DOCSLIB.ORG

WO 2007/070082 Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WO 2007/070082 Al (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date PCT (10) International Publication Number 21 June 2007 (21.06.2007) WO 2007/070082 Al (51) International Patent Classification: (74) Agent: YAO, Gene; 2600 Aramark Tower, 1101 Market A61K 9164 (2006.01) Street, Philadelphia, Pennsylvania 19107 (US). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/US2006/0 18000 kind of national protection available): AE, AG, AL, AM, AT,AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN, (22) International Filing Date: IMay 2006 (09.05.2006) CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, (25) Filing Language: English KG, KM, KN, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, LY,MA, MD, MG, MK, MN, MW, MX, MZ, NA, NG, NI, (26) Publication Language: English NO, NZ, OM, PG, PH, PL, PT, RO, RU, SC, SD, SE, SG, SK, SL, SM, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, YU, ZA, ZM, ZW (30) Priority Data: 60/679,424 10 May 2005 (10.05.2005) US (84) Designated States (unless otherwise indicated, for every 11/372,857 10 March 2006 (10.03.2006) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (71) Applicant (for all designated States except US): ELAN ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), PHARMA INTERNATIONAL LIMITED [IE/IE]; European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, Monksland, Athlone, County Westmeath (IE). FR, GB, GR, HU, IE, IS, IT, LT, LU, LV,MC, NL, PL, PT, RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, (72) Inventors; and GN, GQ, GW, ML, MR, NE, SN, TD, TG). (75) Inventors/Applicants (for US only): DEVANE, John [IE/IE]; Barrymore, Athlone, County Westmeath (IE). Declaration under Rule 4.17: STARK, Paul [GB/TE]; 37 Auburn Heights, Athlone, — of inventorship (Rule 4.17 (iv)) County Westmeath (IE). FANNING, Mall [IE/IE]; 23 Coolevin Park, Coosan, Athlone, County Westmeath Published: (IE). REKHI, Gurvinder [US/US]; 1492 Riverview Run — with international search report Lane, Suwanee, Georgia 30024 (US). JENKINS, Scott [US/US]; 1451 Carolina Place, Downingtown, Pennsyl For two-letter codes and other abbreviations, refer to the "G uid vania 19335 (US). LIVERSIDGE, Gary [US/US]; 258 ance Notes on Codes and Abbreviations" appearing at the beg in Colwyn Terrace, West Chester, Pennsylvania 19380 (US). ning of each regular issue of the PCT Gazette. (54) Title: NANOPARTICULATE AND CONTROLLED RELEASE COMPOSITIONS COMPRISING TEPRENONE (57) Abstract: The present invention is directed to compositions comprising a nanoparticulate teprenone having improved bioavail- ability. The nanoparticulate teprenone particles of the composition have an effective average particle size of less than about 2000 nm and are useful in the prevention and treatment of gastritis and gastric ulcers. The invention also relates to a controlled release composition comprising a teprenone or a nanoparticulate teprenone that in operation delivers the drug in a pulsed or multi-modal manner for the prevention and treatment of gastritis and gastric ulcers. NANOPARTICULATE AND CONTROLLED RELEASE COMPOSITIONS COMPRISING TEPRENONE FIELD OF INVENTION The present invention relates to compositions and methods for the prevention and treatment of gastric disease. In particular, the present invention relates to compositions comprising teprenone-containing particles and methods for making and using such a composition. In an embodiment of the invention, teprenone is in nanoparticulate form. The present invention relates also to novel dosage forms for the controlled delivery of teprenone. BACKGROUND OF INVENTION A. Background Regarding Teprenone Teprenone is an effective therapeutic against gastric disease. A healthy stomach and proper digestive processes require a fine balance of stomach acid and stomach mucosa. However, aging, body condition, and eating habits, among other factors, can disrupt this delicate balance resulting in a reduction in the amount of stomach mucous, and reduced gastric peristalsis. When this occurs, digestion time can increase, leading to conditions such as stomach heaviness and heartburn. Moreover, gastric mucosal lesions as a result of erosion, hemorrhage, redness and edema can lead to gastritis and gastric ulcers. Teprenone increases gastric mucous, and also protects gastric mucosa from stomach acid, thereby helping to restore normal gastric mucosa and treat gastric diseases. Gastritis is not necessarily clear in the special definition thereof in view of the fact that it is usually divided into acute gastritis and chronic gastritis in the discussion thereof. In the present invention, the term is used as including both types of gastritis. Chronic gastritis is usually classified into superficial gastritis and atrophic gastritis, and further into atrophic hyperplastic gastritis, hypertrophic gastritis, etc. Representative examples of chronic gastritis symptoms include anorexia, esophagostenosis, pyrosis, nausea, emesis, epigastrium dysphoria, epigastralgia, and flatulence. Acute gastritis is generally an inflammatory lesion of tunica mucosa ventriculi which is rapidly caused by an endogenous or xenogenic stimulus, and is usually accompanied by erosion. Clinical studies have demonstrated that teprenone has a potent anti-ulcer effect and is very effective against various gastric mucosal lesions. Specifically, teprenone is thought to increase gastric mucus by promoting mucus synthesis and secretion in mucosal epithelial cells. Teprenone also increases gastric mucosal blood flow and has been shown to protect the gastric mucosa from, for example, ethanol-induced injury and increases in lipid peroxide levels. Further, teprenone enhances gastric mucosal cell proliferation and thus helps to maintain the homeostasis of the gastric mucosal cell proliferation zone. Teprenone may be administered as part of a dosage form offered under the registered trademark SELBEX® by Eisai Co., Ltd. of Japan. Its chemical name is 3:2 (5E:5Z) geometric mixture of (9E,13E)-6,10,14,18-tetramethyl-5,9,13,17- nonadecatetraen-2-one. The molecular formula of teprenone is C23H38O and it has a molecular weight of 330.55. The chemical structure of teprenone is: Teprenone occurs as a colorless to pale yellow, oily liquid. It has a slight characteristic odor, and is tasteless. It is miscible with methanol, ethanol (95), acetone, chloroform, and hexane, and is practically insoluble in water. Conventional teprenone is administered orally, either as a capsule or in fine granules, in 50 mg quantities three times daily after a meal. Teprenone is described in, for example, U.S. Pat. No. 4,814,353 for "Therapeutic and Prophylactic Agent for Gastritis". U.S. Pat. No. 4,814,353 describes the teprenone compound and a method for treating gastritis comprising administering a therapeutic amount of teprenone to a patient suffering from gastritis. Teprenone has high therapeutic value for the treatment of patients suffering from gastritis and gastric ulcers. However, given the need to take teprenone three times a day and the further need to take teprenone after meals, strict patient compliance is a critical factor in the efficacy of teprenone in the treatment of gastritis and gastric ulcers. Moreover, such frequent administration often requires the attention of health care workers and contributes to the high cost associated with treatments involving teprenone. Thus, there is a need in the art for teprenone compositions which overcome these and other problems associated with their use in the treatment of gastritis and gastric ulcers. B. Background Regarding Nanoparticulate Compositions Nanoparticulate active agent compositions, first described in U.S. Patent No. 5,145,684 ("the '684 patent"), are particles consisting of a poorly soluble therapeutic or diagnostic agent having adsorbed onto or associated with the surface thereof a non- crosslinked surface stabilizer. The '684 patent does not describe nanoparticulate compositions of teprenone. Methods of making nanoparticulate active agent compositions are described in, for example, U.S. Patent Nos. 5,518,187 and 5,862,999, both for "Method of Grinding Phaπnaceutical Substances;" U.S. Patent No. 5,718,388, for "Continuous Method of Grinding Pharmaceutical Substances;" and U.S. Patent No. 5,510,1 18 for "Process of Preparing Therapeutic Compositions Containing Nanoparticles." Nanoparticulate active agent compositions are also described, for example, in U.S. Patent Nos. 5,298,262 for "Use of Ionic Cloud Point Modifiers to Prevent Particle Aggregation During Sterilization;" 5,302,401 for "Method to Reduce Particle Size Growth During Lyophilization;" 5,3 18,767 for "X-Ray Contrast Compositions Useful in Medical Imaging;" 5,326,552 for "Novel Formulation For Nanoparticulate X-Ray Blood Pool Contrast Agents Using High Molecular Weight Non-ionic Surfactants;" 5,328,404 for "Method of X-Ray Imaging Using Iodinated Aromatic Propanedioates;" 5,336,507 for "Use of Charged Phospholipids to Reduce Nanoparticle Aggregation;" 5,340,564 for "Formulations Comprising Olin 10-G to Prevent Particle Aggregation and Increase Stability;" 5,346,702 for "Use of Non-Ionic Cloud Point Modifiers to Minimize Nanoparticulate Aggregation During Sterilization;" 5,349,957 for "Preparation and Magnetic Properties of Very Small Magnetic-Dextran Particles;" 5,352,459 for "Use of Purified Surface
Load more

Recommended publications
  • Research Article the Protective Effect of Teprenone on Aspirin-Related Gastric Mucosal Injuries
    Hindawi Gastroenterology Research and Practice Volume 2019, Article ID 6532876, 7 pages https://doi.org/10.1155/2019/6532876 Research Article The Protective Effect of Teprenone on Aspirin-Related Gastric Mucosal Injuries Jing Zhao ,1,2 Yihong Fan ,1,2 Wu Ye ,1 Wen Feng ,1 Yue Hu ,1,2 Lijun Cai ,1,2 and Bin Lu 1,2 1Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou 310006, China 2Key Laboratory of Digestive Pathophysiology of Zhejiang Province, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China Correspondence should be addressed to Bin Lu; [email protected] Received 16 July 2018; Accepted 28 November 2018; Published 18 June 2019 Academic Editor: Haruhiko Sugimura Copyright © 2019 Jing Zhao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. Aspirin usage is associated with increased risk of gastrointestinal bleeding. The present study explored the potential of teprenone, an antiulcerative, in preventing aspirin-related gastric mucosal injuries. Methods. 280 patients with coronary diseases, naïve to aspirin medication, were admitted between 2011 and 2013 at the First Affiliated Hospital of Zhejiang Chinese Medical University and randomized into two groups (n = 140). The aspirin group received aspirin enteric-coated tablets 100 mg/day, while the aspirin+teprenone group received teprenone 50 mg 3 times/day along with aspirin. The patients were recorded for gastrointestinal symptoms and gastric mucosal injuries during a follow-up period of 12 months with 3-month intervals.
    [Show full text]
  • Aggravation by Paroxetine, a Selective Serotonin Re-Uptake Inhibitor, of Antral Lesions Generated by Nonsteroidal Anti-Inflammatory Drugs in Rats
    JPET Fast Forward. Published on June 24, 2011 as DOI: 10.1124/jpet.111.183293 JPET ThisFast article Forward. has not been Published copyedited andon formatted.June 24, The 2011 final versionas DOI:10.1124/jpet.111.183293 may differ from this version. JPET #183293 . Aggravation by Paroxetine, A Selective Serotonin Re-Uptake Inhibitor, of Antral Lesions Generated by Nonsteroidal Anti-inflammatory Drugs in Rats Downloaded from Koji Takeuchi, Akiko Tanaka, Kazuo Nukui, Azusa Kojo, Melinda Gyenge, and Kikuko Amagase jpet.aspetjournals.org at ASPET Journals on September 25, 2021 Division of Pathological Sciences Department of Pharmacology and Experimental Therapeutics Kyoto Pharmaceutical University Misasagi, Yamashina, Kyoto 607-8414, Japan (K.T., A.T., K.N., A.K., M.G., K.A.) 1 Copyright 2011 by the American Society for Pharmacology and Experimental Therapeutics. JPET Fast Forward. Published on June 24, 2011 as DOI: 10.1124/jpet.111.183293 This article has not been copyedited and formatted. The final version may differ from this version. JPET #183293 . Short title: Aggravation by SSRIs of NSAID-Induced Antral Damage Address correspondence to: Dr. Koji Takeuchi Division of Pathological Sciences Department of Pharmacology and Experimental therapeutics Kyoto Pharmaceutical University Downloaded from Misasagi, Yamashina, Kyoto 607-8414, Japan Tel: (Japan) 075-595-4679; Fax: (Japan) 075-595-4774 E-mail: [email protected] jpet.aspetjournals.org Document statistics: text ------------------------ 21 pages (page 4~page 25) at ASPET Journals on September 25, 2021 figures ----------------------- 10 figures references ----------------------- 43 references (page 27~page 31) Number of words: abstract ----------------------- 247 introduction ----------------------- 410 discussion -----------------------1685 Recommended section: Gastrointestinal, Hepatic, Pulmonary, & Renal 2 JPET Fast Forward.
    [Show full text]
  • Jp Xvii the Japanese Pharmacopoeia
    JP XVII THE JAPANESE PHARMACOPOEIA SEVENTEENTH EDITION Official from April 1, 2016 English Version THE MINISTRY OF HEALTH, LABOUR AND WELFARE Notice: This English Version of the Japanese Pharmacopoeia is published for the convenience of users unfamiliar with the Japanese language. When and if any discrepancy arises between the Japanese original and its English translation, the former is authentic. The Ministry of Health, Labour and Welfare Ministerial Notification No. 64 Pursuant to Paragraph 1, Article 41 of the Law on Securing Quality, Efficacy and Safety of Products including Pharmaceuticals and Medical Devices (Law No. 145, 1960), the Japanese Pharmacopoeia (Ministerial Notification No. 65, 2011), which has been established as follows*, shall be applied on April 1, 2016. However, in the case of drugs which are listed in the Pharmacopoeia (hereinafter referred to as ``previ- ous Pharmacopoeia'') [limited to those listed in the Japanese Pharmacopoeia whose standards are changed in accordance with this notification (hereinafter referred to as ``new Pharmacopoeia'')] and have been approved as of April 1, 2016 as prescribed under Paragraph 1, Article 14 of the same law [including drugs the Minister of Health, Labour and Welfare specifies (the Ministry of Health and Welfare Ministerial Notification No. 104, 1994) as of March 31, 2016 as those exempted from marketing approval pursuant to Paragraph 1, Article 14 of the Same Law (hereinafter referred to as ``drugs exempted from approval'')], the Name and Standards established in the previous Pharmacopoeia (limited to part of the Name and Standards for the drugs concerned) may be accepted to conform to the Name and Standards established in the new Pharmacopoeia before and on September 30, 2017.
    [Show full text]
  • Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
    US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG .
    [Show full text]
  • Evidence-Based Clinical Practice Guidelines for Peptic Ulcer Disease 2015
    J Gastroenterol DOI 10.1007/s00535-016-1166-4 SPECIAL ARTICLE Evidence-based clinical practice guidelines for peptic ulcer disease 2015 1,2 2 2 2 Kiichi Satoh • Junji Yoshino • Taiji Akamatsu • Toshiyuki Itoh • 2 2 2 2 Mototsugu Kato • Tomoari Kamada • Atsushi Takagi • Toshimi Chiba • 2 2 2 2 Sachiyo Nomura • Yuji Mizokami • Kazunari Murakami • Choitsu Sakamoto • 2 2 2 2 Hideyuki Hiraishi • Masao Ichinose • Naomi Uemura • Hidemi Goto • 2 2 2 2 Takashi Joh • Hiroto Miwa • Kentaro Sugano • Tooru Shimosegawa Received: 25 December 2015 / Accepted: 6 January 2016 Ó Japanese Society of Gastroenterology 2016 Abstract The Japanese Society of Gastroenterology bleeding is first treated by endoscopic hemostasis. If it (JSGE) revised the evidence-based clinical practice fails, surgery or interventional radiology is chosen. Second, guidelines for peptic ulcer disease in 2014 and has created medical therapy is provided. In cases of NSAID-related an English version. The revised guidelines consist of seven ulcers, use of NSAIDs is stopped, and anti-ulcer therapy is items: bleeding gastric and duodenal ulcers, Helicobacter provided. If NSAID use must continue, the ulcer is treated pylori (H. pylori) eradication therapy, non-eradication with a proton pump inhibitor (PPI) or prostaglandin analog. therapy, drug-induced ulcer, non-H. pylori, non-nons- In cases with no NSAID use, H. pylori-positive patients teroidal anti-inflammatory drug (NSAID) ulcer, surgical receive eradication and anti-ulcer therapy. If first-line treatment, and conservative therapy for perforation and eradication therapy fails, second-line therapy is given. In stenosis. Ninety clinical questions (CQs) were developed, cases of non-H.
    [Show full text]
  • Prevention of Gastric Ulcers
    24 Prevention of Gastric Ulcers Mohamed Morsy and Azza El-Sheikh Pharmacology Department, Minia University Egypt 1. Introduction Upper gastrointestinal tract integrity is dependent upon the delicate balance between naturally occurring protective factors as mucus or prostaglandins and damaging factors as hydrochloric acid present normally in the digestive juices. An imbalance causes peptic ulcer formation and destruction of gastrointestinal tract mucosal lining. Ulcer may develop in the esophagus, stomach, duodenum or other areas of elementary canal. In women, gastric ulcers are more common than duodenal ulcers, while in men the opposite is true. The ulcer irritates surrounding nerves and causes a considerable amount of pain. Obstruction of the gastrointestinal tract may occur as a result of spasm or edema in the affected area. The ulcer may also cause the erosion of major blood vessels leading to hemorrhage, hematemesis and/or melena. Deep erosion of the wall of the stomach or the intestine may cause perforation and peritonitis, which is a life-threatening condition needing emergency intervention. Duodenal ulcers are almost always benign but stomach ulcers may turn malignant. Although mortality rates of peptic ulcer are low, the high prevalence of the disease, the accompanying pain and its complications are very costly. The ongoing rapidly expanding research in this field provides evidence suggesting that, with therapeutic and dietetic advances, gastric ulcer may become preventable within the next decade. This could be achieved by strengthening the defense mechanisms of the gastric mucosa and, in parallel, limiting the aggression of predisposing factors causing gastric ulceration. The defenses of the gastric mucosa are incredibly efficient under normal mechanical, thermal or chemical conditions.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,986,901 B2 Meisel Et Al
    USOO698.6901B2 (12) United States Patent (10) Patent No.: US 6,986,901 B2 Meisel et al. (45) Date of Patent: Jan. 17, 2006 (54) GASTROINTESTINAL COMPOSITIONS 6,121,301 A 9/2000 Nagasawa et al. 6,127,418 A 10/2000 Bueno et al. (75) Inventors: Gerard M. Meisel, Budd Lake, NJ 6,156,771. A 12/2000 Rubin et al. S. Arthur A. Ciociola, Far Hills, NJ FOREIGN PATENT DOCUMENTS CA 967977 5/1975 (73) Assignee: Warner-Lambert Company LLC, CA 2136164 3/1995 Morris Plains, NJ (US) CN 1092314 3/1993 CN 1118267 5/1994 (*) Notice: Subject to any disclaimer, the term of this DE 9859.499 : 12/1998 patent is extended or adjusted under 35 E. O S. A1 3.10: U.S.C. 154(b) by 234 days. FR 2244469 8/1973 FR 4506 8/1993 (21) Appl. No.: 10/196,053 FR 277 1009 11/1997 JP 56128719 3/1980 (22) Filed: Jul. 15, 2002 JP 306.6627 8/1989 O O JP 9052829 6/1995 (65) Prior Publication Data WO WO 95.01803 A1 * 1/1995 US 2004/0013741 A1 Jan. 22, 2004 WO WO 9725,979 1/1996 WO WOOO765OO 12/2000 (51) Int. Cl. WO WOO121601 3/2001 A6IF I3/00 (2006.01) ZA 61O1840 8/1993 A6F 99.6A06 3032006.O1 OTHER PUBLICATIONS A6 IK 948 (2006.01) JW Read, JL Abitbol, KD Bardhan, PJ Whorwell, B Fraitag-"Efficacy and Safety of the peripheral kappa ago (52) U.S. Cl. ....................... 424/436; 424/422; 424/430; nist fedotoZine verSuS placebo in the treatment of functional 424/433; 424/451; 424/464; 424/489 dyspepsia see comments)." Gut Nov., 1997 41(5):664-8.
    [Show full text]
  • Management of Duodenal Ulcer with Gastroesophageal Reflux Disease (GERD) with Intravenous Pantoprazole
    CASE REPORT Management of Duodenal Ulcer with Gastroesophageal Reflux Disease (GERD) with Intravenous Pantoprazole Ari Fahrial Syam, Murdani Abdullah, Marcellus Simadibrata, Dadang Makmun, Chudahman Manan, Daldiyono Hardjodisasto Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia/Dr. Cipto Mangunkusumo General National Hospital ABSTRACT Proton pump inhibitors (PPIs) are the most effective anti secretory drugs available for controlling gastric acid acidity and volume. They are the drug of choice in the treatment for gastro esophageal reflux disease (GERD), Helicobacter pylori eradication, peptic ulcer and non steroidal anti-inflammatory drug (NSAID) gastropathy: For acute cases, an intravenous PPI is needed, especially for hospitalized patient. Recently, intravenous pantoprazole represents an alternative to intravenous histamine-2 receptor antagonists. We observed 2 patients who were treated with pantoprazole for duodenal ulcer, where one case had a complication of bleeding with a history of long term use of NSAID. After two weeks of treatment with pantoprazole, significant lesion healing from endoscopy findings was achieved in both cases. Keywords: peptic ulcer - upper gastrointestinal bleeding – proton pump inhibitors – pantoprazole INTRODUCTION Up to now, there has been no report on the use of Proton pump inhibitor (PPI) is currently the most pantoprazole in Indonesia. This paper reports two cases effective acid suppression, replacing histamine-2 of duodenal ulcer, where one case had a complication of bleeding with a history of long-term use of NSAID. The receptor antagonists (H2RA). At this time, this group of drugs has become the standard treatment for other case was that of duodenal ulcer in a patient with a gastroesophageal reflux disease (GERD), Helicobacter high dose of steroid.
    [Show full text]
  • Efficiency of the Inclusion of Rebamipide in The
    Journal of Clinical Medicine Article Efficiency of the Inclusion of Rebamipide in the Eradication Therapy for Helicobacter pylori Infection: Meta-Analysis of Randomized Controlled Studies Dmitrii N. Andreev * , Igor V. Maev and Diana T. Dicheva Moscow State University of Medicine and Dentistry named after A.I. Evdokimov, 127473 Moscow, Russia; [email protected] (I.V.M.); [email protected] (D.T.D.) * Correspondence: [email protected]; Tel.: +7(495)6096700 Received: 14 August 2019; Accepted: 18 September 2019; Published: 19 September 2019 Abstract: Background: There has been a negative trend in the effectiveness of classic eradication therapy regimens for Helicobacter pylori (H. pylori), which has largely been determined from the emergence and spread of antibiotic resistance. Several studies have shown that adding rebamipide to eradication regimens leads to an increase in the effectiveness of treatment. Aim: To evaluate the efficacy and safety of including rebamipide in the eradication regimens for H. pylori infection. Methods: The literature search was conducted in the MEDLINE/PubMed, EMBASE, Cochrane Central Register, Korean Medical Citation Index, and Russian Science Citation Index databases. All identified randomized controlled trials comparing rebamipide supplementation with non-rebamipide-containing eradication regimens for the treatment of H. pylori infection were included in the final analysis. Results: We identified 11 randomized controlled trials (RCTs) involving 1227 patients (631 in groups with rebamipide and 596 in groups without rebamipide). The meta-analysis showed that the addition of rebamipide to eradication regimens significantly increased the effectiveness of treatment (odds ratio (OR) 1.753, 95% confidence interval (CI) 1.312–2.333, p < 0.001).
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • Functional Dyspepsia
    Erwin Budi Cahyono DEFINITION : Symptoms like pain or nausea in epigastrium accompanied by disgust, vomit, bloat, easy to full, fullness or nitre, which is suspected come from the abnormality of upper gastro- intestinal tractus. Dyspepsia: pathogenic mechanisms Dysmotility H. pylori infection/ Altered gastric inflammation acid secretion Mechanisms of dyspepsia Psychosocial Gut hypersensitivity factors Witteman & Tytgat, Netherlands J Med 1995; 46: 205–11. Talley et al., BMJ 2001; 323:1294–7. Tack et al., Curr Gastroenterol Rep 2001; 3: 503–8. Dyspepsia: symptom assessment Nature of symptoms Severity of Character symptoms Radiation Timing, duration and frequency Modifying factors Assessment of symptoms Patient’s degree Alarm features of distress Paré, Can J Gastroenterol 1999; 13: 647–54. acute dyspepsia (new onset dyspepsia) Suddenly Sigh with the quality of sigh which is usually more tremendous with a longer response to the medication. chronic dyspepsia Sigh which is sometimes disappear, sometimes appear, more than two weeks. The sigh is not as tremendous as acute dyspepsia with a quick response to the medication. Organic Dyspepsia : There is an organ abnormality as ulcer gastro- duodenal, gastro esofageal reflux and gastric carcinoma (Talley, 1998) A common term which is given to the patient as : abdominal pain or nausea on the upper of stomach which is repeatedly happen more than three months, and at least a long of that time 25% symptoms of dyspepsia appear and no evidence organic disease which is responsible to that symptoms
    [Show full text]
  • Protective Effects of Gastric Mucus
    1 Protective Effects of Gastric Mucus Takafumi Ichikawa and Kazuhiko Ishihara Kitasato University Graduate School of Medical Sciences Japan 1. Introduction The gastric mucosa is continuously exposed to many noxious factors and substances. How the gastric mucosa maintains structural integrity and resists auto-digestion by substances such as acid and pepsin puzzled clinicians and investigators for more than 200 years. The gastric epithelium must also resist damage from extrinsic agents, including Helicobacter pylori (H. pylori) and noxious ingestions such as ethanol and nonsteroidal anti-inflammatory drugs (NSAIDs). The luminal surface of the stomach is covered by a viscoelastic mucus gel layer that acts as a protective barrier against the harsh luminal environment. The structural characteristics of this barrier are primary indicators of its physiological function and changes of its composition have been identified in gastrointestinal pathologies. This chapter presents recent insights into the implication of the gastric mucus barrier as “no mucus, no protection”. While acid, pepsin, and H. pylori are thought to be major factors in the pathophysiology of gastritis, the importance of the mucosal defense system has also been emphasized. Gastric ‘cytoprotection’ refers to a reduction or prevention of chemically induced acute hemorrhagic erosions by compounds such as prostaglandin (PG) and SH derivatives without inhibiting acid secretion in rodents (Robert, 1979; Szabo et al., 1981). Since the concept of ‘cytoprotection’ was introduced, increasing attention has been paid to the effect of medications on the gastric mucosal defensive mechanisms. Although the exact mechanisms of the mucosal defense system are unknown, it involves one or more of the naturally occurring gastric mucosal defensive factors such as mucus metabolism.
    [Show full text]