DOCSLIB.ORG

III III III US005595759A United States Patent (19) 11 Patent Number: 5,595,759 Wright Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
III III III US005595759A United States Patent (19) 11 Patent Number: 5,595,759 Wright Et Al III III III US005595759A United States Patent (19) 11 Patent Number: 5,595,759 Wright et al. (45) Date of Patent: Jan. 21, 1997 (54) PROCESS FOR PROVIDING THERAPEUTIC 4,309,996 l/1982 Theeuwes ............................... 128/260 COMPOSITION 4,320,759 3/1982. Theeuwes ..... ... 128/260 4,449,983 5/1983 Cortese et al. ..... 604/892 (75. Inventors: Jeri D. Wright, Dublin; Brian L. 2. Esthet al. 3. V at aal Cal. .... o E. styleEa. f Calif 4,948,593 8/1990 Wright et al...... 424/473 son, Porto ey, all of Calli. 5,032,406 7/1991 Dansereau et al. 424/472 73) Assignee:rena Ms Alza Corporation,o Palo Alto, Calif. 5,200,1975,098,714 3/19924/1993 Wright et al.......al. ........................... 424/473 (21 Appl. No.: 337,701 OTHER PUBLICATIONS 22 Filed: Nov. 10, 1994 Wurster,(1960) pp. Dale 82-84. E. J. Am. Pharm. Assn., Sci. Ed., vo. 49, (51) Int. Cl. ... A61K 9/20 Wurster, Dale E., J. Am. Pharm. Assn., Sci. Ed., vol. 48 52 U.S. Cl. .......................... 424/464; 424/465; 424/474; (1959) pp. 451-454. 424/480 The Pharmacological Basis of Therapeutics, by Goodman & (58) Field of Search ..................................... 424/464, 465, Gilman, 7th Ed. (1985) pp. 1430-1439. 424/473, 474, 479, 484, 486, 426 Pharmaceutical Sciences, by Remington, 14th Ed., (1970) I Wr ws pp. 1626-1680. 56) References Cited Primary Examiner-Thurman K. Page U.S. PATENT DOCUMENTS Assistant Examiner Sharon Howard Attorney, Agent, or Firm-Paul L. Sabatine; Mary Ann 2,799,241 7/1957 Wurster ..................................... 18/24 Dillahunty; Felissa H. Cagan 3,133,132 5/1964 Loeb et al. ................................ 264/49 3,845,770 1 1/1974 Theeuwes et al....................... 128/130 (57) ABSTRACT 3,916,899 11/1975 Theeuwes et al...... 4,063,064 12/1977 Saunders et al. ...... As A process is disclosed and claimed for preparing a thera 4.088,864 5/1978 Theeuwes et al. ou 219/260 peutic composition comprising asteroid or a dosage form 4,160,020 7/1979 Ayer et al. ............. - - - - - - 424/15 comprising the composition, which therapeutic composition 4,177.256 12/1979 Michaels et al. ......................... 424/22 or dosage form is indicated for human administration. 4,200,098 4/1980 Ayer et al. .............................. 128/260 4,285,987 8/1981. Ayer et al. .................................. 427/3 7 Claims, No Drawings 5,595,759 1. 2 PROCESS FOR PROVIDING THERAPEUTIC gon-4-en-3-one oxime, d-133-ethyl-17o-ethinyl-17B-hy COMPOSITION roxygon-4-en-3-one, 133-ethyl-173-hydroxygon-4-en-3- One, 133,17B-diethyl-17B-hydroxygon-4-en-3-one, FIELD OF THE INVENTION ethylnodiol diacetate, medroxyprogesterone, chlormadione acetate, 17o-ethinyl-173-acetoxy-17-norandrost-4-en-3- This invention pertains to a therapeutic composition, to a one, 3-ketodesogestrel, desogestrel, gestodene, gestodene dosage form, and to a process for preparing the therapeutic acetate, levonorgestrel-2-methylbutanoate, levonorgestrel composition, and the dosage form. The therapeutic compo acetate, levonorgestrel butanoate, levonorgestrel butyrate, sition and the dosage form comprise a drug, for example, a levonorgestrel cyanoacetate, levonorgestrel cyclobutane car pharmaceutically acceptable steroid selected from an estro boxylate, levonorgestrel cyclopropylcarboxylate, norgestrel gen, or a progestin, or both an estrogen and a progestin. 10 decanoate, norgestrel pentanoate, norgestrel-2-methyl-2- enoate, norgestrel formate, norgestrel glycidol, norgestrel BACKGROUND OF THE INVENTION keptanoate, norgestrel hexanoate, northisterone methoxyac The direction of much medical and scientific research in etate, northisterone nonanoate, northisterone pentanoate, recent prior art endeavors has been to provide a therapeutic 15 desogestrel propanoate, desogestrel valerate, desogestrel-2- composition comprising a drug, or to provide a dosage form ethylbutanoate, desogestrel cyclobutylheptanoate, and d, comprising a drug indicated in both instances for therapy, or I-norgestrel. The dosage of progestin or progestin deriva for contraception. In the latter, the therapeutic composition, tives in a composition is 10 ng to 500 mg. and the dosage form are a means for administering a In providing the process for producing the composition, therapeutically acceptable progestin to a human. The prior 20 and the dosage form containing the composition the process art, in recent patents, U.S. Pat. Nos. 4,948,593; 5,098,714; provides also a combination of an estrogen and a progestin and 5,200,197 all issued to Wright et al, there are disclosed selected from the combination consisting of ethinyl estradiol compositions comprising an estrogen and a progestin that and cyproterone acetate, ethinyl estradiol and desogestrel, are administered for contraceptive purposes. While these ethinyl estradiol and dimethisterone, ethinyl estradiol and compositions operate successfully for their intended pur 25 ethylnodiol diacetate, ethinyl estradiol and ethynodiol diac pose, it has now been discovered a process can be provided etate, ethinyl estradiol and gestodene, ethinyl estradiol and that improves the manufacture of the composition and gestodene, ethinyl estradiol and levonorgestrel, ethinyl correspondingly a dosage form containing the composition. estradiol and lynestrenol, ethinyl estradiol and norethin The present invention has an object to provide a process for drone acetate, ethinyl estradiol and norethindrone propi preparing a therapeutic composition comprising a member 30 onate, ethinyl estradiol and norethindrone, ethinyl estradiol selected from the group consisting of an estrogen, a proges and norethindrone butyrate, ethinyl estradiol and norethin tin, or a combination of an estrogen and a progestin, which drone palmitate, ethinyl estradiol and norethisterone, ethinyl can be administered as a composition, or administered from estradiol and norgestrel, ethinyl estradiol and norgestimate, a dosage form. The invention further has an object to provide ethinyl estradiol and norethynodrel, ethinyl estradiol and a method for administering a composition for contraception 35 progesterone, ethinyl estradiol and hydroxyprogesterone, which composition is produced by the process of the inven estrone and progesterone, estrogen and progesterone, estro tion. gen and levonorgestrel, estrogen and norgestrel, estrogen and norethindrone, estrogen and norgestimate, estrogen and DESCRIPTION FOR PROVIDING THE norethisterone, estrogen and norethynodrel, estrogen and INVENTION hydroxyprogesterone, estrogen and desogestrel, estrogen and gestodene, estriol and desogestrel, estriol and gestodene, In providing the process to produce the composition, and estriol and desogestrel, estriol and gestodene, estriol and the dosage form, the estrogen contraceptively acceptable for levonorgestrel, estriol and norethindrone, estriol and norg these purposes comprise a member selected from the group estrel, estriol and norgestimate, estriol and progesterone, consisting of estrogen, estradiol, estradiol valerate, estradiol 45 estriol and hydroxyprogesterone, estriol and desogestrel, benzoate, estradiol cypionate, estradiol ether, estradiol ester, estriol and dimethisterone, and estriol and norethisterone. estradiol propionate, estradiol dipropionate, estradiol The composition consisting of a contraceptive pair of an acetate, ethinyl estradiol esters, 17o-ethinyl estradiol estrogen and progestin comprises 11 ng to 1750 mg of the acetate, 17o-ethinyl estradiol benzoate, 17o-ethinyl estra steroid pair. diol ethers, 17o-ethinyl estradiol ethers, estrone, estrone 50 A process for providing a composition consisting of acetate, estrone sulfate, estriol, estriol succinate, 178-estra levonorgestrel (LNG) and ethinyl estradiol (EE) comprises diol, ethinyl estradiol 17-methyl ether, ethinyl estradiol the following process steps: 3.835 g of micronized ethinyl 3-anthranilate hydrochloride, ethinyl estradiol 3-methyl estradiol is dissolved in an organic solvent, ethyl alcohol, ether, ethinyl estradiol 3, 17-dimethyl ether, ethinyl estra 1777.5g with constant stirring to produce a wet granulation. diol-17-ethyl ether, and estrone phosphate. The dosage 55 Next, separately, 18.335 g of levonorgestrel is mixed in a amount of estrogen or estrogen derivative in a composition blender with 250 g of a hydroxyalkylcellulose, hydroxypro is 1 ng to 1000 mg. pylmethylcellulose possessing a 11,200 molecular weight to In providing the process for producing the therapeutic yield a drug levonorgestrelhydroxypropylmethyl-cellulose composition and the dosage form, the progestin for these homogenous blend. Then, an osmopolymer, poly(alkylene purposes comprise a member selected from the group con 60 oxide), 4702.83 g of poly(ethylene oxide) possessing a sisting of progesterone, d-norgestrel, norethindrone, 200,000 molecular weight, is added to the blend comprising levonorgestrel, norgestimate, norethisterone, norethisterone the levonorgestrel and the hydroxypropyl-methylcellulose acetate, norethynodrel, norethindrone acetate, 17-hydrox and the three ingredients, the poly(ethylene oxide), hydrox yprogesterone, 17-hydroxyprotesterone ester, 17-hydrox ypropylmethylcellulose and the levonorgestrel blended into yprogesterone ether, 19-nor-17-hydroxyprogesterone, 65 a homogenous blend for 10 minutes. Next, the ethinyl 19-nor-17-hydroxyprogesterone ester, 19-nor-17-hydrox estradiol granulation is added slowly to the dry three yprogesterone ether, 17B-acetoxy-133-ethyl-17o-ethinyl ingredient blend and the blending continued for 7 to 9 5,595,759 3 4 minutes. Next, the just prepared wet
Load more

Recommended publications
  • Ecriture These Terminale2
    Université de Poitiers Faculté de Médecine et Pharmacie 2017 Thèse n° THESE POUR LE DIPLOME D’ETAT DE DOCTEUR EN MEDECINE (décret du 16 janvier 2004) présentée et soutenue publiquement le 14 février 2017 à Poitiers par Mathilde COULAIS Quel est l’impact de la contraception oestroprogestative sur la sexualité féminine après au moins trois mois d’utilisation ? Revue de la littérature COMPOSITION DU JURY Président : Monsieur le Professeur Xavier FRITEL Membres : Monsieur le Professeur Nematollah JAAFARI Madame le Docteur Claire LAFAY CHEBASSIER Directeur de thèse : Madame le Docteur Stéphanie GRANDCOLIN 2 3 Remerciements A Monsieur le Professeur Xavier FRITEL Merci de nous avoir fait l’honneur de présider notre jury de thèse. Soyez assuré de notre profond respect. A Monsieur le Professeur Nematollah JAAFARI Merci d’avoir accepté de venir juger cette thèse. Soyez assuré de notre reconnaissance. A Madame le Docteur Claire LAFAY CHEBASSIER Merci d’avoir accepté de faire partie du jury et de vos précieux conseils lors de ce travail A Madame le Docteur Stéphanie GRANDCOLIN Merci d’avoir accepté de diriger cette thèse et de m’avoir aidé tout au long de ce travail. 4 A mes parents : merci pour votre soutien indéfectible. Merci Papa d’avoir eu confiance en moi dès le début de cette aventure et de m’avoir guidée pour être médecin. Merci Maman pour tes encouragements, ton écoute si précieuse et tes bons petits plats. Une pensée toute particulière pour un certain rosier blanc. A ma sœur jumelle et meilleure amie, Clémentine : merci d’avoir partagé avec moi les bons et mauvais moments de cette grande aventure qu’ont été nos études.
    [Show full text]
  • Biodegradable Polymeric Biomaterials in Different Forms for Long-Acting
    University of Tennessee Health Science Center UTHSC Digital Commons Theses and Dissertations (ETD) College of Graduate Health Sciences 5-2017 Biodegradable Polymeric Biomaterials in Different Forms for Long-acting Contraception and Drug Delivery to the Eye and Brain Dileep Reddy Janagam University of Tennessee Health Science Center Follow this and additional works at: https://dc.uthsc.edu/dissertations Part of the Pharmaceutics and Drug Design Commons Recommended Citation Janagam, Dileep Reddy (http://orcid.org/0000-0002-7235-7709), "Biodegradable Polymeric Biomaterials in Different Forms for Long-acting Contraception and Drug Delivery to the Eye and Brain" (2017). Theses and Dissertations (ETD). Paper 425. http://dx.doi.org/10.21007/etd.cghs.2017.0429. This Dissertation is brought to you for free and open access by the College of Graduate Health Sciences at UTHSC Digital Commons. It has been accepted for inclusion in Theses and Dissertations (ETD) by an authorized administrator of UTHSC Digital Commons. For more information, please contact [email protected]. Biodegradable Polymeric Biomaterials in Different Forms for Long-acting Contraception and Drug Delivery to the Eye and Brain Document Type Dissertation Degree Name Doctor of Philosophy (PhD) Program Pharmaceutical Sciences Track Pharmaceutics Research Advisor Tao L. Lowe, Ph.D. Committee Joel Bumgardner, Ph.D. James R. Johnson, Ph.D. Bernd Meibohm, Ph.D. Duane D. Miller, Ph.D. ORCID http://orcid.org/0000-0002-7235-7709 DOI 10.21007/etd.cghs.2017.0429 Comments Two year embargo expires
    [Show full text]
  • Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
    US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG .
    [Show full text]
  • Long-Acting Technologies for the Prevention and Treatment of Major Infectious Diseases
    Bringing innovation to the front line for impact: Long-acting technologies for the prevention and treatment of major infectious diseases COMPENDIUM OF TECHNICAL AND MARKET INFORMATION November 2018 Unitaid SDG 2 How to use this compendium 1 Click or tap 2 3 Experience circles in 1 Public from other Table of Contents Introduction health disease challenges (next slide) to move areas between sections 2 (Cohen at al, 2011) Click or tap author names and images of journal/media articles to access online content (internet connection required) 3 Click or tap underlined text in section breaks to jump ahead to sub-sections 4 5 Click or tap to return to Table of Contents Click or tap to return to beginning of section 4 Science 3 4a 4b Contents of this compendium Injectables Devices 4c Disease- 3 4 specific 2 Experience Science and Public from other technology health disease landscape challenges areas 4d Product summaries 1 Click or tap to move to sections Introduction 5 Target 7 6 product Towards a User and profiles healthy patient market preferences Part 1: Introduction • Overview – a potential new era in medicine? • Why is Unitaid exploring long-acting technologies? • Scope of this project and working definition of ”long-acting” • Purpose of this compendium and how it was developed • Project Reference Group • Theory of change for potential Unitaid investment • Major stakeholders in the development of long-acting drugs and delivery systems/devices for LMICs 5 Overview: A potential new era in medicine • Scientific and technological advances herald a potential new era in delivery of medicines: moving from daily oral medication to weekly, monthly and less frequent long-acting (LA) formulations could accelerate efforts to control/end major global epidemics by improving patient adherence, containing resistance and reducing costs.
    [Show full text]
  • Contraceptive and Reproductive Health Branch, NICHD, Report To
    The information in this document is no longer current. It is intended for reference only. TABLE OF CONTENTS EXECUTIVE SUMMARY .......................................................................................................... 1 INTRODUCTION TO THE BRANCH...................................................................................... 2 PROGRAM AREAS..................................................................................................................... 3 CONTRACEPTIVE RESEARCH AND DEVELOPMENT........................................................................ 3 CONTRACEPTIVE AND REPRODUCTIVE EVALUATION................................................................... 5 PREVENTION OF HIV/AIDS AND OTHER STDS ........................................................................... 6 SELECTED REPRODUCTIVE AND OTHER GYNECOLOGIC HEALTH ISSUES ..................................... 6 RESEARCH TRAINING................................................................................................................... 7 HIGHLIGHTS FROM CRHB-FUNDED RESEARCH IN CONTRACEPTIVE RESEARCH AND DEVELOPMENT ........................................................................................ 8 U54 CONTRACEPTIVE DEVELOPMENT RESEARCH CENTER PROGRAM (CDRCP) ........................ 8 MALE CONTRACEPTION ............................................................................................................... 9 FEMALE CONTRACEPTION.........................................................................................................
    [Show full text]
  • Long-Acting Contraceptive Methods for Women
    LongLongLong-acting--actingacting contraceptivecontraceptive methodsmethods forfor womenwomen CatherineCatherine d’Arcanguesd’Arcanguesd’Arcangues,,, Ph.D.,Ph.D., M.D.M.D. DepartmentDepartment ofof ReproductiveReproductive HealthHealth andand ResearchResearch WorldWorld HealthHealth OrganizationOrganization Geneva,Geneva, 2424 MarchMarch 20032003 Department of reproductive health and research Département santé et recherche génésiques CDA_FIGO_SEPT00/1 RationaleRationale forfor thethe developmentdevelopment ofof longlong--actingacting methodsmethods ofof contraceptioncontraception •• MethodsMethods thatthat dodo notnot requirerequire dailydaily useuse oror interfereinterfere withwith sexualsexual intercourseintercourse [Duration[Duration ofof action:action: 77 daysdays →→ 77 years]years] ¿¿ greatergreater useuse--effectivenesseffectiveness •• MethodsMethods withwith improvedimproved pharmacokineticpharmacokinetic profileprofile ¿¿ reducedreduced sideside--effectseffects Note:Note: ¿¿ dependancedependance onon healthhealth carecare providerprovider Department of reproductive health and research Département santé et recherche génésiques CDA_FIGO_SEPT/00/2 SchematicSchematic representationrepresentation ofof expectedexpected PKPK profilesprofiles ofof progestogensprogestogens administeredadministered byby differentdifferent routesroutes andand inin differentdifferent formulationsformulations Department of reproductive health and research Département santé et recherche génésiques CDA_FIGO_SEPT/00/3 LongLong--actingacting methodsmethods ••
    [Show full text]
  • 10Th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology PEOPLE MAKE GLASGOW
    10th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology 4 Parallel Symposia on Basic Research, R&D, Industrial Practice and Analytics Glasgow, United Kingdom 4 to 7 April 2016 www.worldmeeting.org PEOPLEPEOPLE MAKEMAKE GLASGOWGLASGOW Site Map Key Door 3.1 Door 3.2 Entrance Male toilet Female toilet Door 3B Brasserie Disabled toilet West Quay Door 3.3 Baby changing Hall 3 Cash machine Door 3A Cloakroom Medical Centre Information Food & drink Door 4E Taxi rank Door 4.3 Door 4D Bus stop Exhibition Centre Door 2.2 Door 2B station Door 4.2 Hall 2 Door 4c Hall 4 Door 2.1 Door 2A Door 1.1 Door 4B Hall 1 Door 4.4 Shop Crowne Door 4A Plaza Boisdale 2 Lomond Alsh 1 Hotel Auditorium Box Deli/Bakery Boisdale 1 Fyne Etive Alsh 2 Office Door 5B Escalator Registration Meeting Rooms Link Door 5.1 Corridor Hall 5 Door 5A Exhibition & Poster Clyde Door 5.3 Door 5.2 Built Reception Entrance Clyde Covered Walkway Auditorium West Entrance Forth Room Entrance Exhibition Entrance Entrance The SSE Centre station Hydro East Entrance Multi-Storey Car Park 10th PBP World Meeting · ResearchPharm 2 Glasgow, UK · 4 to 7 April 2016 Welcome to Glasgow 10th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology 4 Parallel Symposia on Basic Research, R&D, Industrial Practice and Analytics Glasgow, United Kingdom 4 to 7 April 2016 SECC Glasgow 10th PBP World Meeting · ResearchPharm Glasgow, UK · 4 to 7 April 2016 3 How to get to from the Conference Centre to the Welcome Reception You leave the building in direction to the Clyde River and walk across Bell’s Bridge or Millenium Bridge, then turn right and you will reach the Glasgow Science Centre, 50 Pacific Quay, Glasgow G51 1EA.
    [Show full text]
  • Contraceptive Research and Development: Looking to the Future Polly F
    http://www.nap.edu/catalog/5156.html We ship printed books within 1 business day; personal PDFs are available immediately. Contraceptive Research and Development: Looking to the Future Polly F. Harrison and Allan Rosenfield, Editors; Committee on Contraceptive Research and Development, Institute of Medicine ISBN: 0-309-52251-X, 536 pages, 6 x 9, (1996) This PDF is available from the National Academies Press at: http://www.nap.edu/catalog/5156.html Visit the National Academies Press online, the authoritative source for all books from the National Academy of Sciences, the National Academy of Engineering, the Institute of Medicine, and the National Research Council: • Download hundreds of free books in PDF • Read thousands of books online for free • Explore our innovative research tools – try the “Research Dashboard” now! • Sign up to be notified when new books are published • Purchase printed books and selected PDF files Thank you for downloading this PDF. If you have comments, questions or just want more information about the books published by the National Academies Press, you may contact our customer service department toll- free at 888-624-8373, visit us online, or send an email to [email protected]. This book plus thousands more are available at http://www.nap.edu. Copyright © National Academy of Sciences. All rights reserved. Unless otherwise indicated, all materials in this PDF File are copyrighted by the National Academy of Sciences. Distribution, posting, or copying is strictly prohibited without written permission of the National Academies Press. Request reprint permission for this book. Contraceptive Research and Development: Looking to the Future http://www.nap.edu/catalog/5156.html Contraceptive Research and Development Looking to the Future Polly F.
    [Show full text]
  • Perspectives of Contraceptive Choices for Men
    Indian Jouma1 of Experimental Biology Vol. 43, November 2005, pp. 1042-1047 Review Article Perspectives of contraceptive choices for men N K Lohiya*, B Manivannan, S S Bhande, S Panneerdoss & Shipra Garg Reproductive Pbysiology Section, Department of Zoology, University of Rajasthan, Jaipur 302 004, India Apart from condoms and vasectomy, which have several limitations of their own, no other methods of contraception are available to men. Various chemical, honnonal, vas based and herbal contraceptives have been examined and few of them have reached the stage of clinica1 testing. Promising leads have been obtained from testosterone bucic1atelundecanoate, alone or in combination with levonorgestrel butanoate or cyproterone acetate, RlSUG, an injectable intra vasal contraceptive and a few herba1 products, particularly the seed products of Carica papaya. It is feasible that an ideal male contraceptive. that meets out all the essential criteria will be made available to the community in the near future. Keywords: Carica papaya, Herbal methods, Honnonal methods. Male contraception, RISUG. Vas based methods In the new millennium, India has crossed the one lead from sperm production in the testis to sperm egg billion mark. sharing 16% of the world population on interactions and fertilization in the female genital tract 2.4% of the global land area. More than 18 million need to be considered. Accordingly, the biomedical people are added every year, which is almost the options available in control of male fertility are entire population of Australia With the current trend, limited to (1) inhibition of spermatogenesis at the it is projected that India may overtake China in the level of testis, (2) inhibition of sperm maturation at year 2045 to become the most populous country in the the level of epididymis, (3) inhibition of sperm world, the distinction which no Indian would be proud transport at the level of vas deferens, (4) inhibition of of.
    [Show full text]
  • Contraceptive Effectiveness and Obesity
    Contraceptive Effectiveness and Obesity Diana Blithe, PhD Program Director for Contraceptive Development Contraception Research Branch Disclosures: NICHD has a Collaborative Research and Development Agreement (CRADA) with HRA Pharma (Paris, France). The goal of the CRADA is to develop Ulipristal Acetate (CDB-2914) for therapeutic indications. NICHD Principal Investigators: Diana Blithe, PhD & Lynnette Nieman, MD Types of Obesity – Benign vs At-risk • Healthy normal weight - BMI 18.5 - 24.9 kg/m2 0 - 1 metabolic syndrome component: 1) Triglycerides ≥150 mg/dl 2) HDL < 50 mg/dl and/or use of lipid-lowering medication 3) Glucose ≥100 mg/dl 4) Hypertension and/or use of anti-hypertensive medication • As of 2012, ~32% of reproductive age women are obese. Ogden CL et al. Prevalence of Childhood and Adult Obesity in the United States, 2011-2012 . JAMA. 2014;311:806-814 • Benign (Metabolically healthy) obesity - BMI ≥30 kg/m2 0 - 1 metabolic syndrome component (include in contraceptive clinical trials?) • At Risk (Unhealthy) obesity - BMI ≥30 kg/m2 ≥ 2 metabolic syndrome components (exclude from contraceptive clinical trials!) Bleil ME, et al. Pubertal Timing, Androgens, and Obesity Phenotypes in Women at Midlife. J Clin Endocrinol Metab. 2012 97: E1948–52 Midlife for women is age 25-45. Midlife for men? Risk of Venous Thromboembolism: with Hormonal Contraceptives containing Ethinyl Estradiol (EE), with Obesity or with Pregnancy R.R Incidence Young women in general population 1 1- 5 /10,000/y Use of COCs 2.5-5.5* 3-15 /10,000/y Low EE dose COC (BMI 20-25) 2 Low EE dose COC (BMI 30-35) 4 Low EE dose COC (BMI ≥35) 8 Pregnancy: Pregnant Women (BMI ≤25) 12 During Pregnancy 5-20 /10,000/y Post Partum 40-65 /10,000/y Pregnant Women (BMI ≥30) 30 May be a higher PE vs DVT rate in obese pregnant women *de Bastos M, et al .
    [Show full text]
  • Male Contraception: Expanding Reproductive Choice
    Indian Journal of Experimental Biology Vol. 43. November 2005. pp. 1032-1041 Review Article Male contraception: Expanding reproductive choice M RajaJakshmi" Department of Reproductive Biology. All India Institute of Medical Sciences. New Delhi 110 029. India The development of steroid-based oral contraceptives had revolutionized the availability of contraceptive choice for women. In order to expand the contraceptive options for couples by developing an acceptable. safe and effective male contraceptive. scientists have been experimenting with various steroidal/non-steroidal regimens to suppress testicular sperm production. The non-availability of a long-acting androgen was a limiting factor in the development of a male contraceptive regimen since all currently tested anti-spermatogenic agents also concurrently decrease circulating testosterone levels. A combination regimen of long-acting progestogen and androgen would have advantage over an androgen-alone modality since the dose of androgen required would be much smaller in the combination regimen. thereby decreasing the adverse effects of high steroid load. The progestogen in the combination regimen would act as the primary anti-spermatogenic agent. Currently. a number of combination regimens using progestogen or GnRH analogues combined with androgen are undergoing trials. The side effects of long-term use of androgens and progestogens have also undergone evaluation in primate models and the results of these studies need to be kept in view. while considering steroidal regimens for contraceptive use in men. Efforts are also being made to popularize non-scalpel vasectomy and to develop condoms of greater acceptability. The development of contraceptive vaccines for men. using sperm surface epitopes not expressed in female reproductive tract as source.
    [Show full text]
  • Future Methods of Fertility Regulation
    FutureFuture methodsmethods ofof fertilityfertility regulationregulation CatherineCatherine dd’’Arcangues,Arcangues, Ph.D.,Ph.D., M.D.M.D. Department of Reproductive Health and Research World Health Organization Training in Reproductive Health Research Geneva 2006 05_STAG_DRep_Feb/1 1.1. ImprovementImprovement ofof existingexisting methodsmethods Efficacy,Efficacy, sideside--effects,effects, durationduration ofof action,action, manufacturingmanufacturing process,process, costcost 2.2. NewNew approachesapproaches ModeMode ofof actionaction 3.3. NewNew targetstargets forfor contraceptioncontraception 05_STAG_DRep_Feb/2 1.1. ImprovementImprovement ofof existingexisting methodsmethods 05_STAG_DRep_Feb/3 IntraIntra--uterineuterine devicesdevices Copper-releasing Levonorgestrel-releasing 05_STAG_DRep_Feb/4 IntraIntra--uterineuterine devicesdevices Also under development: Swing: copper-releasing with coil stem IUD releasing a progesterone receptor modulator (CDB-2914) Copper IUD releasing indomethacin 05_STAG_DRep_Feb/5 ContraceptiveContraceptive implantsimplants Jadelle: levonorgestrel, 2 rods, 5 years Implanon: etonogestrel, 1 rod, 3 years Nestorone: pure progestogen, 1 rod, 2 years 05_STAG_DRep_Feb/6 InjectablesInjectables (1)(1) ImprovedImproved pharmacokineticpharmacokinetic profileprofile :: BiodegradableBiodegradable microspheresmicrospheres:: norethisterone,norethisterone, norgestimatenorgestimate,, progesteroneprogesterone ControlledControlled particleparticle sizesize distributiondistribution:: DMPA,DMPA, levonorgestrellevonorgestrel
    [Show full text]