DOCSLIB.ORG

Compositions Comprising Corticosteroid Prodrug Such As Dexamethasone Palmitate for the Treatment of Eye Disorders

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Compositions Comprising Corticosteroid Prodrug Such As Dexamethasone Palmitate for the Treatment of Eye Disorders (19) TZZ 56485¥_T (11) EP 2 564 853 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 06.03.2013 Bulletin 2013/10 A61K 31/573 (2006.01) A61K 38/13 (2006.01) A61P 27/00 (2006.01) (21) Application number: 12193075.4 (22) Date of filing: 03.12.2008 (84) Designated Contracting States: • Lambert, Grégory AT BE BG CH CY CZ DE DK EE ES FI FR GB GR 92290 Châtenay-Malabry (FR) HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT • Lallemand, Frédéric RO SE SI SK TR 94260 Fresnes (FR) •Philips,Betty (30) Priority: 04.12.2007 US 992160 P 92160 Antony (FR) (62) Document number(s) of the earlier application(s) in (74) Representative: Icosa accordance with Art. 76 EPC: 83 avenue Denfert-Rochereau 08858069.1 / 2 229 174 75014 Paris (FR) (71) Applicant: Novagali Pharma S.A. Remarks: 91000 Evry (FR) This application was filed on 16-11-2012 as a divisional application to the application mentioned (72) Inventors: under INID code 62. • Rabinovich-Guilatt, Laura 60920 Kadima (IL) (54) Compositions comprising corticosteroid prodrug such as dexamethasone palmitate for the treatment of eye disorders (57) The present invention relates to a new thera- vides methods of treatment involving the administration peutic approach for the treatment of eye diseases or con- of a corticosteroid prodrug, such as dexamethasone ditions that allows for the delivery of corticosteroids to palmitate, to the surface of the eye. Also provided are the eye’s surface but does not cause any of the usual pharmaceutical compositions and kits for carrying out side effects associated with topical administration of cor- such methods of treatment. ticosteroids. More specifically, the present invention pro- EP 2 564 853 A1 Printed by Jouve, 75001 PARIS (FR) EP 2 564 853 A1 Description Background of the Invention 5 [0001] In the past 50 years or so, corticosteroids have been used in a broad spectrum of inflammatory conditions of the eye. In fact, corticosteroids belong to the class of therapeutics the most frequently prescribed in ophthalmology. In particular, topical corticosteroids have revolutionized the practice of ophthalmology and ophthalmic care when it comes to preventing or treating ocular inflammation due to trauma, chemical, infective, allergic or other causes. The most commonly used corticosteroids for topical ocular administration are prednisolone, fluorometholone, dexamethasone, 10 rimexolone, and medrysone. [0002] Corticosteroids are synthetic drugs that mimic steroid hormones naturally produced by the body. These steroid hormones have a wide variety of actions and control functions and are involved in a number of important physiological systems including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism and blood electrolyte levels. In addition to regulating inflammation, corticosteroids also have the ability to 15 affect these other physiological systems, resulting in many potential risks and side effects. [0003] As with most therapeutic drugs, the majority of side effects of corticosteroids are more pronounced with systemic therapy. However, they may occur with all routes of administration. For example, there are several potentially severe ocular side effects that can result from topical corticosteroid use. In particular, topical corticosteroid therapy can cause an increase in intra-ocular pressure (IOP). If IOP remains elevated for a length of time, glaucoma can occur with corre- 20 sponding optic nerve damage and visual field loss. IOP elevation can generally be reversed by discontinuation of the treatment. Another potential side effect that can result from topical corticosteroid use is the development of posterior subcapsular cataracts, which can be visually debilitating and require surgical removal. Topical corticosteroid use can also lead to an increase in corneal thickness, mydriasis (an excessive dilation of the pupil) and ptosis (dropping of the upper eyelid). 25 [0004] Side effects of topical corticosteroid therapy are generally directly related to the dosage and duration of treatment and are more often observed with the use of potent corticosteroids, such as dexamethasone. These side effects are believed to result, at least in part, from penetration of the corticosteroid in internal ocular tissues, such as the aqueous humor. The effectiveness of topical corticosteroid therapy is thus severely limited by these unwanted effects since it is often administered for a shorter period of time than necessary, and/or utilizes a less potent agent than necessary. 30 [0005] Therefore, there is still a need in the art for improved approaches to eliminate or reduce side effects associated with topical administration of corticosteroids in the treatment of eye diseases or conditions. Summary of the Invention 35 [0006] The present invention provides an improved strategy for the delivery of corticosteroids to the eye that does not result in undesirable side effects generally observed in topical corticosteroid therapy. The inventive approach is partic- ularly useful in the treatment of eye diseases and conditions affecting the surface of the eye, such as ocular inflammatory conditions. [0007] In particular, the present invention provides methods and compositions that include topical ocular administration 40 of a corticosteroid prodrug, i.e., a pharmaceutically inactive compound that is converted to and/or releases a pharma- ceutically active corticosteroid via a chemical or physiological process at the eye surface. Preferred corticosteroid pro- drugs according to the present invention are compounds that do not significantly penetrate into internal ocular tissues after delivery to the eye surface, in particular that do not traverse the stroma, thereby not reaching the aqueous humor. Systems of the present invention thus limit or reduce the risk of increase in IOP, formation of glaucoma, formation of 45 cataracts, and other unwanted side effects that can result from the presence of corticosteroids inside the eye. Conse- quently, therapeutic methods according to the present invention do not suffer from the limitations generally associated with topical corticosteroid administration, in that they can be administered for longer periods of time and can employ prodrugs of any suitable corticosteroid including the most potent corticosteroids. [0008] More specifically, in one aspect, the present invention provides pharmaceutical compositions of corticosteroid 50 prodrugs that are formulated for topical administration to the eye. An inventive pharmaceutical composition generally comprises an effective amount of at least one corticosteroid prodrug, or a physiologically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient. [0009] Corticosteroids that may be released from corticosteroid prodrugs may be any corticosteroid suitable for use in the treatment of an eye disease or condition, in particular inflammatory conditions of the eye. In certain embodiments, 55 a prodrug may be converted to and/or release a corticosteroid selected from the group consisting of prednisolone, fluorometholone, dexamethasone, rimexolone, medrysone, physiologically acceptable salts thereof, derivatives thereof, and any combinations thereof. In certain preferred embodiments, a prodrug is converted to and/or releases dexameth- asone, a physiologically acceptable salt thereof or a derivative thereof. More preferably, a prodrug according to the 2 EP 2 564 853 A1 present invention is converted to and/or releases dexamethasone. [0010] In certain preferred embodiments of the present invention, release of a corticosteroid from a prodrug occurs via an enzymatic process at the surface of the eye. Thus, preferably, a corticosteroid prodrug comprises a chemical group or function that can be cleaved by an enzyme present at the eye surface. Such enzymes include any of a wide 5 variety of enzymes including, but not limited to, esterases (e.g., pseudocholinesterase, acetylcholine esterase), oxidore- ductases, transferases, lyases, isomerases, ligases, hydrolases, phosphatases, proteases and peptidases. In certain preferred embodiments, release of a corticosteroid from a prodrug occurs via the action of one or more esterases. [0011] Preferred corticosteroid prodrugs are lipophilic derivatives of corticosteroids, in particular lipoph ilic derivatives of corticosteroids having a log P (partition coefficient) comprised between 1 and 12, preferably higher than or equal to 10 5 and lower than 12. [0012] According to the present invention, the partition coefficient P of a compound is the ratio of concentration of said compound in water to the concentration in octanol, as the neutral molecule. [0013] The logarithm of said ratio is called log P. It can be determined with a suitable HPLC method according to published procedures (Caron, J.C., and Shroot, B., J. Pharm. Sci., 1984). 15 [0014] In particular, the present invention relates to the use of lipophilic long chain esters of corticosteroids. Lipophilic long chains may be selected from the group consisting of linear alkyls, linear alkenyls, branched alkyls, and branched alkenyls, wherein alkyl and alkenyl groups comprise 12, 14, 16, 18 or more than 18 carbon atoms. Preferably, the lipophilic long chains are selected among linear or branched alkyls comprising 12, 14, 16, 18 or more than 18 carbon atoms. In one embodiment, the lipophilic long chains are selected among linear alkyls comprising 12 or 14 carbon atoms. 20 [0015] In certain preferred embodiments, a pharmaceutical
Load more

Recommended publications
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 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. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
    [Show full text]
  • A New Robust Technique for Testing of Glucocorticosteroids in Dogs and Horses Terry E
    Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 2007 A new robust technique for testing of glucocorticosteroids in dogs and horses Terry E. Webster Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Veterinary Toxicology and Pharmacology Commons Recommended Citation Webster, Terry E., "A new robust technique for testing of glucocorticosteroids in dogs and horses" (2007). Retrospective Theses and Dissertations. 15029. https://lib.dr.iastate.edu/rtd/15029 This Thesis is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. A new robust technique for testing of glucocorticosteroids in dogs and horses by Terry E. Webster A thesis submitted to the graduate faculty in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Major: Toxicology Program o f Study Committee: Walter G. Hyde, Major Professor Steve Ensley Thomas Isenhart Iowa State University Ames, Iowa 2007 Copyright © Terry Edward Webster, 2007. All rights reserved UMI Number: 1446027 Copyright 2007 by Webster, Terry E. All rights reserved. UMI Microform 1446027 Copyright 2007 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, MI 48106-1346 ii DEDICATION I want to dedicate this project to my wife, Jackie, and my children, Shauna, Luke and Jake for their patience and understanding without which this project would not have been possible.
    [Show full text]
  • Steroid Use in Prednisone Allergy Abby Shuck, Pharmd Candidate
    Steroid Use in Prednisone Allergy Abby Shuck, PharmD candidate 2015 University of Findlay If a patient has an allergy to prednisone and methylprednisolone, what (if any) other corticosteroid can the patient use to avoid an allergic reaction? Corticosteroids very rarely cause allergic reactions in patients that receive them. Since corticosteroids are typically used to treat severe allergic reactions and anaphylaxis, it seems unlikely that these drugs could actually induce an allergic reaction of their own. However, between 0.5-5% of people have reported any sort of reaction to a corticosteroid that they have received.1 Corticosteroids can cause anything from minor skin irritations to full blown anaphylactic shock. Worsening of allergic symptoms during corticosteroid treatment may not always mean that the patient has failed treatment, although it may appear to be so.2,3 There are essentially four classes of corticosteroids: Class A, hydrocortisone-type, Class B, triamcinolone acetonide type, Class C, betamethasone type, and Class D, hydrocortisone-17-butyrate and clobetasone-17-butyrate type. Major* corticosteroids in Class A include cortisone, hydrocortisone, methylprednisolone, prednisolone, and prednisone. Major* corticosteroids in Class B include budesonide, fluocinolone, and triamcinolone. Major* corticosteroids in Class C include beclomethasone and dexamethasone. Finally, major* corticosteroids in Class D include betamethasone, fluticasone, and mometasone.4,5 Class D was later subdivided into Class D1 and D2 depending on the presence or 5,6 absence of a C16 methyl substitution and/or halogenation on C9 of the steroid B-ring. It is often hard to determine what exactly a patient is allergic to if they experience a reaction to a corticosteroid.
    [Show full text]
  • 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]
  • United States Patent (19) 11 4,360,518 Rovee Et Al
    United States Patent (19) 11 4,360,518 Rovee et al. 45) Nov. 23, 1982 54 TOPICAL ANTI-INFLAMMATORY DRUG Primary Examiner-Stanley J. Friedman THERAPY . 57) ABSTRACT 75) Inventors: David T. Rovee, Bridgewater; John A pharmaceutical composition for topical treatment of R. Marvel; James A. Mezick, both of cutaneous disorders or disruptions characterized by East Brunswick, all of N.J. skin inflammation or hyperproliferative epidermal ac 73) Assignee: Johnson & Johnson, New Brunswick, tivity comprises the combination of a topically active N.J. anti-inflammatory corticosteroid and a non-steroidal 21 Appl. No.: 244,569 anti-inflammatory agent which is an inhibitor of prosta glandin synthetase selected from the group consisting of 22 Filed: Mar. 17, 1981 the hydratropic acid derivatives; acetylsalicylic acid; the pyrazolone derivatives; the fenamic acid deriva Related U.S. Application Data tives; the aroyl-substituted pyrroles and the substituted 60) Division of Ser. No. 64,311, Aug. 6, 1979, abandoned, arylacetohydroxamic acids in a pharmaceutically ac which is a division of Ser. No. 788,453, Apr. 20, 1977, ceptable topical vehicle. Treatment of above cutaneous Pat. No. 4,185, 100, which is a continuation-in-part of disorders may also be effected by concurrent therapy Ser. No. 685,942, May 13, 1976, abandoned. using separate applications of corticosteroid and non 51) Int. Cl. ...................... A61K 31/19; A61K 31/56 steroid. (52) U.S. Cl. ..................................... 424/240; 424/317 58) Field of Search ................................ 424/317, 240 18 Claims, No Drawings 4,360,518 1 2 Ziboh, V. A. and Snyder, D. S. 1974 Naturally occur TOPICAL ANTI-NFLAMMATORY ORUG ring and synthetic inhibitors of prostaglandin synthetase THERAPY of the skin.
    [Show full text]
  • Pharmaceuticals Appendix
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 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. ABAMECTIN 65195-55-3 ADAPALENE 106685-40-9 ABANOQUIL 90402-40-7 ADAPROLOL 101479-70-3 ABECARNIL 111841-85-1 ADEMETIONINE 17176-17-9 ABLUKAST 96566-25-5 ADENOSINE PHOSPHATE 61-19-8 ABUNIDAZOLE 91017-58-2 ADIBENDAN 100510-33-6 ACADESINE 2627-69-2 ADICILLIN 525-94-0 ACAMPROSATE 77337-76-9 ADIMOLOL 78459-19-5 ACAPRAZINE 55485-20-6 ADINAZOLAM 37115-32-5 ACARBOSE 56180-94-0 ADIPHENINE 64-95-9 ACEBROCHOL 514-50-1 ADIPIODONE 606-17-7 ACEBURIC ACID 26976-72-7 ADITEREN 56066-19-4 ACEBUTOLOL 37517-30-9 ADITOPRIME 56066-63-8 ACECAINIDE 32795-44-1 ADOSOPINE 88124-26-9 ACECARBROMAL 77-66-7 ADOZELESIN 110314-48-2 ACECLIDINE 827-61-2 ADRAFINIL 63547-13-7 ACECLOFENAC 89796-99-6 ADRENALONE 99-45-6 ACEDAPSONE 77-46-3 AFALANINE 2901-75-9 ACEDIASULFONE SODIUM 127-60-6 AFLOQUALONE 56287-74-2 ACEDOBEN 556-08-1 AFUROLOL 65776-67-2 ACEFLURANOL 80595-73-9 AGANODINE 86696-87-9 ACEFURTIAMINE 10072-48-7 AKLOMIDE 3011-89-0 ACEFYLLINE CLOFIBROL 70788-27-1
    [Show full text]
  • DATA SUPPLEMENT Safety and Efficacy of Combination Nivolumab
    DATA SUPPLEMENT Safety and Efficacy of Combination Nivolumab Plus Ipilimumab in Patients with Advanced Melanoma: Results from a North American Expanded Access Program (CheckMate 218) F. Stephen Hodi, Paul B. Chapman, Mario Sznol, Christopher D. Lao, Rene Gonzalez, Michael Smylie, Gregory A. Daniels, John A. Thompson, Ragini Kudchadkar, William Sharfman, Michael Atkins, David R. Spigel, Anna Pavlick, Jose Monzon, Kevin B. Kim, Scott Ernst, Nikhil I. Khushalani, Wim van Dijck, Maurice Lobo, David Hogg 1 Supplementary Tables Table S1: Summary of adverse events reported between first dose and 30 days after last dose of the EAP therapy that required immune modulating medications in ≥1% of patients Nivolumab plus ipilimumab (N=754) Any grade, Grade 3–4, N (%)a N (%) Any adverse event 600 (80) 332 (44) Diarrhea 132 (18) 52 (7) Maculopapular rash 115 (15) 22 (3) Colitis 76 (10) 57 (8) Increased alanine aminotransferase 72 (10) 47 (6) Increased aspartate aminotransferase 58 (8) 32 (4) Rash 52 (7) 3 (<1) Pruritus 47 (6) 3 (<1) Pneumonitis 39 (5) 9 (1) Hypophysitis 38 (5) 5 (1) Autoimmune hepatitis 37 (5) 28 (4) Pruritic rash 29 (4) 0 Generalized pruritus 22 (3) 3 (<1) Nausea 20 (3) 5 (1) Adrenal insufficiency 18 (2) 3 (<1) Generalized rash 15 (2) 5 (1) Fatigue 14 (2) 3 (<1) Malignant neoplasm progression 12 (2) 11 (1) Arthralgia 12 (2) 2 (<1) Vomiting 12 (2) 2 (<1) Uveitis 11 (1) 1 (<1) Headache 11 (1) 1 (<1) increased transaminases 11 (1) 8 (1) Macular rash 11 (1) 2 (<1) Pyrexia 10 (1) 1 (<1) Increased lipase 10 (1) 9 (1) Acute kidney injury 9 (1) 6 (1) Hepatitis 9 (1) 6 (1) Cough 9 (1) 0 Acneiform dermatitis 9 (1) 0 Abdominal pain 8 (1) 2 (<1) aOne grade 5 adverse event (due to malignant neoplasm progression) was reported.
    [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 7,544,192 B2 Eaton Et Al
    US007544192B2 (12) United States Patent (10) Patent No.: US 7,544,192 B2 Eaton et al. (45) Date of Patent: Jun. 9, 2009 (54) SINUS DELIVERY OF SUSTAINED RELEASE 5,443,498 A 8, 1995 Fontaine THERAPEUTICS 5,512,055 A 4/1996 Domb et al. 5,664,567 A 9, 1997 Linder (75) Inventors: Donald J. Eaton, Woodside, CA (US); 5,693,065. A 12/1997 Rains, III Mary L. Moran, Woodside, CA (US); 5,792,100 A 8/1998 Shantha Rodney Brenneman, San Juan Capistrano, CA (US) (73) Assignee: Sinexus, Inc., Palo Alto, CA (US) (Continued) (*) Notice: Subject to any disclaimer, the term of this FOREIGN PATENT DOCUMENTS patent is extended or adjusted under 35 U.S.C. 154(b) by 992 days. WO WOO1/02024 1, 2001 (21) Appl. No.: 10/800,162 (22) Filed: Mar 12, 2004 (Continued) (65) Prior Publication Data OTHER PUBLICATIONS US 2005/OO437O6A1 Feb. 24, 2005 Hosemann, W. et al. (Mar. 2003, e-pub. Oct. 10, 2002). “Innovative s Frontal Sinus Stent Acting as a Local Drug-Releasing System.' Eur: Related U.S. Application Data Arch. Otorhinolarynolo. 260:131-134. (60) Provisional application No. 60/454,918, filed on Mar. (Continued) 14, 2003. Primary Examiner Kevin C Sirmons (51) Int. Cl Assistant Examiner Catherine NWitczak A. iM sI/00 (2006.01) (74) Attorney, Agent, or Firm Morrison & Foerster LLP (52) U.S. Cl. ........................ 604/506; 604/510; 604/514 (57) ABSTRACT (58) Field of Classification Search .............. 604/93.01, 604/891.1. 890.1, 57, 59-64, 510, 514,506; S lication file f 606/196 The invention provides biodegradable implants for treating ee application file for complete search history.
    [Show full text]
  • Improved Penetrating Topical Pharmaceutical Compositions Containing Corticosteroids
    Europaisches Patentamt ® European Patent Office © Publication number: 0 129 283 Office europeen des brevets A2 © EUROPEAN PATENT APPLICATION © Application number: 84200821.1 ©Int CI.3: A 61 K 31/57 A 61 K 47/00, A 61 K 9/06 © Date of filing: 12.06.84 © Priority: 21.06.83 US 506274 © Applicant: THE PROCTER & GAMBLE COMPANY 01.02.84 US 576065 301 East Sixth Street Cincinnati Ohio 45201 (US) © Date of publication of application: © Inventor: Cooper, Eugene Rex 27.12.84 Bulletin 84/52 2425 Ambassador Drive Cincinnati, OH 45231 (US) © Designated Contracting States: BE CH DE FR GB IT Li NL SE © Inventor: Loomans, Maurice Edward 5231 Jessup Road Cincinnati, OH 45239IUS) © Inventor: Fawzi, Mahdi Bakir 11 Timberline Drive Flanders New Jersey 07836(US) © Representative: Suslic, Lydia et al, Procter & Gamble European Technical Center Temselaan 100 B-1820 Strombeek-Bever(BE) © Improved penetrating topical pharmaceutical compositions containing corticosteroids. Topical pharmaceutical compositions containing a cor- ticosteroid component and a penetration-enhancing vehicle are disclosed. The vehicle comprises a binary combination of a C3-C4 diol and a "cell-envelope disordering compound". The vehicle provides marked transepidermal and percutaneous delivery of corticosteroids. A method of treating certain rheumatic and inflammatory conditions, systemically or loc- ally, is also disclosed. TECHNICAL FIELD The present invention relates to topical compositions effective in delivering high levels of certain pharmaceutically-active cor- ticosteroid agents through the integument. Because of the ease of access, dynamics of application, large surface area, vast exposure to the circulatory and lymphatic networks, and non-invasive nature of the treatment, the delivery of pharmaceutically-active agents through the skin has long been a promising concept.
    [Show full text]
  • Cardiovascular System Drug Poster
    Cardiovascular Drugs Created by the Njardarson Group (The University of Arizona): Edon Vitaku, Elizabeth A. Ilardi, Daniel J. Mack, Monica A. Fallon, Erik B. Gerlach, Miyant’e Y. Newton, Angela N. Yazzie, Jón T. Njarðarson Ethanol Glyceryl Trinitrate Anestisine Quinidine Procaine Adrenaline Adenosine Phenylepherine Heparin Vasoxyl Sotradecol Xylocaine Pronestyl Betamethasone Catapres Cedilanide Dopamine Inversine Metaraminol Acetyldigitoxin Hydrocortisone ( Ethanol ) ( Nitroglycerin ) ( Benzocaine ) ( Quinidine ) ( Procaine ) ( Epinephrine ) ( Adenosine ) ( Phenylephrine ) ( Heparin ) ( Methoxamine ) ( Sodium Tetradecyl Sulfate ) ( Lidocaine ) ( Procainamide ) ( Betamethasone ) ( Clonidine ) ( Deslanoside ) ( Dopamine ) ( Mecamylamine ) ( Metaraminol ) ( Acetyldigitoxin ) ( Hydrocortisone ) VASOPROTECTIVE CARDIAC THERAPY VASOPROTECTIVE CARDIAC THERAPY VASOPROTECTIVE CARDIAC THERAPY CARDIAC THERAPY CARDIAC THERAPY VASOPROTECTIVE CARDIAC THERAPY VASOPROTECTIVE CARDIAC THERAPY CARDIAC THERAPY VASOPROTECTIVE ANTIHYPERTENSIVE CARDIAC THERAPY CARDIAC THERAPY ANTIHYPERTENSIVE CARDIAC THERAPY CARDIAC THERAPY VASOPROTECTIVE Approved 1700s Approved 1879 Approved 1890s Approved 1900s Approved 1903 Approved 1920s Approved 1929 Approved 1930s Approved 1935 Approved 1940s Approved 1946 Approved 1949 Approved 1950 Approved 1950s Approved 1950s Approved 1950s Approved 1950s Approved 1950s Approved 1951 Approved 1952 Approved 1952 Regitine Phenoxybenzamine Serpasol Rescinnamine Diuril Harmonyl Naturetin Hydrochlorothiazide Hydrocortamate Fastin Ismel
    [Show full text]
  • Wo 2008/127291 A2
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date PCT (10) International Publication Number 23 October 2008 (23.10.2008) WO 2008/127291 A2 (51) International Patent Classification: Jeffrey, J. [US/US]; 106 Glenview Drive, Los Alamos, GOlN 33/53 (2006.01) GOlN 33/68 (2006.01) NM 87544 (US). HARRIS, Michael, N. [US/US]; 295 GOlN 21/76 (2006.01) GOlN 23/223 (2006.01) Kilby Avenue, Los Alamos, NM 87544 (US). BURRELL, Anthony, K. [NZ/US]; 2431 Canyon Glen, Los Alamos, (21) International Application Number: NM 87544 (US). PCT/US2007/021888 (74) Agents: COTTRELL, Bruce, H. et al.; Los Alamos (22) International Filing Date: 10 October 2007 (10.10.2007) National Laboratory, LGTP, MS A187, Los Alamos, NM 87545 (US). (25) Filing Language: English (81) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of national protection available): AE, AG, AL, AM, AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY,BZ, CA, CH, (30) Priority Data: CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, 60/850,594 10 October 2006 (10.10.2006) US ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, (71) Applicants (for all designated States except US): LOS LR, LS, LT, LU, LY,MA, MD, ME, MG, MK, MN, MW, ALAMOS NATIONAL SECURITY,LLC [US/US]; Los MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, Alamos National Laboratory, Lc/ip, Ms A187, Los Alamos, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SV, SY, NM 87545 (US).
    [Show full text]