exit means for delivering the beneficial agent.

Abstract: The present invention provides compositions and methods for the transdermal administration of a therapeutically effective amount of a synthetic 19-nor-progesterone (ST-1435) together with, optionally, a suitable permeation enhancer.

Abstract: The present invention provides compositions and methods for the transdermal administration of a therapeutically effective amount of a synthetic 19-nor-progesterone (ST-1435) and an estrogen, in combination, together with, optionally, a suitable permeation enhancer.

Abstract: The present invention is directed to a fluid-imbibing dispensing device for the immediate or almost immediate and extended delivery of an active agent over a prolonged period of time together with the initially delayed pulse delivery of an active agent to a fluid environment of use.

Abstract: The present invention is directed to a fluid-imbibing drug delivery device which is useful for the initial delayed delivery of an active agent formulation to a fluid environment of use, the initial delay period to startup or activation being of a predetermined length of time. The delivery of the agent formulation from the dispensing device, once begun, is continued over a predetermined prolonged period of time.

Abstract: Delivery devices which include a beneficial agent and an activating mechanism in separate compartments separated by a moveable partition are designed to deliver the beneficial agent in a pulsatile manner through an orifice. The pulsatile delivery is achieved by a band of resilient material which is placed over the orifice. The resilient material is sufficiently tight to substantially seal the orifice when the pressure within the device is below a threshold level while at the same time being capable of being stretched when the internal pressure exceeds the threshold.

Abstract: A method and means for reducing sensitization or irritation caused by transdermally delivered drugs, wherein one or more metabolic modulators is coadministered with a sensitizing or irritating drug.

Abstract: A diffusional drug delivery device is described which can provide for delayed onset of therapeutic effect and for delivery of the therapeutic agent in predetermined temporal patterns at optimum rates. Delay means are provided between the agent reservoir and the surface through which the agent is released by diffusion to delay the release of agent at a therapeutic rate for predetermined times after application. Suitable means include a delay membrane disposed between the releasing surface and the agent reservoir, which membrane is preferably free of undissolved agent and/or is initially impermeable to the agent and thereafter becomes permeable. One or more agent chambers defined by one or more of such membranes may be provided, whereby agents are released in predetermined temporal patterns at optimal release rates.

Abstract: A dosage form is disclosed comprising means for lessening the tackiness and/or irritation of the components of the dosage form to mucosal tissue. The dosage form provides means for forming in the dosage form a floc comprising a drug, which floc, when delivered from the dosage form, lessens the tackiness and/or irritation of the mucosal tissue of a warm-blooded recipient.

Abstract: A dosage form is disclosed comprising means for lessening the tackiness and/or irritation of the components of the dosage form to mucosal tissue. The dosage form provides means for forming in the dosage form a floc comprising a drug, which floc, when delivered from the dosage form, lessens the tackiness and/or irritation of the mucosal tissue of a warm-blooded recipient.

Abstract: A dosage form is disclosed comprising means for delaying the delivery of drug from the dosage form following the administration of the dosage form to a patient in need of drug therapy.

Abstract: An osmotic device (10) for delivering a beneficial drug, such as an anti-fungal, into the mouth of a human patient is disclosed. The device (10) has a size and shape adapting it to be comfortably retained in the mouth for extended periods of time. The device (10) comprises a wall (12) surrounding a compartment (13) housing a layer of an agent (14) that is insoluble to very soluble in aqueous biological fluids, e.g., saliva, and a layer (16) of a fluid swellable, hydrophilic polymer. A passageway (17) in the wall (12) connects the agent (14) with the exterior of the device (10). The wall (12) is permeable to the passage of aqueous biological fluid but substantially impermeable to the passage of the hydrophilic polymer (16). In one embodiment the beneficial agent (14) has a different color than the hydrophilic polymer (16). The wall (12) is sufficiently translucent to permit the patient to see the amount of drug/beneficial agent (14) remaining to be delivered.

Abstract: A dosage form is disclosed comprising an antiemetic and antinausea drug for treating vomiting and nausea.

Abstract: A dosage form is provided for administering a drug of the formula ##STR1## to a patient to produce an anxiolytic benefit in the patient.