0001
`
`PSG2026
`Catalent Pharma Solutions v. Patheon Softgels
`IPR2018-00422
`
`

`

`MERCK & CO., INC.
`Whitehouse Station, NJ.
`U.S.A.
`
`Ist Edition—1889
`2nd Edition—1896
`3rd Edition—1907
`4th Edition—1930
`5th Edition—1940
`6th Edition—1952
`7th Edition—1960
`8th Edition—1968
`9th Edition—1976
`10th Edition—1983
`11th Edition—1989
`
`Library of Congress Catalog
`Card Number 89-60001
`ISBN Number 0911910-12-3
`
`First Printing—March 1996
`Second Printing—April 1997
`
`Copyright © 1996 by MERCK & CO., INC.
`All rights reserved. Copyright under the Universal Copyright Convention
`and the International: Copyright Convention.
`Copyright reserved under the Pan-American Copyright Convention.
`Printed in the U.S.A.
`
`0002
`
`0002
`
`

`

`A.S.T.M.
`
`as-, aSyYM-
`at.
`ATCC
`atm, atmos
`at. no.
`ATP
`ATPase
`at. wt.
`BAN
`B cell
`
`BCG
`Bé
`Beilstein
`
`Belg. pat.
`Ber.
`
`BGG
`biol
`B.ILOS.
`
`
`
`Abbreviations and Selected Definitions
`Please consult the Glossary (Misc. Tables Section)for additional definitions.
`adenine; adenosine; absorbance .
`American Society for Testing
`(extinction)
`Materials
`Angstrom units
`asymmetrical, unsymmetrical
`Q,-antitrypsin
`atomic
`antibody -
`American Type Culture Collection
`absolute; absorption
`atmosphere(s), atmospheric
`absolute configuration
`atomic number
`abstract
`adenosine triphosphate
`c-aminobutyric acid
`adenosine triphosphatase
`acetyl CH;CO—
`atomic weight
`according
`British Approved Name
`angiotensin converting enzyme
`bone marrow or bursa of Fabricius
`acetyl coenzyme A
`derived cell
`acetic anhydride
`Bacillus Calmette-Guerin
`ethyl acetate
`Baumé(a specific gravity scale)
`acetic acid
`Beilstein’s Handbuch der
`acyl carrier protein
`Organischen Chemie
`American Chemical Society
`Belgian patent
`adrenocorticotropic hormone
`Chemische Berichte (Berichte der
`acyl coenzyme A
`Deutschen Chemischen
`antibody-dependent cellular
`Gesellschaft)
`cytotoxicity
`bovine gammaglobulin
`adding, addition
`biological
`adenine
`British Intelligence Objectives
`alcohol dehydrogenase
`Subcommittee
`adenosine diphosphate
`tert-butoxycarbonyl
`(United States) Atomic Energy
`biochemical oxygen demand
`Commission
`boiling
`antigen, silver
`basepair; boiling point; boils at;
`anaphylotoxin inhibitor
`boiling at Example: bp7 48°
`acquired immunodeficiency
`means boils at 48°C if the pressure
`syndrome
`is 70 mm Hi:
`alanine
`British Pharmacopeia
`alcohol(ic); ethanol: ethyl alcohol
`British Pharmaceutical Codex
`anti-lymphocyte globulin
`British patent
`alkali(ne)
`biological response modifier
`specific optical rotation at 25° C for
`bovine seram albumin
`D (sodium) line; absence of
`British thermal units
`brackets indicates optical rotation
`butyl
`of a liquid in a 1 decimeter cell,
`neat
`benzoyl C-H;CO—
`benzaldehyde
`anti-lymphocyte serum, amyotrophic
`benzoic acid
`lateral sclerosis
`concentration by volume(g/1 00m!)
`molar absorptivity (concn in
`after optical rotations only
`g-moles/l)
`cytosine; cytidine; complement
`amorphous
`Centigrade degrees: Celsius
`adenosine 5 ‘monophosphate
`degrees
`(adenylic acid)
`heat capacity (constant pressure)
`cyclic AMP
`(circa) about
`ampules
`Chemical Abstracts
`amount(s)
`calorie(s)
`anti-nuclear factor; atrial natriuretic
`calculate, calculated
`factor
`Canadian patent
`anhydrous
`carbobenzoxy
`stereodescriptor, see Glossary
`complete blood count
`Justus Liebig’s Annalen der Chemie
`cubic centimeter(s) (milliliter)
`American Pharmaceutical
`cholecystokinin
`Association
`circular dichroism
`approximate(ly)
`cytidine diphosphate
`alum precipitated toxoid
`carcinoembryonic antigen
`aqueous
`(confer) compare
`aryl
`complete Freund’s adjuvant (same as
`analytical reagent
`FCA)
`AIDSrelated complex
`complement fixation test
`Naunyn Schmiedebergs Archivfiir
`Experimentelle Pathologie und
`coronary heart disease
`congestive heart failure
`Pharmakologie
`chemical
`aromatic acyl radical
`Journal of the Chemical Society,
`arginine
`Chemical Communications.
`B-carboxyaspartic acid
`curie
`asparagine
`Colour Index (British)
`aspartic acid
`stereodescriptor, see Glossary
`association; associated
`centimeter(s)
`
`BOC
`B.O.D.
`boil.
`bp
`
`BP.
`B.PLC.
`Brit. pat.
`BRM
`
`CFT
`CHD
`CHF
`chem
`Chem. Commun.
`
`Ci
`CL
`cis-
`cm
`
`Xili
`
`0003
`
`A A A
`
`AT
`Ab
`abs
`abs config
`abstr
`Abu
`Ac
`acc
`ACE
`Acetyl CoA
`AO
`AcOEt
`AcOH
`ACP
`ACS,
`ACTH
`AcylSCoA
`ADCC
`
`add(n)
`Ade
`ADH
`ADP
`AEC
`
`Ag
`AI
`AIDS
`
`Ala
`alc, alcoh
`ALG
`alk
`[ole
`
`ALS
`
`any
`
`amorph
`AMP
`
`cAMP
`amps
`amt(s
`ANF
`
`anhydr
`anti
`Ann.
`APhA
`
`approx
`APT
`aq
`Ar
`AR.
`ARC
`Archiv Exp.
`Pathol.
`Pharmakol.
`
`Arg
`Asa
`Asn
`Asp
`assoc(d)
`
`0003
`
`

`

`(Deutsches Reichs-Patent)-German
`patent
`double stranded
`dithiothreitol
`dynes
`entgegen, stereodescriptor, see
`Glossary
`the absorbance of a solution
`containing one gram per 100 ml
`contained in a cell having an
`absorption path of one cm
`molar extinction coefficient (concn in
`g-moles/l)
`excitatory amino acid
`erythrocyte coated by antibody and
`complement
`experimental allergic
`encephalomyelitis
`electron capture
`eosinophil chemotactic factor of
`anaphylaxis
`electrocardiogram
`Enzyme Commission Number
`edition
`effective dose
`editor(s)
`ethylenediaminetetraacetic acid
`electroencephalogram
`{exempli gratia) for example
`epidermal growth factor
`the same (authors), plural of idem
`European Inventory of Existing
`Chemical Substances
`electrocardiogram
`enzyme-linked immunosorbent assay
`electromotive force
`ethylenediamine (in formulas)
`stereochemical descriptor, see
`Glossary
`Environmental Protection Agency
`erythropoietin; European Patent
`Office
`molar extinction coefficient (concn in
`g-moles/)); dielectric constant
`equation
`equilibrium
`equivalent
`especially
`electrostatic units of electrical charge
`ethyl C.H;—
`Viscosity
`(et alii) and others
`ef cetera
`ether
`ethyl alcohol
`European patent application
`electron volt
`evacuated
`evaporation
`stereochemical descriptor, see
`Glossary
`experimental(ly)
`extract, extracted
`externally
`Pabrenheit degrees: also Fourneau
`fructose 1-phosphate
`fructose 6-phosphate
`fatty acid
`fast atom bombardment
`flavin adenine dinucleotide (reduced
`form)
`Freund’s complete adjuvant (same as
`CFA)
`ferredoxin
`Food and Drug Administration
`CUS.A.)
`.
`Food, Drug and Cosmetic (U.S.A).
`
`D.R.P.
`
`ds
`DIT
`dyn
`(£)-
`1%
`Elan
`
`Ev
`
`EAA
`EAC
`
`eidem
`EINECS
`
`EKG
`ELISA
`emf
`en
`endo-
`
`EPA
`EPO
`
`(epsilon)
`
`eq
`equilib
`equiv
`esp
`esu
`Et
`1 (eta)
`et al.
`etc.
`Eto
`BtOH
`Hur. pat. Appi.
`ev
`evac
`evapn
`exo-
`
`O-(carboxymethy]) cellulose
`cell-mediated immunity
`cell-mediated lymphocytotoxicity
`cytidine 5’-monophosphate (cytidylic
`acid)
`ceniral nervous system
`coenzyme A
`collective volume
`compound
`composition
`concanavalin A
`concentrated
`concentration
`configuration
`constituent
`continued
`containing
`coenzyme Q (ubiquinone)
`corrected
`corresponding, corresponds
`centipoise
`chemically pure
`compound
`critical pressure
`critical temperature
`crystalline, crystals
`crystallization
`colony stimulating factor; cerebral
`spinal fluid
`Cosmetic, Toiletry and Fragrance
`Assoc.
`cytidine triphosphate
`cysteine
`cytosine
`density; specific gravity (d)° specific
`gravity at 19° referred to water at
`4
`dextro(rotatory), the opposite of /
`dextro (in configurational sense
`only), the opposite of L
`daltons
`O-(diethylaminoethyl)cellulose
`decompose(s), decomposition
`decomposition
`degree
`deliquescent
`indicates the locant of the double
`bond
`derivative
`determination
`diisopropyl fluorophosphate or
`diisopropy! phosphofluoridate
`dihydroalanine
`dehydrobutyrine,
`6-methyldehydroalanine
`difference
`dilute, diluted, dilution
`distillation
`racemic
`optically inactive by external
`compensation as contrasted with
`expt(ly)
`meso-
`exi(d)
`decimeter(s)
`exter
`dimethylacetamide
`disease modifying antirheumatic drug | °F
`dimethylformamide
`F-1-P
`dimethylsulfoxide
`F-6-P
`deoxyribonucleic acid
`FA
`complementary DNA
`| FAB
`mitochondrial DNA
`FAD (FADHL)
`deoxyribonuclease
`2,4-dinitro-1-fluorobenzene
`2,4-dinitrophenyl or 2,4-
`dinitrophenol
`dihydroxyphenylalanine
`degree of polymerization (number of
`monomeric units in the polymer)
`
`
`
`FCA
`
`Pd
`PDA.
`
`FD&C
`
`xiv
`
`0004
`
`CM-cellulose
`CMI
`CML
`CMP
`
`CNS
`CoA or CoASH
`coll. vol.
`compd.
`compn
`Con A
`conc(d)
`concn
`config
`constit
`contd
`contg
`CoQ
`cor(r)
`corresp
`P,
`epd
`crit press
`crit temp
`cryst
`crystn
`CSF
`
`cC
`
`CTFA
`
`CTP
`Cys
`
`Da
`DEAE cellulose
`dec, decomp
`decompn
`deg
`deliquesc
`A (delta)
`
`deriv
`determn
`DFP, DIFP, DIPF
`
`Dha
`Dhb
`
`diff
`dil(d}, (n)
`distin
`al-
`DL-
`
`DNFB
`
`0004
`
`€
`

`

`
`
`FDNB
`FDP
`if
`PFA
`EEC
`FIA
`
`FIAT
`
`FMN (FMNH))
`
`Fmoc
`Fortschr. Chem.
`Org. Naturst.
`
`fp
`FP
`FPLC
`Fr. pat.
`Fradl.
`
`GicA
`GicN
`GicNAc
`GICUA
`Gin
`Glu
`GluA
`Gly
`Glycerol-3-P
`Gmelin’s
`
`1-flnoro-2,4-dinitrobenzene
`fructose 1,6-diphosphate
`following
`tree fatty acid
`free from chlorine
`Freund’s incomplete adjuvant (same
`as ICFA)
`Field Information Agency, Technical
`(U.S. reports)
`flavin mononucleotide (reduced
`form); same as riboflavin
`phosphate
`9-tuorenylmethoxycarbonyl
`Fortschritte der Chemie Organischer
`Naturstoffe (Progress in the
`Chemistry of Organic Natural
`Products)
`freezing point
`flavoprotein
`fast protein liquid chromatography
`French patent
`P. Friedlander Fortschritte der Teer-
`Jarbenfabrikation, a collection of
`patents
`fructose
`follicle-stimulating hormone
`Fourier transform
`gram(s)
`guanine; guanosine
`glucose 1-phosphate
`glyceraldehyde 3-phosphate
`glucose 6-phosphate
`y-aminobutyric acid
`gallon(s)
`galactose
`N-acetyl-D-galactosamine
`microgram(s)
`gas chromatography
`glutamate dehydrogenase
`guanosine diphosphate
`geminal, stereodescriptor see
`Glossary
`geological
`German patent
`growth hormone
`gastrointestinal
`grams per liter
`y-carboxyglutamic acid
`glucose
`gas-liquid chromatography
`gluconic acid
`glucosamine
`N-acety]-b-glucosamine
`glucuronic acid
`glutamine
`glutamic acid
`glucuronic acid
`glycine
`glycerol 3-phosphate
`Gmelin’s Handbuch der
`Anorganischen Chemie, a
`comprehensive German
`encyclopedia of inorganic
`chemistry
`guanosine 5’~monophosphate
`(guanylic acid)
`cyclic GMP
`granulocyte macrophage colony
`stimulating factor
`government
`glycoprotein
`growth hormonereleasing factor
`glutathione (reduced)
`glutathione (oxidized)
`guanosine triphosphate
`genitourinary
`guanine
`
`XV
`
`GVH
`habit.
`Har
`Hb
`HbCO
`
`HbO.
`HCG
`Hey
`HDL
`HeLa
`
`HGG
`HGH
`His
`HIV
`Hiv
`HLA
`HMG-CoA
`
`Houben
`
`Houben Weyl
`
`TARC
`
`IARC Monographs
`
`ibid.
`LCC,
`ICPA
`
`ICSH
`
`IDDM
`idem
`
`incl
`incompat
`INN
`
`graft-versus-host
`habitat
`homoarginine
`hemoglobin
`carbon monoxide hemoglobin;
`carboxyhemogiobin
`oxyhemogiobin
`human chorionic gonadotropin
`homocysteine
`high density lipoproteins
`cells of the first continuously
`cultured (human cervical)
`carcinoma strain
`buman gamma globulin
`human growth hormone
`histidine
`human immunodeficiency virus
`o-hydroxyisovaline
`human leukocyte antigen
`3-hydroxy-3-methylelutaryl
`coenzyme A
`a German collection of medicinal
`patents
`Houben-Weyl Methoden der
`Organischen Chemie, a German
`collection of preparative methods
`in organic chemistry
`high performance (pressure, power)
`liquid chromatography
`hour
`human serum albumin
`homoserine
`herpes simplex virus
`hydroxytryptamine (serotonin)
`human T lymphotropic virus see also
`HIV
`hydroxylysine
`hydroxyproline
`optically inactive by internal
`compensation as i-inositol!: archaic
`for meso-
`inosine
`L-region antigen
`International Association of Cancer
`Registries
`international Agency for Research on
`Cancer
`IARC Monographs on the Evaluation
`of Carcinogenic Risk of Chemicals
`to Man
`Gbidem)at the same place
`Interstate Commerce Commission
`incomplete Freund’s adjuvant (same
`as
`interstitial cell-stimulating hormone
`(same as LH)
`insulin dependent diabetes mellitis
`the same (author); plural: eidem, the
`same (authors)
`inosine diphosphate
`(id est) that is
`Isoelectric focusing
`interferon
`intragastric
`immunoglobulin
`Interessengemeinschaft der
`Farbenindustrie, Aktiengesellschaft-
`the German dye trust
`insulin-like growth factor 1
`interleukin
`isoleucine
`intramuscular
`inosine 5’-monophosphate (inosinic
`acid)
`including
`incompatibility
`International Nonproprietary Name
`
`0005
`
`

`

`microgram
`millicurie
`
`molecular rotation
`
`[alp < mol wt
`100
`
`malate Cpeenase
`methyl CH,—
`acetone
`methyl alcohol
`Mellor’s Comprehensive Treatise on
`Inorganic and Theoretical
`Chemis
`milli-equivalent (0.001 of an
`equivalent)
`methionine
`N-formylmethionine
`methemoglobin
`millielectron volts
`manufacturing
`manufacture
`milligram
`major histocompatibility complex
`miicrocurie
`microgram
`microcrystalline
`migration inhibition factor
`minimum; minute(s)
`Mullerian inhibiting substance
`miscible
`mixture
`milliliter (cubic centimeter)
`minimum lethal dose
`mixed lymphocyte reaction
`millimeter
`millimicron(s), nm
`molecular weight
`Monatshefte fiir Chemie
`milliosmolar
`melting point; melts, melting at,
`when followed by a figure
`denoting temperature
`relative molecular mass
`magnetic resonance imaging
`meso- (internally compensated)
`mass spectrometry
`melanocyte-stimulating hormone
`(melanotropin)
`index of refraction (n79 for 20° and
`sodium light); normal, as n-propyl
`normal (equivalents per liter, as
`applied to concentration); nitrogen
`(as in N-methylpyridine)
`N-acetylneuraminic acid
`nicotinamide adenine dinucleotide
`(reduced form)
`nicotinamide adenine dinucleotide
`phosphate (reduced form)
`nonaspirin nonsteroidal anti-
`inflammatory drugs
`National Bureau of Standards
`National Collection of Type Cultures
`nucleoside 5’-phosphate
`Netherlands patent application
`National Formulary
`nanogram (107? grams)
`nerve growth factor
`Non-insulin dependent diabetes
`mellitis
`National Institute for Occupational
`Safety and Health
`nanometer
`nicotinamide mononucleotide
`(reduced form)
`nucleoside 5'’-monophosphate
`nuclear magnetic resonance
`New and Nonofficial Drugs
`(Lippincott, 1959-1964)
`
`mcg
`mCi
`
`MD
`
`MDH
`Me
`Me,CO—
`MeOH
`Mellor’s
`
`mEq
`
`Met
`fMet
`MetHb
`meV
`mfg, manuf
`mfr
`mg
`MHC
`mCi
`mg
`miucrocryst
`MIF
`min
`
`MS
`MSH
`
`n N
`
`NAcneu
`NAD* (NADH)
`
`NADP* (NADPH)
`
`NANSAIDS
`
`NBS
`NCTC
`NDP
`Neth. pat. Appl.
`NF.
`ng
`NGF
`NIDDM
`
`NIOSH
`
`nm
`NMN~ (NMN#)
`
`inorganic
`insoluble
`internal
`International
`intraperitoneal
`infrared
`immune response genes
`Internal Organization for
`Standardization
`isolation
`inosine triphosphate; idiopathic
`thrombocytopenic purpura
`international unit
`International Union of Chemistry
`International Union of Pure and
`Applied Chemistry
`.
`intravenous
`Japanese patent (unexamined)
`Japanese patent
`dissociation constant; equilibrium
`constant
`degrees Kelvin
`kilobase
`kilocalories(s)
`killer cell
`kilogram(s)
`a-ketoglutarate
`keyhole limpet hemocyanin
`kidney plasminogen activator
`liter
`levo(rotatory), the opposite of d
`levo (in configurational sense only),
`the opposite of D
`lactose
`lymphocyte-activating determinant
`wavelength
`laser microprobe mass analysis
`long acting thyroid stimulator
`pound(s)
`lethal concentration; liquid
`chromatography
`median lethal concentration, the
`concn of a chemical thatis
`estimated to be fatal to 50% of the
`organisms tested
`lymphocyte choriomeningitis
`lethal dose
`median lethal dose, the quantity of a
`chemical that is estimated to be
`fatal to 50% of the organisms
`tested
`lactate dehydrogenase
`low density lipoproteins
`leucine
`luteinizing hormone (same as ICSH)
`natural logarithm
`(loco citato) in the place cited
`logarithm (common)
`limit of impurities
`lipopolysaccharide
`lysine
`meter; given after mass number
`signifies metastable isomer
`meta chemical locant for ring
`substituents
`molar (concentration)
`monoclonal antibody
`maximum allowable concentration
`macrophage activating factor
`monoamine oxidase
`monoamine oxidase inhibitor
`mass spectrometry
`maximum, maxima
`myoglobin
`oxymyoglobin
`Manufacturing Chemists Association
`(U.S.A,)
`
`
`
`.
`Eva
`
`inorg
`insol
`intern
`Intl
`ip.
`IR
`Ir genes
`ISO
`
`isoln
`TIP
`
`LU.
`LU.C.
`LU
`
`Lv.
`Japan. Kokai
`Japan. pat.
`K
`
`AD
`(lambda)
`LAMMA
`LATS
`Ib
`LC
`
`LCso
`
`Mab, mAb
`MAC
`MAP
`MAO
`MAOI
`mass spec
`max
`Mb
`MbO,
`M.C.A.
`
`0006
`
`

`

`New and Nonofficial Remedies
`alkyl, univalent hydrocarbonradical
`(Lippincott, 1933-1958)
`(or hydrogen)
`nurober
`rectus (tight), stereodescriptor see
`chemical nomenclature descriptor,
`Glossary
`see Glossary
`radioallergosorbent test
`National Research Development
`red blood cell; red blood count
`Corporation
`aliphatic acyl radical
`nonsteroidal anti-inflammatory
`recrystallize, recrystallization
`gs
`reference
`National Service Center
`“roentgen equivalent physical’
`nucleoside 5’-triphosphate; National
`means a dose of ionizing radiation
`Toxicology Program (U.S.)
`capable of producing energy
`ortho chemical locant for ring
`absorption of 93 ergs per gram of
`substituents
`tissue
`denoting attachment to oxygen, as in
`respectively
`O- acetylhydroxylamine
`(in paper chromatography) ratio of
`ovalbumin
`movement of the band to the front
`oxaloacetate
`of the solvent
`RIA
`optical density
`radioimmunoassay
`Rib
`(opere citato) in the work cited
`D-ribose
`RIST
`organic
`radioimmunosorbenttest
`RNA
`Occupational Safety and Health Act
`ribonucleic acid
`hnRNA
`osmolar
`heterogeneous nuclear RNA
`mRNA
`ounce(s)
`messenger RNA
`concentration by weight (after optical|nRNA
`nuclear RNA
`rotations only)
`rRNA
`ribosomal RNA
`page(s)
`snRNA
`small nuclear RNA
`para chemical locantfor ring
`tRNA
`transfer (soluble) RNA
`substituents
`RNase
`ribonuclease
`inorganic phosphate
`RTECS
`Registry of Toxic Effects of Chemical
`pascal
`Substances
`p-aminobenzoic acid
`symmetrical
`platelet-activating factor
`denoting attachmentto sulfur as in
`polyacrylamide gel electrophoresis
`S-methyicysteine
`here and there, scattered
`sinister (left), stereodescriptor see
`patent
`Glossary
`Publication Board Report (United
`Society of Automotive Engineers
`States Department of Commerce,
`S-adenosylmethionine
`Scientific and Industrial Reports)
`saponification
`passive cutaneous anaphylaxis
`sarcosine
`Patent Co-operation Treaty
`saturated
`phosphoenolpyruvate
`subcutaneous
`positron emission tomography
`sodium dodecyl sulfate
`petroleum
`second(s)
`plaque-formingcell
`secondary
`3-phosphoglycerate
`separation
`prostaglandin
`serine
`pteroylglutamic acid (folic acid)
`International System of Units
`3-phosphoglyceroy! phosphate
`systemic lupus erythematosus
`acid-base scale; log of reciprocal of
`serotonin-noradrenaline reuptake
`hydrogen ion concentration
`inhibitor
`phytohemagglutin
`soluble; solubility
`phenylalanine
`solidifies, solidification
`physiological
`solution
`log of the reciprocal of the
`species; specific
`dissociation constant, iAog K
`spectroscopy
`phenylketonuria
`single photon emission computed
`polymorphonuclear leukocyte
`tomography
`inorganic pyrophosphate
`specific gravity
`parts per million
`species (plural)
`precipitate, precipitating
`square
`precipitated
`(sequentia) and following
`plastoquinone
`sheep red blood cells
`propyl (normal)
`slow reacting substance of
`prepared
`anaphylaxis
`preparation
`single stranded
`pressure
`subacute sclerosing panencephalitis
`proline
`selective serotonin reuptake inhibitor
`5-phosphoribosyl 1-pyrophosphate
`standard temperature and pressure
`pseudo
`sublimes
`point
`supplement
`parathyroid hormone
`symmetrical
`coenzyme Q (ubiquinone)
`stereochemical descriptor see
`(quae vide) whichsee, plural
`Glossary
`(quod vide) which see
`thymine; thymidine
`““roentgen’’ unit of radiation
`half-life
`racemic
`tablet(s)
`
`R
`
`(R)-
`
`RAST
`rbc
`RCO-
`reeryst(n)
`re
`rep [REP]
`
`resp
`R; or Re
`
`S-
`S
`
`(S)-
`
`S.A.E.
`SAM
`sapon(if)
`Sar
`satd
`i S.C.
`SDS
`sec
`SEC-
`sepn
`Ser
`SI
`SLE
`SNRI
`
`
`
`NNR.
`
`no.
`nor-
`
`NRDC
`
`NSAID(s)
`
`NsC
`NTP
`
`O-
`
`PAGE
`passim
`pat.
`PB report
`
`PCA
`PCT
`PEP
`PET
`petr, petrol
`PFC
`3PG
`PG
`PGA
`PGP
`pH
`
`PHA
`Phe
`physiol
`pK
`
`PKU
`PMN
`PPj
`ppm
`
`pee)
`PQ
`
`Pr
`Prepd
`Prepn
`press.
`Pry
`
`sol; soly
`solidif
`soln
`sp.
`spec
`SPECT
`
`sp gr
`Spp.
`sq
`Sqq
`SRBC
`SRS-A
`
`SS
`SSPE
`SSRI
`S.T.P.
`subl
`suppl
`sym-
`syn-
`T
`tie
`tabl
`
`xvii
`
`0007
`
`0007
`
`

`

`tuberculosis
`trichloroacetic acid; tricarboxylic
`acid
`thymus derivedcell
`thoracic duct lymphocyte
`thymidine diphosphate
`O-(triethylaminoethyl)-cellulose
`technical
`temperature
`tertiary
`thyrotropic hormone
`tetrahydrofuran
`tetrahydrofolic acid
`threonine
`thymine
`thin-layer chromatography
`thymidine 5’-monophosphate
`tobacco mosaic virus
`tumor necrosis factor
`trinitrophenyl
`tissue plasminogen activator
`thiamine pyrophosphate
`stereodescriptor see Glossary
`tris(hydroxymethylaminomethane;
`2-amino-2-hydroxymethylpropane-
`1,3-diol
`tryptophan
`thyroid-stimulating hormone
`tumor-specific transplantation
`antigens
`thymidine triphosphate
`tyrosine
`uracil or uridine
`uridine diphosphate
`uridine diphosphogalactose
`uridine disphosphoglucose
`United Kingdom
`uridine 5’-monophosphate (uridylic
`acid)
`uncorrected
`unsymmetrical, asymmetrical
`uracil
`United States Atomic Energy
`Commission
`United States Adopted Names
`
`
`
`
`
`U.S_D.
`ULS.D.A.
`
`USP.
`U.S.pat.
`UTP
`uv
`v
`v-
`Val
`var
`viz.
`VLDL
`vol
`vs
`viv
`
`wbe
`WHO
`wks
`wt
`wiv
`
`whw
`
`AMP
`yr(s)
`Z
`(Z)-
`
`Z. Physiol.
`
`~
`=
`>
`<
`
`United States Dispensatory
`United States Department of
`Agriculture
`United States Pharmacopeia
`United States patent
`uridine triphosphate
`ultraviolet
`volt(s)
`vicinal (adjacent)
`valine
`varie
`(videlicet) that is to say; namely
`very low density lipoproteins
`volume
`versus
`percent “‘volume in volume’’
`expresses the numberof milliliters
`of an active constituent in 100
`milliliters of solution
`white blood cell; white blood count
`World Health Organization
`weeks
`weight
`percent “‘weight in volume’’
`expresses the number of grams of
`an active constituent in 100
`milliliters of solution, and is used
`regardless of whether water or
`another liquid is the solvent
`percent “‘weight in weight”’
`expresses the number of grams of
`an active constituent in 100 grams
`of solution or mixture
`xanthosine monophosphate
`year(s)
`carbobenzoxy
`zusammen stereodescriptor see
`Glossary
`Hoppe-Seyler’s Zeitschriftfiir
`Physiologische Chemie
`approximately
`approximately equal
`greater than
`less than
`
`xvii
`
`TEAE cellulose
`tech
`temp
`tert-
`TH
`THF
`THFA
`Thr
`Thy
`TLC
`TMP
`TMV
`TNE
`TNP
`TPA
`TPP, Tapp
`trans-
`Tris
`
`Trp
`TSH
`TSTA
`
`TIP, dTTP
`Tyr
`
`UU
`
`DP
`UDP-gal
`UDP-gic
`ULK.
`UMP
`
`uncor(r)
`uUNS-, USYM-
`ra
`US.AEC.
`
`USAN
`
`0008
`
`

`

`
`>
`2386. Citrazinic Acid. 1,2-Dihydro-6-hydroxy-2
`
`pyridinecarboxylic acid; 2,6-dihydroxyisonicotinic acig. Ong.
`dihydroxy-4-pyridinecarboxylic acid. CgH,;NO,; mo,
`155.11. C 46.46%, H 3.25%, N 9.03%, O 41.26%,
`I
`cy.
`
`from citric acid with aq NH, at 140-160° under p,,.*8
`Bavley, Hamilton, U.S. pat. 2,729,647 (1956 to Pfizer) *U
`tification: Bavley et al, U.S. pat. 2,738,352 (1956 to Paia)
`N.
`OH
`oe
`HO.
`
`ao
`
`Wi
`
`|
`
`SS
`
`COOH
`
`Citramalic Acid
`
`"2384
`
`Separation of isomers: Naves, Bull. Soc. Chim.
`neral.
`France 1952, 521. Comprehensive reviews: J. L. Simonsen,
`The Terpenes, vol, I, 83-100 (1947); E. Guenther, The Essen-
`tial Oils, vol. II, 326-336 (1949); Gildemeister-Hoffmann,
`Die Aetherischen Oele, vol. 1V, 307-356 (4th ed., 1956).
`
`HO
`
`CH,
`
`|
`
`a
`
`|
`
`CH,
`
`H,C
`
`CHs
`
`H,C7
`
`~CHs
`
`Geranial(Citral a)
`
`Neral (Citral b)
`
`Geranial, light oily liquid. Strong lemon odor. bp,, 92-
`93°.
`dZ® 0.8888.
`n?#? 1.48982. Practically insol in water.
`Miscible with alc, ether, benzyl benzoate, diethyl phthalate,
`glycerol, propylene glycol, mineral oil, essential oils.
`Neral, light oily liquid. Lemon odor not as intense but
`sweeter than gerianal. bp,,¢ 91-92°. d} 0.8869. n2 1.48690,
`Solubilities same as gerianal.
`USE:
`In the synthesis of vitamin A, ionone and methyl-
`ionone. As a flavor, for fortifying lemon oil.
`In perfumery
`for its citrus effect in lemon and verbena scents, in cologne
`odors, in perfumes for colored soaps. Not stable to alkalies
`and strong acids. Will cause discoloration of white soaps
`and alkaline cosmetics.
`
`
`
`2384, Citramalic Acid. 2-Hydroxy-2-methylbutanedioic
`acid; 2-methylmalic acid; 2-hydroxy-2-methylsuccinic acid;
`a-hydroxypyrotartaric acid. C,;H,O,;; mol wt 148.12. C
`40.55%, H 5.44%, O 54.01%. Enzymatic synthesis: Barker,
`Blair, Biochem. Prepns. 9, 21 (1962). Chemical synthesis:
`Barker, ibid. 25; J. B. Wilkes, R. G. Wall, J. Org. Chem. 45,
`247 (1980). Stereoselective synthesis: E. G. J. Staring et al,
`Rec. Trav. Chim. 105, 374 (1986).
`HO CH,
`
`Yellowish powder with a greenish tinge; carbonizes ab. mee
`300° without melting. Ultrapure material which is White.if
`_ colorless, has been prepared. Almost insol in water; gj,
`sol in hot HCl; sol in alkali hydroxide or carbonate Sity,
`Alkaline solns turn blue on standing.
`MS.
`
`2387. Citric Acid.
`2-Hydroxy-1,2,3-propanetricarh,. :
`ylic acid; 8-hydroxytricarballylic acid. C,H,O,; Moly :
`192.13. C 37.51%, H 4.20%, O 58.29%. Widely distribu!
`in plants and in animal tissues and fluids. Produced fu
`mycological fermentation on an industrial scale using crud,
`sugar solns, such as molasses and strains of Aspergil};
`niger: See review by Von Loesecke, Chem. & Eng. News 45
`1952 (1945); Schweiger, U.S. pat. 2,970,084 (1961.to Mi
`Labs.); Faith, Keyes & Clark’s Industrial Chemicals, R”
`Lowenheim, M. K. Moran, Eds. (Wiley-Interscience, Ne
`
`York, 4th ed., 1975) pp 275-279. Also extracted from cits
`fruits (lemon juice contains 5 to 8%) and from pinea
`
`waste. Reviews: Wilson, Chem. & Met. Eng. 29, 787.(1923).
`
`Browne, Ind. Eng. Chem. 13, 81 (1921); Warneford, Hardy,
`ibid. 47, 1283 (1925); E. F. Bouchard, E. G. Merritt ig
`Kirk-Otbmer Encyclopedia of Chemical Technology yol:/6
`(Wiley-Interscience, New York, 3rd ed., 1979) pp 150-179.
`
`Toxicity: Gruber, Halbeisen, J. Pharmacol. Exp. Ther.. 9
`65 (1948).
`S
`
`
`
`
`
`
`
`
`
`COOH
`
`HO—C—COOH
`
`COOH
`
`HOOC
`
`COOH
`
`[a]? —23.4° (c = 3 in
`
`[o]#? +23.6° (¢ = 3 in
`
`dl-Form, deliquescent monoclinic prisms from ethyl ace-
`tate + petr ether, mp 117°. Sublimes. Freely sol in water,
`acetone. Sol in ethyl acetate, ether. Practically insol in petr
`ether, benzene.
`d-Form, crystals, mp 112.2-112.8°.
`H,0).
`i-Form, crystals, mp 112-113°.
`H,O)
`3-Hydroxy-8’-apo-8,/-carotenal;
`2385, £$-Citraurin.
`citraurin. C3g3HyO, mol wt 432.65. C 83.29%, H 9.32%, O
`7.40%. Carotenoid pigment found only in orange peel.
`Isoln by chromatography: Zechmeister, Tuzson, Ber. 69,
`1878 (1936); 70, 1966 (1937). The peels from 100 kilos of
`oranges yield about 35 mg. Structure: Zechmeister, Tuz-
`son,
`loc. cit.; Karrer, Solmssen, Helv. Chim. Acta 20, 682
`(1937); Karrer et al.,
`ibid. 1020; Zechmeister, v. Cholnoky,
`Ann. 530, 291 (1937); Karrer et al, Helv. Chim. Acta 21, 445
`(1938). Abs config: Bartlett et al, J. Chem. Soc. (C) 1969,
`2527. Synthesis: H. Pfander et al, Helv. Chim. Acta 63,
`1377 (1980).
`
`
`
`Thin orange or yellow-colored plates from benzene + petr
`ether, mp 147°. Absorption max (benzene): 497, 467 nm.
`Freely sol in acetone, ethanol, ether, benzene, and carbon
`disulfide. Sparingly sol in petr ether.
`.
`
`|
`
`Anhydr form, mp 153°. Crystais are monoclinic. holo:
`hedra and crystallize from hot coned aq soln. d 1.665.-"At..
`25°, pK, 3.128 pK, 4.761; pK, 6.396, Bates, Pinching,.J.
`
`Am. Chem. Soc. 71, 1274 (1949). Soly in water: 54.0% w/w.
`
`at 10°; 59.2% at 20°; 64.3% at 30°; 68.6% at 40°; 70.9% at 50%.
`73.5% at 60°; 76.2% at 70°; 78.8% at 80°; 81.4% at 90°; 84.0%:
`at 100°.
`oes
`Monohydrate, orthorhombic crystals from cold aq solns.:
`Pleasant, sour taste. d 1.542. Monohydrate crystals lose
`water of crystn in dry air or when heated at about 40 to'50',.
`slightly deliquescent in moist air.
`Softens at 75°. MP.
`~100°. pH of 0.1N soln = 2.2. Densities of aqueous soll”
`(15°/159):
`10% = 1.0392; 20% = 1.0805; 30% = 1.1244
`40% = 1.1709; 50% = 1.2204; 60% = 1.2738. Soly.B
`g/100 g satd soln:
`ether 2.17; chloroform 0.007; amyl:
`alcohol 15.43; amyl acetate 5.98; ethyl acetate 5.28. Soly at.
`19° in g/100 g solvent: methanol 197; propanol 62.8: LDs..
`ip. in rats: 975 mg/kg (Gruber, Halbeisen).
`.
`Pharmaceutical Incompatibilities: Potassium tartrate; al-
`kali and alkaline earth carbonates and bicarbonates, 2¢¢
`tates, sulfides. Dilute aq solns may ferment on standing-
`Barium salt heptahydrate, C,,H,)Ba,0,,.7H,O, barium
`citrate. Powder. Loses all H,O at 150°. Sol in 1750 paris
`water; freely sol in dil HCl or HNOpractically insol 3°
`alcohol.
`oe
`Ethyl ester, C,,H,9O,, ethyl citrate, triethyl citrate. Bitte}
`oily lig. d?° 1.137.
`bpygq 294°; bp) 127°. Viscosity at 25:
`35.2 cps. Pour pt ~10°. 20 1.4455. Soly: water ~6.9%;
`peanut oil 0.8%. Misc with alc, ether.
`t
`USE: Acidulant in beverages, confectionery, effervesc®™
`salts, in pharmaceutical syrups, elixirs, in effervescent pOW*
`ders and tablets, to adjust the pH of foods and as synet
`
`Page 392
`
`Consult the Name Index before using this section.
`
`0009
`
`

`

`
`
`B-Citronellol
`
`2391
`
`HO.
`
`HO’
`
`HOOG
`
`oO
`
`fe)
`
`A
`(OL ee
`
`CH,
`
`Dibydrate, yellow crystals, effervescence at 155°, dec 290-
`300° (considerable antecedent blackening).
`Freely sol
`in
`ethanol; readily sol in aq sodium carbonate soln; sparingly
`sol in water, chloroform.
`Insol in benzene, hexane. Stable
`to acid and alkali at 100°.
`
`3,7-Dimethyl-6-octenal. C4)H,,0;
`2390. Citronellal.
`mol wt 154.25. C 77.87%, H 11.76%, O 10.37%. Chief
`constituent of citronella oil; also found in many other vola-
`tile oils, such as lemon, lemon grass, melissa: Tiemann, Ber.
`32, 834 (1899); Spoon, Chem. Weekbl. 54, 236 (1958).
`Structure: Naves, Bull. Soc. Chim. France 1951, 505;
`Eschinazi, J. Org. Chem. 26, 3072 (1961).
`CH,
`
`Hes,
`
`HC
`
`CHg
`
`“etic antioxidant, in processing cheese. Used in beverages,
`gist 5, jams, preserves and candy to provide tartness. In the
`jellies of alkyd resins; in esterified form as plasticizer, foam
`m ‘pitor.
`In the manufofcitric acid salts. As sequestering
`jolt
`to remove trace metals. As mordant to brighten
`agen 5; in electroplating; in special inks; in analytical chem-
`color for determining citrate-soluble P,O,; as reagent for
`isttY 4, mucin, glucose, bile pigments.
`aDAP caT: Component of anticoagulant citrate solns
`Gijrate dextrose soln; citrate phosphate dextrose soln; citric
`acid syTUP)-
`388. Citrinin.
`(3R-trans)-4,6-Dihydro-8-hydroxy-3,4,5-
`. ethyl-6-0x0-3H-2-benzopyran-7-carboxylic acid; Antimy-
`trim C4gH4Os. mol wt 250.25. C 62.39%, H 5.64%, O
`cin 7%. Antibiotic substance produced by a white spore
`31. sgillus which has been placed under the species name
`aseillus niveus (Thorn and Raper). Also produced in
`ASP!at quantities by Penicillium citrinum: Hetherington,
`smmtcick, Trans. Roy. Soc. London B220, 269 (1931); Rais-
`Rav smith, Chem. & Ind (London) 60, 828 (1941); Timo-
`tric ence 96, 494 (1942); Timonin, Rovatt, Can. J. Pub.
`ealth 35, 80 (1944).
`Identity with antimycin: Haese,
`eh Pharm. 296, 227 (1963). Structure: Brown et al, J.
`nem. Soc. 1949, 867; Warren et al, J. Am. Chem. Soc. 79,
`3812 (1957); Kovac et al, Nature 190, 1104 (1961). Synthe-
`is: Cartwright et al, J. Chem. Soc. 1949, 1563; J. A. Bar-
`per et al, J. Chem. Soc. Perkin Trans. I 1986, 2101. Stereo-
`chemistry: Cram, J. Am. Chem. Soc. 72, 1001 (1950); Meh-
`ta, Whalley, J. Chem. Soc. 1963, 3777; Mathieson, Whalley,
`ibid: 4964, 4640. Physical characteristics and toxicity:
`Nagai et al, Chem. Zentr. 1958, 8088, C.A. 55, 1914 (1961.
`‘Crystal and molecular structure: Rodig, Chem. Commun.
`4971, 1553. Biosynthesis:
`J. Barber et al, J. Chem. Soc.
`‘perkin Trans. I 1981, 2577; L. Colombo etal., ibid: 2594.
`Physicochemical data: A. E. Pohland et al, Pure Appl.
`“Chem. 54, 2219 (1982). Toxicology: A. M. Ambrose, F. De
`Eds, J. Pharmacol. Exp. Ther. 88, 173 (1946). Review: Saito
`“et al, “Yellowed Rice Toxins” in Microbial Toxins, A. Cieg-
`Jer, S. Kadis, A. Ajl, Eds. (Academic Press, New York,
`“4971 vol. VI, pp 357-367.
`
`:
`
`HOOC.
`
`°
`
`OH
`
`Oo
`
`™y9
`
`“CH
`
`CH,
`
`CH,
`
`
`
`d 0.848-
`[ol +11.50°.
`n® 1.4460.
`bp, 47.
`Liquid.
`0.856. Soluble in alcohols; very slightly sol in water.
`a-citronellal, 3,7-Dimethyl-7-octenal, rhodinal. Liquid.
`bp,, 51°.
`12? 1.4410.
`[a]? +9.75°.
`UsE:
`In soap perfumes; insect repellent.
`2391, $-Citronellol. 3,7-Dimethyl-6-octen-1-ol; 2,6-di-
`methyl-2-octen-8-ol; citronellol; cephrol. C,gH0; mol wt
`156.27. C 76.86%, H 12.90%, O 10.24%.
`I-Form is a con-
`stituent of rose and geranium oils. d-Form occurs in Ceylon
`and Java citronella oils. History:
`J. L. Simonsen, L. N.
`Owen, The Terpenes vol. I (University Press, Cambridge,
`2nd ed, 1947). Prepn of (+)-form: Adams, Garvey, J. Am.
`Chem. Soc. 48, 477 (1926); Ofner et al, Helv. Chim. Acta 42,
`2577 (1959). Prepn of (+)-form: Rienicker, Ohloff, Angew.
`Chem. 73, 240 (1961); Naves, Tullen, Hely. Chim. Acta 44,
`1867 (1961); Eschinazi, J. Org. Chem. 26, 3072 (1961); Rie-
`nicker, Chimia 27, 97 (1973); C. G. Overberger, J. L. Weise,
`J. Am. Chem. Soc. 90, 3525 (1968); T. Sato et al, Tetrahe-
`dron Letters 1980, 3377. Prepn-of (—)-form: Ohloff,
`loc.
`cit.; Rienacker,
`loc. cit.; Shono et al, Tetrahedron Letters
`1974, 1295; K. Mori, T. Sugai, Synthesis 1982, 752. Syn-
`thesis of (+) or (—)-form from isoprene: Hidai et al, Chem.
`Commun. 1975, 170. Stereospecific prepn via microbiologi-
`cal (Saccharomyces cerevisiae) reduction: P. Gramatica et
`al., Experientia 38, 775 (1982). Manuf: Worochet al; Bain;
`Webb, U.S. pats, 2,990,422; 3,005,845; 3,028,431 (1961,
`1961, 1962, all to Glidden); Eschinasi, U.S. pat. 3,052,730
`(1962 to Givaudan). Abs config of the (+)-form: Freuden-
`berg, Hohmann, Ann. 584, 54 (1953); Freudenberg, Lwow-
`ski, ibid. 587, 213 (1954). NMR, HPLC determn of R/S
`Gone ratios: D. Valentine et al, J. Org. Chem. 41, 62
`1976).
`HCH,
`
`
`
`fal}
`Lemon-yellow needles from alcohol, dec 175°.
`—37.4(c = 1.15 in alc.). uv max: 250, 331 nm (E}%, 370,
`418). Strong acid. Practically insol in water. Sol in alco-
`hol, dioxane, dilute alkali. Solns change color with changes
`im pH, from lemon-yellow at pH 4.6 to cherry-red. at pH
`2.9. Poisonous! LDgy in mice, rats (mg/kg):
`35, 67 ip.
`(Ambrose, De Eds).
`Methyl citrinin, C,,H,,O5, plates from benzene, d