DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 9.402,811 B2 Merkus (45) Date of Patent: Aug

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 9.402,811 B2 Merkus (45) Date of Patent: Aug USOO9402811 B2 (12) United States Patent (10) Patent No.: US 9.402,811 B2 Merkus (45) Date of Patent: Aug. 2, 2016 (54) OROMUCOSAL LIQUIDESTRADIOL 8,647,665 B2 * 2/2014 Simes et al. .................. 424/449 COMPOSITIONS 2003/0077229 A1 4/2003 Dugger 2007/0219 171 A1* 9, 2007 Lulla et al. .................... 514,177 (71) Applicant: INNOTESTO BVBA, Kasterlee (BE) FOREIGN PATENT DOCUMENTS (72) Inventor: Franciscus Wilhelmus Henricus Maria JP HO6321771 A 11, 1994 Merkus, Kasterlee (BE) WO WO-97,38662 A2 10, 1997 WO WO-2005/041943 A1 5, 2005 (73) Assignee: INNOTESTO BVBA, Kasterlee (BE) WO WO-2005049026 A1 6, 2005 WO WO-2009036355 A1 3, 2009 (*) Notice: Subject to any disclaimer, the term of this WO WO-2010/089078 A1 8, 2010 patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days. OTHER PUBLICATIONS Hassan et al., "Chemical permeation enhancers for transbuccal drug (21) Appl. No.: 14/370,435 delivery.” Expert Opon Drug Deliv Jan. 2010;7(1):97-112 (22) PCT Fled: Jan. 4, 2013 (Abstract).* Database Biosis Online Biosciences Information Service, Philadel (86) PCT NO.: PCT/EP2013/05O110 phia, PA, US; 1995, Goldberg-Cettina Melinda et al: “Enhanced transdermal delivery of estradiol in vitro using binary vehicles of S371 (c)(1), isopropyl myristate and short-chain alkanols', XP009 167205, Data (2) Date: Jul. 2, 2014 base accession No. PREV 199598097252 abstract & International Journal of Pharmaceutics (Amsterdam), vol. 114, No. 2, 1995, pp. (87) PCT Pub. No.: WO2013/102665 237-245, ISSN: 0378-5173. Database Biosis Online Biosciences Information Service, Philadel PCT Pub. Date: Jul. 11, 2013 phia, PA, US; Nov. 15, 1998, Kitano Manabu et al: “Buccal absorp tion through golden hambster cheek pouch in vitro and in vivo of (65) Prior Publication Data 17beta-estradiol from hydrogels containing three types of absorption enhancers'. XP009 167375, Database accession No. US 2014/O371191 A1 Dec. 18, 2014 PREV 199900000654 absract & International Journal of Pharmaceutics (Amsterdam), vol. 174, No. 1-2, Nov. 15, 1998, pp. (30) Foreign Application Priority Data 19-28, ISSN: 0378-5 173. International Search Report of PCT/EP2013/050110 filed Jan. 4, Jan. 4, 2012 (GB) ................................... 12OOO62.6 2013. Liu et al. “Effects of Isopropanol-Isopropyl Myristate Binary (51) Int. Cl. Enhancers on InVitro Transport of Estradiol in Human Epidermis: A A6 IK3I/56 (2006.01) Mechanistic Evaluation.” J. Pharma. Sci. 98.2(2009):565-572. A6 IK9/00 (2006.01) A6 IK9/08 (2006.01) * cited by examiner A6 IK3I/565 (2006.01) A6 IK 47/10 (2006.01) A6 IK 47/4 (2006.01) Primary Examiner — Jared D Barsky (52) U.S. C. (74) Attorney, Agent, or Firm — Mintz Levin Cohn Ferris CPC. A61 K9/006 (2013.01); A61 K9/08 (2013.01); Glovsky and Popeo, P.C.; Muriel Liberto, Esq. A6 IK3I/565 (2013.01); A61 K47/10 (2013.01); A61 K47/14 (2013.01) (58) Field of Classification Search (57) ABSTRACT None The present invention relates to low dose estradiol solutions See application file for complete search history. for oromucosal administration Suitable in replacement therapy or suppletion of low estradiol levels and also for (56) References Cited preventing, alleviating or treating symptoms associated with U.S. PATENT DOCUMENTS low endogenous levels of estradiol in female Subjects. 5,766,620 A * 6, 1998 Heiber et al. ................. 424/436 6,110,486 A * 8/2000 Dugger, III ................... 424/435 8 Claims, No Drawings US 9,402,811 B2 1. 2 OROMUCOSAL LIQUIDESTRADIOL comprising estradiol are disclosed in EP 0371466 and WO COMPOSITIONS 2010/089078. Medicated papers for oromucosal administra tion containing estradiol and a cyclodextrin are described in RELATED APPLICATION EP 1867 321. Formulations of dimethyl-3-cyclodextrin complexes of This application is a national stage application filed under 17B-estradiol and/or progesterone in an aqueous solution for 35 U.S.C. 371, of International Application No. PCT/ nasal application have been described in EP 0349091. One EP2013/050110, filed Jan. 4, 2013, which claims priority to Such formulation containing 17 B-estradiol complexed in GB 1200062.6 filed Jan. 4, 2012, the contents of which are methylated-B-cyclodextrin has been authorized for medical hereby fully incorporated by reference. 10 use under the trade name AerodiolTM. This nasal spray prod The present invention relates to low dose estradiol solu uct, administered in a low dose of 300 g/day, was as effective tions for oromucosal administration Suitable in replacement as a 2 mg oral tablet/day in treating menopausal symptoms. It therapy or suppletion of low estradiol levels and also for preventing, alleviating or treating symptoms associated with showed reduced adverse effects, i.e. fewer incidences of mas 15 talgia and withdrawal bleedings. Furthermore, beneficial low endogenous levels of estradiol in female Subjects. effects on Some lipid parameters, on markers of bone resorp BACKGROUND OF THE INVENTION tion, bone formation and bone mineral density were reported. Finally, less breast tenderness was found with intranasal Current estradiol therapy includes oral, transdermal, administration of estradiol as compared to oral treatment. injectable and vaginal formulations. Transdermal delivery Because of the side effects of frequent nasal administra comprises patches, gels, lotions and sprays, while Vaginal tion, AerodiolTM is recommended for once daily administra products include Suppositories, creams, and rings. tion in a high dose resulting in high peak estradiol levels. Estradiol, when taken orally as tablets, pills or capsules, is These are reached within 10-30 min. and the levels return to converted for a large part to estrone after absorption in the 10% of the peak value in about two hours after administration gastrointestinal tract and metabolism in the liver (first-pass 25 (Devissaguet et al., Eur. J. Drug Metabol. Pharmacokinetics metabolism). This causes an imbalance in the estradiol/es 1999; 24; 265-271). This means that once daily intranasal trone ratio, which is normally 1:1 in premenstrual women. administration of AerodiolTM results in a “pulsatile' profile, This imbalance is mainly responsible for a change in lipids comprising one large peak per day, followed by a period and clotting factors. Non-oral products (transdermal, vaginal) during which estradiol levels remain at a low level. Peak avoid this hepatic first-pass metabolism and therefore are 30 levels after administration of 300 g estradiol by the required considered first choice in estradiol Suppletion. quantity of AerodiolTM nasal spray reach values of 1400 pg/l. In general, it is advisable to use the lowest dose of the Normal estradiol levels differ slightly per laboratory, but hormone estradiol possible, because overdosing may lead to range from 100-500 pg/ml during a menstrual cycle. This side effects related to unphysiological hormone levels. Low means that the peak level of 1400 pg/ml, obtained with nasal dose non-oral products are first choice because of (1) the 35 AerodiolTM, is about 3 times higher than the highest normal low-dose administered, (2) the physiological ratio between levels in premenopausal women. levels of estradiol and its metabolite estrone, and (3) as a A further disadvantage related to nasal administration is consequence the decreased risk of adverse effects. The use of that the access to the nasal mucosa can be compromised in very low doses may also be beneficial as opposed treatment instances such as common cold or allergy resulting in a run (continuous or cyclic co-administration of a progestogen) is 40 ning or blocked nose. This results in inconsistent or even no not an absolute requirement because the endometrium does nasal absorption. The product characteristics of AerodiolTM not proliferate upon administration of very low doses of estra teach that in that instance the patient, should administer a diol. double dose of AerodiolTM via the oromucosal route to reach In the research into new estradiol products, non-oral similar estradiol serum levels. administration has been considered, including products for 45 Moreover, nasal administration may give rise to local side nasal and oromucosal administration. U.S. Pat. No. effects in the nose. Such as local irritation, itching, rhinor 5.955,098 discloses a buccal aerosol spray, comprising a pro rhoea, Sneezing and nosebleeds. Multiple nasal administra pellant 50-95%, a non-polar solvent 5-50%, the active drug tions increase these undesired side effects. compound 0.001-15% (including estradiol), and a flavoring It is a first object of the invention to avoid nasal adminis agent 0.05-5%. U.S. Pat. No. 6,110,486 discloses a buccal 50 tration of estradiol and the side effects associated therewith. spray containing estradiol, dissolved in a pharmacologically It is a second object of the invention to provide an estradiol acceptable polar solvent, comprising in weight '% of total composition for oromucosal administration that does not composition: polar solvent 75-99.8%, active compound 0.68 require the administration of high doses of estradiol. Such as 40%. As solvents for the sprays there are used low molecular for example the double dose required for oromucosal admin weight polyethylene glycols (PEG) of 200-1000 MW (pref 55 istration of AerodioITM. erably 200-600) and also low molecular weight alcohols and Further, it is an object of the invention to provide a new polyols, such as glycerin and water. Illustrated is a spray dosage regimen for estradiol administration that provides a formulation containing estradiol and 85% polyethylene gly physiological pharmacokinetic profile approaching normal col. However, this solvent has a bitter, burning taste in the estradiol plasma levels. A particular object is the provision of mouth, making a spray, based mainly on Such an ingredient, 60 a dosage regimen with low estradiol peak levels, in particular poorly acceptable for chronic use. a regimen that keeps the highest estradiol levels under 500 US 2011/0097405 discloses an oromucosal estradiol prod pg/ml, and avoids the high peak serum levels seen with the uct, which is absorbed mainly in the oral cavity and not in the administration of existing nasal formulations.
Load more

Recommended publications
  • The Influence of Hypothalamic Steroid Implants on Ovulation and Ovarian Growth and Function in the Iguanid Lizard, Sceleporus Cyanogenys
    W&M ScholarWorks Dissertations, Theses, and Masters Projects Theses, Dissertations, & Master Projects 1970 The Influence of Hypothalamic Steroid Implants on Ovulation and Ovarian Growth and Function in the Iguanid Lizard, Sceleporus cyanogenys William F. McConnell College of William & Mary - Arts & Sciences Follow this and additional works at: https://scholarworks.wm.edu/etd Part of the Physiology Commons Recommended Citation McConnell, William F., "The Influence of Hypothalamic Steroid Implants on Ovulation and Ovarian Growth and Function in the Iguanid Lizard, Sceleporus cyanogenys" (1970). Dissertations, Theses, and Masters Projects. Paper 1539624685. https://dx.doi.org/doi:10.21220/s2-1smx-cy32 This Thesis is brought to you for free and open access by the Theses, Dissertations, & Master Projects at W&M ScholarWorks. It has been accepted for inclusion in Dissertations, Theses, and Masters Projects by an authorized administrator of W&M ScholarWorks. For more information, please contact [email protected]. THE INFLUENCE OF HYPOTHALAMIC STEROID IMPLANTS ON OVULATION AND OVARIAN GROWTH AND FUNCTION IN THE IGUANID LIZARD, SCELOPORUS CYANOGENYS A Thesis Presented to The Faculty of the Department of Biology The College of William and Mary in Virginia In Partial Fulfillment Of the Requirements for the Degree of Master of Arts By William F. McConnell 1970 ProQuest Number: 10625114 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion.
    [Show full text]
  • 35 Cyproterone Acetate and Ethinyl Estradiol Tablets 2 Mg/0
    PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION PrCYESTRA®-35 cyproterone acetate and ethinyl estradiol tablets 2 mg/0.035 mg THERAPEUTIC CLASSIFICATION Acne Therapy Paladin Labs Inc. Date of Preparation: 100 Alexis Nihon Blvd, Suite 600 January 17, 2019 St-Laurent, Quebec H4M 2P2 Version: 6.0 Control # 223341 _____________________________________________________________________________________________ CYESTRA-35 Product Monograph Page 1 of 48 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION ....................................................................... 3 SUMMARY PRODUCT INFORMATION ............................................................................................. 3 INDICATION AND CLINICAL USE ..................................................................................................... 3 CONTRAINDICATIONS ........................................................................................................................ 3 WARNINGS AND PRECAUTIONS ....................................................................................................... 4 ADVERSE REACTIONS ....................................................................................................................... 13 DRUG INTERACTIONS ....................................................................................................................... 16 DOSAGE AND ADMINISTRATION ................................................................................................ 20 OVERDOSAGE ....................................................................................................................................
    [Show full text]
  • Use of Estrogen-Dihydropyridine Compounds For
    Europaisches Patentamt J European Patent Office © Publication number: 0 220 844 Office europeen des brevets A2 EUROPEAN PATENT APPLICATION © Application number: 86307536.2 © int. ci.<: A61K 31/57 A61 K , 31/565 , A61K 31/44 © Date of filing: 01.10.86 The title of the invention has been amended © Applicant: UNIVERSITY OF FLORIDA (Guidelines for Examination in the EPO, A-lll, 207 Tigert Hall 7.3). Gainesville Florida 32611 (US) @ Inventor: Bodor, Nicholas S. ® Priority: 22.10.85 US 790159 7211 Southwest 97th Lane Gainesville Florida 32608(US) © Date of publication of application: Inventor: Estes, Kerry S. 06.05.87 Bulletin 87/19 5604 Southwest 83rd Drive Gainesville Florida 32608(US) © Designated Contracting States: Inventor: Simpkins, James W. AT BE CH DE ES FR GB GR IT LI LU NL SE 1722 Northwest 11th Road Gainesville Florida 32605(US) © Representative: Pendlebury, Anthony et al Page, White & Fairer 5 Plough Place New Fetter Lane London EC4A 1HY(GB) © Use of estrogen-dihydropyridlne compounds for weight control. © The invention provides the use of a compound of the formula [E-DHC] (I) or a non-toxic pharmaceutically acceptable salt thereof, wherein [E] is an estrogen and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating, lipoidal form of a dihydropyridines*pyridinium salt redox carrier in the preparation of a medicament for controlling mammalian body weight. Novel compositions for weight control comprising a compound of formula (I) or its salt are also disclosed. A preferred compound for use herein is an I estradiol derivative, namely, 1 7/3-[(1 -methyl-1 ,4-dihydro-3-pyridinyl)carbonyloxy]estra-1 ,3,5(1 0)-trien-3-ol.
    [Show full text]
  • Network-Based Characterization of Drug-Protein Interaction Signatures
    Tabei et al. BMC Systems Biology 2019, 13(Suppl 2):39 https://doi.org/10.1186/s12918-019-0691-1 RESEARCH Open Access Network-based characterization of drug-protein interaction signatures with a space-efficient approach Yasuo Tabei1*, Masaaki Kotera2, Ryusuke Sawada3 and Yoshihiro Yamanishi3,4 From The 17th Asia Pacific Bioinformatics Conference (APBC 2019) Wuhan, China. 14–16 January 2019 Abstract Background: Characterization of drug-protein interaction networks with biological features has recently become challenging in recent pharmaceutical science toward a better understanding of polypharmacology. Results: We present a novel method for systematic analyses of the underlying features characteristic of drug-protein interaction networks, which we call “drug-protein interaction signatures” from the integration of large-scale heterogeneous data of drugs and proteins. We develop a new efficient algorithm for extracting informative drug- protein interaction signatures from the integration of large-scale heterogeneous data of drugs and proteins, which is made possible by space-efficient representations for fingerprints of drug-protein pairs and sparsity-induced classifiers. Conclusions: Our method infers a set of drug-protein interaction signatures consisting of the associations between drug chemical substructures, adverse drug reactions, protein domains, biological pathways, and pathway modules. We argue the these signatures are biologically meaningful and useful for predicting unknown drug-protein interactions and are expected to contribute to rational drug design. Keywords: Drug-protein interaction prediction, Drug discovery, Large-scale prediction Background similar drugs are expected to interact with similar pro- Target proteins of drug molecules are classified into a pri- teins, with which the similarity of drugs and proteins are mary target and off-targets.
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • Evsjv‡`K †M‡RU
    †iwR÷vW© bs wW G-1 evsjv‡`k †M‡RU AwZwi³ msL¨v KZ…©cÿ KZ…©K cÖKvwkZ e„n¯úwZevi, wW‡m¤^i 17, 2009 MYcÖRvZš¿x evsjv‡`k miKvi A_© gš¿Yvjq Af¨šÍixY m¤ú` wefvM ( ïé I g~j¨ ms‡hvRb Ki ) cÖÁvcb ZvwiL, 01 †cŠl 1416 e½vã/15 wW‡m¤^i 2009 wLª÷vã Gm, Avi, I bs 266-AvBb/2009/2268/ïé|⎯Customs Act, 1969 (Act IV of 1969) Gi section 19(1) G cÖ`Ë ÿgZve‡j Rb¯^v‡_©, RvZxq ivR¯^ †ev‡W©i mwnZ civgk©µ‡g, Ges g~j¨ ms‡hvRb Ki AvBb, 1991 (1991 m‡bi 22 bs AvBb) Gi aviv 14(1) G cÖ`Ë ÿgZve‡j miKvi wbgœewY©Z kZ© mv‡c‡ÿ wb‡gœ wea„Z⎯ (K) TABLE-I Gi Kjvg (2) G ewY©Z H.S. Code Gi wecix‡Z Kjvg (3) G DwjøwLZ c‡Y¨i Dci Av‡ivcbxq Avg`vwb ïé †h cwigv‡Y 5%; Ges (L) TABLE-II Gi Kjvg (2) G ewY©Z H.S. Code Gi wecix‡Z Kjvg (3) G DwjøwLZ c‡Y¨i Dci Av‡ivcbxq Avg`vwb ïé †h cwigv‡Y 15%- ( 7843 ) g~j¨ t UvKv 60⋅00 7844 evsjv‡`k †M‡RU, AwZwi³, wW‡m¤^i 17, 2009 Gi AwZwi³ nq †mB cwigvY Avg`vwb ïé I mgy`q m¤ú~iK ïé (hw` _v‡K) GZ`&Øviv Ae¨vnwZ cÖ`vb Kwij t Z‡e kZ© _v‡K †h, `dv (K) Ges (L) †Z ewY©Z cY¨ MYcÖRvZš¿x evsjv‡`k miKvi KZ©„K Aby‡gvw`Z Jla cÖ¯‘ZKvix cÖwZôvb‡K, Jla cÖkvmb cwi`ßi KZ©„K Aby‡gvw`Z eøK wj‡÷ wbw`©óK…Z g~j¨ I cwigv‡Yi mxgvi g‡a¨, Jla cÖ¯‘‡Zi Rb¨ Avg`vwb Kwi‡Z nB‡e, h_v t⎯ TABLE-I Heading H.S.Code Description (1) (2) (3) 12.11 1211.90.21 Buchhu powder/extracts/leaves 1211.90.21 Cinchona/Cinchona Brak/Powder 1211.90.21 Ergot of Rye/Lobelia powder/Powdered paricap of sennapod 1211.90.29 Buchhu powder/extracts/leaves 1211.90.29 Cinchona/Cinchona Bark/Powder 1211.90.29 Ergot of Rye/Lobelia powder/Powdered paricap of sennapod 13.02 1302.11.00 Vegetable extract-opium, pharmaceutical
    [Show full text]
  • PHARMACEUTICAL APPENDIX to the HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2008) (Rev
    Harmonized Tariff Schedule of the United States (2008) (Rev. 1) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2008) (Rev. 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. ABACAVIR 136470-78-5 ACIDUM GADOCOLETICUM 280776-87-6 ABAFUNGIN 129639-79-8 ACIDUM LIDADRONICUM 63132-38-7 ABAMECTIN 65195-55-3 ACIDUM SALCAPROZICUM 183990-46-7 ABANOQUIL 90402-40-7 ACIDUM SALCLOBUZICUM 387825-03-8 ABAPERIDONUM 183849-43-6 ACIFRAN 72420-38-3 ABARELIX 183552-38-7 ACIPIMOX 51037-30-0 ABATACEPTUM 332348-12-6 ACITAZANOLAST 114607-46-4 ABCIXIMAB 143653-53-6 ACITEMATE 101197-99-3 ABECARNIL 111841-85-1 ACITRETIN 55079-83-9 ABETIMUSUM 167362-48-3 ACIVICIN 42228-92-2 ABIRATERONE 154229-19-3 ACLANTATE 39633-62-0 ABITESARTAN 137882-98-5 ACLARUBICIN 57576-44-0 ABLUKAST 96566-25-5 ACLATONIUM NAPADISILATE 55077-30-0 ABRINEURINUM 178535-93-8 ACODAZOLE 79152-85-5 ABUNIDAZOLE 91017-58-2 ACOLBIFENUM 182167-02-8 ACADESINE 2627-69-2 ACONIAZIDE 13410-86-1 ACAMPROSATE
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • United States Patent (19) 11) 4,383,993 Hussain Et Al
    United States Patent (19) 11) 4,383,993 Hussain et al. 45) May 17, 1983 (54) NASAL DOSAGE FORMS CONTAINING 4,315,925 2/1982 Hussain et al. ...................... 424/239 NATURAL FEMALE SEX HORMONES Primary Examiner-Elbert L. Roberts Attorney, Agent, or Firm-Burns, Doane, Swecker & 75 Inventors: Anwar A. Hussain; Shinichiro Hirai; Rima Bawarshi, all of Lexington, Ky. Mathis 73) Assignee: University of Kentucky Research (57) ABSTRACT Foundation, Lexington, Ky. The invention relates to a novel method of administer ing the natural female sex hormones, 17 g-estradiol and 21 Appl. No.: 277,000 progesterone, to achieve enhanced bioavailability thereof. The invention further relates to novel dosage (22) Fied: Jun. 24, 1981 forms of 17 g-estradiol and/or progesterone which are adapted for nasal administration, such as solutions, sus Related U.S. Application Data pensions, gels and ointments. The dosage forms contain (63) Continuation of Ser. No. 154,995, May 30, 1980, Pat. ing a combination of 17 g-estradiol and progesterone No. 4,315,925. are particularly useful as contraceptives, while the dos (51) Int. Cl. ............................................. AON 45/00 age forms containing only one of the hormonal compo (52) 4 - - - - - - - - - - 4 424/239 nents find utility in the treatment of conditions such as Field of Search ................................ 424/239, 238 menopause, menstrual disorders, etc., which are known (58) to respond to administration of a natural or synthetic 56) References Cited female hormone. U.S. PATENT DOCUMENTS 4, 145,416 3/1979 Lachnit-Fixson et al. ......... 424/239 26 Claims, 5 Drawing Figures a WAPS, AI WWSW of %2- Aftffff;7 fr A/FAO/WSIPt.
    [Show full text]
  • Review on Hormone Replacement Therapy and Its Impact on Morbidity and Longevity Literature Review
    Review on Hormone Replacement Therapy and its Impact on Morbidity and Longevity Literature Review by Nurunnahar Akter, School of Computing Sciences, University of East Anglia, United Kingdom (UK) The Actuarial Research Centre (ARC) is the Institute and Faculty of Actuaries’ (IFoA) network of actuarial researchers around the world. The ARC delivers industry-led, cutting edge research programmes that address some of the significant challenges in actuarial science. It does this by bridging academic rigour with practitioner needs - working collaboratively with academics, industry and other actuarial bodies. This piece of ARC research has been commissioned by the IFoA. DISCLAIMER The views expressed in this publication are those of invited contributors and not necessarily those of the Institute and Faculty of Actuaries. The Institute and Faculty of Actuaries do not endorse any of the views stated, nor any claims or representations made in this publication and accept no responsibility or liability to any person for loss or damage suffered as a consequence of their placing reliance upon any view, claim or representation made in this publication. The information and expressions of opinion contained in this publication are not intended to be a comprehensive study, nor to provide actuarial advice or advice of any nature and should not be treated as a substitute for specific advice concerning individual situations. On no account may any part of this publication be reproduced without written permission of the Institute and Faculty of Actuaries. Literature Review on Hormone Replacement Therapy and its Impact on Morbidity and Longevity By Nurunnahar Akter School of Computing Sciences Supervisor: Prof. Elena Kulinskaya Co-supervisor: Dr.
    [Show full text]
  • Centre for Reviews and Dissemination Parenteral Oestrogens for Prostate
    Centre for Reviews and Dissemination A Systematic Review of Parenteral Oestrogens for Prostate Cancer Parenteral Oestrogens for Prostate Cancer: A Systematic Review of Clinical Effectiveness and Dose Response 33 Promoting the use of research based knowledge REPORT 33 CRD Parenteral oestrogens for prostate cancer: A systematic review of clinical effectiveness and dose response Michael Emmans Dean2 Gill Norman1 Zoé Hodges6 Gill Ritchie3 Kate Light1 Alison Eastwood1 Ruth Langley4 Matthew Sydes4 Mahesh Parmar4 Paul Abel5 1 Centre for Reviews and Dissemination, University of York, York YO10 5DD 2 Department of Health Sciences, University of York, York YO10 5DD 3National Collaborating Centre for Primary Care, Frazer House, 32-38 Leman Street, London, E1 8EW 4MRC Clinical Trials Unit, 222 Euston Road, London 5Imperial College, London, W12 0NN 6 Department of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, WC1B 3RE September 2006 © 2006 Centre for Reviews and Dissemination, University of York ISBN 1 900640 37 6 This report can be ordered from: Publications Office, Centre for Reviews and Dissemination, University of York, York YO10 5DD. Telephone 01904 321458; Facsimile: 01904 321035: email: [email protected] Price £12.50 The Centre for Reviews and Dissemination is funded by the NHS Executive and the Health Departments of Wales and Northern Ireland. The views expressed in this publication are those of the authors and not necessarily those of the NHS Executive or the Health Departments of Wales or Northern Ireland. Printed by York Publishing Services Ltd. ii CENTRE FOR REVIEWS AND DISSEMINATION The Centre for Reviews and Dissemination (CRD) is a facility commissioned by the NHS Research and Development Division.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7,867,986 B2 Houze (45) Date of Patent: Jan
    US007867986B2 (12) United States Patent (10) Patent No.: US 7,867,986 B2 Houze (45) Date of Patent: Jan. 11, 2011 (54) ENHANCED DRUG DELIVERY IN 5,780,050 A 7/1998 Jain et al. TRANSIDERMAL SYSTEMS 5,811,117 A 9, 1998 Hashimoto et al. 5,849,729 A * 12/1998 Zoumas et al. .............. 514,169 (75) Inventor: David Houze, Coconut Grove, FL (US) 5,898,032 A 4/1999 Hodgen 5,958,446 A * 9/1999 Miranda et al. ............. 424/448 (73) Assignee: Noven Pharmaceuticals, Inc., Miami, 6,024,974 A 2, 2000 Li FL (US) 6,143,319 A 11/2000 Meconi et al. (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 (21) Appl. No.: 10/330,361 FOREIGN PATENT DOCUMENTS (22) Filed: Dec. 30, 2002 CL 49-95 1, 1994 (65) Prior Publication Data US 2003/O152615A1 Aug. 14, 2003 (Continued) Related U.S. Application Data OTHER PUBLICATIONS (63) Continuation of application No. 09/948,107, filed on M.D. Mashkovsky, The Medicaments, Guidelines for Medical Doc Sep. 7, 2001, now abandoned. tors, vol. 1, 2001, 2 pgs... translation provided. (60) Provisional application No. 60/298,381, filed on Jun. (Continued) 18, 2001. Primary Examiner San-ming Hui (51) Int. Cl. 74) Attorney,V, AgAgent, or Firm—Foleyy & Lardner LLP A6 IK3I/56 (2006.01) (52) U.S. Cl. ...................................................... S14/171 (57) ABSTRACT (58) Field of Classification Search ................. 514/170, 514/171, 180 See application file for complete search history. A composition for transdermal administration resulting from an admixture includes: a therapeutically effective amount of (56) References Cited a pharmaceutically active agent that includes a corresponding U.S.
    [Show full text]