Abstract: The present invention provides methods and compositions for treating hypercholesterolemia using therapeutic apoE proteins. A therapeutic apoE protein is a naturally-occurring apoE protein (e.g., apoE1, apoE2, apoE2*, apoE2**, apoE3, and apoE4) that has one or more amino acid substitutions in the carboxy-terminal region which, when administered to a mammal having hypercholesterolemia, reduces the plasma cholesterol levels without inducing hypertriglyceridemia. The invention also provides a method for reducing plasma cholesterol using low doses of naturally-occurring apoE proteins.

Abstract: A method and dispenser for treating a systemic disease in a patient in need of such treatment is disclosed. The method comprising maintaining the inspiratory flow rate and volume of the patient to a certain value and then administering a medicament aerosol formulation to the patient using a breath activated inhalation device.

Abstract: The present invention features a method for the formation of superporous hydrogels using an ion-equilibration technique. Anionic polysaccharides are included in the hydrogel reaction mixture and cations are introduced either during or after hydrogel formation. Properties of the resulting hydrogel can be subsequently adjusted by treating the cation-complexed gel with a different cation or cation mixture under equilibrating conditions. It has been found that by properly adjusting the cations and the sequence in which they are used in the equilibration process, superporous hydrogels can be formed that are highly absorbent while maintaining favorable structural properties, including strength, ruggedness, and resiliency. It has also been found that applying appropriate dehydration conditions to them after their formation can further stabilize the superporous hydrogels formed by the method of the invention.

Abstract: An orally administered antihyperlipidemia composition according to the present invention includes from about 250 to about 3000 parts by weight of nicotinic acid, and from about 5 to about 50 parts by weight of hydroxypropyl methylcellulose. Also, a method of treating hyperlipidemia in a hyperlipidemic having a substantially periodic physiological loss of consciousness, includes the steps of forming a composition having an effective antihyperlipidemic amount of nicotinic acid and a time release sustaining amount of a swelling agent. The method also includes the step of orally administering the composition to the hyperlipidemic once per day “nocturnally,” that is in the evening or at night.

Abstract: Intermediate release nicotinic acid formulations having unique biopharmaceutical characteristics, such as Cmax, Tmax and AUC, which are suitable for oral administration once per day during the evening or at night for treating hyperlipidemia without causing drug-induced hepatotoxicity to such a level that requires the therapy to be discontinued, are disclosed. The intermediate nicotinic acid formulations can be administered as tablets in dosage strengths of, for example, 375 mg, 500 mg, 750 mg and 1000 mg.

Abstract: Intermediate release nicotinic acid formulations having unique biopharmaceutical characteristics, which are suitable for oral administration once per day as a single dose preferably administered during the evening or at night for treating hyperlipidemia without causing drug-induced hepatotoxicity to such a level that requires the therapy to be discontinued, are disclosed. The intermediate nicotinic acid formulations can be administered as tablets in dosage strengths of, for example, 375 mg, 500 mg, 750 mg and 1000 mg. The 375 mg, 500 mg and 750 mg nicotinic acid tablets of the present invention have a dissolution curve similarity fit factor F2 of at least about 79, and the 1000 mg nicotinic acid tablets of the present invention have a dissolution curve similarity fit factor F2 of at least 44.

Abstract: Methods for reducing flushing in individuals being treated for hyperlipidemia with nicotinic acid are disclosed. According to the methods of the present invention, flushing can be reduced in individuals under going nicotinic acid therapy without causing drug-induced hepatotoxicity to a level that would require the nicotinic acid therapy to be discontinued by orally administering to the individuals intermediate nicotinic acid formualtions having unique biopharmaceutical characteristics as a single dose once per day. While the methods of the present invention contemplate administering the intermediate release nicotinic acid formulations at any time during a 24 hour period, it is preferable to administer them once-a-day as a single dose during the evening or at night between about 6:00 pm. and 12:00 a.m., preferably between about 8:00 p.m. and 12:00 a.m., and most preferably between about 8:00 p.m. and 10:00 p.m.

Abstract: Intermediate release nicotinic acid formulations having unique biopharmaceutical characteristics, which are suitable for oral administration once per day as a single dose preferably administered during the evening or at night for treating hyperlipidemia without causing drug-induced hepatotoxicity to such a level that requires the therapy to be discontinued, are disclosed. The intermediate nicotinic acid formulations can be administered as tablets in dosage strengths of, for example, 375 mg, 500 mg, 750 mg and 1000 mg. The 375 mg, 500 mg and 750 mg nicotinic acid tablets of the present invention have a dissolution curve similarity fit factor F2 of at least about 79, and the 1000 mg nicotinic acid tablets of the present invention have a dissolution curve similarity fit factor F2 of at least 44.

Abstract: Intermediate release nicotinic acid formulations having unique biopharmaceutical characteristics, which are suitable for oral administration once per day as a single dose preferably administered during the evening or at night for treating hyperlipidemia without causing drug-induced hepatotoxicity to such a level that requires the therapy to be discontinued, are disclosed. The intermediate nicotinic acid formulations can be administered as tablets in dosage strengths of, for example, 375 mg, 500 mg, 750 mg and 1000 mg. The 375 mg, 500 mg and 750 mg nicotinic acid tablets of the present invention have a dissolution curve similarity fit factor F2 of at least about 79, and the 1000 mg nicotinic acid tablets of the present invention have a dissolution curve similarity fit factor F2 of at least 44.

Abstract: A controlled release pharmaceutical formulation is disclosed. The formulation comprises a construct having a matrix of a material selected from the group comprising (a) a high melting point fatty acid ester, (b) an oil, (c) a polymeric cellulose derivative and (d) a mixture of any of the foregoing. Associated with the matrix is a selected medicament. Preferably, the matrix comprises at least two of the aforementioned materials or components.

Abstract: Intermediate release nicotinic acid formulations having unique urinary metabolite profiles, which are suitable for oral administration once-a-day as a single dose during a 24 hour period for treating hyperlipidemia without causing drug-induced hepatotoxicity or drug-induced elevations in uric acid or glucose or both to levels that require the therapy to be discontinued, are disclosed.

Abstract: An improved breath coordinated inhaler is provided for administering medication to a patient in aerosol form for respiratory inhalation therapy. The improved inhaler comprises a compact housing adapted to receive and support a medication cannister including a valve assembly actuatable to deliver a dosage of the medication in aerosol form. The housing includes a plunger mounted at a first end thereof for displacing the cannister against a spray nozzle located at a second end of the housing to actuate the valve assembly and deliver the medication through a mouthpiece to the patient. The plunger is associated with a seal arrangement for venting the housing when the plunger is depressed to allow the patient to draw in air in timed relation to the medication delivery, and to substantially re-seal the housing against ingress of contaminants when the plunger is released.

Abstract: A method of reducing or blocking a stress-related atopic skin disease such as exzema or uticaria in a subject comprising administering to the patient an agent that antagonizes CRH-induced activation of skin mast cells, the agent being used alone or together with a second agent that inhibits activation of skin mast cells. Such agents include compositions that reduce the production or secretion of CRH, neurotensin or somatostatin or an agent that inhibitos the physiological action of CRH, neurotensin or somostatin on skin mast cells. The effects of CRH on skin mast cells can also be inhibited by histamine-3 receptor antagonists and by inhibitors of the phosphorylation of skin mast cell moesin.

Abstract: Non-traumatic immobilization (restrain) stress causes rapid degranulation of rat dura mast cells, as shown both by light and electron microscopy. These morphologic findings were accompanied by elevation of rat mast cell protease cerebrospinal fluid. Mast cell activation due to stress was abolished in animals that had been treated neonatally with capsaicin, indicating that neuropeptides in sensory nerve endings are involved in this response. Complete inhibition was also achieved by pretreating the animals intraperitoneally with antiserum to corticotropin releasing hormone (CRH). Mast cells in the dura were localized close to nerve processes containing substance P, but no CRH-fibers were identified even though these were found close to mast cells elsewhere in the brain, i.e., in the median eminence. This is the first time that stress is shown to activate intracranial mast cells, apparently through the sequential actions of CRH and one or more sensory neuropeptides such as Substance P.

Abstract: A method for treating endogenous, painful gastrointestinal conditions of non-inflammatory, non-ulcerative origin, such as abdominal migraine and irritable bowel syndrome, entails administering a pharmacologically effective amount of a mast cell degranulation-blocking agent.

Abstract: A method of preventing or alleviating a migraine headache which comprises administering a pharmaceutically effective amount of a mast cell degranulation blocking agent just prior to or during the prodromal phase of the migraine in the absence of an analgesic. The agent can also be administered in combination with a central nervous system stimulant.