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(12) Patent Application Publication (10) Pub. No.: US 2006/0079514 A1 Preston (43) Pub US 2006007.9514A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0079514 A1 Preston (43) Pub. Date: Apr. 13, 2006 (54) METHODS AND COMPOSITIONS Publication Classification INCLUDING METHSCOPOLAMINE BROMIDE (51) Int. Cl. (75) Inventor: David M. Preston, Chapel Hill, NC A61K 3 I/5513 (2006.01) (US) A6II 3 L/46 (2006.01) A6II 3/44 (2006.01) Correspondence Address: (52) U.S. Cl. ........................... 514/221; 514/304: 514/357 HUTCHISON & MASON PLLC PO BOX 31686 RALEIGH, NC 27612 (US) (57) ABSTRACT (73) Assignee: Victory Pharma Incorporated Therapeutic pharmaceutical compositions are provided that Appl. No.: 11/001,748 include an anticholinergic agent and a sedative agent. Par (21) ticularly preferred anticholinergic agents include anticholin (22) Filed: Dec. 2, 2004 ergic agents which do not substantially cross the blood-brain barrier. Methscopolamine bromide is the preferred anticho Related U.S. Application Data linergic agent. The sedative agent may be chlordiazepoxide hydrochloride or diazepam. Various methods using the com (63) Continuation-in-part of application No. 10/964.252, positions to alleviate gastrointestinal disorders or symptoms filed on Oct. 13, 2004. thereof are also provided. US 2006/007.9514 A1 Apr. 13, 2006 METHODS AND COMPOSITIONS INCLUDING tract disorders or symptoms thereof and methods for admin METHSCOPOLAMINE BROMIDE istration of the therapeutic pharmaceutical compositions are still needed. Thus, there is still a need in the art for a CROSS-REFERENCE TO RELATED formulation of anticholinergic agents which is Substantially APPLICATIONS free of the disadvantages, defects and limitations of the formulations disclosed in the art. 0001. This is a continuation-in-part application of U.S. patent application Ser. No. 10/964,252, filed Oct. 13, 2004, SUMMARY the entire contents of which are hereby incorporated herein by reference. 0007. In accordance with the foregoing, there are pro vided by the embodiments of the present invention thera FIELD peutic pharmaceutical preparations consisting essentially of 0002 The present invention is directed to therapeutic a therapeutically effective amount of an anticholinergic agents for the treatment of gastrointestinal disorders and agent and a sedative agent whereby the combination of methods for administering those agents. The invention gen anticholinergic agent and sedative agent alleviates one or erally relates to therapeutic pharmaceutical compositions more gastrointestinal disorders or one or more symptom including an anticholinergic agent and a sedative agent. The thereof. therapeutic pharmaceutical compositions may be used in 0008. In one embodiment, a therapeutic pharmaceutical methods for treating gastrointestinal tract disorders or con composition is provided consisting essentially of a thera ditions or symptoms of Such disorders or conditions. peutically effective amount of a blended mixture of an anticholinergic agent comprising methScopolamine bromide BACKGROUND and a sedative agent comprising chlordiazepoxide hydro chloride. In a preferred embodiment, the ratio of the meth 0003 Anticholinergic agents are typically antagonistic to scopolamine bromide to the chlordiazepoxide hydrochloride the action of parasympathetic or other cholinergic nerve is about 0.5:1 to about 1:1. In another preferred embodiment, fibers. Generally, anticholinergic agents block or inhibit the the methScopolamine bromide is present in an amount of effects of acetylcholine which is produced by the body and about 2.0 to about 5.0 mg per dose (about 8.0 mg to about is responsible for certain nervous system activities. Various 20.0 mg per day) and the chlordiazepoxide hydrochloride is anticholinergic compounds are known which have a variety present in an amount of about 5.0 mg per dose (about 20.0 of effects on the human body depending on the particular mg per day). The therapeutic pharmaceutical composition structure of the compound. Anticholinergic agents derived preferably is administered orally in an immediate release from the belladonna alkaloids may produce a number of form given four times a day or is in a Sustained release effects in the body, including relief from spasms of the preparation given less than four times a day, and is available gastrointestinal tract, the bladder and the biliary tract. Bel in powder form for delivery to a patient in need of the ladonna alkaloid anticholinergic compounds include the therapeutic pharmaceutical composition. tertiary amines atropine, hyoscyamine and Scopolamine, which are believed to cross the blood brain barrier and exert 0009. In another embodiment, a therapeutic pharmaceu an effect on the central nervous system. The effects on the tical composition is provided consisting essentially of a central nervous system may be a negative consequence of therapeutically effective amount of a blended mixture of an the use of these anticholinergic compounds, causing a vari anticholinergic agent comprising methScopolamine bromide ety of unwanted side effects. and a sedative agent comprising diazepam. In a preferred embodiment, the methScopolamine bromide is present in an 0004 Quaternary ammonium anticholinergic agents have amount of about 2.0 to about 5.0 mg per dose (about 8.0 mg been derived from the belladonna alkaloids by such modi to about 20.0 mg per day) and the diazepam is present in an fications as, for example, by the addition of a second methyl amount of about 2.0 to about 5.0 mg per dose (about 8.0 mg group to the nitrogen. Such quaternary ammonium anticho to about 20.0 mg per day). The therapeutic pharmaceutical linergic agents are believed to not cross the blood brain composition preferably is administered orally in an imme barrier, and, thus, do not exert the same effect on the central diate release form given four times a day or is in a Sustained nervous system as the belladonna alkaloids from which release preparation given less than four times a day, and is these compounds may be derived. available in powder form for delivery to a patient in need of 0005 Clidinium bromide is a quaternary ammonium the therapeutic pharmaceutical composition. anticholinergic agent. It has been used in LibraxTM, which 0010. In yet another embodiment, a method of alleviating contains clidinium bromide and chlordiazepoxide hydro at least one gastrointestinal disorder or at least one symptom chloride, a benzodiazepine. LibraxTM has been prescribed of a gastrointestinal disorder in a human patient is provided, for the treatment of a variety of gastrointestinal disorders the method comprising administering to the patient a thera Such as peptic ulcer, irritable bowel syndrome and acute peutic pharmaceutical composition consisting essentially of enterocolitis. The Food and Drug Administration, FDA, a therapeutically effective amount of a blended mixture of however, has questioned the effectiveness of this compound. methScopolamine bromide and chlordiazepoxide hydrochlo In addition, while clidinium bromide may not have the ride. In a preferred embodiment, the ratio of the methsco effects of the belladonna alkaloids on the central nervous polamine bromide to the chlordiazepoxide is about 0.5:1 to system, it is postulated that clidinium bromide has the about 1:1. In another preferred embodiment, the methsco potential to cause liver toxicity in some patients. polamine bromide is present in an amount of about 2.0 to 0006. In view of the foregoing, therapeutic pharmaceu about 5.0 mg per dose (about 8.0 mg to about 20.0 mg per tical compositions useful for the treatment of gastrointestinal day) and the chlordiazepoxide hydrochloride is present in an US 2006/007.9514 A1 Apr. 13, 2006 amount of about 5.0 mg per dose (about 20 mg per day). The of active ingredient deemed necessary in the formulation to therapeutic pharmaceutical composition preferably is provide the desired amount upon administration. administered orally in an immediate release form given four 0017 “Available for immediate delivery” means the times a day or is in a Sustained release preparation given less therapeutic pharmaceutical composition is provided in a than four times a day, and is available in powder form for formulation allowing the blended mixture of anticholinergic delivery to a patient in need of the therapeutic pharmaceu agent and sedative agent to begin acting in a therapeutic tical composition. manner Substantially as soon as the agents become available 0011. In yet a further embodiment, a method of alleviat in the body and/or bloodstream of the patient. ing at least one gastrointestinal disorder or at least one 0018 “Sustained release” means the therapeutic pharma symptom of a gastrointestinal disorder in a human patient is ceutical composition is provided in a formulation Such that provided, the method comprising administering to the the composition provides an initial therapeutic effect and patient a therapeutic pharmaceutical composition consisting also an ongoing or additional therapeutic release of thera essentially of a therapeutically effective amount of a blended peutic pharmaceutical composition or therapeutic effect over mixture of methScopolamine bromide and diazepam. In a preferred embodiment, the methscopolamine bromide is a desired period of time. present in an amount of about 2.0 to about 5.0 mg per dose 0019 “Substantially no liver toxicity” means that a (about 8.0 mg to about 20.0 mg per day) and the diazepam patient ingesting a therapeutic pharmaceutical composition is present in an amount of about 2.0 to about 5.0 mg per dose consisting
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