DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 8,778,998 B2 Zhang (45) Date of Patent: Jul

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 8,778,998 B2 Zhang (45) Date of Patent: Jul US008778998B2 (12) United States Patent (10) Patent No.: US 8,778,998 B2 Zhang (45) Date of Patent: Jul. 15, 2014 (54) BIPHENYL-3-CARBOXYLICACID WO 2008107446 A1 9, 2008 MODULATORS OF WO 2008124803 A1 10, 2008 WO 2009056.232 A2 5, 2009 BETA-3-ADRENORECEPTOR WO 2009 151569 A2 12/2009 WO 2010118291 A2 10, 2010 (75) Inventor: Chengzhi Zhang, San Diego, CA (US) WO 2010118291 A3 10, 2010 WO 2010 147830 ?2 12/2010 (73) Assignee: Auspex Pharmaceuticals, Inc., Vista, CA (US) OTHER PUBLICATIONS Dyck et al. Journal of Neurochemistry vol. 46 Issue 2, pp. 399-404 (*) Notice: Subject to any disclaimer, the term of this (1986).* patent is extended or adjusted under 35 Tonnet al. Biological Mass Spectrometry vol. 22 Issue 11, pp. 633 U.S.C. 154(b) by 629 days. 642 (1993).* Haskins, Biomedical Spectrometry vol. 9 Issue 7, pp. 269-277 (21) Appl. No.: 12/757,444 (1982).* Wolen, Journal of Clinical Pharmacology 1986; 26: 419-424.* (22) Filed: Apr. 9, 2010 Browne, Journal of Clinical Pharmacology 1998; 38: 213-220.* Baillie, Pharmacology Rev. 1981: 33:81-132.* (65) Prior Publication Data Gouyette, Biomedical and Environmental Mass Spectrometry, vol. US 2010/0286275A1 Nov. 11, 2010 15, 243-247 (1988).* CRC, CRC Handbook of Chemistry and Physics, 1989, CRC Press, Inc., Boca Raton, FL, p. B-228.* Related U.S. Application Data Pieniaszek et al., J. Clin Pharmacol. 1999; 39: 817-825.* Honma et al., Drug Metab Dispos 15 (4): 551 (1987).* (60) Provisional application No. 61/168.248, filed on Apr. Hicks, k et al., GW427353 (Solabegron), a Novel, Selective Beta3 10, 2009. Adrenergic Receptor Agonist, Evokes Bladder Relaxation and Increases Micturition Reflex Threshold in the Dog, JPET, 2007, 323, (51) Int. Cl. 2O2-09. A 6 IKI 3/95 (2006.01) Uehling, D. et al., Synthesis and Evaluation of Potent and Selective C07C 59/48 (2006.01) Beta3-Adrenergic Receptor Agonists Containing Acylsulfonamide, (52) U.S. Cl. Sulfonylsulfonamide, and Sulfonylurea Carboxylic Acid Isosteres, J. USPC ......................................................................... 514/564:562/457 Med. Chem. 2002, 45,567-583. Uehling, D. et al., Biarylaniline Phenethanolamines as Potent and (58) Field of Classification Search Selective Beta3 Adrenergic Receptor Agonists, J. Med. Chem. 2006, CPC . C07C 229/52; C07B 59/001; A61 K 31/196 49, 2758-2771. See application file for complete search history. Kushner, D. Jet al., Pharmacological uses and perspectives of heavy water and deuterated compounds, Can. J. Physiol. Pharmacol., 1999, (56) References Cited 77, 79-88. U.S. PATENT DOCUMENTS (Continued) 6,221,335 B1 * 4/2001 Foster .......................... 424f1.81 Primary Examiner – Paul A Zucker 6,251,925 B1* 6/2001 Donaldson et al. ... 514,354 6,440,710 B1* 8/2002 Keinan et al. ................. 435/148 (74) Attorney, Agent, or Firm — Dennis A. Bennett; Michael 6,548,523 B2 4/2003 Lawrence S. Sertic 6.603.008 B1 * 8/2003 Ando et al. ................ 546,269.7 7,425,639 B2 9, 2008 Cooke (57) ABSTRACT 7,517.990 B2 * 4/2009 Ito et al. ........ 546, 184 2002fOO13372 A1 1/2002 Ekins The present invention relates to new biphenyl-3-carboxylic 2002fO198220 A1 12/2002 Lawrence acid modulators of beta-3-adrenoceptor activity, pharmaceu 2004/OO77868 A1 4/2004 Cooke tical compositions thereof, and methods of use thereof, 2007/0082929 A 1 * 4/2007 Gant et al. .................... 514,338 wherein R-R are independently selected from the group 2007/0197695 A1* 8/2007 Potyen et al. ............. 524/110 2008, OO33011 A1 2/2008 Tung consisting of hydrogen and deuterium; and at least one of 2008/O132555 A1 6/2008 Gant et al. R-R is deuterium. 2008/0242596 A1 10/2008 Chen 2008/0306160 A1 12/2008 Kobayashi et al. 2008/0306.278 A1 12/2008 Cooke 2009.0075937 A1 3/2009 Engel 2009.0312242 A1 12, 2009 Castro 2010, OOO9934 A1 1/2010 Rickles 2010/0286275 A1 1 1/2010 Zhang 2011/0081426 A1 4/2011 Rao et al. FOREIGN PATENT DOCUMENTS WO 9526325 A2 10, 1995 WO 9965877 A1 12/1999 WO O142.195 A1 6, 2001 WO O2O66418 A2 8, 2002 WO 2007026630 A1 8, 2007 WO 2008.000760 A1 1, 2008 5 Claims, No Drawings US 8,778,998 B2 Page 2 (56) References Cited Browne, Thomas, Stable Isotope Techniques in Early Drug Develop ment: An Economic Evaluation, J. Clin. Pharmacol., 1998, 38,213 OTHER PUBLICATIONS 220. Cherrah et al., Study of Deuterium Isotope Effects on Protein Binding Bauer et al., Influence of long-term infusions on lidocaine kinetics, by Gas Chromatography/Mass Spectrometry. Caffeine and Deuter Clin. Pharmacol. Ther., 1982, 31(4), 433-7. ated Isomers, Biomedical and Environmental Mass Spectrometry, Borgstrom et al., Comparative Pharmacokinetics of Unlabeled and 1987, 14,653-657. Deuterium-Labeled Terbutaline: Demonstration of a Small Isotope Dyck et al., Effects of Deuterium Substitution on the Catabolism of Effect, J Pharm Sci., 77(11) 952-4 (1988). Beta-Phenethylamine: Anin Vivo Study, J. Neurochem., 1986, 46(2), Browne et al., Chapter 2. Isotope Effect: Implications for pharma 399-404. ceutical investigations, Stable isotopes in pharmaceutical research; Gouyette Alain, Use of Deuterium-Labelled Elliptinium and Its Use Elsevier; Amsterdam, 1997. in Metabolic Studies, Biomedical and Environmental Mass Spec Browne et al., Pharmacokinetic equivalence of stable-isotope-la trometry, 1988, 15, 243-247. beled and unlabeled drugs. Phenobarbital in man, J. Clin Pharmacol, Haskins, n. J., The Application of Stable Isotopes in Biomedical 1982,22,309-15. Research, Biomedical Mass Spectrometry, 1982, 9(7), 269-277. Burm et al., Pharmacokinetics of Lidocaine and Bupivacaine and Honma et al., The Metabolism of Roxatidine Acetate Hydrochloride, stbel isotope labelled analogues: a study in healthy volunteers, Drug Metabolism and Disposition, 1987, 15(4), 551-559. Biopharma & Drug Disp, 1988, 9, 85-95. Pieiaszek et al., Moricizine Bioavailability Via Simultaneous, Dual, Elison et al., Effect of deuteration of N-CH3 Group on Potency and Stable Isotope Administration: Bioecuivalence Implications, J. Clin. enzymatic N-demethylation of morphine, Science, 1961,134(3485), Pharmacol., 1999, 39, 817-825. 1078-9. Tonn et al., Simultaneous Analysis of Diphenylhydramine and a Farmer et al., Synthesis, metabolism, and antitumor activity of Stable Isotope Analog (2H10) Diphenylhydramine Using Capillary deuterated analogues of 1-(2-chloroethyl)-3-cyclohexyl-1- Gas Chromatography With Mass Selective Detection in Biological nitrosourea, J Med Chem, 1978, 21(6), 514-520. Fluids From Chronically Instrumented Pregnant EWES, Biomedical Fisher et al., The complexities inherent in attempts to decrease drug Mass Spectrometry, 1993, 22, 633-642. clearance by blocking sites of CYP-mediated metabolism, Curr Opin Wolen et al., The Application of Stable Isotopes to Studies of Drug in Drug Disc & Develop, 2006, 9(1), 101-9. Bioavailibility and Bioecuivalence, J. Clin. Pharmacol., 1986, 26. Foster et al., Deuterium isotope effects in studies of drug metabolism, 419-424. Trends in Pharma Sci, 1984,524-7. Grudell et al., Dose-Response Effect of a Beta-3-Adrenergic Recep Helfenbein et al., Isotopic Effect Study of Propofol Deuteration on tor Agonist, Solabegron, on Gastrointestinal Transit, Bowel Func the Metabolism, Activity, and Toxicity of the Anesthetic, J Med tion, and Somatostatin Levels in Health, Grudell et al., Am. J. Chem, 2002, 45,5806-8. Physiol. Gastointest. Liver Physiol., 2008, G11 14-G1 119. Lee et al., Deuterium magic angle spinning studies of Substrates Foster AB, Deuterium Isotope Effects in the Metabolism of Drugs bound to cytochrome P450, Biochem., 1999, 38, 10808-13. and Xenobiotics: Implications for Drug Design, Foster AB, Adv. Mamada et al., Pharmacokinetic equivalence of deuterium-labeled Drug Res., Academic Press, London, GB, vol. 14, 1 Jan. 1985, pp. and unlabeled phenytoin, Drug Metab Disp., 1986, 14(4) 509-11. 1-40. Nelson et al., The use of deuterium isotope effects to probe the active Zhang, Chengzhi, Biphenyl-3-Carboxylic Acid Modulators of Beta site properties, mechanism, of cytochrome P450-catalyzed reactions, 3-Adrenoreceptor, WO 2010118291-IPRP International Preliminary and mechanisms of metabolically dependent toxicity, Drug Metab Report on Patentability, Oct. 10, 2014. Disp., 2003, 31(12), 1481-98. Imanishietal. Discovery of a Novel Series of Biphenyl Benzoic Acid Nelson et al., Primary and B-Secondary Deuterium Isotope Effects in Derivatives as Highly Potent and Selective Human Beta-3 Adrenergic N-Deethylation reactions, J Med Chem., 1975, 18 (11) 1062-5. Receptor Agonists with Good Oral Bioavailability. Part II, J. Med. Pohl et al., Determination of Toxic Pathways of Metabolism by Chem., 2008, 51(13), 4002-20. Deuterium Substitution, Drug Metab Rev., 1984, 15(7), 1335-51. Rao et al., Aminothiazole Modulators of Beta-3-Adrenoreceptor, Rampe et al., Deuterated analogs of Verapamil and nifedipine. Syn U.S. Appl. No. 12/796.781—Prosecution History, Auspex Pharma thesis and biological activity, Eur J Med Chem., 1993, 28, 259-63. ceuticals, Inc. Downloaded Jun. 16, 2013. Baillie, Thomas, The Use of Stable Isotopes in Pharmaceutical Research, Pharmacological Reviews, 1981, 33(2), 81-132. * cited by examiner US 8,778,998 B2 1. 2 BIPHENYL 3-CAR BOXYLICACID tates a reaction process by lowering the activation energy MODULATORS OF leading to a transition State. Enzymes are examples of bio BETA-3-ADRENORECEPTOR logical catalysts. Carbon-hydrogen bond strength is directly proportional to This application claims the benefit of priority of U.S. pro- 5 the absolute value of the ground-state vibrational energy of visional application No. 61/168.248, filed Apr. 10, 2009, the the bond. This vibrational energy depends on the mass of the disclosure of which is hereby incorporated by reference as if atoms that form the bond, and increases as the mass of one or written herein in its entirety. both of the atoms making the bond increases. Since deuterium Disclosed herein are new substituted biphenyl-3-carboxy (D) has twice the mass ofprotium ("H), a C-D bondis stron lic acid compounds, pharmaceutical compositions made ger than the corresponding C–H bond.
Load more

Recommended publications
  • Order in Council 1243/1995
    PROVINCE OF BRITISH COLUMBIA ORDER OF THE LIEUTENANT GOVERNOR IN COUNCIL Order in Council No. 12 4 3 , Approved and Ordered OCT 121995 Lieutenant Governor Executive Council Chambers, Victoria On the recommendation of the undersigned, the Lieutenant Governor, by and with the advice and consent of the Executive Council, orders that Order in Council 1039 made August 17, 1995, is rescinded. 2. The Drug Schedules made by regulation of the Council of the College of Pharmacists of British Columbia, as set out in the attached resolution dated September 6, 1995, are hereby approved. (----, c" g/J1"----c- 4- Minister of Heal fandand Minister Responsible for Seniors Presidin Member of the Executive Council (This pan is for adnwustratlye purposes only and is not part of the Order) Authority under which Order Is made: Act and section:- Pharmacists, Pharmacy Operations and Drug Scheduling Act, section 59(2)(1), 62 Other (specify): - Uppodukoic1enact N6145; Resolution of the Council of the College of Pharmacists of British Columbia ("the Council"), made by teleconference at Vancouver, British Columbia, the 6th day of September 1995. RESOLVED THAT: In accordance with the authority established in Section 62 of the Pharmacists, Pharmacy Operations and Drug Scheduling Act of British Columbia, S.B.C. Chapter 62, the Council makes the Drug Schedules by regulation as set out in the attached schedule, subject to the approval of the Lieutenant Governor in Council. Certified a true copy Linda J. Lytle, Phr.) Registrar DRUG SCHEDULES to the Pharmacists, Pharmacy Operations and Drug Scheduling Act of British Columbia The Drug Schedules have been 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]
  • Additional Drug Coverage
    Additional Drug Coverage Additional prescription drug coverage Your plan includes extra coverage for certain drugs and supplies as shown below. This is not a complete list of prescription drugs and supplies covered by our plan. For a complete list, please call Customer Service toll-free at (866) 868-0609 (TTY: 711), 7 a.m. – 7 p.m. CT, Monday – Friday and 7 a.m. – 3 p.m. CT, Saturday. Lower-cost Medicare prescription drugs and supplies Your plan covers some of your Medicare prescription drugs and supplies at a $0 copay. If you have questions, call us toll-free at (866) 868-0609 (TTY: 711), 7 a.m. – 7 p.m. CT, Monday – Friday and 7 a.m. – 3 p.m. CT, Saturday. These drugs and supplies are part of your Medicare prescription drug coverage.1 Breast cancer preventive medications PEG-3350/NaCl/Na Bicarbonate/KCl TriLyte Anastrozole Exemestane Certain diabetic supplies for the Raloxifene administration of insulin Tamoxifen Insulin Syringes & Pen Needles Certain cholesterol-lowering medications Shingles vaccine Atorvastatin 10mg & 20mg Tablet Shingrix Lovastatin 10mg, 20mg & 40mg Tablet Zostavax Simvastatin 5mg, 10mg, 20mg & 40mg Tablet Tobacco cessation medications Certain colon prep products Buproban 150mg GaviLyte-C Chantix GaviLyte-G Nicotrol Inhaler PEG-3350/Electrolytes Nicotrol Nasal Spray Y0066_200527_081500_C Lower-cost non-Medicare over-the-counter drugs These drugs are covered in addition to the drugs in your plan’s drug list (formulary).2 Your plan covers these over-the-counter drugs at a $0 copay. Certain colon preparation products Tobacco cessation medications Bisacodyl Tablets Nicotine Gum Magnesium Citrate Solution Nicotine Lozenges Polyethylene Glycol Powder Nicotine Patches 1Information about the appeals and grievance process for these prescription drugs and supplies can be found in your Evidence of Coverage.
    [Show full text]
  • Tenncare Preferred Drug List (PDL)
    TennCare Preferred Drug List (PDL) Effective October 1, 2021 PA – Prior Authorization required, subject to specific PA criteria; QL – Quantity Limit (PA & NP agents require a PA before dispensing); B – Budgetary Reduction edit for utilization control (Standard NP PA criteria does not apply); ID – Class PA for patients with Intellectual or Developmental Disability Please note the following: • All agents must be prescribed by a provider with a Tennessee Medicaid Provider ID • Approval of NP agents requires trial and failure, contraindication, or intolerance of 2 preferred agents, unless otherwise indicated • With the exception of the “Branded Drugs Classified as Generics” list, TennCare is a mandatory generic program in accordance with state law (TCA 53-10-205). Approval of a branded product when a generic is available requires documentation of a serious adverse reaction from the generic via an FDA MedWatch form OR contraindication to an inactive ingredient in the AB-rated generic equivalent. Therapeutic Failure of an AB-rated generic equivalent may be considered for approval of branded products in the following high-risk medication classes: Anticonvulsants, Atypical Antipsychotics, HIV antivirals, Immunosuppressants, and Oncology Agents. • Unless otherwise noted, all agents listed on the PDL are referencing legend drugs which are prescription-required agents. Coverage of Over-the Counter (OTC) Products is listed at: https://www.optumrx.com/content/dam/openenrollment/pdfs/Tenncare/presciber/program-information/Covered%20OTC%20List.pdf Preferred
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2006/0078604 A1 Kanios Et Al
    US 20060078604A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0078604 A1 Kanios et al. (43) Pub. Date: Apr. 13, 2006 (54) TRANSDERMAL DRUG DELIVERY DEVICE Related U.S. Application Data INCLUDING AN OCCLUSIVE BACKING (60) Provisional application No. 60/616,861, filed on Oct. 8, 2004. (75) Inventors: David Kanios, Miami, FL (US); Juan A. Mantelle, Miami, FL (US); Viet Publication Classification Nguyen, Miami, FL (US) (51) Int. Cl. Correspondence Address: A 6LX 9/70 (2006.01) DCKSTEIN SHAPRO MORN & OSHINSKY (52) U.S. Cl. .............................................................. 424/449 LLP (57) ABSTRACT 2101 L Street, NW Washington, DC 20037 (US) A transdermal drug delivery system for the topical applica tion of one or more active agents contained in one or more (73) Assignee: Noven Pharmaceuticals, Inc. polymeric and/or adhesive carrier layers, proximate to a non-drug containing polymeric backing layer which can (21) Appl. No.: 11/245,180 control the delivery rate and profile of the transdermal drug delivery system by adjusting the moisture vapor transmis (22) Filed: Oct. 7, 2005 sion rate of the polymeric backing layer. Patent Application Publication Apr. 13, 2006 Sheet 1 of 2 US 2006/0078604 A1 Fis ZZZZZZZZZZZZZZZZZZZ :::::::::::::::::::::::::::::::: Patent Application Publication Apr. 13, 2006 Sheet 2 of 2 US 2006/0078604 A1 3. s s 3. a 3 : 8 g US 2006/0078604 A1 Apr. 13, 2006 TRANSIDERMAL DRUG DELVERY DEVICE 0008. In the “classic' reservoir-type device, the active INCLUDING AN OCCLUSIVE BACKING agent is typically dissolved or dispersed in a carrier to yield a non-finite carrier form, Such as, for example, a fluid or gel.
    [Show full text]
  • Early Refill Drug Utilization Review Drugs
    Early Refill Drug Utilization Review Drugs Published: 05/01/2012 Point-of-Sale Drug Authorization and Policy Drug Name Effective Date Override Override Center Override Acarbose X 11/8/2008 Acebutolol hydrochloride X 11/8/2008 acetaminophen X 11/8/2008 acetazolamide X 11/8/2008 acetazolamide sodium X 11/8/2008 acetylcholine X 11/8/2008 acetylcysteine X 11/8/2008 Acitretin X 11/8/2008 Acrivastine X 11/8/2008 activated charcoal X 11/8/2008 adalimumab X 11/8/2008 Adapalene X 11/8/2008 Adenosine X 11/8/2008 albumin human X 11/8/2008 Albuterol X 11/8/2008 albuterol sulfate X 11/8/2008 alclometasone dipropionate X 11/8/2008 aldesleukin X 11/8/2008 alendronate sodium X 11/8/2008 alfentanil hydrochloride X 11/8/2008 aliskiren hemifumarate X 11/8/2008 Alitretinoin X 11/8/2008 almotriptan malate X 11/8/2008 alosetron hydrochloride X 11/8/2008 Alprazolam X 1/6/2010 Aluminum X 11/8/2008 aluminum sulfate X 11/8/2008 amantadine hydrochloride X 11/8/2008 amcinonide X 11/8/2008 amino acids X 11/8/2008 aminophylline X 11/8/2008 amiodarone hydrochloride X 11/8/2008 amitriptyline hydrochloride X 11/8/2008 amlodipine besylate X 11/8/2008 Ammonium X 11/8/2008 Ammonium chloride X 11/8/2008 amobarbital X 1/6/2010 Point-of-Sale Drug Authorization and Policy Drug Name Effective Date Override Override Center Override Amoxicillin trihydrate X 11/8/2008 amphetamine X 1/6/2010 amyl nitrite X 11/8/2008 Amylase X 11/8/2008 apraclonidine hydrochloride X 11/8/2008 arformoterol tartrate X 11/8/2008 Arginine X 11/8/2008 arginine hydrochloride X 11/8/2008 aripiprazole X
    [Show full text]
  • Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act
    Updated June 07, 2021 Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act Three categories of bulk drug substances: • Category 1: Bulk Drug Substances Under Evaluation • Category 2: Bulk Drug Substances that Raise Significant Safety Risks • Category 3: Bulk Drug Substances Nominated Without Adequate Support Updates to Categories of Substances Nominated for the 503B Bulk Drug Substances List1 • Add the following entry to category 2 due to serious safety concerns of mutagenicity, cytotoxicity, and possible carcinogenicity when quinacrine hydrochloride is used for intrauterine administration for non- surgical female sterilization: 2,3 o Quinacrine Hydrochloride for intrauterine administration • Revision to category 1 for clarity: o Modify the entry for “Quinacrine Hydrochloride” to “Quinacrine Hydrochloride (except for intrauterine administration).” • Revision to category 1 to correct a substance name error: o Correct the error in the substance name “DHEA (dehydroepiandosterone)” to “DHEA (dehydroepiandrosterone).” 1 For the purposes of the substance names in the categories, hydrated forms of the substance are included in the scope of the substance name. 2 Quinacrine HCl was previously reviewed in 2016 as part of FDA’s consideration of this bulk drug substance for inclusion on the 503A Bulks List. As part of this review, the Division of Bone, Reproductive and Urologic Products (DBRUP), now the Division of Urology, Obstetrics and Gynecology (DUOG), evaluated the nomination of quinacrine for intrauterine administration for non-surgical female sterilization and recommended that quinacrine should not be included on the 503A Bulks List for this use. This recommendation was based on the lack of information on efficacy comparable to other available methods of female sterilization and serious safety concerns of mutagenicity, cytotoxicity and possible carcinogenicity in use of quinacrine for this indication and route of administration.
    [Show full text]
  • Wo 2010/118291 A2
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 14 October 2010 (14.10.2010) WO 2010/118291 A2 (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07C 229/54 (2006.01) A61K 31/136 (2006.01) kind of national protection available): AE, AG, AL, AM, C07C 229/38 (2006.01) A61P 13/12 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US20 10/030488 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 9 April 2010 (09.04.2010) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, (26) Publication Language: English TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/168,248 10 April 2009 (10.04.2009) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, (71) Applicant (for all designated States except US): AUS- ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, PEX PHARMACEUTICALS, INC.
    [Show full text]
  • Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act
    Updated July 30, 2020 Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act Three categories of bulk drug substances: • Category 1: Bulk Drug Substances Under Evaluation • Category 2: Bulk Drug Substances that Raise Significant Safety Risks • Category 3: Bulk Drug Substances Nominated Without Adequate Support Notice of Updates to Categories of Substances Nominated for the 503B Bulk Drug Substances List • Additions to category 1: Betahistine Hydrochloride L-Proline Citrulline Papaverine Hydrochloride* Copper Gluconate Phosphatidylcholine Diiodohydroxyquinoline Podophyllum Resin Glucosamine Sulfate Potassium Chloride Sodium Molybdate Glucosamine Sulfate Sodium Chloride Sodium Nitroprusside Hydrochloric Acid* Sodium Selenite/Sodium Selenite Pentahydrate* Ibutamoren Mesylate Trichloroacetic Acid* L-Citrulline* Ubidecarenone (Coenzyme Q10)* L-Lysine * Bulk drug substance is currently in Category 3 and is being moved to Category 1. • Minor revision to entry in Category 1 to correct a misspelling: o Correct the misspelling of “cimatidine” to “cimetidine” 1 Updated July 30, 2020 503B Category 1: Bulk Drug Substances Under Evaluation • 5-Methyltetrahydrofolate Calcium • Chromic Chloride • 17-alpha-Hydroxyprogesterone • Chromium chloride/ Chromium Chloride • Acetylcysteine Hexahydrate • Acyclovir • Ciclopirox Oleate • Adapalene • Cimetidine • Adenosine • Ciprofloxacin HCl • Allantoin • Citric Acid Anhydrous • Alpha Lipoic Acid • Citrulline/L-Citrulline • Alprostadil • Clindamycin Phosphate
    [Show full text]
  • Paramount Advantage™ Preferred Drug List
    Paramount Advantage™ Preferred Drug List (11/01/2019) INTRODUCTION ........................................................................................................................................................................................................................4 NOTICE OF NONDISCRIMINATION AND ACCESSIBILITY: DISCRIMINATION IS AGAINST THE LAW ............................................................................ 4 HOW TO SEARCH THIS DOCUMENT ...................................................................................................................................................................................... 6 PREFACE ...................................................................................................................................................................................................................................6 PHARMACY AND THERAPEUTICS COMMITTEE .................................................................................................................................................................. 6 DRUG LIST PRODUCT DESCRIPTIONS.................................................................................................................................................................................. 6 GENERIC SUBSTITUTION ........................................................................................................................................................................................................ 6 PLAN DESIGN ...........................................................................................................................................................................................................................7
    [Show full text]
  • Each Capsule Contains: Methenamine
    Pregnancy/Reproduction - Hyoscyamine and methenamine cross the placenta. Studies concerning the effect of hyoscyamine and methenamine on pregnancy and reproduction have not been done in animals or humans. Thus it is not known whether Uribel capsules cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Uribel capsules should be given to a pregnant woman only if clearly needed. Breastfeeding - Problems in humans have not been documented; however, methenamine and traces of hyoscyamine are excreted in breast milk. Accordingly, Uribel capsules should be given to a nursing mother with caution and only if clearly needed. Prolonged use - There have been no studies to establish the safety of prolonged use in humans. No known long-term animal studies have been performed to evaluate carcinogenic potential. Rx Only Pediatric use - Infants and young children are especially susceptible to the toxic effect of the belladonna alkaloids. DESCRIPTION: Uribel® capsules for oral administration. Geriatric use - Use with caution in elderly patients as they may respond to usual doses of hyoscyamine with excitement, agitation, drowsiness or confusion. Each capsule contains: ADVERSE REACTIONS: Methenamine ....................................................................................... 118 mg Cardiovascular: rapid heartbeat, flushing Sodium Phosphate Monobasic ............................................................. 40.8 mg Central Nervous System: blurred vision, dizziness, drowsiness Genitourinary: difficult micturition,
    [Show full text]
  • Miochol-E (Acetylcholine Chloride) Dose, Indications, Adverse Effects, Interactions
    Miochol-E (acetylcholine chloride) dose, indications, adverse effects, interactions... from PDR.net 5/8/18 18:45 print Close window CLASSES Parasympathomimetic Ophthalmological Surgical Aids DEA CLASS Rx DESCRIPTION Direct-acting parasympathomimetic ophthalmic agent; naturally-occurring neurohormone that mediates nerve impulse transmission at cholinergic sites. Used intraocularly to produce rapid miosis during ophthalmic surgery. COMMON BRAND NAMES Miochol-E HOW SUPPLIED Miochol-E Intraocular Inj Pwd F/Sol: 20mg DOSAGE & INDICATIONS For miosis induction in cataract surgery, in penetrating keratoplasty, iridectomy and other anterior segment ocular surgery where rapid miosis may be required. Intraocular dosage (Miochol-E 1% solution) Adults In most cases, 0.5 to 2 mL of the 1% intraocular solution instilled into the anterior chamber produces satisfactory miosis. Intraocular irrigation with the drug must be gentle. Note that the syringe filter supplied with Miochol-E has a priming volume of 0.6 mL (approximately). For prolonged miosis, a second application may be used. MAXIMUM DOSAGE Adults 20 mg (2 mL of 1% Miochol-E solution) intraocularly per eye is usually sufficient. A second application may be needed for prolonged miosis. Geriatric 20 mg (2 mL of 1% Miochol-E solution) intraocularly per eye is usually sufficient. A second application may be needed for prolonged miosis. Adolescents Safety and efficacy have not been established. Children Safety and efficacy have not been established. Infants Safety and efficacy have not been established. Neonates Safety and efficacy have not been established. DOSING CONSIDERATIONS Hepatic Impairment No dosage adjustments are needed for intraocular use. Renal Impairment No dosage adjustments are needed for intraocular use.
    [Show full text]
  • Pharmaceutical Management and Formulary Manual (Pdf)
    PHARMACEUTICAL MANAGEMENT and FORMULARY MANUAL Approved by: The Chief Medical Officer Washington State Department of Corrections Note: Appendices II – Formulary Drug Listings and IV – Alternate Choices for Non-formulary Medications may be updated frequently as clinical data or contract prices change. Page 1 of 170 Formulary 600-HA002 Washington Department of Corrections (December 2019) DOC Formulary Table of Contents Definitions.......................................................................................................................... 5 Definitions...................................................................................................................... 5 Section I.............................................................................................................................. 7 Purpose ........................................................................................................................... 7 Section II ............................................................................................................................ 8 Promulgation of Policy ................................................................................................. 8 Section III ........................................................................................................................... 9 Voting Members ............................................................................................................ 9 Section IV ........................................................................................................................
    [Show full text]