DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 7.427.405 B2 Agrawal Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 7.427.405 B2 Agrawal Et Al USOO7427405B2 (12) United States Patent (10) Patent No.: US 7.427.405 B2 Agrawal et al. (45) Date of Patent: Sep. 23, 2008 (54) IMMUNOSTIMULATORY Tokunaga et al., “Antitumor Activity of Deoxyribonucleic Acid Frac OLGONUCLEOTDE MULTIMERS tion from Mycobaterium bovis BCG. I. Isolation. Physicochemical Characterization, and Antitumor Activity”. J. Natl. Cancer Inst. 72: (75) Inventors: Sudhir Agrawal, Shrewsbury, MA (US); 955-962(1984). Pisetsky et al., “Stimulation of in vitro proliferation of murine lym Ekambar Kandimala, Southboro, MA phocytes by synthetic oligodeoxynucleotides'. Molecular Biology (US); Dong Yu, Westboro, MA (US) Reports 18:217-221 (1993). Krieg et al., “CpG motifs in bacterial DNA trigger direct B-cell (73) Assignee: Idera Pharmaceuticals, Inc., activation”, Nature 374: 546-549 (1995). Cambridge, MA (US) Sato et al., “Immunostimulatory DNA Sequence Necessary for Effective Intradermal Gene Immunization', Science 273: 352-354 (*) Notice: Subject to any disclaimer, the term of this (1996). patent is extended or adjusted under 35 Krieg et al., “CpG Motifs in Bacterial DNA and their Immune U.S.C. 154(b) by 209 days. Effects”, Annu. Rev. Immunol. 20: 709-760 (2002). Dalpke et al., “Immunopharmacology of CpG DNA'. Biol. Chem. (21) Appl. No.: 11/174,282 383: 1491-1500 (2002). Kandimala et al., “Towards Optimal Design of Second-Generation (22) Filed: Jul. 1, 2005 Immunomodulatory Oligonucleotides'. Curr. Opin. Mol. Ther. 4(2): 122-129 (2002). (65) Prior Publication Data Kandimala et al., “Immunomers-novel 3'-3'-Linked CpG Oligodeoxyribonucleotides as Potent Immunomodulatory Agents'. US 2006/OO19919 A1 Jan. 26, 2006 Nucleic Acids Res. 30: 4460-4469 (2002). Kandimala et al. “Secondary Structures in CpG Oligonucleotides Related U.S. Application Data affect Immunostimulatory Activity”. Biochem. Biophys. Res. Com mun. 306:948-953 (2003). (63) Continuation of application No. 10/892,550, filed on Remington's Pharmaceutical Sciences, 18th Edition, ed. A. Gennaro, Jul. 15, 2004, and a continuation of application No. Mack Publishing Co., Easton, PA, 1990, ISBN: 0-912734-04-3. 11/153,054, filed on Jun. 15, 2005. Burgstaller, P. et al., "Aptamers and AptaZymes: Accelerating Small (60) Provisional application No. 60/579,985, filed on Jun. Molecule Drug Discovery'. Curr Opin Drug Discov Devel. 5(5): 15, 2004, provisional application No. 60/599,362, 690-700 (2002). Iyer R.P. et al., “3H-1,2-Benzodithiole-3-one 1,1-Dioxide as an filed on Aug. 6, 2004. Improved Sulfurizing Reagent in the Solid-Phase Synthesis of Oligodeoxyribonucleoside Phosphorothioates'. J. Am. Chem. Soc. (51) Int. Cl. 112: 1253-1254 (1990). A6 IK 39/00 (2006.01) Zhao, Q., et al., “Effect of Different Chemically Modified C7H 2L/02 (2006.01) Oligodeoxynucleotides on Immune Stimulation'. Biochem (52) U.S. Cl. ................. 424/277.1; 424/277.1536/23.1 Pharmacol. 51: 173-182 (1996). (58) Field of Classification Search .............. 424/277.1; Branda, R.F., et al., “Immune Stimulation by an antisense oligomer 536/23.1 complementary to the rev Gene of HIV-1'. Biochem. Pharmacol. See application file for complete search history. 45(10): 2037-2043 (1993). Bhagat L., et al., "CpG penta- and Hexadeoxyribonucleotides as (56) References Cited potent immunomodulatory agents'. Biochem. BiophyS. Res. Com mun. 300: 853-861 (2003). U.S. PATENT DOCUMENTS Hemmi H., et al., “A Toll-Like Receptor Recognizes Bacterial DNA'. 5,366,878 A 11/1994 Pederson et al. Nature 408: 740–745 (2000). 5,635,377 A 6, 1997 Pederson et al. Yi A.K., et al., “Rapid Induction of Mitogen-Activated Protein 5,652,355 A 7, 1997 Metelev et al. Kinases by Immune Stimulatory CpG DNA'. J. Immunol. 161:4493 5,912,332 A 6/1999 Agrawal et al. 4497 (1998). 6,143,881 A 11/2000 Metelev et al. Stacey, K.J., et al., “Macrophages Ingest and Are Activated by Bac 6,346,614 B1 2/2002 Metelev et al. terial DNA”, J. Immunol. 157: 21 16-2122 (1996). Yu D., et al., “Potent CpG Oligonucleotides Containing OTHER PUBLICATIONS Phosphodiester Linkages: in vitro and in vivo immunostimulatory properties”. Biochem. Biophys. Res. Commun. 297: 83-90 (2002). Moldoveanu et al (Vaccine 16:1216-1224, 1998).* Kuramoto etal (Jpn. J. Cancer Res. 83:1128-1131, 1992).* * cited by examiner Krieg etal (Nature 371:546-549, 1995).* Liang etal (J. Clin. Invest. 98: 1119-1129, 1996).* Primary Examiner Brandon J Fetterolf McCluskie and Davis (J. Immunol. 161:4463-4466, 1998).* (74) Attorney, Agent, or Firm—Keown & Zucchero, LLP: Baral et al (Cancer Immunol. Immunother. 52(3):317-327, 2003).* Wayne A. Keown; Joseph C. Zucchero Kandimala et al (Bioconjugate Chem. 13, 966-974, 2002; Nucleic Acid Research vol. 31, No. 9, 2003).* (57) ABSTRACT Kandimala et al (PNAS 100(24): 14303-14308, 2003).* Donnelly et al (Nature Medicine, 9(11): 1354-1356, 2003).* The invention provides an immunostimulatory nucleic acid. DeGruijl et al. Nature Medicine, 51.10: 1124-1125, 1999.* Bitton R.J. (Current Opinion in Molecular Therapeutics 611: 17-26, In certain embodiments according to this aspect of the inven 2004).* tion, the sequence of the immunostimulatory oligonucleotide Weiner (J. Leukoc. Biol. 68: 455-463, 2000).* and/or immunomer is at least partially self-complementary. Ballas et al (J. Immunol. 167: 4878-4886, 2001).* Agrawaletal (Trends in Molecular Medicine 8(3): 114-120, 2002).* 7 Claims, 6 Drawing Sheets U.S. Patent Sep. 23, 2008 Sheet 1 of 6 US 7.427.405 B2 U.S. Patent Sep. 23, 2008 Sheet 2 of 6 US 7.427.405 B2 U.S. Patent US 7.427.405 B2 U.S. Patent US 7.427.405 B2 U.S. Patent Sep. 23, 2008 Sheet 6 of 6 US 7.427.405 B2 US 7,427,405 B2 1. 2 IMMUNOSTIMULATORY ythymidine, 1-(2'-deoxy-f-D-ribofuranosyl)-2-oxo-7-deaza OLGONUCLEOTDE MULTIMERS 8-methyl-purine, 2-dideoxy-5-halocytosine, 2'-dideoxy-5- nitrocytosine, arabinocytidine, 2'-deoxy-2-substituted RELATED APPLICATIONS arabinocytidine, 2'-O-substituted arabinocytidine, 2'-deoxy 5-hydroxycytidine, 2'-deoxy-N4-alkyl-cytidine, 2'-deoxy-4- This application is a continuation-in-part of U.S. patent thiouridine, or other pyrimidine nucleoside analogs, G is application Ser. No. 10/892,550, filed Jul. 15, 2004 and a 2'-deoxy-7-deazaguanosine, 2'-deoxy-6-thioguanosine, ara continuation of U.S. patent application Ser. No. 1 1/153,054, binoguanosine. 2'-deoxy-2'substituted-arabinoguanosine, filed Jun. 15, 2005, which claims the benefit of U.S. Provi 2'-O-substituted-arabinoguanosine. 2'-deoxyinosine, or other sional Application Ser. No. 60/579,985, filed Jun. 15, 2004, 10 purine nucleoside analogs, and p is an internucleoside linkage and U.S. Provisional Application Ser. No. 60/599,362, filed selected from the group consisting of phosphodiester, phos on Aug. 6, 2004. The entire teachings of the above-referenced phorothioate, and phosphorodithioate. Applications are incorporated herein by reference. In Some embodiments, the immunostimulatory nucleic acid is from about 2 to about 50 nucleotides in length. In BACKGROUND OF THE INVENTION 15 certain embodiments the immunostimulatory nucleic acid is from about 12 to about 26 nucleotides in length. In some 1. Field of the Invention embodiments, the oligonucleotides each have from about 3 to The invention relates to immune stimulation by oligo about 35 nucleoside residues, in further embodiments from nucleotide analogs. about 4 to about 30 nucleoside residues, in even further 2. Summary of the Related Art embodiments from about 4 to about 20 nucleoside residues. Tokunaga et al., J. Natl. Cancer Inst. 72 (1984) 955-96. In some embodiments, the oligonucleotides have from about Pisetsky et al.; Reich et al., Mol. Biol. Rep. 18 (1993) 217 5 to about 18, or from about 5 to about 14, nucleoside resi 221; Krieg et al., Yi et al., Nature 374 (1995) 546-549 and dues. As used herein, the term “about implies that the exact Sato et al., Science 273 (1996) 352-354 teach that bacterial number is not critical. Thus, the number of nucleoside resi DNA, synthetic oligodeoxynucleotides, and DNA vaccines 25 dues in the oligonucleotides is not critical, and oligonucle containing unmethylated CpG-dinucleotides in specific otides having one or two fewer nucleoside residues, or from sequence contexts (CpG DNA) activate the vertebrate one to several additional nucleoside residues are contem immune system. plated as equivalents of each of the embodiments described Krieg et al., Annu. Rev. Immunol. 20 (2002) 709-760; above. In some embodiments, one or more of the oligonucle Dalpke et al., Biol. Chem. 383 (2002) 1491-1500 and Kan 30 otides have 11 nucleotides. dimala et al., Curr. Opin. Mol. Ther. 4 (2002) 122-129 teach In a second aspect the invention provides an immunomer that CpG DNAS induce innate immune cells to produce Th1 comprising at least two oligonucleotides linked by a non cytokines that promote cytotoxic T lymphocyte (CTL) nucleotide linker, wherein the sequences of the immuno responses and production of immunoglobulins by B cells. stimulatory oligonucleotides are at least partially self The immunostimulatory properties of CpG DNAs have 35 complementary. In certain embodiments according to this allowed their use as therapeutic agents for a broad spectrum aspect of the invention at least one of the oligonucleotides of disease indications including cancers, viral and bacterial contains at least one dinucleotide selected from the group infections, inflammatory disorders and as adjuvant in immu consisting of CpG, CpG, CpG* and CpG*, wherein C is notherapy. cytidine or 2'-deoxycytidine, G is guanosine or 2'-deoxygua In addition to chemical modifications, a number of struc 40 nosine, C* is 2'-deoxythymidine, 1-(2'-deoxy-f-D-ribofura tural modifications influenced the activity of CpG DNAs. nosyl)-2-oxo-7-deaza-8-methyl-purine, 2-dideoxy-5-halo Kandimalla et al., Nucleic Acids Res.
Load more

Recommended publications
  • Journal of Arthroscopy and Joint Surgery 6 (2019) 98E102
    Journal of Arthroscopy and Joint Surgery 6 (2019) 98e102 Contents lists available at ScienceDirect Journal of Arthroscopy and Joint Surgery journal homepage: www.elsevier.com/locate/jajs Comparative evaluation of periarticular infiltration of two cocktail regimens for analgesia in post-operative patients of total knee replacement * V.K. Gautam a, Ajeet Kumar a, Munisha Agarwal b, Bushu Harna a, , Rishabh Saini a, Siddharth Sharma a, Dhananjaya Sabat a a Dept. of Orthopaedics, Maulana Azad Medical College, New Delhi, India b Dept. of Anaesthesia, Maulana Azad Medical College, New Delhi, India article info abstract Article history: Purpose: To compare the efficacy of two periarticular cocktail regimens for analgesia in postoperative Received 30 April 2018 patients of total knee replacement. Received in revised form Method: This is a Randomized Control study done over the duration of 1.5 years. Twenty-five knees of 28 October 2018 either gender were selected with inclusion criteria (All osteoarthritis patients planned for TKA) and Accepted 9 November 2018 exclusion criteria (Inflammatory arthritis, patients allergic to local anaesthetic e.g. Ropivacaine, bupi- Available online 19 November 2018 vacaine, known cardiac disorder patient having AV block, arrhythmia) & divided into 2 groups. Group A was given a cocktail of Ropivacaine, adrenaline, clonidine & cefuroxime. Keywords: & Periarticular Group B was given a cocktail of bupivacaine, fentanyl, methylprednisolone cefuroxime. The preoper- Multimodal approach ative pain of the patient was assessed using VAS score. Combined spinal and epidural anaesthesia was Perioperative analgesia given using 0.5% 2 ml of bupivacaine heavy in all patients. After taking bone cuts & before the placement Corticosteroids of the implant, cocktail of the drug was infiltrated using sterile technique into 9 specific sites.
    [Show full text]
  • Adverse Effects of Xenogenic Scaffolding in the Context of A
    Lamas et al. Trials (2019) 20:387 https://doi.org/10.1186/s13063-019-3504-3 RESEARCH Open Access Adverse effects of xenogenic scaffolding in the context of a randomized double-blind placebo-controlled study for repairing full- thickness rotator cuff tears José Ramón Lamas1†, Carlos García-Fernández2, Pilar Tornero-Esteban1, Yaiza Lópiz2, Luis Rodriguez-Rodriguez1, Luis Ortega3, Benjamín Fernández-Gutiérrez1*† and Fernando Marco2† Abstract Purpose: The purpose of the study was to compare the safety and efficacy of autologous mesenchymal stem cells (MSCs) embedded in a xenogenic scaffold for repairing the supraspinatus tendon. Methods: This was a randomized, double-blind and placebo-controlled trial evaluating patients with full-thickness rotator cuff tears (Eudra-CT, 2007–007630-19). Effectiveness was evaluated using the Constant score and a visual analogue pain scale (VAS). Constant score has four domains including pain (15 possible points), activities of daily living (20 possible points), mobility (40 possible points), and strength (25 possible points). Scores range from 0 points (most disability) to 100 points (least disability). The structural integrity of the repaired tendon was assessed by magnetic resonance imaging (MRI) according to Patte and Thomazeau classification criteria. The primary study end point was an improvement in the Constant score by 20 points at one year compared to initial assessment. Results: The trial was stopped due to adverse effects observed in both groups. Only thirteen patients were included and analyzed. The Constant questionnaire showed a significant improvement in the MSC treatment group compared with the preoperative data (p = 0.0073). Secondary outcome measures were similar in both groups.
    [Show full text]
  • New Zealand Regulatory Guidelines for Medicines
    New Zealand Regulatory Guidelines for Medicines Part G: Resources Edition 6.13 March 2011 (consolidation of fifth edition and subsequent updates) Table of Contents PART G: RESOURCES Section 1: Description of Dosage Form...............................................................................2 Section 2: Routes of Administration....................................................................................4 Section 3: Shelf Life and Storage Conditions .....................................................................5 Section 4: Abbreviations.......................................................................................................6 Description of Dosage Form The dosage form description for a product should be selected from the following list: Block Granules, oral Capsule Implant, subcutaneous Capsule, combination Implant, intracranial Capsule, liquid filled Implant, intraocular Capsule, modified release Infusion, concentrate Capsule, powder filled Infusion, emulsion Capsule, powder filled, nasal inhalation Infusion, powder for Capsule, soft gelatin Infusion, powder for concentrate Cement, bone, liquid component Infusion, solution Cement, bone, powder component Inhalation, capsule, liquid filled Cement, dental Inhalation, capsule, powder filled Chewing gum Inhalation, powder Chocolate, medicated Inhalation, solution Combination Inhalation, solution, powder for Condom, medicated Inhalation, suspension Condom with spermicide Inhalation, volatile liquid Cream, rectal Inhaler, aerosol, metered Cream, topical Injection
    [Show full text]
  • JMSCR Vol||05||Issue||01||Page 15625-15629||January 2017
    JMSCR Vol||05||Issue||01||Page 15625-15629||January 2017 www.jmscr.igmpublication.org Impact Factor 5.84 Index Copernicus Value: 83.27 ISSN (e)-2347-176x ISSN (p) 2455-0450 DOI: https://dx.doi.org/10.18535/jmscr/v5i1.71 Transdermal Patch: A Comprehensive Overview of Newer Drug Delivery System in Modern Medical Science Authors Dr Neelkanth Kote1, Dr. Poornima B2 Department of Physiology and Department of Pharmacology Raja Rajeswari Medical Collegeand Hospital Bangalore, Karnataka– 560074 Corresponding Author Dr Neelkanth Kote Department of Physiology, RRMC Bangalore, Karnataka -560074 Email: [email protected] Abstract Background: Oral route of drug administration has been the most common route of drug administration since the beginning of the therapeuticarea in medical science. However this route of drug administration fails at bypassing the first pass metabolism of the drug in liver with poor bio availability. Oral route of drug administration also fails in uncooperative /unconscious semiconscious / pediatric subjects. Transdermal patch, a new drug delivery system through skin to the parenteral circulation has been the most recently discussed topic in pharmacology and medicine as it is a noninvasive route of drug administration, delivered in a sustained / pre fixed dosage with no / extremely less first pass metabolism and better bio availability. Most importantly it can be used in semiconscious / unconscious & pediatric subjects without affecting their hemodynamics. The transdermal patches have many beneficial factors however they also come with some major drawbacks like varieties of formulation, design and quality of adhesiveness. This articles provides an insight of transdermal patch in terms of its mechanism of action, advantages, disadvantages and future scope of it in the medical science.
    [Show full text]
  • WV Medical Cannabis Act
    Medical Cannabis Overview Legalized Marijuana • Medical marijuana is legal in 33 states and D.C. • Recreational marijuana is legal in 10 states and D.C. The Endocannabinoid System (ECS) • Anandamide (AEA) • Arachidonoylgycerol (2-AG) • Receptors: • CB1 • CB2 Cannabinoids • Three principle cannabinoids in cannabis: • Tetrahydrocannibinol (THC) • Cannabidiol (CBD)—the primary cannabinoid in medical marijuana • Cannabinol (CBN) Dr. Ralph Mechoulam GW Pharmaceuticals • Epidiolex—purified CBD used to control seizures • Sativex—for treatment of spasticity due to MS WV Medical Cannabis Act • Becomes effective July 1, 2019 • To be implemented and administered by Public Heath Bureau • Requires a “serious medical condition” to be certified Qualifying Medical Conditions • Cancer • Huntington’s disease • HIV • Crohn’s Disease • Amyotrophic lateral • PTSD sclerosis • Intractable seizures • Parkinson’s • Sickle cell anemia • MS • Severe chronic pain • Spinal cord damage • Terminally ill • Epilepsy • Neuropathies Lawful Use • Medical cannabis may only be dispensed to: • A patient who receives a certification from a practitioner and is in possession of a valid ID card from bureau • A caregiver in possession of valid ID card from bureau Acceptable Forms • Pill • Oil • Topical forms, including gels, creams, or ointment • A form medical appropriate for administration by vaporization or nebulization (excluding dry leaf or plant form) • Tincture • Liquid • Dermal patch Unlawful Use • Smoking and edible cannabis • No joints or brownies • Growing, unless the
    [Show full text]
  • WO 2017/172802 Al 5 October 2017 (05.10.2017) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/172802 Al 5 October 2017 (05.10.2017) P O P C T (51) International Patent Classification: 1 DNA Way, South San Francisco, California 94080-4990 C07C 381/10 (2006.01) C07D 211/22 (2006.01) (US). C07D 401/12 (2006.01) C07D 211/42 (2006.01) (74) Agents: HARRIS, Robert J. et al; Viksnins Harris & C07D 205/04 (2006.01) C07D 213/69 (2006.01) Padys PLLP, 785 1 Metro Parkway, Suite 325, Blooming- (21) International Application Number: ton, Minnesota 55425 (US). PCT/US2017/024584 (81) Designated States (unless otherwise indicated, for every (22) International Filing Date: kind of national protection available): AE, AG, AL, AM, 28 March 2017 (28.03.2017) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, (25) Filing Language: English DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (26) Publication Language: English HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, (30) Priority Data: MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, 62/3 15,469 30 March 2016 (30.03.2016) US NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, (71) Applicants: GENENTECH, INC. [US/US]; 1 DNA Way, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, South San Francisco, California 94080-4990 (US).
    [Show full text]
  • Literature and Registry Review
    _____________________________________________________________________________________ Literature and Registry Review 2005 - 2015 ______________________________________________________________________ “HEMICAP RESURFACING PROVIDES A UNIQUE AND FAVORABLE ALTERNATIVE TO PRIOR IMPLANT DESIGNS BY PROVIDING ANATOMIC RE-APPROXIMATION” Patellofemoral Kinematics After Limited Resurfacing of the Trochlea. Provencher M, Ghodadra N, Verma N, Cole BJ, Zaire S, Shewman E, Bach B. J Knee Surg. 2009;22:310-316 ______________________________________________________________________ Matthias R. Schurhoff _____________________________________________________________________________________ Arthrosurface Literature and Registry Review 2005-2015 _____________________________________________________________________________________________ Foreword his report is a review of the past decade outlining the introduction of inlay arthroplasty for arthrosis, early T arthritis and traumatic lesions. Arthrosurface, Inc. (Franklin, MA) was launched in 2002 bringing innovation and a sports medicine approach to primary arthroplasty. In the past decade, Arthrosurface has invested and re-invested more than $100 Million dollars in the development and commercialization of patient specific joint solutions that place the individual patient at the forefront of clinical decision making. The intraoperative choice of implant diameters and contour shapes allow the surgeon to not only cover the defect effectively, but also fit the implant to the patient while preserving healthy bone
    [Show full text]
  • Transdermal Drug Delivery System: a Review
    Indian Journal of Pharmacy and Pharmacology 2021;8(1):5–9 Content available at: https://www.ipinnovative.com/open-access-journals Indian Journal of Pharmacy and Pharmacology Journal homepage: https://www.ijpp.org.in/ Review Article Transdermal drug delivery system: A review Neha Choudhary1,*, Ajeet Pal Singh1, Amar Pal Singh1 1St. Soldier Institute of Pharmacy, Lidhran Campus, Jalandhar, Punjab, India ARTICLEINFO ABSTRACT Article history: Transdermal Drug Delivery System is controlled medicated that is set on the skin to deliver a particular Received 15-03-2021 portion of medicine through the skin and into the circulatory system. It is likewise significant because of its Accepted 17-03-2021 interesting benefit such as less absorption, more uniform plasma levels, improved bioavailability, decrease Available online 19-04-2021 side effect, efficacy and quality of the product. Transdermal dose structures may give clinicians a chance to offer more therapeutic alternatives to their patients to upgrade their consideration. Keywords: © This is an open access article distributed under the terms of the Creative Commons Attribution Advantages/Disadvantages License (https://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and Skin types reproduction in any medium, provided the original author and source are credited. Factors affecting permeation Components Evaluations 1. Introduction 4. Drug duration of action are extendable 5. GIT incompatibilities get avoided Now a day many drugs are administered orally, but they are 6. Number of dosage frequency reduced observed not more effective as desired so to upgrade such 7. Easier to remember and used character TDDS was created. Drug delivery administered 8. Large area of application in comparison with nasal and by the skin and attain a systemic effect of drug is called buccal cavity as transdermal drug delivery system.
    [Show full text]
  • A Fully Integrated Microneedle-Based Transdermal Drug Delivery System
    A Fully Integrated Microneedle-based Transdermal Drug Delivery System Niclas Roxhed MICROSYSTEM TECHNOLOGY LABORATORY SCHOOL OF ELECTRICAL ENGINEERING ROYAL INSTITUTE OF TECHNOLOGY ISBN 978-91-7178-751-4 ISSN 1653-5146 TRITA-EE 2007:046 Submitted to the School of Electrical Engineering KTH—Royal Institute of Technology, Stockholm, Sweden, in partial fulfillment of the requirements for the degree of Doctor of Philosophy Stockholm 2007 ii A Fully Integrated Microneedle-based Transdermal Drug Delivery System The left picture on the front cover shows an integrated microneedle-based drug delivery system fabricated and used for experiments by the author. An array of microneedles is located on the other side of the device. The right picture on the cover shows a magnified view of these side-opened hollow microneedles, likewise fabricated by the author. The needles are designed to penetrate skin tissue using a low insertion force. The needles are fabricated by deep reactive ion etching of silicon and the length of the needles is 400 μm. Copyright 2007 by Niclas Roxhed All rights reserved to the summary part of this thesis, including all pictures and figures. No part of this publication may be reproduced or transmitted in any form or by any means, without prior permission in writing from the copyright holder. The copyrights for the appended journal papers belong to the publishing houses of the journals concerned. The copyrights for the appended manuscripts belong to their authors. Printed by Universitetsservice US AB, Stockholm 2007. Thesis for the degree of Doctor of Philosophy at the Royal Institute of Technology, Stockholm, Sweden, 2007.
    [Show full text]
  • How to Treat Nicotine Dependence in Smokers with Schizophrenia
    pSYCHIATRY How to treat nicotine dependence in smokers with schizophrenia Improve patients’ health, help them kick addiction with this practical approach r. V, age 49, has stable but ®symptomaticDowden Health Media schizophrenia and a 33-year cigarette smoking Mhistory. He is very concerned because his primary care physicianCopyright told him heFor has personal2 serious use only smoking-related health problems: diabetes and hypertension. He tried a smoking cessation program for the general public, but it was a poor fit because of his schizophrenia symptoms. Despite adhering to his medications (ziprasidone, 20 mg hs; perphenazine, 8 mg hs; lorazepam, 1 mg hs; zonisamide, 200 mg/d, and benztropine mesylate, 2 mg hs), Mr. V has residual auditory hallucinations, paranoid ideation, and impaired concentration and attention. He smokes approximately 1.5 packs per day, particularly when VEER.COM very ill, to alleviate chronic boredom, and to diminish 2007 © distress from the hallucinations. All of his friends smoke, and they do not support his attempts to quit. Jennifer D. Gottlieb, PhD Schizophrenia clinical and research program Massachusetts General Hospital Successfully treating nicotine dependence can seem a Instructor in psychiatry formidable challenge in patients with schizophrenia: Harvard Medical School • 72% to 90% smoke cigarettes, compared with 21% A. Eden Evins, MD, MPH of the general population1 (Box, page 66).2-12 Schizophrenia and depression clinical and research programs • They tend to smoke heavily, spending about one- Director, Center for Addiction Medicine third of their incomes on cigarettes.13 and addiction research program • Their negative symptoms (such as apathy), posi- Massachusetts General Hospital Assistant professor of psychiatry tive symptoms (such as disorganized thinking), Harvard Medical School and cognitive impairment can reduce motivation to quit and adhere to a smoking cessation strategy.
    [Show full text]
  • How a Painless Patch Could One Day Deliver Vaccines
    How a painless patch could one day deliver vaccines pbs.org/newshour/health/how-a-painless-patch-could-one-day-deliver-vaccines Isabella Isaacs-Thomas July 31, 2020 When you pull up your sleeve to get your yearly flu shot, you might feel a twinge of anxiety as a health care provider readies the needle and syringe. Maybe you find yourself looking away or taking deep breaths to steel yourself, even though it’s over in just a few seconds. So what if there was a painless vaccine you could administer yourself? What if, rather than heading to the pharmacy, you could simply place the equivalent of a Band-Aid on your arm, leave it there for a few minutes to a few hours, then take it off and let your physician know you’ve been innoculated? That’s one of the main goals of vaccine patch technology. Multiple research teams have designed patches that use microneedle arrays made out of materials like stainless steel or sugar to deliver quick and pain-free vaccination by taking advantage of the key role that skin plays in training our immune system. One group is even developing a completely needle-free method to confer immunity. Vaccination is a crucial public health measure against serious, preventable illnesses, but the fear of needles — or of vaccines themselves — can be a hurdle to protection for individuals and their communities. In many places around the world, extreme conditions or lack of health care can stifle accessibility to traditional vaccines, too. Vaccine patches haven’t yet been approved for commercial use, but both global vaccine experts and researchers have acknowledged their potential for years, particularly when it comes to making vaccines more accessible worldwide.
    [Show full text]
  • 1050 GR Ondrugdelivery Issue 49
    TRANSDERMAL DELIVERY: INTERVIEW: DESIGNING AN A NEW SOURCE FOR PATRICK ALEXANDRE, CEO, ULTRASOUND-ENABLED P04 BIOPHARMA INNOVATION P18 CROSSJECT P22 INSULIN PATCH TRANSDERMAL DELIVERY, MICRONEEDLES & NEEDLE-FREE INJECTION 49 O TM ISSUE N • 2014 2014 TH MAY 16 MAY Contents ONdrugDelivery Issue No 49, May 16th, 2014 Transdermal Delivery, Microneedles CONTENTS & Needle-Free Injection This edition is one in the ONdrugDelivery series of publications from Frederick Furness Publishing. Each Introduction: Skin in the Game: issue focuses on a specific topic within the field of Transdermal Delivery as a New Source for drug delivery, and is supported by industry leaders BioPharma Innovation in that field. 04 - 06 Dr Kevin Pang, Research Director EDITORIAL CALENDAR 2014/15 Lux Research May: Pulmonary & Nasal Drug Delivery Overview: Transdermal Delivery Device Design May/June: Injectable Drug Delivery: Devices Focus Bruce K Redding, Jr, President & CEO June: Injectable Drug Delivery: 08 - 09 Transdermal Specialties, Inc Pharmaceutics Focus July: Novel Oral Delivery Systems Your Solution for Successful Sep: Drug Formulation & Delivery Solutions Intradermal Delivery & Services Dr Paul Vescovo, Project Manager, Oct: Prefilled Syringes 10 - 14 and Dr Laurent-Dominique Piveteau, Nov: Pulmonary & Nasal Drug Delivery Chief Operating Officer Dec: Delivering Biotherapeutics Debiotech SA Jan: Ophthalmic Drug Delivery Feb: Prefilled Syringes Dermal Delivery of Biologics Dr Richard Toon, SUBSCRIPTIONS: 16 - 17 Technical and Business Development Manager To arrange
    [Show full text]