DOCSLIB.ORG

2 12/ 35 74Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

(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 22 March 2012 (22.03.2012) 2 12/ 35 74 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 9/16 (2006.01) A61K 9/51 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 9/14 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/EP201 1/065959 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 14 September 201 1 (14.09.201 1) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, (25) Filing Language: English RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, (26) Publication Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/382,653 14 September 2010 (14.09.2010) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant (for all designated States except US): GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, NANOLOGICA AB [SE/SE]; P.O Box 8182, S-104 20 ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, Stockholm (SE). TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, ΓΓ, LT, LU, (72) Inventors; and LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, (75) Inventors/ Applicants (for US only): ZHOU, Chunfang SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, [CN/SE]; Frejgatan 22, S-11349 Stockholm (SE). XIA, GW, ML, MR, NE, SN, TD, TG). Xin [CN/SE]; Gubbkarrsvagen 21-09b, S-16840 Bromma (SE). GARCIA-BENNETT, Alfonso, E. [SE/SE]; War- Declarations under Rule 4.17 : gentinsgatan 6, S-l 1229 Stockholm (SE). — of inventorship (Rule 4.1 7(iv)) (74) Agents: GIAVARINI, Francesco et al; Zanoli & Gi- Published: avarini S.R.L, Via Melchiorre Gioia, 64, 1-20125 Milano (ΓΓ). — with international search report (Art. 21(3)) (54) Title: SUPER-SATURATING DELIVERY VEHICLES FOR POORLY WATER-SOLUBLE PHARMACEUTICAL AND COSMETIC ACTIVE INGREDIENTS 250 300 250 300 250 300 250 300 o Wavelength (nm) © Figure 1 © (57) Abstract: A pharmaceutical or cosmetic composition, comprising: a substantially poorly water-soluble pharmaceutical active ingredient; and a nanoporous folic acid material, wherein the active pharmaceutical ingredient is incorporated inside the Q nanoporous channels of the particles. SUPER- SATURATING DELIVERY VEHICLES FOR POORLY WATER-SOLUBLE PHARMACEUTICAL AND COSMETIC ACTIVE INGREDIENTS DESCRIPTION Field of the invention The present invention relates to a super-saturating drug delivery system which comprises nanoporous materials and poorly water-soluble bioactive pharmaceutical compounds, capable of functioning even in the presence of proton pump inhibitors. Wet impregnation techniques, rotary evaporation techniques, co-spray drying technique or freeze-drying techniques can be applied to prepare the super-saturating delivery system. The mechanism of enhancement of dissolution is based on nano-confinement of the poorly soluble pharmaceutical active material within an ordered porous material via suppression of crystallization. Background of the invention More than one third of the drugs listed in the US Pharmacopoeia and up to 40% new chemical entities discovered by pharmaceutical industry are poorly soluble or lipophilic compounds. The solubility of active pharmaceutical ingredients (APIs) is one of the most challenging issues in the improvement of many existing pharmaceutical formulations or the development of new chemical entities for commercialization, because the maximum achievable intraluminal drug concentration will limit the drug adsorption and bioavailability. Furthermore, improvements in bioavailability of APIs can yield to reduction in toxic secondary effects due to the use of less active, improvements in patient comfort due to the possibility of administering drugs without decreases in gastrointestinal pH, and improvements in patient compliance through a reduction of the number of doses required to achieve an adequate therapeutic level of the API. Therefore, the configuration of supersaturating drug delivery systems is a promising concept to obtain adequate oral bioavailability and improve overall pharmacokinetic properties. Additionally reduction in compound dose through better pharmacokinetic properties directly yields a reduction in costs of treatment. Much effort has been made to enhance the solubility of the poorly soluble drugs to increase the adsorption and bioavailability. One most common method is to reduce the drug particle size to increase surface area and curvature of particles which may improve the solubility and bioavailability of the drugs. The use of nanoparticles may further enhance the capacity to generate supersaturation [see: Matteucci ME,et al., Design of potent amorphous drug nanoparticles for rapid generation of highly supersaturated media. Mol Pharm 4:782-793. (2007); Overhoff KA, et al. Effect of stabilizer on the maximum degree and extent of supersaturation and oral absorption of tacrolimus made by ultra-rapid freezing. Pharm Res 25:167-175. (2008)]. However, the nanoparticles with high surface energy are easily aggregated, more costly than porous particles described in the present invention and may possess additional toxicological profiles. The amorphous form of a drug has the highest apparent solubility, so amorphous-based dosage forms are a popular formulation strategy for poorly water-soluble drugs. Spray-drying of drug compounds has been somewhat successful in processing amorphous formulations of drug compounds. However, amorphous drugs are thermodynamically unstable and often lead to re-crystallization in the presence of small amounts of moisture. It is a major issue to avoid recrystallization during storage. Scientific and economic efforts have been made to avoid recrystallization of the drugs adding to the overall cost of treatments. One or more polymers (e.g., polyvinylpyrrolidone (PVP), polyethyleneglycols (PEG), polymethacrylates, cellulose derivatives, inulin, etc.) and/or (polymeric) surfactants (e.g., Inutecl SP1, Gelucirel, poloxamer 407, etc.) have been used to disperse amorphous drug particles [see: Serajuddin AT. Solid dispersion of poorly water-soluble drugs: Early promises, subsequent problems, and recent breakthroughs. J Pharm Sci 88:1058-1066; Leuner C, Dressman J . Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 50:47-60. (2000); Vasconcelos T, et al. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discovery Today 12:1068-1075 (2007)]. However, the incorporation of surfactants in formulation of poorly water-soluble drugs may cause irritation and side effects after oral administration in some cases, and they are liable to additional stability issues. Recently, ordered nano (meso-)porous materials (e.g. silica) have been studied as carrier for the delivery of poorly water-soluble drugs [see: Salonen J, et al. Mesoporous silicon microparticles for oral drug delivery: Loading and release of five model drugs. J Control Release 108:362-374 (2005); Kaukonen AM, et al. Enhanced in vitro permeation of furosemide loaded into thermally carbonized mesoporous silicon (TCPSi) microparticles. Eur J Pharm Biopharm 66:348-356 (2007); Shen S.C. Mesoporous materials excipients for poorly aqueous soluble ingredients, International Publication Number WO 2010/050897 Al]. Ordered nanoporous materials exhibits a 2-dimensionally or 3-dimensional ordered array of cylindrical or cage type pores (in the range of 2-50nm) separated by thin silica walls. Bioactive drugs can be molecularly dispersed in these pores up to a certain loading (ca. 10- 50% by weight). The influx diffusion of water to the pore surfaces provides for a rapid release of poorly water-soluble drugs if the drug compound is loaded in an amorphous state. It has been shown that the release of the weak base itraconazole from mesoporous materials gave rise to supersaturation in simulated gastric fluid; a subsequent pH shift to simulated intestinal fluid caused only limited precipitation and supersaturated concentrations were maintained for at least 4 h [see: Mellaerts R, et al. Enhanced release of itraconazole from ordered mesoporous SBA-15 silica materials. Chem Commun 13:1375-1377 (2007); Mellaerts R, et al. Ordered mesoporous silica induces pH-independent supersaturation of the basic low solubility compound itraconazole resulting in enhanced transepithelial transport. Int J Pharm 357:169-179 (2008); Mellaerts R, et al. Increasing the oral bioavailability of the poorly water soluble drug itraconazole with ordered mesoporous silica. Eur J Pharm Biopharm 69:223-230 (2008)]. Ordered nanoporous materials have been attracting much attention because of the regular and adjustable pore size, different pore structures, high surface area and pore volume, high concentrations of silanol groups which make the channels like wet environment. Much work has been made to enhance the solubility of poorly water-soluble drugs on SBA-15 with the bigger pore size. Herein the present invention discloses methods that provide for enhancements in poorly water-soluble drugs loaded in the mesoporous material with the smaller pore size showing higher apparent solubility, where additionally 2d-hexagonal pore structure show improvements over 3d-cubic pore structures. In addition, the super-saturating state produced from the nanoporous materials with smaller pore size could maintain longer time than the samples with bigger pore size. Therefore, it is necessary to apply the mesoporous materials with the smaller pore size and 2-D pore structure to deliver poorly water-soluble drugs. Recently, one mesoporous materials named nanoporous folic acid materials ( M-1) have been developed by using the folic acid as template [see: Garcia-Bennett A.E.
Recommended publications
  • Antinociceptive Effects of Monoamine Reuptake Inhibitors in Assays of Pain-Stimulated and Pain-Depressed Behaviors

    Antinociceptive Effects of Monoamine Reuptake Inhibitors in Assays of Pain-Stimulated and Pain-Depressed Behaviors

    Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2012 Antinociceptive Effects of Monoamine Reuptake Inhibitors in Assays of Pain-Stimulated and Pain-Depressed Behaviors Marisa Rosenberg Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Medical Pharmacology Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/2715 This Thesis is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. ANTINOCICEPTIVE EFFECTS OF MONOAMINE REUPTAKE INHIBITORS IN ASSAYS OF PAIN-STIMULATED AND PAIN-DEPRESSED BEHAVIOR A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University By Marisa B. Rosenberg Bachelor of Science, Temple University, 2008 Advisor: Sidney Stevens Negus, Ph.D. Professor, Department of Pharmacology/Toxicology Virginia Commonwealth University Richmond, VA May, 2012 Acknowledgement First and foremost, I’d like to thank my advisor Dr. Steven Negus, whose unwavering support, guidance and patience throughout my graduate career has helped me become the scientist I am today. His dedication to education, learning and the scientific process has instilled in me a quest for knowledge that I will continue to pursue in life. His thoroughness, attention to detail and understanding of pharmacology has been exemplary to a young person like me just starting out in the field of science. I’d also like to thank all of my committee members (Drs.
  • Prevention of Coronary Heart Disease

    Prevention of Coronary Heart Disease

    PREVENTION OF CORONARY PATIENT WITH CHD HEART DISEASE • Obese male patient with previous angina, cardiac catheterization with placement of two stents and now stable. • Notable clinical characteristics: Thomas F . Wh ayne, J r, MD , PhD, FACC Triglycerides 354 mg/dl. Professor of Medicine (Cardiology) HDL 28 mg/dl in men. Gill Heart Institute BP 140/90 mm/Hg. University of Kentucky Fasting glucose 120 mg/dl. November, 2009 • Specific management? Characteristics of Plaques Prone to HIGH SENSENSITIVITY Rupture From Inflammation and LDL CREACTIVE PROTEIN (hs-CRP) Fibrous cap Media • A MARKER OF INFLAMMATION: CRP AND Lumen Lipid hsCRP ARE SAME PROTEIN Core • MAY BE ANOTHER RISK FACTOR AND PLAY A ROLE IN PLAQUE FORMATION “Vulnerable” plaque • MAY PREDICT HIGH RISK ACUTE CORONARY SYNDROME • MAY INDICATE PATIENTS MOST LIKELY TO Lumen RESPOND TO STATINS T lymphocyte Lipid • STATINS SHOWN TO REDUCE CRP Core Macrophage foam cell (tissue factor) “Activated” Intimal SMC (HLA-DR+) – EZETIMIBE ACCENTUATES THIS EFFECT* “Stable” plaque Normal medial SMC • NEED STATIN DOSE RESPONSE CURVE Libby P. Circulation. 1999; 91:284491:2844--2850.2850. *Sager PT, et al. Am J Cardiol. 2003;92:1414-1418. Resultados Estudio VYTAL sobre PCR: Ezetimiba/Simvastatina vs. Atorvastatina en pts con DM II e Hipercolesterolemia (n=1229) CURRENT CLINICALLY USEFUL MARKERS OF INFLAMMATION Atorvastatina E/Simvas Atorvas E/S 10 mg 20 mg 10/20 40 mg 10/40 0 • LIPOPROTEIN-ASSOCIATED Ezetimiba/ --55 Simvastatina PHOSPHOLIPASE A2*. Atorvastatina ® asales --1010 a Sensibilidad – PLAC TEST. t b --1515 --13.713.7 de Al --13.813.8 • HIGH SENSITIVITY C-REACTIVE --2020 # PCR PROTEIN (hsCRP) .
  • (AAV1-LPLS447X) Gene Therapy for Lipoprotein Lipase Deficiency

    (AAV1-LPLS447X) Gene Therapy for Lipoprotein Lipase Deficiency

    Gene Therapy (2013) 20, 361–369 & 2013 Macmillan Publishers Limited All rights reserved 0969-7128/13 www.nature.com/gt ORIGINAL ARTICLE Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial D Gaudet1,2,JMe´ thot1,2,SDe´ry1, D Brisson1,2, C Essiembre1, G Tremblay1, K Tremblay1,2, J de Wal3, J Twisk3, N van den Bulk3, V Sier-Ferreira3 and S van Deventer3 We describe the 2-year follow-up of an open-label trial (CT-AMT-011–01) of AAV1-LPLS447X gene therapy for lipoprotein lipase (LPL) deficiency (LPLD), an orphan disease associated with chylomicronemia, severe hypertriglyceridemia, metabolic complications and potentially life-threatening pancreatitis. The LPLS447X gene variant, in an adeno-associated viral vector of serotype 1 (alipogene tiparvovec), was administered to 14 adult LPLD patients with a prior history of pancreatitis. Primary objectives were to assess the long-term safety of alipogene tiparvovec and achieve a X40% reduction in fasting median plasma triglyceride (TG) at 3–12 weeks compared with baseline. Cohorts 1 (n ¼ 2) and 2 (n ¼ 4) received 3 Â 1011 gc kg À 1, and cohort 3 (n ¼ 8) received 1 Â 1012 gc kg À 1. Cohorts 2 and 3 also received immunosuppressants from the time of alipogene tiparvovec administration and continued for 12 weeks. Alipogene tiparvovec was well tolerated, without emerging safety concerns for 2 years. Half of the patients demonstrated a X40% reduction in fasting TG between 3 and 12 weeks. TG subsequently returned to baseline, although sustained LPLS447X expression and long-term changes in TG-rich lipoprotein characteristics were noted independently of the effect on fasting plasma TG.
  • (12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao Et Al

    (12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao Et Al

    USOO9498481 B2 (12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao et al. (45) Date of Patent: *Nov. 22, 2016 (54) CYCLOPROPYL MODULATORS OF P2Y12 WO WO95/26325 10, 1995 RECEPTOR WO WO99/O5142 2, 1999 WO WOOO/34283 6, 2000 WO WO O1/92262 12/2001 (71) Applicant: Apharaceuticals. Inc., La WO WO O1/922.63 12/2001 olla, CA (US) WO WO 2011/O17108 2, 2011 (72) Inventors: Tadimeti Rao, San Diego, CA (US); Chengzhi Zhang, San Diego, CA (US) OTHER PUBLICATIONS Drugs of the Future 32(10), 845-853 (2007).* (73) Assignee: Auspex Pharmaceuticals, Inc., LaJolla, Tantry et al. in Expert Opin. Invest. Drugs (2007) 16(2):225-229.* CA (US) Wallentin et al. in the New England Journal of Medicine, 361 (11), 1045-1057 (2009).* (*) Notice: Subject to any disclaimer, the term of this Husted et al. in The European Heart Journal 27, 1038-1047 (2006).* patent is extended or adjusted under 35 Auspex in www.businesswire.com/news/home/20081023005201/ U.S.C. 154(b) by Od en/Auspex-Pharmaceuticals-Announces-Positive-Results-Clinical M YW- (b) by ayS. Study (published: Oct. 23, 2008).* This patent is Subject to a terminal dis- Concert In www.concertpharma. com/news/ claimer ConcertPresentsPreclinicalResultsNAMS.htm (published: Sep. 25. 2008).* Concert2 in Expert Rev. Anti Infect. Ther. 6(6), 782 (2008).* (21) Appl. No.: 14/977,056 Springthorpe et al. in Bioorganic & Medicinal Chemistry Letters 17. 6013-6018 (2007).* (22) Filed: Dec. 21, 2015 Leis et al. in Current Organic Chemistry 2, 131-144 (1998).* Angiolillo et al., Pharmacology of emerging novel platelet inhibi (65) Prior Publication Data tors, American Heart Journal, 2008, 156(2) Supp.
  • Human Histamine H2 Receptor, Frozen Cells Product No.: ES-391-AF

    Human Histamine H2 Receptor, Frozen Cells Product No.: ES-391-AF

    TECHNICAL AequoZen® DATA SHEET Research use only. Not for use in diagnostic procedures. You are authorized to utilize these frozen cell preparations one time only. Any attempt to transfer, re-use, or propagate these cells is expressly unauthorized and a violation of the product terms and conditions of sale. Human Histamine H2 Receptor, Frozen Cells Product No.: ES-391-AF Lot No.: 2562845 Material Provided Cells: 1 x 1 mL frozen aliquot Format: ~10 x 106 cells/mL in Ham’s F12, 10% FBS with 10 % DMSO Product Information Cellular Background: CHO-K1 Parental Frozen Cells (control): A19 (replaced with Cat # ES-000-A2F) Frozen Cells Info: Frozen recombinant, CHO-K1 cells expressing mitochondrially- targeted Aequorin, Gα16 and the human Histamine H2 receptor. DNA Sequence: Identical to coding sequence of GenBank NM_022304.2. Corresponding Protein Sequence: Identical to GenBank NP_071640.1. Storage Conditions: Store in liquid nitrogen (vapor phase) immediately upon receipt, or maximum 15 days at -80°C. AequoZen® is designed for single use only. Do not refreeze. Quality Control ® EC50 for a reference agonist is determined using an AequoScreen assay (Figure 1). Mycoplasma test is performed using MycoAlert® Mycoplasma detection kit. We certify that these results meet our quality release criteria. Amthamine dihydrobromide (EC50): 6.9 nM Mycoplasma: This cell line tested negative for Mycoplasma. TDS-ES-391-AF-04 Page 1 of 5 Recommended Thawing Conditions and Handling of Frozen Cells Carefully follow instructions below to obtain the expected results. Most Frozen cells are intended to be assayed immediately upon thawing. Exceptionally, where specified, some frozen cell products require an overnight incubation in Cell Medium to enable them to perform optimally.
  • Guidelines for the Forensic Analysis of Drugs Facilitating Sexual Assault and Other Criminal Acts

    Guidelines for the Forensic Analysis of Drugs Facilitating Sexual Assault and Other Criminal Acts

    Vienna International Centre, PO Box 500, 1400 Vienna, Austria Tel.: (+43-1) 26060-0, Fax: (+43-1) 26060-5866, www.unodc.org Guidelines for the Forensic analysis of drugs facilitating sexual assault and other criminal acts United Nations publication Printed in Austria ST/NAR/45 *1186331*V.11-86331—December 2011 —300 Photo credits: UNODC Photo Library, iStock.com/Abel Mitja Varela Laboratory and Scientific Section UNITED NATIONS OFFICE ON DRUGS AND CRIME Vienna Guidelines for the forensic analysis of drugs facilitating sexual assault and other criminal acts UNITED NATIONS New York, 2011 ST/NAR/45 © United Nations, December 2011. All rights reserved. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. This publication has not been formally edited. Publishing production: English, Publishing and Library Section, United Nations Office at Vienna. List of abbreviations . v Acknowledgements .......................................... vii 1. Introduction............................................. 1 1.1. Background ........................................ 1 1.2. Purpose and scope of the manual ...................... 2 2. Investigative and analytical challenges ....................... 5 3 Evidence collection ...................................... 9 3.1. Evidence collection kits .............................. 9 3.2. Sample transfer and storage........................... 10 3.3. Biological samples and sampling ...................... 11 3.4. Other samples ...................................... 12 4. Analytical considerations .................................. 13 4.1. Substances encountered in DFSA and other DFC cases .... 13 4.2. Procedures and analytical strategy...................... 14 4.3. Analytical methodology .............................. 15 4.4.
  • ELECTRONIC CLAIMS MANAGEMENT ENGINE (ECME) Version 1.0

    ELECTRONIC CLAIMS MANAGEMENT ENGINE (ECME) Version 1.0

    ELECTRONIC CLAIMS MANAGEMENT ENGINE (ECME) Version 1.0 USER MANUAL December 2020 Department of Veterans Affairs Office of Information and Technology (OIT) Product Development Revision History Date Description (Patch # if applicable) Project Manager Technical Writer 12/2020 Updated for BPS*1*27 MCCF EDI TAS MCCF EDI TAS Updated Potential Secondary Rx Claims Report ePharmacy ePharmacy Screen Display Development TeamDevelopment Team Updated Title Page date and footers 04/2020 Updated for BPS*1*26 REDACTED REDACTED Updated section 5.6 Add/View Comments Updated Title Page date and footers 1/2019 Updated for BPS*1*24 REDACTED REDACTED Change label on Claim Log, Modify Change View (CV), Enhance Claim Reports 08/2018 Updated for BPS*1*23 REDACTED REDACTED Update Title page date, footer date Modification filter questions CV Change View action, Rx Activity Log to add Date of Service to ECME Log, Resubmit with Edits action, Process Secondary/TRICARE Rx to ECME option, Payable Claims Report, Rejected Claims Report, Reversal Claims Report, Claims Submitted Not Yet Released Report, Recent Transactions Report, Closed Claims Report, View ePharmacy Rx Report Option 11/2017 Updated for BPS*1*22 REDACTED REDACTED Update Title page date, modification to Change View action; change auto-reverse parameter and auto-reversal bulletin; add Facility ID Qualifier and Reconciliation ID to Claim Log and Claim Response Inquiry; add new action PR Print Reports to VER View ePharmacy Rx. 05/2017 Updated for BPS*1*21 REDACTED REDACTED 08/2016 Updated for BPS*1*20 REDACTED
  • Chapter 2 Molecular Aspects of Histamine Receptors

    Chapter 2 Molecular Aspects of Histamine Receptors

    VU Research Portal Shedding Light on the Histamine H3 Receptor Mocking, T.A.M. 2020 document version Publisher's PDF, also known as Version of record Link to publication in VU Research Portal citation for published version (APA) Mocking, T. A. M. (2020). Shedding Light on the Histamine H3 Receptor: Photopharmacology and bioluminescent assays to study GPCRs. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. E-mail address: [email protected] Download date: 06. Oct. 2021 Chapter 2 Molecular aspects of histamine receptors Histamine mediates a multitude of physiological effects in the human body by activating four histamine receptor subtypes. Histamine receptors have proven to be promising drug targets in the treatment of a variety of diseases, including hay fever, gastric ulcers, inflammatory and neuropathological diseases. In this chapter the molecular aspects of histamine receptors are described, including expression profile, intracellular signaling, and how histamine receptor activity can be attenuated by ligands targeting the histamine receptor binding sites.
  • The In¯Uence of Medication on Erectile Function

    The In¯Uence of Medication on Erectile Function

    International Journal of Impotence Research (1997) 9, 17±26 ß 1997 Stockton Press All rights reserved 0955-9930/97 $12.00 The in¯uence of medication on erectile function W Meinhardt1, RF Kropman2, P Vermeij3, AAB Lycklama aÁ Nijeholt4 and J Zwartendijk4 1Department of Urology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; 2Department of Urology, Leyenburg Hospital, Leyweg 275, 2545 CH The Hague, The Netherlands; 3Pharmacy; and 4Department of Urology, Leiden University Hospital, P.O. Box 9600, 2300 RC Leiden, The Netherlands Keywords: impotence; side-effect; antipsychotic; antihypertensive; physiology; erectile function Introduction stopped their antihypertensive treatment over a ®ve year period, because of side-effects on sexual function.5 In the drug registration procedures sexual Several physiological mechanisms are involved in function is not a major issue. This means that erectile function. A negative in¯uence of prescrip- knowledge of the problem is mainly dependent on tion-drugs on these mechanisms will not always case reports and the lists from side effect registries.6±8 come to the attention of the clinician, whereas a Another way of looking at the problem is drug causing priapism will rarely escape the atten- combining available data on mechanisms of action tion. of drugs with the knowledge of the physiological When erectile function is in¯uenced in a negative mechanisms involved in erectile function. The way compensation may occur. For example, age- advantage of this approach is that remedies may related penile sensory disorders may be compen- evolve from it. sated for by extra stimulation.1 Diminished in¯ux of In this paper we will discuss the subject in the blood will lead to a slower onset of the erection, but following order: may be accepted.
  • Classification of Medicinal Drugs and Driving: Co-Ordination and Synthesis Report

    Classification of Medicinal Drugs and Driving: Co-Ordination and Synthesis Report

    Project No. TREN-05-FP6TR-S07.61320-518404-DRUID DRUID Driving under the Influence of Drugs, Alcohol and Medicines Integrated Project 1.6. Sustainable Development, Global Change and Ecosystem 1.6.2: Sustainable Surface Transport 6th Framework Programme Deliverable 4.4.1 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Due date of deliverable: 21.07.2011 Actual submission date: 21.07.2011 Revision date: 21.07.2011 Start date of project: 15.10.2006 Duration: 48 months Organisation name of lead contractor for this deliverable: UVA Revision 0.0 Project co-funded by the European Commission within the Sixth Framework Programme (2002-2006) Dissemination Level PU Public PP Restricted to other programme participants (including the Commission x Services) RE Restricted to a group specified by the consortium (including the Commission Services) CO Confidential, only for members of the consortium (including the Commission Services) DRUID 6th Framework Programme Deliverable D.4.4.1 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Page 1 of 243 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Authors Trinidad Gómez-Talegón, Inmaculada Fierro, M. Carmen Del Río, F. Javier Álvarez (UVa, University of Valladolid, Spain) Partners - Silvia Ravera, Susana Monteiro, Han de Gier (RUGPha, University of Groningen, the Netherlands) - Gertrude Van der Linden, Sara-Ann Legrand, Kristof Pil, Alain Verstraete (UGent, Ghent University, Belgium) - Michel Mallaret, Charles Mercier-Guyon, Isabelle Mercier-Guyon (UGren, University of Grenoble, Centre Regional de Pharmacovigilance, France) - Katerina Touliou (CERT-HIT, Centre for Research and Technology Hellas, Greece) - Michael Hei βing (BASt, Bundesanstalt für Straßenwesen, Germany).
  • 1 CETP Inhibition Improves HDL Function but Leads to Fatty Liver and Insulin Resistance in CETP-Expressing Transgenic Mice on A

    1 CETP Inhibition Improves HDL Function but Leads to Fatty Liver and Insulin Resistance in CETP-Expressing Transgenic Mice on A

    Page 1 of 55 Diabetes CETP inhibition improves HDL function but leads to fatty liver and insulin resistance in CETP-expressing transgenic mice on a high-fat diet Lin Zhu1,2, Thao Luu2, Christopher H. Emfinger1,2, Bryan A Parks5, Jeanne Shi2,7, Elijah Trefts3, Fenghua Zeng4, Zsuzsanna Kuklenyik5, Raymond C. Harris4, David H. Wasserman3, Sergio Fazio6 and John M. Stafford1,2,3,* 1VA Tennessee Valley Healthcare System, 2Division of Diabetes, Endocrinology, & Metabolism, 3Department of Molecular Physiology and Biophysics, 4Devision of Nephrology and Hypertension, Vanderbilt University School of Medicine. 5Division of Laboratory Sciences, Centers for Disease Control and Prevention. 6The Center for Preventive Cardiology at the Knight Cardiovascular Institute, Oregon Health & Science University. 7Trinity College of Art and Science, Duke University. * Address correspondence and request for reprints to: John. M. Stafford, 7445D Medical Research Building IV, Nashville, TN 37232-0475, phone (615) 936-6113, fax (615) 936- 1667 Email: [email protected] Running Title: CETP inhibition and insulin resistance Word Count: 5439 Figures: 7 Tables: 1 1 Diabetes Publish Ahead of Print, published online September 13, 2018 Diabetes Page 2 of 55 Abstract In clinical trials inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels but doesn’t robustly improve cardiovascular outcomes. About 2/3 of trial participants were obese. Lower plasma CETP activity is associated with increased cardiovascular risk in human studies, and protective aspects of CETP have been observed in mice fed a high-fat diet (HFD) with regard to metabolic outcomes. To define if CETP inhibition has different effects depending on the presence of obesity, we performed short- term anacetrapib treatment in chow- and HFD-fed CETP-transgenic mice.
  • Electronic Claims Management Version 1.0 Engine User Manual

    Electronic Claims Management Version 1.0 Engine User Manual

    Electronic Claims Management Engine (ECME) Version 1.0 User Manual May 2021 Department of Veterans Affairs Office of Information and Technology (OIT) Revision History Description (Patch # if Date Project Manager Technical Writer applicable) 05/2021 Updated for BPS*1*28 MCCF EDI TAS MCCF EDI TAS Updated Title Page date and ePharmacy ePharmacy footers Development Development Added Section 6.3.3 SC Team Team Prescriptions for Active Duty Prescriptions Added Section 8.1.11 Duplicate Claims Report 12/2020 Updated for BPS*1*27 MCCF EDI TAS MCCF EDI TAS Updated Potential Secondary Rx ePharmacy ePharmacy Claims Report Screen Display Development Development Updated Title Page date and Team Team footers 04/2020 Updated for BPS*1*26 REDACTED REDACTED Updated section 5.6 Add/View Comments Updated Title Page date and footers 1/2019 Updated for BPS*1*24 REDACTED REDACTED Change label on Claim Log, Modify Change View (CV), Enhance Claim Reports 08/2018 Updated for BPS*1*23 REDACTED REDACTED Update Title page date, footer date Modification filter questions CV Change View action, Rx Activity Log to add Date of Service to ECME Log, Resubmit with Edits action, Process Secondary/TRICARE Rx to ECME option, Payable Claims Report, Rejected Claims Report, Reversal Claims Report, Claims Submitted Not Yet Released Report, Recent Transactions Report, Closed Claims Report, View ePharmacy Rx Report Option Electronic Claims Management Engine V. 1.0 User Manual ii May 2021 Description (Patch # if Date Project Manager Technical Writer applicable) 11/2017 Updated for BPS*1*22 REDACTED REDACTED Update Title page date, modification to Change View action; change auto-reverse parameter and auto-reversal bulletin; add Facility ID Qualifier and Reconciliation ID to Claim Log and Claim Response Inquiry; add new action PR Print Reports to VER View ePharmacy Rx.