DOCSLIB.ORG

United States Patent Office Patented June 9, 1959 1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
United States Patent Office Patented June 9, 1959 1 2,890,152 United States Patent Office Patented June 9, 1959 1. 2 of its stability. It is indeed surprising that of the large 2,890,152 number of anticholinergic agents of the quaternary amine type which are in common use in medical therapy, TOPICAL ANTI-INFLAMMATORY COMPOSITIONS only one, diphemanil methylsulfate, is stable under hy George Babcock, Jr., North Caldwell, and George Ken 5 drous conditions. This distinct property is not easily neth Hawkins, Glen Ridge, N.J., assignors to Schering explained but may be due to the chemical structure of Stration, Bloomfield, N.J., a corporation of New diphemanil methylsulfate. The substance is a piperi ersey dyiidene derivative while for the most part all other anti No Drawing. Application November 29, 1956 cholinergics are structurally related to atropine and/or Serial No. 624,961 10 contain a dialkaminoalkyl grouping. Laboratory test ing of other anticholinergic agents such as methantheline 7 Claims. (CI. 167-65) bromide, methscopolamine bromide, propantheline bro mide, tricyclamol methylsulfate, and the like, have dem This invention relates to therapeutic compositions and onstrated their incompatibility with hydrous media. more particularly to compositions which are useful in 5 Thus our compositions are inherently unique in their the treatment of various dermatogical conditions. content. We have found that topical preparations comprising a The active ingredients of our novel compositions can combination of diphemanil methylsulfate (4-diphenyl be incorporated into any suitable ointment or cream methylene-1,1-dimethylpiperidinium methyl sulfate) with base to provide the topical preparations of the present hydrocortisone or prednisolone (1,4-pregnadiene-11g,17c, 20 invention. Representative examples of suitable bases 21-triol-3,20-dione) offer a long-awaited adjunct in the are given in the specific examples hereinafter set forth. treatment of a variety of skin diseases. Our new com The nature and composition of such bases are well-known positions are useful in treating conditions Such as and well understood by those skilled in the prepara dyshidrotic eczematous lesions caused by drug allergies. tion and employment of topical medications. While In place of the free sterol there may be used, in some 25 each of the active ingredients present in the composi cases, an ester such as a 21-acetate or soluble stable tions of the present invention is ordinarily employed in ester of phosphoric acid and the like. The composition proportions of from about 0.1 percent to 2.5 percent by is especially applicable in the treatment of the disease weight of the final composition, proportions outside this generally known as intertrigo which is aggravated by range can also be used, such as 0.1 to 4 percent di sweating and friction between opposing skin surfaces. 30 phemanil methylsulfate and 0.1 to 4 percent steroid. Lesions which occur in the armpit due from sensitivity For achievement of optimum results, it has been deter to a deodorant, for example, and the common "diaper mined that the preferred proportions of the active in rash” quickly disappear following local application of gredients present in the composition should be one per our therapeutic combination. Furthermore, many der cent of the cortical hormone and two percent of anti matological conditions such as lichen planus, those aris 35 cholinergic agent. ing from food or drug allergies, athlete's foot, inter The compositions of the present invention can be trigo, and the like, are accompanied by severe pruritis, readily prepared by conventional procedures used in the or itching, with weeping of the lesion. The new com preparation of topical ointments or creams. For exam positions of this invention have demonstrated remark ple, the active ingredients can be incorporated into any able ability in overcoming pruritic and weeping manifes 40 suitable ointment of cream base by simply admixing in tations. By so removing the desire to scratch and further a suitable agitating device, such as a mixer or blender. aggravate the sores, the topical preparations hasten the The novel topical medications of the persent inven cure of the disease. tion are illustrated by the following examples which are The new therapeutic combinations, described in more presented for illustrative purposes only. detail below, are thus highly effective agents in combat 45 ting a host of skin diseases. It is indeed surprising that EXAMPLE the particular combination of diphemanil methylsulfate Water soluble cream with hydrocortisone or prednisolone enables control of Parts conditions which are resistant to the action of either Prednisolone ------------------------------- 5.0 active ingredient when used alone. 50 Diphemanil methylsulfate -------------------- 20.0 The mode of action of the composition is unknown al Zinc stearate ------------------------------- 60.0 though absorption of the medicament at the site ap Polyethylene Glycol 1500 -------------------- 405.0 parently occurs whereby the development of tissue re Polyethylene Glycol 6000 -------------------- 120.0 action is counteracted. No toxic reactions arising from Propylene glycol ---------------------------- 350.0 the composition have been observed. 55 Distilled H2O ------------------------------ 40.0 There appears to be a potentiation of each of the active The steroid, prednisolone, is dissolved in the mixture ingredients upon each other. Although large doses of of glycols by stirring and heating on a steam bath at hydrocortisone have been used internally or topically to about 75° C. Diphemanil methylsulfate is dissolved in combat certain skin diseases, the presence of diphemanil the distilled water. The aqueous solution is added to methylsulfate permits the use of a smaller dose of the 60 the stirred steroid solution. When a homogeneous mix corticoid. ture has been obtained, zinc stearate is dispersed through Our new compositions consist essentially of the active out the mixture and the entire batch is homogenized in ingredients suspended or dissolved in a carrier suitable an ointment mill. for topical application such as a hydrocarbon base of the petrolatum type, absorption bases, hydrophilic petro 65 EXAMPLE 2 latum bases, water-soluble bases containing polyethylene Water soluble ointment glycols and lotions. In certain instances a water-soluble Parts base is preferred so as to permit proper healing of weep Diphemanil methylsulfate -------------------- 20.0 ing lesions and overcome intertrigo. Diphemanil methyl Hydrocortisone ----------------------------- 10.0 sulfate is particularly adaptable to incorporation into 70 Zinc stearate ------------------------------- 200.0 water-soluble bases and water containing bases by virtue CarboWax 1500 ----------------------------- 549.0 Distilled Water ----------------------------- 221.0 2,890,152 3 4. Hydrocortisone is dissolved in Carbowax 1500 by heat EXAMPLE 6 ing and stirring. The remaining ingredients are added Lotion preparation in the same manner as described in Example 1. Parts EXAMPLE 3 5 Diphemanil methylsulfate --------------------- 30 Prednisolone -------------------------------- 5 Water-removable or hydrophilic preparation Methyl Paraben ----------------------------- 0.25 Parts Propyl Paraben ------------------------------ 0.15 Hydrocortisone ---------------------------- 10.00 Stearyl alcohol ------------------------------ 245 Diphemanil methylsulfate ------------------- 40.00 O Propylene glycol ----------------------------- 50 Methyl Paraben --------------------------- 0.25 Polyoxyethylene lauryl alcohol----------------- 10 Propyl Paraben ---------------------------- 0.15 Distilled water, q.s. to a total of 1000 parts. Steryl alcohol ----------------------------- 245.00 This formulation is prepared in the same manner as the White petrolatum -------------------------- 245.00 hydrophilic preparation of Example 3 except that the Propylene glycol --------------------------- 120.00 5 etrolatum is omitted. Polyoxyethylene lauryl alcohol --------------- 50.00 Having disclosed our invention, what we claim to be Distilled Water ---------------------------- 290.00 new and wish to secure by Letters Patent is: - 1000.00 1. A therapeutic composition of matter comprising a Steryl alcohol and white petrolatum are melted to steroid of the group consisting of hydrocortisone and gether on a steam bath at about 75°. The remaining 20 prednisolone in combination with diphemanil methylsul ingredients, except for the steroid, are dissolved in water. fate and a carrier. The aqueous mixture is stirred into the stearyl-alcohol 2. A therapeutic composition of matter comprising petrolatum melt. The resultant mixture is thoroughly from about 0.1 percent to about 4.0 percent of a steroid stirred at 75° C. When proper mixing has been ob defined in claim 1, from about 0.1 percent to about 4.0 tained, the mixture is allowed to cool to 50° C. Hydro 25 percent diphemanil methylsulfate, the remainder of the cortisone is then added and the preparation is stirred composition comprising a viscous supporting carrier. and allowed to cool until it completely congeals. 3. A therapeutic composition of matter comprising from about 0.1 percent to about 2.5 percent of a steroid EXAMPLE 4 defined in claim 1, from about 0.1 percent to about 2.5 Hydrocarbon ointment 30 percent of diphemanil methylsulfate, the remainder of the Parts composition comprising a viscous supporting carrier. Prednisolone -------------------------------- 10 4. A therapeutic composition of matter according to Diphemanil methylsulfate ---------------------
Load more

Recommended publications
  • Title 16. Crimes and Offenses Chapter 13. Controlled Substances Article 1
    TITLE 16. CRIMES AND OFFENSES CHAPTER 13. CONTROLLED SUBSTANCES ARTICLE 1. GENERAL PROVISIONS § 16-13-1. Drug related objects (a) As used in this Code section, the term: (1) "Controlled substance" shall have the same meaning as defined in Article 2 of this chapter, relating to controlled substances. For the purposes of this Code section, the term "controlled substance" shall include marijuana as defined by paragraph (16) of Code Section 16-13-21. (2) "Dangerous drug" shall have the same meaning as defined in Article 3 of this chapter, relating to dangerous drugs. (3) "Drug related object" means any machine, instrument, tool, equipment, contrivance, or device which an average person would reasonably conclude is intended to be used for one or more of the following purposes: (A) To introduce into the human body any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (B) To enhance the effect on the human body of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (C) To conceal any quantity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; or (D) To test the strength, effectiveness, or purity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state. (4) "Knowingly" means having general knowledge that a machine, instrument, tool, item of equipment, contrivance, or device is a drug related object or having reasonable grounds to believe that any such object is or may, to an average person, appear to be a drug related object.
    [Show full text]
  • Hyperhidrosis: Anatomy, Pathophysiology and Treatment with Emphasis on the Role of Botulinum Toxins
    Toxins 2013, 5, 821-840; doi:10.3390/toxins5040821 OPEN ACCESS toxins ISSN 2072-6651 www.mdpi.com/journal/toxins Review Hyperhidrosis: Anatomy, Pathophysiology and Treatment with Emphasis on the Role of Botulinum Toxins Amanda-Amrita D. Lakraj 1, Narges Moghimi 2 and Bahman Jabbari 1,* 1 Department of Neurology, Yale University School of Medicine; New Haven, CT 06520, USA; E-Mail: [email protected] 2 Department of Neurology, Case Western Reserve University; Cleveland, OH 44106, USA; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +1-203-737-2464; Fax: +1-203-737-1122. Received: 12 February 2013; in revised form: 27 March 2013 / Accepted: 12 April 2013 / Published: 23 April 2013 Abstract: Clinical features, anatomy and physiology of hyperhidrosis are presented with a review of the world literature on treatment. Level of drug efficacy is defined according to the guidelines of the American Academy of Neurology. Topical agents (glycopyrrolate and methylsulfate) are evidence level B (probably effective). Oral agents (oxybutynin and methantheline bromide) are also level B. In a total of 831 patients, 1 class I and 2 class II blinded studies showed level B efficacy of OnabotulinumtoxinA (A/Ona), while 1 class I and 1 class II study also demonstrated level B efficacy of AbobotulinumtoxinA (A/Abo) in axillary hyperhidrosis (AH), collectively depicting Level A evidence (established) for botulinumtoxinA (BoNT-A). In a comparator study, A/Ona and A/Inco toxins demonstrated comparable efficacy in AH. For IncobotulinumtoxinA (A/Inco) no placebo controlled studies exist; thus, efficacy is Level C (possibly effective) based solely on the aforementioned class II comparator study.
    [Show full text]
  • NORIG 2BC - Blood Collection for DNABC109 Mar 09 BC - Blood Collection for DNA
    Keyed: ( ) NORIG 2BC - Blood Collection for DNABC109 Mar 09 BC - Blood Collection for DNA Purpose: Document the collection of whole blood for shipment to NIDDK Genetics Repository at Rutgers University for DNA extraction and banking. Complete this form only if the patient signed the consent for genetic research. When: Screening visit s1 or s2 and as needed during follow-up due to a low yield (less than 50 μg) of DNA (during follow-up, use the visit code of the follow-up visit that is open). By whom: Clinical Coordinator and laboratory personnel responsible for collection of whole blood. Instructions: (1) Apply MACO labels specific for the patient and visit to the EDTA vacutainer tubes; these labels are generated by the clinical center upon registration (screening labels) or after randomization (follow-up visit labels). Affix duplicate tube label in item 13. (2) Fill two 10 mL EDTA vacutainer tubes with whole blood (see SOP I, section 6.2). (3) Pack the whole blood tubes in the specimen shippers supplied by the NIDDK Genetics Repository and ship to the NIDDK Genetic Repository at Rutgers University on the same day blood is collected. Ship blood at ambient room temperature. Use the preprinted Federal Express shipping label, marked for Priority Overnight Delivery, to ship whole blood to the NIDDK Genetics Repository Monday-Friday. A. Center, patient and visit identification C. Specimen for Genetics Repository 1. Center code: Attach MACO labels to two 10mL EDTA tubes and fill each with whole blood; invert each tube gently 6 times to mix blood with additives; keep tubes at 2.
    [Show full text]
  • Pharmaceuticals As Environmental Contaminants
    PharmaceuticalsPharmaceuticals asas EnvironmentalEnvironmental Contaminants:Contaminants: anan OverviewOverview ofof thethe ScienceScience Christian G. Daughton, Ph.D. Chief, Environmental Chemistry Branch Environmental Sciences Division National Exposure Research Laboratory Office of Research and Development Environmental Protection Agency Las Vegas, Nevada 89119 [email protected] Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada Why and how do drugs contaminate the environment? What might it all mean? How do we prevent it? Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada This talk presents only a cursory overview of some of the many science issues surrounding the topic of pharmaceuticals as environmental contaminants Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada A Clarification We sometimes loosely (but incorrectly) refer to drugs, medicines, medications, or pharmaceuticals as being the substances that contaminant the environment. The actual environmental contaminants, however, are the active pharmaceutical ingredients – APIs. These terms are all often used interchangeably Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada Office of Research and Development Available: http://www.epa.gov/nerlesd1/chemistry/pharma/image/drawing.pdfNational
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9,283,192 B2 Mullen Et Al
    US009283192B2 (12) United States Patent (10) Patent No.: US 9,283,192 B2 Mullen et al. (45) Date of Patent: Mar. 15, 2016 (54) DELAYED PROLONGED DRUG DELIVERY 2009. O1553.58 A1 6/2009 Diaz et al. 2009,02976O1 A1 12/2009 Vergnault et al. 2010.0040557 A1 2/2010 Keet al. (75) Inventors: Alexander Mullen, Glasgow (GB); 2013, OO17262 A1 1/2013 Mullen et al. Howard Stevens, Glasgow (GB); Sarah 2013/0022676 A1 1/2013 Mullen et al. Eccleston, Scotstoun (GB) FOREIGN PATENT DOCUMENTS (73) Assignee: UNIVERSITY OF STRATHCLYDE, Glasgow (GB) EP O 546593 A1 6, 1993 EP 1064937 1, 2001 EP 1607 O92 A1 12/2005 (*) Notice: Subject to any disclaimer, the term of this EP 2098 250 A1 9, 2009 patent is extended or adjusted under 35 JP HO5-194188 A 8, 1993 U.S.C. 154(b) by 0 days. JP 2001-515854. A 9, 2001 JP 2001-322927 A 11, 2001 JP 2003-503340 A 1, 2003 (21) Appl. No.: 131582,926 JP 2004-300148 A 10, 2004 JP 2005-508326 A 3, 2005 (22) PCT Filed: Mar. 4, 2011 JP 2005-508327 A 3, 2005 JP 2005-508328 A 3, 2005 (86). PCT No.: PCT/GB2O11AOOO3O7 JP 2005-510477 A 4/2005 JP 2008-517970 A 5, 2008 JP 2009-514989 4/2009 S371 (c)(1), WO WO99,12524 A1 3, 1999 (2), (4) Date: Oct. 2, 2012 WO WOO1 OO181 A2 1, 2001 WO WOO3,O266.15 A2 4/2003 (87) PCT Pub. No.: WO2011/107750 WO WOO3,O26625 A1 4/2003 WO WO 03/026626 A2 4/2003 PCT Pub.
    [Show full text]
  • Topical and Systemic Anticholinergic for Treating Hyperhidrosis
    Review Article Page 1 of 6 Topical and systemic anticholinergic for treating hyperhidrosis Ada Regina Trindade de Almeida1, Vanessa Rocha de Moura Moreira2, Fernanda Ferrari2 1Dermatologist, Responsible for the Cosmiatry Sector of the Dermatology Clinic of Hospital do Servidor Público Municipal de São Paulo, São Paulo, Brazil; 2Dermatology Resident of the Dermatology Clinic of Hospital do Servidor Público Municipal de São Paulo, São Paulo, Brazil Contributions: (I) Conception and design: Ada Regina Trindade de Almeida (II) Administrative support: Ada Regina Trindade de Almeida (III) Provision of study materials or patients: All authors (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Ada Regina Trindade de Almeida. Dermatologist, Responsible for the Cosmiatry Sector of the Dermatology Clinic of Hospital do Servidor Público Municipal de São Paulo, Rua Turiassu, 390, cj 113/114, Perdizes, São Paulo, SP, Brazil. Email: [email protected]. Abstract: Topical and systemic anticholinergic drugs continue to be useful medications in the management of Hyperhidrosis and accordingly to the International Hyperhidrosis Society (IHHS) algorithm for treatment, they are the initial therapeutic option for all primary forms of excessive sweating. In this article, several topical and systemic agents will be reviewed and information about efficacy, safety and side effects will be discussed. Keywords: Topical anticholinergic drugs; systemic anticholinergic drugs; hyperhidrosis Received: 27 January 2019; Accepted: 14 June 2019; Published: 06 August 2019. doi: 10.21037/shc.2019.07.02 View this article at: http://dx.doi.org/10.21037/shc.2019.07.02 Topical agents of the eccrine secretory cells.
    [Show full text]
  • Drug Schedules Regulation B.C
    Pharmacy Operations and Drug Scheduling Act DRUG SCHEDULES REGULATION B.C. Reg. 9/98 Deposited and effective January 9, 1998 Last amended June 28, 2018 by B.C. Reg. 137/2018 Consolidated Regulations of British Columbia This is an unofficial consolidation. Point in time from June 28 to December 6, 2018 B.C. Reg. 9/98 (O.C. 35/98), deposited and effective January 9, 1998, is made under the Pharmacy Operations and Drug Scheduling Act, S.B.C. 2003, c. 77, s. 22. This is an unofficial consolidation provided for convenience only. This is not a copy prepared for the purposes of the Evidence Act. This consolidation includes any amendments deposited and in force as of the currency date at the bottom of each page. See the end of this regulation for any amendments deposited but not in force as of the currency date. Any amendments deposited after the currency date are listed in the B.C. Regulations Bulletins. All amendments to this regulation are listed in the Index of B.C. Regulations. Regulations Bulletins and the Index are available online at www.bclaws.ca. See the User Guide for more information about the Consolidated Regulations of British Columbia. The User Guide and the Consolidated Regulations of British Columbia are available online at www.bclaws.ca. Prepared by: Office of Legislative Counsel Ministry of Attorney General Victoria, B.C. Point in time from June 28 to December 6, 2018 Pharmacy Operations and Drug Scheduling Act DRUG SCHEDULES REGULATION B.C. Reg. 9/98 Contents 1 Alphabetical order 2 Sale of drugs 3 [Repealed] SCHEDULES Alphabetical order 1 (1) The drug schedules are printed in an alphabetical format to simplify the process of locating each individual drug entry and determining its status in British Columbia.
    [Show full text]
  • Alphabetical Listing of ATC Drugs & Codes
    Alphabetical Listing of ATC drugs & codes. Introduction This file is an alphabetical listing of ATC codes as supplied to us in November 1999. It is supplied free as a service to those who care about good medicine use by mSupply support. To get an overview of the ATC system, use the “ATC categories.pdf” document also alvailable from www.msupply.org.nz Thanks to the WHO collaborating centre for Drug Statistics & Methodology, Norway, for supplying the raw data. I have intentionally supplied these files as PDFs so that they are not quite so easily manipulated and redistributed. I am told there is no copyright on the files, but it still seems polite to ask before using other people’s work, so please contact <[email protected]> for permission before asking us for text files. mSupply support also distributes mSupply software for inventory control, which has an inbuilt system for reporting on medicine usage using the ATC system You can download a full working version from www.msupply.org.nz Craig Drown, mSupply Support <[email protected]> April 2000 A (2-benzhydryloxyethyl)diethyl-methylammonium iodide A03AB16 0.3 g O 2-(4-chlorphenoxy)-ethanol D01AE06 4-dimethylaminophenol V03AB27 Abciximab B01AC13 25 mg P Absorbable gelatin sponge B02BC01 Acadesine C01EB13 Acamprosate V03AA03 2 g O Acarbose A10BF01 0.3 g O Acebutolol C07AB04 0.4 g O,P Acebutolol and thiazides C07BB04 Aceclidine S01EB08 Aceclidine, combinations S01EB58 Aceclofenac M01AB16 0.2 g O Acefylline piperazine R03DA09 Acemetacin M01AB11 Acenocoumarol B01AA07 5 mg O Acepromazine N05AA04
    [Show full text]
  • BMJ Open Is Committed to Open Peer Review. As Part of This Commitment We Make the Peer Review History of Every Article We Publish Publicly Available
    BMJ Open: first published as 10.1136/bmjopen-2018-027935 on 5 May 2019. Downloaded from BMJ Open is committed to open peer review. As part of this commitment we make the peer review history of every article we publish publicly available. When an article is published we post the peer reviewers’ comments and the authors’ responses online. We also post the versions of the paper that were used during peer review. These are the versions that the peer review comments apply to. The versions of the paper that follow are the versions that were submitted during the peer review process. They are not the versions of record or the final published versions. They should not be cited or distributed as the published version of this manuscript. BMJ Open is an open access journal and the full, final, typeset and author-corrected version of record of the manuscript is available on our site with no access controls, subscription charges or pay-per-view fees (http://bmjopen.bmj.com). If you have any questions on BMJ Open’s open peer review process please email [email protected] http://bmjopen.bmj.com/ on September 26, 2021 by guest. Protected copyright. BMJ Open BMJ Open: first published as 10.1136/bmjopen-2018-027935 on 5 May 2019. Downloaded from Treatment of stable chronic obstructive pulmonary disease: a protocol for a systematic review and evidence map Journal: BMJ Open ManuscriptFor ID peerbmjopen-2018-027935 review only Article Type: Protocol Date Submitted by the 15-Nov-2018 Author: Complete List of Authors: Dobler, Claudia; Mayo Clinic, Evidence-Based Practice Center, Robert D.
    [Show full text]
  • Cumulative Use of Strong Anticholinergics and Incident Dementia: a Prospective Cohort Study
    Supplementary Online Content Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. Published online January 26, 2015. doi:10.1001/jamainternmed.2014.7663. eTable 1. List of Anticholinergics and Minimum Effective Daily Dose eTable 2. Risk for Incident Dementia and Alzheimer Disease With 10-Year Cumulative Anticholinergic Use According to Subtype eTable 3. Risk for Incident Dementia and Alzheimer Disease With 10-Year Cumulative Anticholinergic Use Adjusted for Recent Depressive Symptoms eTable 4. Risk for Incident Dementia and Alzheimer Disease With 9-Year Cumulative Anticholinergic Use With 2-Year Lag Time eTable 5. Risk for Incident Dementia and Alzheimer Disease Dividing Heavy Anticholinergic Use Into Past, Recent, and Continuous eFigure 1. Example Calculation of Total Standardized Daily Dose eFigure 2. Scheme for Exposure Definition for Primary and Exploratory Analysis This supplementary material has been provided by the authors to give readers additional information about their work. © 2015 American Medical Association. All rights reserved. 1 Downloaded From: https://jamanetwork.com/ on 09/30/2021 eTable 1. List of anticholinergics and minimum effective daily dosea Antihistamines Antiparkinson agents Gastrointestinal antispasmodics b Azatadine (2 mg) Benztropine (0.5 mg) Adiphenine Bromodiphenhydramine Biperiden Alverine Brompheniramine (12 mg) Chlorphenoxamine Anisotropine Carbinoxamine Cycrimine Atropine products (0.0582 Chlorpheniramine
    [Show full text]
  • Management of Parkinson's Disease: an Evidence-Based Review
    Movement Disorders Vol. 17, Suppl. 4, 2002, p. i 2002 Movement Disorder Society Published by Wiley-Liss, Inc. DOI 10.1002/mds.5554 Editorial Management of Parkinson’s Disease: An Evidence-Based Review* Although Parkinson’s disease is still incurable, a large number tomatic control of Parkinson’s disease; prevention of motor com- of different treatments have become available to improve quality plications; control of motor complications; and control of non- of life and physical and psychological morbidity. Numerous jour- motor features. Based on a systematic review of the data, efficacy nal supplements have appeared in recent years highlighting one conclusions are provided. On the basis of a narrative non-system- or more of these and disparate treatment algorithms have prolifer- atic approach, statements on safety of the interventions are given ated. Although these are often quite useful, this “mentor analy- and finally, a qualitative approach is used to summarize the impli- sis” approach lacks the scientific rigor required by modern evi- cations for clinical practice and future research. dence-based medicine standards. The Movement Disorder Soci- This mammoth task has taken two years to complete and the ety, with generous but unrestricted support from representatives task force members, principal authors and contributors are to be of industry, have, therefore, commissioned a systematic review congratulated for their outstanding work. Physicians, the of the literature dealing with the efficacy and safety of available Parkinson’s disease research community and most of all patients treatments. The accompanying treatise is the result of a scrupu- themselves should welcome and embrace the salient findings of lous evaluation of the literature aimed at identifying those treat- this report as an effort to improve clinical practice.
    [Show full text]
  • Agonists of Guanylate Cyclase Useful for the Treatment of Gastrointestinal Disorders, Inflammation, Cancer and Other Disorders
    (19) TZZ ¥__T (11) EP 2 998 314 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 23.03.2016 Bulletin 2016/12 C07K 7/08 (2006.01) A61K 38/10 (2006.01) A61K 47/48 (2006.01) A61P 1/00 (2006.01) (21) Application number: 15190713.6 (22) Date of filing: 04.06.2008 (84) Designated Contracting States: (72) Inventors: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR • SHAILUBHAI, Kunwar HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT Audubon, PA 19402 (US) RO SE SI SK TR • JACOB, Gary S. New York, NY 10028 (US) (30) Priority: 04.06.2007 US 933194 P (74) Representative: Cooley (UK) LLP (62) Document number(s) of the earlier application(s) in Dashwood accordance with Art. 76 EPC: 69 Old Broad Street 12162903.4 / 2 527 360 London EC2M 1QS (GB) 08770135.5 / 2 170 930 Remarks: (71) Applicant: Synergy Pharmaceuticals Inc. This application was filed on 21-10-2015 as a New York, NY 10170 (US) divisional application to the application mentioned under INID code 62. (54) AGONISTS OF GUANYLATE CYCLASE USEFUL FOR THE TREATMENT OF GASTROINTESTINAL DISORDERS, INFLAMMATION, CANCER AND OTHER DISORDERS (57) The invention provides novel guanylate cycla- esterase. The gastrointestinal disorder may be classified se-C agonist peptides and their use in the treatment of as either irritable bowel syndrome, constipation, or ex- human diseases including gastrointestinal disorders, in- cessive acidity etc. The gastrointestinal disease may be flammation or cancer (e.g., a gastrointestinal cancer).
    [Show full text]