DOCSLIB.ORG

Use of Angiotensin-Converting Enzyme Inhibitors in Macular Degeneration

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Use of Angiotensin-Converting Enzyme Inhibitors in Macular Degeneration Europaisches Patentamt ® European Patent Office @ Publication number: 0 220 107 Office europeen des brevets A2 EUROPEAN PATENT APPLICATION (§) Application number: 86402219.9 © Int.CI.": A 61 K 31/47 A 61 K 31/55, A 61 K 31/505, © Date of filing: 07.10.86 A 61 K 31/195, A 61 K 31/66, A 61 K 31/40, A 61 K 31/495, A 61 K 31/405 ® Priority: 09.10.85 US 785925 © Applicant: MERCK & CO. INC. 126, East Lincoln Avenue P.O. Box 2000 @ Date of publication of application : Rahway New Jersey 07065 (US) 29.04.87 Bulletin 87/18 @ Inventor: Veber, Daniel F. Designated Contracting States: 290 Batleson Road CH DE FR GB IT LI NL Ambler Pennsylvania 19002 (US) Baldwin, John J. 621 Gypsy Hill Circle Gwynedd Valley Pennsylvania 19437 (US) @ Representative: Warcoin, Jacques et al Cabinet Regimbeau 26, avenue Kleber F-75116 Paris (FR) The title of the invention has been amended (Guidelines for Examination in the EPO. A-lll, 7.3). @ Use of angiotensin-convertlng enzyme inhibitors in macular degeneration. @ Angiotensin converting enzyme inhibitors are useful in the treatment of senile macular degeneration. O O CM CM Q. UJ Bundesdruckerei Berlin 0 220 107 Description ACE INHIBITORS IN MACULAR DEGENERATION SUMMAHY OF THE INVENTION 5 This invention is concerned with the use of angiotensin converting enzyme (ACE) inhibitors in the treatment of senile macular degeneration, a leading cause of visual diminution in the elderly BACKGROUND OF THE INVENTION Senile macular degeneration is a poorly characterized disease state of the elderly which appears to result 10 from a poor blood supply to the macular region of the eye. As a result, vision is lost in the central region of the eye while partial peripheral vision is retained. The disease progresses with increased vision loss, one eye at a time. Until the present invention, there was no known treatment of the disease or its symptoms although vasodilators and antihypercholesterolemics have been tried without success. Experience with ACE inhibitors as antihypertensive agents has shown a tendency for them to accumulate in 15 the eye resulting in unexpectedly high concentrations in ocular tissue [Igic et ai., Exp. Eye Res. 30, 299 (I980)]. These high concentrations result in selective ocular vasodilation thereby increasing local blood flow to the otherwise ischemic tissue thus preventing damage to the eye. It is therefore an object of this invention to provide a novel method of treating senile macular degeneration by the administration of an ACE inhibitor. 20 it is a further object of this invention to provide pharmaceutical formulations comprising an ACE inhibitor as an active ingredient for use in the novel method of treatment. DETAILED DESCRIPTION OF THE INVENTION The novel method of treatment of senile macular degeneration of this invention comprises the 25 administration to a patient in need of such treatment of an effective amount of an angiotensin converting enzyme inhibitor. The angiotensin converting enzyme inhibitor useful as the active ingredient in the novel method of treatment and pharmaceutical formulations of this invention is selected from: enalapril, enalaprilat, lisinopril, captopril, ranipril, perindopril, zofenopril, quinapril, pentopril, cilazaprii, pivopril, fosenopril, indolapril, indalapril, 30 phenacein, fentiapril, alacepril, perindopril, murgenic acid, ancovenin, CI 925, CGS 14824a, CGS 14831, WY 44221, CI 928, SQ 28853, SQ 27786, CGS 16617, MC 838, K 26. The company codes used above serve to identify the compounds designated in the following table: vVi»K»P4ijr ^uuc ^nemicai name CI-925 2-[2-[ [l-(l-(ethoxycarbonyl)-3- phenylpropyl]amino]-l-oxopropyl-6,7- dimethoxy-1 , 2 , 3 , 4-tet rahydro-3- isoquinolinecarboxylic acid. CGS-14824a 3-[ [l-ethoxycarbonyl-3-phenyl-(lS> propyl] amino] -2,3/4, 5-tetrahydro-2- oxo-l-(3S)-benzazepine-l-acetic acid HC1. CGS-14831 3- t I l-carboxylate-3-phenyl-l(S) -pro- pyl] amino] -2,3,4, 5-tet rahydro-2-oxo- l(3S)-benzazepine-l-acetic acid HC1. :i~928 2t2-[[l-carbonyl-3-phenylpropyl]- amino] -1-oxopropyl] -1 , 2 , 3 , 4-tet ra- hydro-3-isoquinoline-carboxylic acid. 3Q-28853 [l-(S)-4S]-4-[ [2-[6-<aminosulfonyl)- 7-chloro-l,2,3,4-tetrahydro-4-oxo- 2-quinazolinyl] ethyl] -thioj -l-(3- mercapto-2-methyl-l-oxo-propyl)-L- proline monosodium salt. 0 220107 &U-2//B6 il-(S)-4S]-4-[4-[6-(aminosulfonyl)- 7-chloro-l , 2,3, 4-tetrahydro-4-oxo-2- quinazolinyl]phenoxy]-l-(3-mercapto- 2-methyl-l-oxopropyl)-L-proline. Calcium N-[(S)-3-(N-cyclohexane- carbonyl-D-alanylthio)-2-methylpro- panoyl]-L-prolinate. MeCO-Ile-Tyr-NH-CH-PO(OH) 2 wy-44221 (-)-(S)-l-[ (S) -3-mercaptc~2-methyl- 1-oxopropyl] indoline-2-carboxylic acid. CGS-16617 3-[(5-amino-l-carboxy-lS-pentyl)- amino] -2,3,4, 5-tetrahydro-2-oxo-3S- lH-l-benzazepine-l-acetic acid. The preferred inhibitors are captopril, disclosed in U.S. Patent 4,046,889, enalapril, enalaprilat or lisinapril disclosed in U.S. Patent 4,374,829, which patents are incorporated herein by reference. The route of administration can be orally; parenteral injection, for example intravenously, intramuscularly or subcutaneously; or transdermally. An effective amount of angiotensin converting enzyme inhibitor in the novel method of treatment of this nvention is the same as the effective amount normally employed for the treatment of hypertension, i.e. about ).l mg to about I g and preferably about 5 to 500 mg per day. The dosage regimen can be one to four times a Jay depending on the daily total required and the unit dosage. The novel pharmaceutical formulations of this invention for oral administration can be in the form of tablets in ;ombination with other compounding ingredients customarily used, such as, talc, vegetable oils, polyols, jenzylalcohols, gums, gelatins, starches or other carriers; dissolved, dispersed or emulsified in a suitable iquid carrier; or in capsules in a suitable encapsulating material. For transdermal administration, the active ngredient can be in the form of an ointment, a gel, a solution, suspension or emulsion in a suitable vehicle or in he form of a patch. For parenteral administration the active ingredient may be dissolved, dispersed, suspended or emulsified with an appropriate injectable vehicle. A further object of the present invention is the jse of an angiotesin converting enzyme inhibitor as listed above for the manufacture of a pharmaceutical ;omposition useful for the treatment of senile macular degeneration. 0 220 107 Pry Fiueo capsule Per Capsule cnaiaprn 50 mg 149 mg nagnesium bcearate capsule (size no. l) 200 mg ■ ne it. uve oompouna is reaucea to a no. wj Kowaer and then lactose and magnesium stearate are passed through a No. 60 bolting cloth onto the powder and the combined ingredients are mixed for 10 minutes and filled into the No. I dry gelatin capsule. Any of the other ACE inhibitors can be substituted for enalapril in the above Example I. -AfAiyiri_c: c « lypi^ci wuiei domains capiopni izo mgj, pregeiatinized starch USP (82 mg), microcrystalline cellulose (82 rig) and magnesium stearate (I mg). In like manner, for example, N-(l(S)-carboxy-3-phenylpropyl)-L-lysyl-L- jroline (20 mg) may be formulated in place of N-(l(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline with he composition of pregeiatinized starch, microcrystalline cellulose and magnesium stearate described above. Any of the other ACE inhibitors can be substituted for captopril in the above Example 2. n ly^ai iiijei;iiiuie lormuiaxion contains enaiapniat (o.4k! mg), sodium phosphate diabasic anhydrous (li.4 ng), benzyl alcohol (0.01 ml), and water for injection (1.0 ml). Similarly, this formulation can be Prepared smploying, for example, N-(l(S)-carboxy-3-phenyfpropyl)-L-lysyl-L-proline in place of N-(l(S)-ethoxycarbonyl- l-phenylpropyl)-L-alanyl-L-proline. >iami9 1. « pndrmaceuucai composition userui tor the treatment of senile macular degeneration which lomprises, as an active substance, an angiotensin converting enzyme inhibitor which is selected from : malapril, enalaprilat, lisinopril, captopril, ranipril, perindopril, zofenopril, quinapril, pentopril, cilazapril, •ivopril, fosenopril, indolapril, indaiapril, phenacein, fentiapril, alacepril, perindopril, murgenic acid Jicovenin, CI 925, CGS 14824a, CGS 14831, WY 44221, CI 928, SQ 28853, SQ 27786, CGS 16617 MC 838 K 6. 2. Ihe pharmaceutical composition of Claim I wherein the angiotensin converting enzyme inhibitor is nalapril. 3. The pharmaceutical composition of Claim I wherein the angiotensin converting enzyme inhibitor is sinopril. 4. The pharmaceutical composition of Claim I wherein the angiotensin converting enzyme inhibitor is nalaprilat. 5. The pharmaceutical composition of Claim I wherein the angiotensin converting enzyme inhibitor is aptopril. 6. The pharmaceutical composition of Claims 1-5, which comprises an appropriate vehicle for an oral a ansdermal or a parenteral administration. 7. Use of an angiotensin converting enzyme inhibitor as listed in claim I for the manufacture of a harmaceutical composition useful for the treatment of senile macular degeneration. .
Load more

Recommended publications
  • Supplementary Appendix 1. Search Strategy for the Systematic Review and Meta-Analysis
    BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) Thorax Supplementary Appendix 1. Search strategy for the systematic review and meta-analysis # COVID-19 AND (ACEI or ARB) Pubmed #1. COVID-19 ((((novel[Title/Abstract]) AND (((corona[Title/Abstract]) AND virus[Title/Abstract]) OR (coronavirus[Title/Abstract]))) OR ((COVID[Title/Abstract]) OR (COVID-19[Title/Abstract]) OR (nCoV[Title/Abstract]) OR (2019-nCoV[Title/Abstract]) OR (Novel Coronavirus Pneumon.ia[Title/Abstract]) OR (NCP[Title/Abstract]) OR (severe acute respiratory infection[Title/Abstract]) OR (SARI[Title/Abstract]) OR (SARS-CoV-2[Title/Abstract]))) #2. ARB (("Angiotensin Receptor Antagonists"[Mesh]) OR (((angiotensin receptor blocker[Title/Abstract]) OR angiotensin receptor blockers[Title/Abstract]) OR ARB.*[Title/Abstract]) OR (((angiotensin[Title/Abstract]) AND receptor[Title/Abstract]) AND (antagonist.*[Title/Abstract] OR inhibitor.*[Title/Abstract] OR blocker.*[Title/Abstract]))) OR (ARB[Title/Abstract]) OR (olmesartan[Title/Abstract]) OR (valsartan[Title/Abstract]) OR (eprosartan[Title/Abstract]) OR (irbesartan[Title/Abstract]) OR (candesartan[Title/Abstract]) OR (losartan[Title/Abstract]) OR (telmisartan[Title/Abstract]) OR (azilsartan[Title/Abstract]) OR (tasosartan[Title/Abstract]) OR (embusartan[Title/Abstract]) OR (forasartan[Title/Abstract]) OR (milfasartan[Title/Abstract]) OR (saprisartan[Title/Abstract]) OR (zolasartan[Title/Abstract])
    [Show full text]
  • Alacepril Tablet 6 Mg Alacepril Tablet 12.5 Mg Alacepril Tablet 25 Mg
    The following is an English translation of the package insert for the drug sold in Japan (as of December 2012). Chronic Heart Failure Drug for Dogs Veterinary Drug Prescription Legend Drug Alacepril Tablet 6 mg Alacepril Tablet 12.5 mg Alacepril Tablet 25 mg Alacepril Tablet is a mild, long-acting angiotensin-converting enzyme (ACE, kininase II) inhibitor synthesized and developed by Dainippon Sumitomo Pharma Co., Ltd. The active ingredient alacepril is converted in the body to deacetylalacepril, which is then further metabolized to captopril. Deacetylalacepril is effectively delivered to the arterial wall, where it directly inhibits peripheral sympathetic activity, resulting in vasodilation without modulation of the renin-angiotensin-aldosterone (RAA) system. In addition, the active metabolite captopril inhibits ACE, thereby producing both arterial and venous dilation through modulation of the RAA system. In an experimental chronic heart failure model in dogs, a single dose of 1 to 3 mg of alacepril was shown to result in sustained reduction of preload and afterload. In clinical field studies, Alacepril Tablet was administered as a single agent or in combination with diuretic or cardiotonic agents to dogs with chronic heart failure from mitral regurgitation. The results showed that Alacepril Tablet more effectively inhibited the progression of heart disease and increased the exercise tolerance of animals when compared to treatment with conventional diuretic and cardiotonic agents alone, thereby demonstrating that Alacepril Tablet produces a significant improvement in symptoms. Composition Alacepril Tablet 6 mg contains 6 mg of alacepril per tablet. Alacepril Tablet 12.5 mg contains 12.5 mg of alacepril per tablet.
    [Show full text]
  • Drugs for Primary Prevention of Atherosclerotic Cardiovascular Disease: an Overview of Systematic Reviews
    Supplementary Online Content Karmali KN, Lloyd-Jones DM, Berendsen MA, et al. Drugs for primary prevention of atherosclerotic cardiovascular disease: an overview of systematic reviews. JAMA Cardiol. Published online April 27, 2016. doi:10.1001/jamacardio.2016.0218. eAppendix 1. Search Documentation Details eAppendix 2. Background, Methods, and Results of Systematic Review of Combination Drug Therapy to Evaluate for Potential Interaction of Effects eAppendix 3. PRISMA Flow Charts for Each Drug Class and Detailed Systematic Review Characteristics and Summary of Included Systematic Reviews and Meta-analyses eAppendix 4. List of Excluded Studies and Reasons for Exclusion This supplementary material has been provided by the authors to give readers additional information about their work. © 2016 American Medical Association. All rights reserved. 1 Downloaded From: https://jamanetwork.com/ on 09/28/2021 eAppendix 1. Search Documentation Details. Database Organizing body Purpose Pros Cons Cochrane Cochrane Library in Database of all available -Curated by the Cochrane -Content is limited to Database of the United Kingdom systematic reviews and Collaboration reviews completed Systematic (UK) protocols published by by the Cochrane Reviews the Cochrane -Only systematic reviews Collaboration Collaboration and systematic review protocols Database of National Health Collection of structured -Curated by Centre for -Only provides Abstracts of Services (NHS) abstracts and Reviews and Dissemination structured abstracts Reviews of Centre for Reviews bibliographic
    [Show full text]
  • Effects of the Angiotensin-Converting Enzyme Inhibitor Alacepril in Dogs with Mitral 3 Valve Disease
    Advance Publication The Journal of Veterinary Medical Science Accepted Date: 3 Jun 2018 J-STAGE Advance Published Date: 22 Jun 2018 1 1 FULL PAPER, Internal medicine 2 Effects of the angiotensin-converting enzyme inhibitor alacepril in dogs with mitral 3 valve disease 4 5 Yasutomo Hori1), Kensuke Nakamura2), Nobuyuki Kanno3),Makoto Hitomi4), Yohei 6 Yamashita5,6), Satoshi Hosaka7), Noriko Isayama8) and Takahiro Mimura9) 7 8 1) School of Veterinary Medicine, Rakuno Gakuen University, 582 Midori-machi, 9 Bunkyodai, Ebetsu, Hokkaido 069-8501, Japan. 10 2) University of Miyazaki, 1-1 Gakuenkibanadai-nishi, Miyazaki, 889-2192 Japan. 11 3) Veterinary Internal Medicine, Department of Veterinary Medicine, College of 12 Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 13 252-8510, Japan. 14 4) Hitomi Animal Hospital, 37-7 Yoshidakamiadachicho, Sakyo, Kyoto, 606-8307, 15 Japan. 16 5) Ebisu Animal Hospital, 3-3-43 Nishitaga, Taihaku, Sendai, Miyagi 982-0034, 17 Japan. 18 6) Laboratory of Small Animal Internal Medicine II, School of Veterinary Medicine, 19 Kitasato University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan 20 7) Hosaka Animal Hospital, 4-17-1 Nihonmatsu Midori, Sagamihara, Kanagawa, 21 252-0137, Japan. 22 8) Uenonomori Animal Clinic, 1-5-11 Yanaka Taito, Tokyo, 110-0001, Japan. 23 9) Olieve Animal Medical Center, 12-5 Shinomiyakandacho, Yamashina, Kyoto 24 607-8035, Japan. 25 26 Address correspondence to: Yasutomo Hori 27 School of Veterinary Medicine, Rakuno Gakuen University, 582 Midori-machi, 28 Bunkyodai, Ebetsu, Hokkaido 069-8501, Japan. 29 E-mail: [email protected] 30 31 RUNNING HEAD: EFFECTS OF ALACEPRIL IN DOGS 1 2 32 ABSTRACT 33 Alacepril is a relatively novel angiotensin-converting enzyme inhibitor; however, the 34 safety, tolerance, and efficacy of alacepril in terms of cough suppression in dogs with 35 mitral valve disease (MVD) remain unknown.
    [Show full text]
  • Antihypertensive Drugs
    Antihypertensive Drugs Treatment of Hypertension: 7 classification Categories Risk factors BP Systolic Diastolic 1. Age above 55 and 65 in Normal >120 <80 Men and Woman Prehypertension 120-139 80-89 respectively Stage1 149-159 90-99 2. Family History Stage2 >160 >100 3. Smoking 4. DM and Dyslipidemia 5. Hypertension 6. Obesity 7. Microalbuminuria Antihypertensive Drugs • Diuretics: – Thiazides: Hydrochlorothiazide, chlorthalidone – High ceiling: Furosemide – K+ sparing: Spironolactone, triamterene and amiloride MOA: Acts on Kidneys to increase excretion of Na and H2O – decrease in blood volume – decreased BP • Angiotensin-converting Enzyme (ACE) inhibitors: – Captopril, lisinopril., enalapril, ramipril and fosinopril MOA: Inhibit synthesis of Angiotensin II – decrease in peripheral resistance and blood volume • Angiotensin (AT1) receptor blockers: – Losartan, candesartan, valsartan and telmisartan MOA: Blocks binding of Angiotensin II to its receptors Antihypertensive Drugs • Centrally acting: – Clonidine, methyldopa MOA: Act on central α2A receptors to decrease sympathetic outflow – fall in BP • ß-adrenergic blockers: – Non selective: Propranolol (others: nadolol, timolol, pindolol, labetolol) – Cardioselective: Metoprolol (others: atenolol, esmolol, betaxolol) MOA: Bind to beta adrenergic receptors and blocks the activity • ß and α – adrenergic blockers: – Labetolol and carvedilol • α – adrenergic blockers: – Prazosin, terazosin, doxazosin, phenoxybenzamine and phentolamine MOA: Blocking of alpha adrenergic receptors in smooth muscles
    [Show full text]
  • Summary of Investigation Results Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers
    Pharmaceuticals and Medical Devices Agency This English version is intended to be a reference material to provide convenience for users. In the event of inconsistency between the Japanese original and this English translation, the former shall prevail. Summary of investigation results Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers June 3, 2014 Non-proprietary Name See Annex Brand Name (Marketing Authorization Holder) See Annex Indications See Annex Summary of revision The following information should be added in Precautions for concomitant use section: Renal impairment, hyperkalaemia, and/or hypotension may occur when angiotensin- converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are concomitantly used. Background of the revision and investigation results A meta-analysis was conducted to evaluate the efficacy and safety of the concomitant use of ACEIs and ARBs. A literature on the meta-analysis reported that risks of renal impairment, hyperkalaemia, and hypotension were significantly higher in the concomitant therapy group than in the monotherapy group. Following an investigation result based on opinions of expert advisors and available evidence, the MHLW/PMDA concluded that revision of the package inserts was necessary. Pharmaceuticals and Medical Devices Agency Office of Safety I 3-3-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-0013 Japan E-mail: [email protected] Pharmaceuticals and Medical Devices Agency This English version is intended to be a reference material to provide
    [Show full text]
  • Telmisartan Versus Angiotension-Converting
    Journal of Human Hypertension (2009) 23, 339–349 & 2009 Macmillan Publishers Limited All rights reserved 0950-9240/09 $32.00 www.nature.com/jhh ORIGINAL ARTICLE Telmisartan versus angiotension- converting enzyme inhibitors in the treatment of hypertension: a meta-analysis of randomized controlled trials Z Zou1,3, G-L Xi2,3, H-B Yuan1, Q-F Zhu1 and X-Y Shi1 1Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of China and 2Center for New Drug Evaluation, Institute of Basic Medical Science, Second Military Medical University, Shanghai, People’s Republic of China Telmisartan and angiotensin-converting enzyme inhibi- 0.33–2.62). Telmisartan also showed a greater DBP tors (ACEIs) are both effective and widely used response rate than enalapril (relative risk (RR) 1.15, antihypertensive drugs targeting renin–angiotensin– 95% CI 1.05–1.26), ramipril (RR 1.34, 95% CI 1.11–1.61) aldosterone system. The study aimed to estimate the and perindopril (RR 1.22, 95% CI 1.05–1.41). There was efficacy and tolerability of telmisartan in comparison no statistical difference in DBP reduction or therapeutic with different ACEIs as monotherapy in the treatment of response rate between telmisartan and lisinopril (WMD hypertension. Cochrane Central Register of Controlled À0.30, 95% CI À0.65 to 0.05; RR 0.99, 95% CI 0.80–1.23, Trials, PubMed and Embase were searched for relevant respectively). Telmisartan had fewer drug-related studies. A meta-analysis of all randomized controlled adverse events than enalapril (RR 0.57, 95% CI 0.44–0.74), trials fulfilling the predefined criteria was performed.
    [Show full text]
  • Effect of Angiotensin Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker on the Patients with Sepsis
    ORIGINAL ARTICLE Korean J Intern Med 2021;36:371-381 https://doi.org/10.3904/kjim.2019.262 Effect of angiotensin converting enzyme inhibitor and angiotensin II receptor blocker on the patients with sepsis Hyun Woo Lee1,*,†, Jae Kyung Suh2,*, Eunjin Jang3, and Sang-Min Lee1 1Division of Pulmonary and Critical Background/Aims: Inhibitors of the renin-angiotensin system, angiotensin-con- Care Medicine, Department of verting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), Internal Medicine, Seoul National University Hospital, Seoul; 2National reportedly have anti-inflammatory effects. This study assessed the association of Evidence-Based Healthcare prior use of ACE inhibitors and ARBs with sepsis-related clinical outcomes. Collaborating Agency, Seoul; 3 Methods: A population-based observational study was conducted using the Department of Information Statistics, Andong National University, Andong, Health Insurance Review and Assessment Service claims data. Among the adult Korea patients hospitalized with new onset of sepsis in 2012, patients who took ARBs or ACE inhibitors at least 30 days prior to hospitalization were analyzed. Generalized linear models and logistic regression were used to examine the relation between the prior use of medication and clinical outcomes, such as in-hospital mortality, mechanical ventilation, and length of stay. Results: Of a total of 27,628 patients who were hospitalized for sepsis, the ACE in- Received : August 8, 2019 hibitor, ARB, and non-user groups included 1,214 (4.4%), 3,951 (14.4%), and 22,463 Revised : October 19, 2019 (82.1%) patients, respectively. As the patients in the ACE inhibitor and ARB groups Accepted : November 25, 2019 had several comorbid conditions, higher rates of intensive care unit admission, Correspondence to hemodialysis, and mechanical ventilation were observed.
    [Show full text]
  • Harmonized Tariff Schedule of the United States (2004) -- Supplement 1 Annotated for Statistical Reporting Purposes
    Harmonized Tariff Schedule of the United States (2004) -- Supplement 1 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2004) -- Supplement 1 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABACAVIR 136470-78-5 ACEXAMIC ACID 57-08-9 ABAFUNGIN 129639-79-8 ACICLOVIR 59277-89-3 ABAMECTIN 65195-55-3 ACIFRAN 72420-38-3 ABANOQUIL 90402-40-7 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABCIXIMAB 143653-53-6 ACITEMATE 101197-99-3 ABECARNIL 111841-85-1 ACITRETIN 55079-83-9 ABIRATERONE 154229-19-3 ACIVICIN 42228-92-2 ABITESARTAN 137882-98-5 ACLANTATE 39633-62-0 ABLUKAST 96566-25-5 ACLARUBICIN 57576-44-0 ABUNIDAZOLE 91017-58-2 ACLATONIUM NAPADISILATE 55077-30-0 ACADESINE 2627-69-2 ACODAZOLE 79152-85-5 ACAMPROSATE 77337-76-9 ACONIAZIDE 13410-86-1 ACAPRAZINE 55485-20-6 ACOXATRINE 748-44-7 ACARBOSE 56180-94-0 ACREOZAST 123548-56-1 ACEBROCHOL 514-50-1 ACRIDOREX 47487-22-9 ACEBURIC ACID 26976-72-7
    [Show full text]
  • The Potential Therapeutic Use of Reninangiotensin System Inhibitors
    The potential therapeutic use of renin-angiotensin system inhibitors in the treatment of inflammatory diseases Article (Accepted Version) Ranjbar, Reza, Shafiee, Mojtaba, Hesari, AmirReza, Ferns, Gordon A, Ghasemi, Faezeh and Avan, Amir (2019) The potential therapeutic use of renin-angiotensin system inhibitors in the treatment of inflammatory diseases. Journal of Cellular Physiology, 234 (3). pp. 2277-2295. ISSN 0021-9541 This version is available from Sussex Research Online: http://sro.sussex.ac.uk/id/eprint/77293/ This document is made available in accordance with publisher policies and may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher’s version. Please see the URL above for details on accessing the published version. Copyright and reuse: Sussex Research Online is a digital repository of the research output of the University. Copyright and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable, the material made available in SRO has been checked for eligibility before being made available. Copies of full text items generally can be reproduced, displayed or performed and given to third parties in any format or medium for personal research or study, educational, or not-for-profit purposes without prior permission or charge, provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. http://sro.sussex.ac.uk The potential therapeutic use of renin-angiotensin system inhibitors in the treatment of inflammatory diseases Reza Ranjbar1, Mojtaba Shafiee1,2, AmirReza Hesari3, Gordon A Ferns4, Faezeh Ghasemi3#, Amir Avan5,6# 1.
    [Show full text]
  • Selective AT2 Receptor Agonists for Use in Treatment of Cachexia
    (19) TZZ ¥ ¥_T (11) EP 2 832 357 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 04.02.2015 Bulletin 2015/06 A61K 31/4174 (2006.01) A61P 43/00 (2006.01) (21) Application number: 13178319.3 (22) Date of filing: 29.07.2013 (84) Designated Contracting States: • Anker, Stefan AL AT BE BG CH CY CZ DE DK EE ES FI FR GB 13053 Berlin (DE) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO • Coats, Andrew PL PT RO RS SE SI SK SM TR St. Kilda, 3168 (AU) Designated Extension States: BA ME (74) Representative: Gulde & Partner Patent- und Rechtsanwaltskanzlei mbB (71) Applicant: Charité - Universitätsmedizin Berlin Wallstraße 58/59 10117 Berlin (DE) 10179 Berlin (DE) (72) Inventors: • Springer, Jochen 14612 Falkensee (DE) (54) Selective AT2 receptor agonists for use in treatment of cachexia (57) The present invention is directed to selective AT2 receptor agonist or a pharmaceutically acceptable salt thereof for use in treatment of cachexia, preferably for use in treatment of cancer cachexia. EP 2 832 357 A1 Printed by Jouve, 75001 PARIS (FR) EP 2 832 357 A1 Description [0001] Cachexia is a severe complication of multiple separate illnesses and an area of significant unmet medical need. Successful treatment or prevention of cachexia may lead to improved quality of life and prolonged life expectancy in 5 affected patients. [0002] It has already been described that the renin-angiotensin system (RAS) is involved in development of cachexia, see e.g. WO 99/20260. [0003] The octapeptide angiotensin II is the main biologically active component of the renin-angiotensin-system (RAS) in humans.
    [Show full text]
  • Pimobendan to Be Used for the Reduction of Heart Size
    (19) TZZ_ ¥_T (11) EP 1 778 234 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 31/501 (2006.01) A61K 31/4412 (2006.01) 05.10.2011 Bulletin 2011/40 A61K 31/4427 (2006.01) A61K 31/444 (2006.01) A61K 31/4166 (2006.01) A61P 9/00 (2006.01) (21) Application number: 05716238.0 (86) International application number: (22) Date of filing: 19.03.2005 PCT/EP2005/002957 (87) International publication number: WO 2005/092343 (06.10.2005 Gazette 2005/40) (54) PIMOBENDAN TO BE USED FOR THE REDUCTION OF HEART SIZE IN MAMMALS SUFFERING FROM HEART FAILURE PIMOBENDAN ZUR VERWENDUNG ZUR VERRINGERUNG DER HERZGRÖSSE VON SÄUGETIEREN MIT HERZINSUFFIZIENZ PIMOBENDAN UTILISE POUR LA REDUCTION DE LA TAILLE DU COEUR CHEZ DES MAMMIFERES SOUFFRANT D’INSUFFICANCES CARDIAQUES (84) Designated Contracting States: • KLEEMANN, Rainer AT BE BG CH CY CZ DE DK EE ES FI FR GB GR 55218 Ingelheim (DE) HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR Designated Extension States: (74) Representative: Hammann, Heinz BA HR LV Boehringer Ingelheim Pharma GmbH & Co. KG Binger Strasse 173 (30) Priority: 25.03.2004 EP 04007179 55216 Ingelheim am Rhein (DE) (43) Date of publication of application: (56) References cited: 02.05.2007 Bulletin 2007/18 US-A- 4 361 563 US-A- 4 654 342 US-A- 4 868 182 US-A- 4 906 628 (73) Proprietor: Boehringer Ingelheim Vetmedica US-A- 5 151 420 US-A- 5 569 657 GmbH 55216 Ingelheim am Rhein (DE) • BEERS, M.H.
    [Show full text]