US 2007OOO3490A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0003490 A1 Nijhawan (43) Pub. Date: Jan. 4, 2007 (54) MEDICATED GUMSTICK FOR TREATMENT (22) Filed: Jun. 29, 2005 IN ANTI-NFLAMMLATORY CONDITIONS AND PROPHYLAXIS AGAINST NSAID Publication Classification GASTROPATHY (51) Int. Cl. (75) Inventor: Pardeep Nijhawan, Richmond Hill A6IR 9/68 (2006.01) (CA) (52) U.S. Cl. ................................................................ 424/48 Correspondence Address: (57) ABSTRACT IVOR M. HUGHES, BARRISTER & A Stick of gum is provided containing therapeutic benefits of SOLICITOR, non-steroid anti-inflammatory drugs for inflammation in PATENT & TRADEMARKAGENTS conditions such as arthritis, and also alleviates Subsequent 175 COMMERCE VALLEY DRIVE WEST side effects of NSAID administration, as well as antacid SUTE 200 effects from compounds such as an H2 antagonist (raniti THORNHILL, ON L3T 7P6 (CA) dine, cimetidine, famotidine) and/or a proton pump inhibitor (such as lansoprazole, pantoprazole, omeprazole, esomepra (73) Assignee: MEDICAL FUTURES INC. Zole or rabeprazole) and/or an acid pump antagonist selected from the group of Soraprazan, AZD0865, YH1885 and (21) Appl. No.: 11/168,526 CS-526. Patent Application Publication Jan. 4, 2007 Sheet 1 of 2 US 2007/0003490 A1 FIGURE 1 Calcium, Flavouring layer 12 11 Patent Application Publication Jan. 4, 2007 Sheet 2 of 2 US 2007/0003490 A1 FIGURE 2 13 YY N 11 12 US 2007/0003490 A1 Jan. 4, 2007 MEDCATED GUMISTICK FOR TREATMENT IN likely to use NSAIDs and also other medications. These ANTI-NFLAMMATORY CONDITIONS AND medications can lead to an increase in the incidence of pill PROPHYLAXIS AGAINST NSAID GASTROPATHY induced esophagitis. Once again, this can be prevented by using a GPA when ingesting pills. FIELD OF THE INVENTION 0007. These complications formed the basis for intensive 0001. The present invention provides a composition research on the inflammatory state, and it was in the early capable of eliminating or reducing the undesirable side 1990s that a solution to this problem presented itself with the effects resulting from NSAID administration. This compo identification of two structurally related cyclo-oxygenase sition is formulated as a stick chewing gum for convenience isoforms. Labelled COX-1 and COX-2, it was the COX-2 and ease of use. isoform that was identified as the principal isoform involved in inflammation. This concept led to the development and BACKGROUND OF THE INVENTION clinical introduction of COX-2-specific NSAIDs, drugs 0002 The efficacy of non-steroidal antiinflammatories noted for their reduced GI toxicity. (NSAIDs) for treatment of pain, inflammation and fever, has 0008 Unfortunately, after a decade of use, retrospective made these drugs the most commonly used in the world. analysis confirmed the incidence of increased cardiac tox Unfortunately, this class has been limited by their gas icities associated with long term use of COX-2 NSAIDs. trointestinal (GI) toxicity, a side effect that has caused This realization has recently prompted a return to the use of numerous problems. These complications can include dys traditional non-selective NSAIDs for treatment of inflam pepsia, GI upset, gastric ulceration, gastric erosion, duode mation. With this return a rise in the occurrence of NSAID nal ulceration and esophagitis. NSAID gastropathy affects GI complications is anticipated. millions of people annually and results in increased hospi talizations and deaths due to complications from gas 0009. In light of the clinical failure of the COX-2 selec troduodenal bleeds. Furthermore, the incidence of dyspepsia tive NSAIDs for long-term treatment of inflammatory con has been reported to be at 15% in patients taking either ditions, there is a need once again for the relief provided by NSAIDs or COX-2 inhibitors. These patients require addi traditional NSAID therapy. At the same time there is a dire tional medications, such as gastroprotective agents to help need for treatment of the aforesaid harmful side effects reduce the incidence of dyspepsia. arising from NSAID therapy. This urgent and long felt need 0003) In addition, NSAID induced gastropathy can affect has been met with the present invention. up to 80% of all patients who use NSAIDs chronically. Even in those patients using NSAIDs for the short term, gastr PRIOR ART opathy can begin within 72 hours of ingestion of the first 0010 Within the prior art there are several compositions dose of the medication, leading to gastric mucosa damage. formulated including tablets and also chewing gum formu In some cases, patients will arrive at the emergency room lations. All of these fail to address the unique benefits with massive upper gastrointestinal tract bleeds that may be achieved by the present invention. life-threatening. In fact, gastrointestinal complications from 0011. The prior art includes U.S. Pat. No. 5,037,815 by NSAIDs are the most common single side effect of any class Lukacsko et al, wherein NSAIDs are combined with a of drugs in America today. different group of gastroprotective agents, including H2 0004. In patients who do develop gastrointestinal bleed antagonists. This patent outlines how an NSAID and H2 ing from use of NSAIDs, urgent endoscopy and therapy with antagonists can be combined in a tablet formulation. How a group of drugs known as proton pump inhibitors (PPI) is ever, it does not include a gum formulation for increased required. Proton pump inhibitors include lanSoprazole, pan salivation and increased buccal mucosa absorption for toprazole, omeprazole, esomeprazole and rabeprazole. improved treatment of migraine headaches. These drugs have replaced the older histamine receptor 0012 U.S. Pat. No. 6,537,525 describes a chewing gum blockers as the new gastrointestinal protective agent of composition useful for treatment for gastroesophageal reflux choice, although H2 antagonists still play a major role in disease. The composition is taught to include at least one prevention of NSAID gastropathy. PPI are useful for treating ingredient from the group consisting of an acid neutralizing active ulcers, decreasing the incidence of recurrence of agent, and anti-gas agent, and an acid production inhibitor. ulcers, decreasing gastric and esophageal inflammation and Acid production inhibitors include H2 receptor antagonists decreasing the incidence of gastrointestinal bleeding. PPIs and PPIs, as taught within this patent. Examples of H2 and H2 antagonists are collectively referred to as gastropro receptor antagonists are listed as cimetidine, ranitidine and tective agents (GPA). famotidine. Examples of PPIs are listed as lansoprazole and 0005 NSAID induced gastropathy can affect all patients omeprazole. However, the advantage of these agents com including otherwise young and health adults. However, of bined with an NSAID for delivery with the chewing gum the great number of patients requiring NSAID therapy, composition is not contemplated, nor are the benefits taught certain groups are at increased risk of developing the GI of a distinct separation of active ingredients within the complications. These groups include those of advanced age chewing gum. The stick of gum of the present invention is and co morbid conditions such as significant heart disease or unique in that it aims primarily to relieve inflammatory rheumatoid arthritis. Unfortunately, it is in these groups that conditions using an NSAID, while simultaneously amelio relief of inflammatory conditions would be most desired and rating consequences of Such a therapeutic regimen through appreciated. the inclusion of GPAs. 0006 Adding to these increased complications, there is 0013 U.S. Pat. No. 6,773,716 relates to a chewing gum Suggestion from several reports that as we age, we are more product containing a medicament in the coating. The medi US 2007/0003490 A1 Jan. 4, 2007 cament is selected from a group consisting of antacids and approach. The present invention has met this need with a soft anti-inflammatories, including famotidine and omeprazol. chewing gum formulated delivered as a soft stick. and indomethacin and ibuprofen. The present invention addresses the need for a chewing gum Stick which allows for 0018. However, in spite of the general discussions in the ease of use (as opposed to blister packs) in the affected above-mentioned patent literature there is no discussion of arthritic population while provided enhanced absorption the problems facing the elderly in handling blister packages through the buccal mucosa from a larger Surface area. or the like. Blister packages require a certain amount of Furthermore, the immediate invention does not formulate a strength and effort potentially beyond patients Suffering medicament in the coating, but rather is unique in the from arthritis in the joints. The manual dexterity required to placement and separation of active ingredients in the chew open and consume such packaging can be an inhibiting ing gum Stick, designed to enhance stability. factor for those in dire need of the required medicaments. 0014 WO 2004/004478 teaches a compressed chewing 0019. It is therefore a primary object of this invention to gum tablet, and sets out methods for encapsulating the provide a stick gum based pharmaceutical which is easy to chewing gum centre fully or partly with a barrier layer. The art teaches methods of layering gum tablets outlined in the SC. disclosure, along with an improved method for obtaining a 0020. It is a further object of this invention to provide the barrier layer. This barrier layer is taught to protect the gum Stick gum based product which includes two separate com centre during manufacture. Although this patent application ponents separated by an enteric layer. contemplates different pharmaceutical ingredients including acetaminophen, ibuprofen, and indomethacin, along with 0021. It is a further object of this invention to provide the other NSAIDs, ranitidine and other H2 agonists, and lanso stick gum based product which includes an NSAID com prazole and other PPIs, these are formulated in a tablet. The ponent and a PPI component or H2 antagonist component present invention is formulated to provide enhanced absorp separated by an enteric layer.