DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2010/0304998 A1 Sem (43) Pub

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

US 20100304998A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0304998 A1 Sem (43) Pub. Date: Dec. 2, 2010 (54) CHEMICAL PROTEOMIC ASSAY FOR Related U.S. Application Data OPTIMIZING DRUG BINDING TO TARGET (60) Provisional application No. 61/217,585, filed on Jun. PROTEINS 2, 2009. (75) Inventor: Daniel S. Sem, New Berlin, WI Publication Classification (US) (51) Int. C. GOIN 33/545 (2006.01) Correspondence Address: GOIN 27/26 (2006.01) ANDRUS, SCEALES, STARKE & SAWALL, LLP C40B 30/04 (2006.01) 100 EAST WISCONSINAVENUE, SUITE 1100 (52) U.S. Cl. ............... 506/9: 436/531; 204/456; 435/7.1 MILWAUKEE, WI 53202 (US) (57) ABSTRACT (73) Assignee: MARQUETTE UNIVERSITY, Disclosed herein are methods related to drug development. Milwaukee, WI (US) The methods typically include steps whereby an existing drug is modified to obtain a derivative form or whereby an analog (21) Appl. No.: 12/792,398 of an existing drug is identified in order to obtain a new therapeutic agent that preferably has a higher efficacy and (22) Filed: Jun. 2, 2010 fewer side effects than the existing drug. Patent Application Publication Dec. 2, 2010 Sheet 1 of 22 US 2010/0304998 A1 augavpop, Patent Application Publication Dec. 2, 2010 Sheet 2 of 22 US 2010/0304998 A1 g Patent Application Publication Dec. 2, 2010 Sheet 3 of 22 US 2010/0304998 A1 Patent Application Publication Dec. 2, 2010 Sheet 4 of 22 US 2010/0304998 A1 tg & Patent Application Publication Dec. 2, 2010 Sheet 5 of 22 US 2010/0304998 A1 Patent Application Publication Dec. 2, 2010 Sheet 6 of 22 US 2010/0304998 A1 s Patent Application Publication Dec. 2, 2010 Sheet 7 of 22 US 2010/0304998 A1 Patent Application Publication Dec. 2, 2010 Sheet 8 of 22 US 2010/0304998 A1 Patent Application Publication Dec. 2, 2010 Sheet 9 of 22 US 2010/0304998 A1 s Patent Application Publication Dec. 2, 2010 Sheet 10 of 22 US 2010/0304998 A1 Patent Application Publication Dec. 2, 2010 Sheet 11 of 22 US 2010/0304998 A1 : 8& & S S 8 S & N Patent Application Publication Dec. 2, 2010 Sheet 12 of 22 US 2010/0304998 A1 Patent Application Publication Dec. 2, 2010 Sheet 13 of 22 US 2010/0304998 A1 Patent Application Publication Dec. 2, 2010 Sheet 14 of 22 US 2010/0304998 A1 Patent Application Publication Dec. 2, 2010 Sheet 15 of 22 US 2010/0304998 A1 Patent Application Publication Dec. 2, 2010 Sheet 16 of 22 US 2010/0304998 A1 Patent Application Publication Dec. 2, 2010 Sheet 17 of 22 US 2010/0304998 A1 Patent Application Publication Dec. 2, 2010 Sheet 18 of 22 US 2010/0304998 A1 Patent Application Publication Dec. 2, 2010 Sheet 19 of 22 US 2010/0304998 A1 **************************************************^*^®^^^*^®^^^*^®^^^*^- laenol wur.6) ??????. wunog ?umizu Patent Application Publication Dec. 2, 2010 Sheet 20 of 22 US 2010/0304998 A1 g Patent Application Publication Dec. 2, 2010 Sheet 21 of 22 US 2010/0304998 A1 Patent Application Publication Dec. 2, 2010 Sheet 22 of 22 US 2010/0304998 A1 Papwaissapixiisweswuri, US 2010/0304998 A1 Dec. 2, 2010 CHEMICAL PROTEOMIC ASSAY FOR preferably has an affinity for the non-target protein that is less OPTIMIZING DRUG BINDING TO TARGET than the affinity of the existing drug for the target protein. PROTEINS 0007. In some embodiments, the methods include the fol lowing steps: (a) passing a biological sample comprising a CROSS-REFERENCE TO RELATED target protein and optionally a non-target protein over a col APPLICATIONS umn, the column comprising an affinity resin for the target protein, the affinity resin comprising a resin conjugated or 0001. The present application claims the benefit under 35 covalently attached to a first chemical compound that binds to U.S.C. S 119(e) to U.S. Provisional Application No. 60/217, the target protein; (b) washing the column and removing 585, filed on Jun. 2, 2009, the contents of which are incorpo proteins that are not bound to the affinity resin; (c) eluting rated herein by reference. proteins from the column that are bound to the affinity resin BACKGROUND by passing a solution comprising a second chemical com pound over the column; and (d) identifying proteins in the 0002 The field of the present invention relates to drug eluate and optionally obtaining a proteomic profile for the development. In particular, the invention relates to methods second chemical compound. Optionally, the methods further for modifying or repurposing existing drugs to obtain a new may include: (e) comparing the identified proteins of the therapeutic having higher efficacy and fewer side effects. eluate obtained using the second chemical compound to iden 0003. The drug discovery process is costly and often inef tified proteins of an eluate obtained using the first chemical ficient. Genomics and proteomics advances have presented compound (e.g., comparing the proteomic profile of the sec the promise of improving efficiency, but this has largely trans ond chemical compound to the proteomic profile of the first lated into the identification of new drug targets, not new chemical compound. drugs. What is needed is a better coupling of the chemistry of 0008. The first and second chemical compounds utilized drug design to advances in genomics and proteomics. in the method may be related or unrelated. In some embodi 0004 Drugs typically exert their desired therapeutic ments, the second chemical compound is a derivative orana effects and their undesired side effects by virtue of binding log of the first chemical compound and binds to the target interactions with protein target(s) and anti-target(s), respec protein. In other embodiments, the first chemical compound tively. Better strategies are therefore needed to efficiently and the second chemical compound are selected from Table monitor and manipulate cross-target binding profiles (i.e. the 6-9, and optionally, the second chemical compound binds to collection of proteins that a drug molecule binds to), as an the target protein. integrated part of the drug design process. Notably, it was 0009. In some embodiments of the disclosed methods, the only recently discovered that two widely-used drugs, ima first chemical compound is an existing drug for which a target tinib and isoniazid, actually bind to multiple proteins. This protein has been identified in the art and the second chemical was only discovered years after these drugs were in use. It compound is a derivative or analog of the existing drug which should also be noted that drug binding to other proteins, while binds to the target protein. In the methods, the biological Sometimes leading to toxic side-effects, can in some cases, sample includes the target protein. Typically, the biological such as imatinib (4-(4-Methyl-1-piperazinyl)methyl-N-(4- sample is obtained from a physiologically relevant tissue with methyl-3-4-(3-pyridinyl)-2-pyrimidinyl)amino-phenyl respect to the therapeutic target of the existing drug. For benzamide methanesulfonate) and isoniazid, actually con example, where the existing drug is utilized as a neurological tribute to drug efficacy, thereby calling into question the one therapeutic and is known to have a target protein that is target/one-drug dogma that has long served as the foundation present in neural tissue, the biological sample for the present for rational drug design. methods may be obtained from neural tissue. Where an exist 0005. The methods disclosed herein may be utilized to ing drug is observed to cause side effects due to toxicity, the define proteomic profiles early in the drug discovery process. existing drug may be observed to bind to a non-target protein As such, lead drugs may be modified in order to tune or adjust which may be present in physiologically non-relevant tissue these proteomic profiles. The methods disclosed herein also with respect to the therapeutic target of the existing drug (e.g., may be utilized to assay for off-target binding events, for non-neural tissue Such as liver tissue or heart tissue for exist example, so that multi-target binding can be better correlated ing drugs utilized as neurological therapeutics), and which with desired therapeutic effects. optionally may be present in physiologically relevant tissue with respect to the therapeutic target of the existing drug (e.g., SUMMARY neural tissue for existing drugs utilized as neurological thera 0006 Disclosed herein are methods related to drug devel peutics). opment. The methods typically include steps whereby an 0010. In the disclosed methods, the proteins of the biologi existing drug is modified to obtain a derivative form or cal sample are bound to the column containing the affinity whereby an analog of an existing drug is identified in order to resin and Subsequently the proteins are eluted. For example, obtain a new therapeutic agent which preferably has a higher the proteins bound to the column may be eluted by washing efficacy and fewer side effects than the existing drug. In some the column with a solution comprising the first chemical embodiments, the existing drug is utilized as an affinity agent compound (e.g., an existing drug) or a derivative or analog in order to identify proteins in a biological sample that bind to thereof, where the affinity resin of the first column is made of the existing drug, including a target protein and optionally a a resin conjugated or covalently attached to the first chemical non-target protein. A derivative or analog of the existing drug compound. then is tested in order to determine: (1) whether the derivative 0011. In the disclosed methods, the proteins in the eluates or analog preferably has an affinity for the target protein that typically are identified, for example, in order to obtain a is no less than the affinity of the existing drug for the target proteomic profile.
Recommended publications
  • United States Patent Office

    United States Patent Office

    3,092,548 United States Patent Office Patented June 4, 1963 2 are the various side effects that occur in an appreciable 3,092,548 number of patients, the foremost of which are a blurring METHOD OF TREATING PEPTICULCERS WITH PANTOTHENECACD of vision, drowsiness and a general dry condition mani Albert G. Worton, Columbus, Ohio, assignor to The fested by a retarded salivation, reduction of perspiration Warren-Teed Products Company, Columbus, Ohio, a 5 and diminished urinary output. Other side effects which corporation of Ohio occur in some cases are glaucoma, stimulation of the cen No Drawing. Filed Oct. 27, 1960, Ser. No. 65,256 trol nervous system and in severe cases cardiac and respi 5 Claims. (Ci. 67-55) ratory collapse. These side effects increase to Some de gree with the increase in dosage. Despite the side effects This invention relates to preparation adapted for use O these compounds are fairly selective and highly effective in treating disorders of the gastro-intestinal tract, more in decreasing the volume and acidity of gastric secretion particularly in treating peptic ulcer, both of the duodenal and in reducing gastrointestinal motility. and gastric type, for hyperacidity, hypertropic gastritis, Understandably, the main problem in the past has been splenic flexure syndrome, biliary dyskinesia (postchole to provide a dosage of anticholinergic drug which will cystectomy syndrome) and hiatal hernia or other condi achieve the most beneficial results possible and yet mini tions where anticholinergic effect, either spasmolytic or mize the undesired side effects. One of the objects of antisecretory is indicated or where antiuicerogenic effect this invention is to provide novel compositions containing is indicated.
  • Isopropamide Iodide

    Isopropamide Iodide

    www.chemicalland21.com ISOPROPAMIDE IODIDE SYNONYMS (3-Carbamoyl-3,3-diphenylpropyl)diisopropylmethylammonium iodide; 2,2-Diphenyl-4- diisopropylaminobutyramide methiodide; 4-(Diisopropylamino)-2,2-diphenylbutyramide methiodide; gamma-(Aminocarbonyl)-N-methyl-N,N-bis(1-methylethyl)-gamma-phenylbenzenepropanaminium iodide; Iodure d'isopropamide; Ioduro de isopropamida; Isopropamide ioduro; Isopropamidi iodidum; Isoproponum iodide; PRODUCT IDENTIFICATION CAS RN 71-81-8 EINECS RN 200-766-8 FORMULA C23H33IN2O MOL WEIGHT 480.43 PHYSICAL AND CHEMICAL PROPERTIES PHYSICAL STATE white to off-white powder MELTING POINT 199 C BOILING POINT DENSITY SOLUBILITY IN WATER pH VAPOR DENSITY REFRACTIVE INDEX FLASH POINT GENERAL DESCRIPTION Isopropamide is a long-acting anticholinergic and antimuscarinic drug of quaternary ammonium structure. It is used in the form of the iodide, (also bromide or chloride) to treat peptic ulcer and to suppress gastric secretion other gastrointestinal disorders. Brands of Isopropamide drugs: Darbid Dipramide Isamide Marygin-M Piaccamide Priamide Priazimide Sanulcin Tyrimide Quaternary ammonium anticholinergics (Synthetic) ATC Code Product CAS RN. A03AB01 Benzilonium bromide 1050-48-2 A03AB02 Glycopyrrolate 596-51-0 A03AB03 Oxyphenonium 14214-84-7 A03AB04 Penthienate 22064-27-3 A03AB05 Propantheline 50-34-0 A03AB06 Otilonium bromide 26095-59-0 A03AB07 Methantheline 5818-17-7 Please mail us if you want to sell your product or need to buy some products) www.chemicalland21.com ISOPROPAMIDE IODIDE A03AB08 Tridihexethyl 60-49-1 A03AB09 Isopropamide 7492-32-2 A03AB10 Hexocyclium 6004-98-4 A03AB11 Poldine 596-50-9 A03AB12 Mepenzolic acid 25990-43-6 A03AB13 Bevonium 33371-53-8 A03AB14 Pipenzolate 13473-38-6 A03AB15 Diphemanil methylsulfate 62-97-5 A03AB16 (2-Benzhydryloxyethyl)diethyl-methylammonium iodide A03AB17 Tiemonium iodide 144-12-7 A03AB18 Prifinium bromide 4630-95-9 A03AB19 Timepidium bromide 35035-05-3 A03AB21 Fenpiverinium bromide 125-60-0 03AB53 Oxyphenonium, combinations STABILITY AND REACTIVITY STABILITY Stable under normal conditions.
  • The National Drugs List

    The National Drugs List

    ^ ^ ^ ^ ^[ ^ The National Drugs List Of Syrian Arab Republic Sexth Edition 2006 ! " # "$ % &'() " # * +$, -. / & 0 /+12 3 4" 5 "$ . "$ 67"5,) 0 " /! !2 4? @ % 88 9 3: " # "$ ;+<=2 – G# H H2 I) – 6( – 65 : A B C "5 : , D )* . J!* HK"3 H"$ T ) 4 B K<) +$ LMA N O 3 4P<B &Q / RS ) H< C4VH /430 / 1988 V W* < C A GQ ") 4V / 1000 / C4VH /820 / 2001 V XX K<# C ,V /500 / 1992 V "!X V /946 / 2004 V Z < C V /914 / 2003 V ) < ] +$, [2 / ,) @# @ S%Q2 J"= [ &<\ @ +$ LMA 1 O \ . S X '( ^ & M_ `AB @ &' 3 4" + @ V= 4 )\ " : N " # "$ 6 ) G" 3Q + a C G /<"B d3: C K7 e , fM 4 Q b"$ " < $\ c"7: 5) G . HHH3Q J # Hg ' V"h 6< G* H5 !" # $%" & $' ,* ( )* + 2 ا اوا ادو +% 5 j 2 i1 6 B J' 6<X " 6"[ i2 "$ "< * i3 10 6 i4 11 6! ^ i5 13 6<X "!# * i6 15 7 G!, 6 - k 24"$d dl ?K V *4V h 63[46 ' i8 19 Adl 20 "( 2 i9 20 G Q) 6 i10 20 a 6 m[, 6 i11 21 ?K V $n i12 21 "% * i13 23 b+ 6 i14 23 oe C * i15 24 !, 2 6\ i16 25 C V pq * i17 26 ( S 6) 1, ++ &"r i19 3 +% 27 G 6 ""% i19 28 ^ Ks 2 i20 31 % Ks 2 i21 32 s * i22 35 " " * i23 37 "$ * i24 38 6" i25 39 V t h Gu* v!* 2 i26 39 ( 2 i27 40 B w< Ks 2 i28 40 d C &"r i29 42 "' 6 i30 42 " * i31 42 ":< * i32 5 ./ 0" -33 4 : ANAESTHETICS $ 1 2 -1 :GENERAL ANAESTHETICS AND OXYGEN 4 $1 2 2- ATRACURIUM BESYLATE DROPERIDOL ETHER FENTANYL HALOTHANE ISOFLURANE KETAMINE HCL NITROUS OXIDE OXYGEN PROPOFOL REMIFENTANIL SEVOFLURANE SUFENTANIL THIOPENTAL :LOCAL ANAESTHETICS !67$1 2 -5 AMYLEINE HCL=AMYLOCAINE ARTICAINE BENZOCAINE BUPIVACAINE CINCHOCAINE LIDOCAINE MEPIVACAINE OXETHAZAINE PRAMOXINE PRILOCAINE PREOPERATIVE MEDICATION & SEDATION FOR 9*: ;< " 2 -8 : : SHORT -TERM PROCEDURES ATROPINE DIAZEPAM INJ.
  • Specifications of Approved Drug Compound Library

    Specifications of Approved Drug Compound Library

    Annexure-I : Specifications of Approved drug compound library The compounds should be structurally diverse, medicinally active, and cell permeable Compounds should have rich documentation with structure, Target, Activity and IC50 should be known Compounds which are supplied should have been validated by NMR and HPLC to ensure high purity Each compound should be supplied as 10mM solution in DMSO and at least 100µl of each compound should be supplied. Compounds should be supplied in screw capped vial arranged as 96 well plate format.
  • Upregulation of Peroxisome Proliferator-Activated Receptor-Α And

    Upregulation of Peroxisome Proliferator-Activated Receptor-Α And

    Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer Chih-Yang Wang, Ying-Jui Chao, Yi-Ling Chen, Tzu-Wen Wang, Nam Nhut Phan, Hui-Ping Hsu, Yan-Shen Shan, Ming-Derg Lai 1 Supplementary Table 1. Demographics and clinical outcomes of five patients with ampullary cancer Time of Tumor Time to Age Differentia survival/ Sex Staging size Morphology Recurrence recurrence Condition (years) tion expired (cm) (months) (months) T2N0, 51 F 211 Polypoid Unknown No -- Survived 193 stage Ib T2N0, 2.41.5 58 F Mixed Good Yes 14 Expired 17 stage Ib 0.6 T3N0, 4.53.5 68 M Polypoid Good No -- Survived 162 stage IIA 1.2 T3N0, 66 M 110.8 Ulcerative Good Yes 64 Expired 227 stage IIA T3N0, 60 M 21.81 Mixed Moderate Yes 5.6 Expired 16.7 stage IIA 2 Supplementary Table 2. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of an ampullary cancer microarray using the Database for Annotation, Visualization and Integrated Discovery (DAVID). This table contains only pathways with p values that ranged 0.0001~0.05. KEGG Pathway p value Genes Pentose and 1.50E-04 UGT1A6, CRYL1, UGT1A8, AKR1B1, UGT2B11, UGT2A3, glucuronate UGT2B10, UGT2B7, XYLB interconversions Drug metabolism 1.63E-04 CYP3A4, XDH, UGT1A6, CYP3A5, CES2, CYP3A7, UGT1A8, NAT2, UGT2B11, DPYD, UGT2A3, UGT2B10, UGT2B7 Maturity-onset 2.43E-04 HNF1A, HNF4A, SLC2A2, PKLR, NEUROD1, HNF4G, diabetes of the PDX1, NR5A2, NKX2-2 young Starch and sucrose 6.03E-04 GBA3, UGT1A6, G6PC, UGT1A8, ENPP3, MGAM, SI, metabolism
  • Infant Antibiotic Exposure Search EMBASE 1. Exp Antibiotic Agent/ 2

    Infant Antibiotic Exposure Search EMBASE 1. Exp Antibiotic Agent/ 2

    Infant Antibiotic Exposure Search EMBASE 1. exp antibiotic agent/ 2. (Acedapsone or Alamethicin or Amdinocillin or Amdinocillin Pivoxil or Amikacin or Aminosalicylic Acid or Amoxicillin or Amoxicillin-Potassium Clavulanate Combination or Amphotericin B or Ampicillin or Anisomycin or Antimycin A or Arsphenamine or Aurodox or Azithromycin or Azlocillin or Aztreonam or Bacitracin or Bacteriocins or Bambermycins or beta-Lactams or Bongkrekic Acid or Brefeldin A or Butirosin Sulfate or Calcimycin or Candicidin or Capreomycin or Carbenicillin or Carfecillin or Cefaclor or Cefadroxil or Cefamandole or Cefatrizine or Cefazolin or Cefixime or Cefmenoxime or Cefmetazole or Cefonicid or Cefoperazone or Cefotaxime or Cefotetan or Cefotiam or Cefoxitin or Cefsulodin or Ceftazidime or Ceftizoxime or Ceftriaxone or Cefuroxime or Cephacetrile or Cephalexin or Cephaloglycin or Cephaloridine or Cephalosporins or Cephalothin or Cephamycins or Cephapirin or Cephradine or Chloramphenicol or Chlortetracycline or Ciprofloxacin or Citrinin or Clarithromycin or Clavulanic Acid or Clavulanic Acids or clindamycin or Clofazimine or Cloxacillin or Colistin or Cyclacillin or Cycloserine or Dactinomycin or Dapsone or Daptomycin or Demeclocycline or Diarylquinolines or Dibekacin or Dicloxacillin or Dihydrostreptomycin Sulfate or Diketopiperazines or Distamycins or Doxycycline or Echinomycin or Edeine or Enoxacin or Enviomycin or Erythromycin or Erythromycin Estolate or Erythromycin Ethylsuccinate or Ethambutol or Ethionamide or Filipin or Floxacillin or Fluoroquinolones
  • Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017

    Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017

    Q UO N T FA R U T A F E BERMUDA PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 BR 111 / 2017 The Minister responsible for health, in exercise of the power conferred by section 48A(1) of the Pharmacy and Poisons Act 1979, makes the following Order: Citation 1 This Order may be cited as the Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017. Repeals and replaces the Third and Fourth Schedule of the Pharmacy and Poisons Act 1979 2 The Third and Fourth Schedules to the Pharmacy and Poisons Act 1979 are repealed and replaced with— “THIRD SCHEDULE (Sections 25(6); 27(1))) DRUGS OBTAINABLE ONLY ON PRESCRIPTION EXCEPT WHERE SPECIFIED IN THE FOURTH SCHEDULE (PART I AND PART II) Note: The following annotations used in this Schedule have the following meanings: md (maximum dose) i.e. the maximum quantity of the substance contained in the amount of a medicinal product which is recommended to be taken or administered at any one time. 1 PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 mdd (maximum daily dose) i.e. the maximum quantity of the substance that is contained in the amount of a medicinal product which is recommended to be taken or administered in any period of 24 hours. mg milligram ms (maximum strength) i.e. either or, if so specified, both of the following: (a) the maximum quantity of the substance by weight or volume that is contained in the dosage unit of a medicinal product; or (b) the maximum percentage of the substance contained in a medicinal product calculated in terms of w/w, w/v, v/w, or v/v, as appropriate.
  • Playing Chicken: Avoiding Arsenic in Your Meat Around the World Through Research and Education, Science and Technology, and Advocacy

    Playing Chicken: Avoiding Arsenic in Your Meat Around the World Through Research and Education, Science and Technology, and Advocacy

    Playing Chicken Avoiding Arsenic in Your Meat Institute for Agriculture and Trade Policy Food and Health Program The Institute for Agriculture and Trade Policy About this publication promotes resilient family farms, rural communities and ecosystems Playing Chicken: Avoiding Arsenic in Your Meat around the world through research and education, science and technology, and advocacy. Written by David Wallinga, M.D. 2105 First Avenue South We would like to thank Ted Schettler, M.D., Minneapolis, Minnesota 55404 USA Karen Florini and Mardi Mellon for their helpful comments Tel.: (612) 870-0453 on this manuscript. We would especially like to acknowledge Fax: (612) 870-4846 the major contributions of Alise Cappel. We would like [email protected] iatp.org to thank the Quixote Foundation for their support of this work. iatp.org/foodandhealth Published April 2006 © 2006 IATP. All rights reserved. Table of contents Executive summary . 5 I. The modern American chicken: Arsenic use in context . 11 II. Concerns with adding arsenic routinely to chicken feed . 14 II. What we found: Arsenic in chicken meat . 21 Appendix A. FDA-approved feed additives containing arsenic . 26 Appendix B. Testing methodology . 29 References . 31 Playing Chicken: Avoiding Arsenic in Your Meat 3 4 Institute for Agriculture and Trade Policy Executive summary Arsenic causes cancer even at the low levels currently feed additive, are given each year to chickens. Arsenic found in our environment. Arsenic also contributes to other is an element—it doesn’t degrade or disappear. Arsenic diseases, including heart disease, diabetes and declines subsequently contaminates much of the 26-55 billion pounds in intellectual function, the evidence suggests.
  • (12) United States Patent (10) Patent No.: US 9,005,660 B2 Tygesen Et Al

    (12) United States Patent (10) Patent No.: US 9,005,660 B2 Tygesen Et Al

    USOO9005660B2 (12) United States Patent (10) Patent No.: US 9,005,660 B2 Tygesen et al. (45) Date of Patent: Apr. 14, 2015 (54) IMMEDIATE RELEASE COMPOSITION 4,873,080 A 10, 1989 Bricklet al. RESISTANT TO ABUSEBY INTAKE OF 4,892,742 A 1, 1990 Shah 4,898,733. A 2f1990 DePrince et al. ALCOHOL 5,019,396 A 5/1991 Ayer et al. 5,068,112 A 11/1991 Samejima et al. (75) Inventors: Peter Holm Tygesen, Smoerum (DK); 5,082,655 A 1/1992 Snipes et al. Jan Martin Oevergaard, Frederikssund 5,102,668 A 4, 1992 Eichel et al. 5,213,808 A 5/1993 Bar Shalom et al. (DK); Joakim Oestman, Lomma (SE) 5,266,331 A 11/1993 Oshlack et al. 5,281,420 A 1/1994 Kelmet al. (73) Assignee: Egalet Ltd., London (GB) 5,352.455 A 10, 1994 Robertson 5,411,745 A 5/1995 Oshlack et al. (*) Notice: Subject to any disclaimer, the term of this 5,419,917 A 5/1995 Chen et al. patent is extended or adjusted under 35 5,422,123 A 6/1995 Conte et al. U.S.C. 154(b) by 473 days. 5,460,826 A 10, 1995 Merrill et al. 5,478,577 A 12/1995 Sackler et al. 5,508,042 A 4/1996 OShlack et al. (21) Appl. No.: 12/701.248 5,520,931 A 5/1996 Persson et al. 5,529,787 A 6/1996 Merrill et al. (22) Filed: Feb. 5, 2010 5,549,912 A 8, 1996 OShlack et al.
  • Multi-Residue Determination of Organic Arsenical Drugs in Feeds by LC-MS/MS

    Multi-Residue Determination of Organic Arsenical Drugs in Feeds by LC-MS/MS

    Multi-Residue Determination of Organic Arsenical Drugs in Feeds by LC-MS/MS Geneviève Grenier, Melanie Titley & Lise-Anne Prescott AAFCO Laboratory Methods and Services Committee meeting 2016-01-18 Background • Animal Feed Division of CFIA identified a high priority need for the determination of three organic arsenicals (arsanilic acid, roxarsone and nitarsone) at residue levels in animal feed • These are withdrawal drugs and are priority food contaminants • Current test methods are at guarantee levels greater than 10% minimum use rate • Therefore, current methods not well suited for residue or traceback testing • Requested feed residue LOQ of 1 mg/kg for all three organic arsenicals 2 Background • UHPLC-PDA Challenges • Extract were very dirty • Tried sample clean-up using Oasis MAX SPE • Still very dirty • HPLC Challenges • Compounds elute too easily • Analytical column must : retain and separate compounds, and give good peak shape • Analytical column : Phenomenex Onyx Monolithic C18 100 X 3.0mm 3 Background • LC/MS/MS method (positive mode) • Column: Phenomenex Onyx Monolithic C18 100 X 3.0mm • Linearity problems with Internal Standard (IS) • Internal standard – 4-hydroxyphenylarsonic acid • Peak area of the internal standard increased with increasing analyte concentration • Cause • 4-hydroxyphenyl arsanic acid co-elute with Arsanilic acid and have similar m/z 4 New method - summary • Liquid chromatography combined with atomic and molecular mass spectrometry for speciation of arsenic in chicken liver. Peng et. al., Journal of Chromatography
  • Identification of Channels Underlying the M-Like Potassium Current In

    Identification of Channels Underlying the M-Like Potassium Current In

    Identification of channeis underiying the M-like potassium current in NG108-15 neurobiastoma-giioma ceiis A thesis submitted for the degree of Doctor of Philosophy University of London by Jennifer Kathleen Hadley Department of Pharmacology University College London Gower Street London WC1E 6BT ProQuest Number: U644085 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U644085 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Abstract NG108-15 cells express a potassium current resembling the IVI-current found in sympathetic ganglia. I contributed to the identification of the channels underlying this NG108-15 current. I used patch-clamp methodology to characterise the kinetics and pharmacology of the M-like current and of three candidate channel genes, all capable of producing “delayed rectifier” currents, expressed in mammalian cells. I studied two Kvi .2 clones: NGK1 (rat Kvi .2) expressed in mouse fibroblasts, and MK2 (mouse brain Kvi .2) expressed in Chinese hamster ovary (OHO) cells. Kvi.2 showed relatively positive activation that shifted negatively on repeated activation, some inactivation, block by dendrotoxin and various cations, and activation by niflumic acid.
  • Drugs Influencing Cognitive Function

    Drugs Influencing Cognitive Function

    Indian J Physiol Phannacol 1994; 38(4) : 241-251 RE\llEW ARTICLE DRUGS INFLUENCING COGNITIVE FUNCTION ALICE KURUYILLA* AND YASUNDARA DEYI Department ofPharmacology. Christian Medical College. Vellore - 632 002 DRUGS INFLUENCING COGNITIVE FUNCTION cerebrovascular disorders with dementias and reversible dementias. Drugs can inOuence cognitive function in several different ways. The cognitrve enhancers or nootropics Primary degenerative disorders include the have become a major issue in drug development during subgroups senile dementia of the Alzheimer's type the last decade. Nootropics arc defined as drugs that (SDAT), Alzheimer's disease, Picks disease and generally increase neuron metabolic activity, improve Huntington's chorea (4). Alzheimer's disease usually cognitive and ,'igilance level and are said to have occurs in individuals past 70 years old and appears to antidemcntia effect (I). These drugs are essential for be in part genetically determin'd (5). the treatment of geriatric disorders like Alzheimer's which have become one of the major problems socially Pathophysiology oj Alzheimer's disease : and medically. Considerable evidence has been gathered Extensive research in the recent years has made major in the last decade to support the observation that advances in understanding the pathogenesis of children with epilepsy have morc learning difficulties Alzheimer's disease (6). The hallmark lesions of than age matched controls (2, 3). Anti-epileptic drugs Alzheimer's disease are neuritic plaques and are useful in controlling the frequency and duration of neurofibrillary tangles. Two amyloid proteins seizures. These drugs can also be the source of side accumulate in Alzheimer's disease, these arc beta effects including cognitive impairment.