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

`

`MERCK & (30., INC.
`Whitehouse Station, N.J .
`U. S .A.
`
`lst 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—4 989
`
`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
`
`

`

`Abbreviations and Selected Definitions
`Please consult the Glossary (Misc. Tables Section)for additional definitions.
`adenine; adenosine; absorbance ~
`A.S.T.M.
`(extinction)
`Angstrom units
`al—antitrypsin
`antibody -
`absolute; absorption
`absolute configuration
`abstract
`or—aminobutyric acid
`acetyl CH3CO—
`according
`angiotensin converting enzyme
`acetyl coenzyme A
`acetic anhydride
`ethyl acetate
`acetic acid
`acyl carrier protein
`American Chemical Society
`adrenocorticotropic hormone
`acyl coenzyme A
`antibody—dependent cellular
`cytotoxicity
`adding, addition
`adenine
`
`alcohol dehydrogenase
`adenosine diphosphate
`(United States) Atomic Energy
`Commission
`antigen, silver
`anaphylotoxin inhibitor
`acquired immunodeficiency
`syndrome
`alanine
`alcohol(ic); ethanol; ethyl alcohol
`antialymphocyte globulin
`alkali(ne)
`specific optical rotation at 25° C for
`D (sodium) line; absence of
`brackets indicates optical rotation
`of a liquid in a l decimeter cell,
`neat
`
`anti—lymphocyte serum, amyotrophic
`lateral sclerosis
`molar absorptivity (concn in
`g—moles/l)
`amorphous
`adenosine 5 ’—monophosphate
`(adenylic acid)
`cyclic AMP
`ampules
`amount(s)
`anti—nuclear factor; atrial natriuretic
`factor
`anhydrous
`stereodescriptor, see Glossary
`Justus Liebig’s Annalen der Chemie
`American Pharmaceutical
`Association
`approximate(ly)
`alum precipitated toxoid
`aqueous
`aryl
`analytical reagent
`AIDS related complex
`Naunyn Schmiedebergs Archivfifiir
`Experimentelle Pathologie und
`Pharmakologie
`aromatic acyl radical
`arginine
`B-carboxyaspartic acid
`asparagine
`aspartic acid
`association; associated
`
`xiii
`
`0003
`
`RP.
`B. P. C.
`Brit. pat.
`BRM
`BSA
`Btu
`Bu
`Bz
`BzH
`132018
`
`c C °
`
`C
`
`CPca.
`CA.
`cal
`calc(d)
`Can. pat
`Cbz
`cbc
`CC
`CCK
`CD
`CDP
`CEA
`cf-
`CPA
`
`CFT
`CHD
`CHF
`chem
`Chem. Commun.
`
`Ci
`Cl.
`cis-
`cm
`
`aS—, asym—
`at.
`ATCC
`atm, atmos
`at. no.
`ATP
`ATPase
`at. Wt.
`BAN
`B cell
`
`BCG
`Be
`Beilstez'n
`
`Belg. pat.
`Ber.
`
`BGG
`biol
`B.I.O.S.
`
`BOC
`B.O.D.
`boil.
`bp
`
`
`
`American Society for Testing
`Materials
`asymmetrical, unsymmetrical
`atomic
`
`American Type Culture Collection
`atmosphere(s), atmospheric
`atomic number
`adenosine triphosphate
`adenosine triphosphatase
`atomic weight
`British Approved Name
`bone marrow or bursa of Fabricius
`derived cell
`Bacillus Calmette-Guerin
`Baumé (a specific gravity scale)
`Beilstein ’s Handbuch der
`Organischen Chemie
`Belgian patent
`Chemische Berichre (Berichte der
`Deutschen Chemischen
`Gesellschaft)
`bovine gamma globulin
`biological
`British Intelligence Objectives
`Subcommittee
`tent—butoxycarbonyl
`biochemical oxygen demand
`boiling
`basepair; boiling point; boils at;
`boiling at Example: bp70 48°
`means boils at 48°C if the pressure
`is 70 mm Hg
`British Pharmacopez'a
`British Pharmaceutical Codex
`British patent
`biological response modifier
`bovine serum albumin
`British thermal units
`butyl
`benzoyl CGHSCO—
`benzaldehyde
`benzoic acid
`concentration by volume (g/l 00ml)
`after optical rotations only
`cytosine; cytidine; complement
`Centigrade degrees; Celsius
`degrees
`heat capacity (constant pressure)
`(circa) about
`Chemical Abstracts
`calorie(s)
`calculate, calculated
`Canadian patent
`carbobenzoxy
`complete blood count
`cubic centimeter(s) (milliliter)
`cholecystokinin
`circular dichroism
`cytidine diphosphate
`carcinoembryonic antigen
`(confer) compare
`complete Freund’s adjuvant (same as
`FCA)
`complement fixation test
`coronary heart disease
`congestive heart failure
`chemical
`Journal of the Chemical Society,
`Chemical Commu ications.
`curie
`
`Colour Index (British)
`stereodescriptor, see Glossary
`centimeter(s)
`
`A A A
`
`AT
`Ab
`abs
`
`abs config
`abstr
`Abu
`Ac
`acc
`ACE
`Acetyl CoA
`AczO
`AcOEt
`AcOH
`ACP
`A.C.S.
`ACTH
`AcylSCoA
`ADCC
`
`add(n)
`Ade
`ADI-l
`ADP
`ABC
`
`Ag
`AI
`AIDS
`
`Ala
`alc, alcoh
`ALG
`alk
`[0:]?
`
`ALS
`
`0M
`
`amorph
`AMP
`
`cAMP
`amps
`amt(s)
`
`anhydr
`anti
`Ann.
`APhA
`
`approx
`APT
`aq
`Ar
`A.R.
`ARC
`Archiv Exp.
`Pathol. _
`Pharmakol.
`
`Asp
`assoc(d)
`
`0003
`
`

`

`CM—cellulose
`CMl
`CML
`CMP
`
`CNS
`CoA or CoASH
`coll. vol.
`compd
`compn
`Con A
`conc(d)
`concn
`
`config
`constit
`contd
`contg
`CoQ
`cor(r)
`corresp
`CP
`(1P,
`cpd
`crit press
`crit temp
`cryst
`crystn
`CSF
`
`CTFA
`
`CTP
`Cy
`Cyt
`
`Da
`DEAE cellulose
`dec, decomp
`decompn
`deg
`deliquesc
`A (delta)
`
`deriv
`determn
`DFP, DEF, DEEP
`
`Dha
`Dhb
`
`diff
`dil(d>7 (n)
`distln
`dl—
`DL-
`
`dm
`DMA
`DMARD
`DM‘E
`DMSO
`DNA
`cDNA
`mtDNA
`DNAase
`DNEB
`DNP
`
`, P
`up, DP
`
`0-(carboxymethyl) cellulose
`cell—mediated immunity
`cell—mediated lymphocytotoxicity
`cytidine 5’—monophosphate (cytidylic
`acid)
`central 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 (dl9 specific
`gravity at 19° referred to water at
`4°)
`dextr0(rotatory), the opposite of l
`dextro (in confi'gurational 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
`diisopropyl phosphofluoridate
`dihydroalanine
`dehydrobutyrine,
`B-methyldehydroalanine
`difference
`dilute, diluted, dilution
`distillation
`racemic
`optically inactive by external
`compensation as contrasted with
`meso—
`
`D.R.P.
`
`ds
`DTT
`dyn
`(E)-
`1%
`Elem
`
`EAA
`EAC
`
`EAE
`
`EC
`ECF—A
`
`ECG
`EC. No.
`ed.
`ED
`Ed(s).
`EDTA
`EEG
`e.g.
`EGF
`eidem
`ElNECS
`
`EKG
`ELISA
`emf
`en
`endo-
`
`EPA
`EPO
`
`a (epsilon)
`
`5%
`equilib
`equiv
`esp
`esu
`Et
`a (eta)
`er al.
`etc.
`EtzO
`EtOl—l
`
`Eur. pat. Appl.
`ev
`evac
`
`evapn
`exo-
`
`]
`
`I
`
`expt(ly)
`extra)
`extern
`°F
`F— l —P
`E—o-P
`FA
`=FAB
`
`
`
`decimeter(s)
`dimethylacetamide
`disease modifying antirheumatic drug I
`dimethylformamide
`dimethylsulfoxide
`deoxyribonucleic acid
`complementary DNA
`mitochondrial DNA
`deoxyribonuclease
`2,4-dinitro—l—fiuorobenzene
`2,4—dinitrophenyl or 2,4—
`dinitrophenol
`dihydroxyphenylalanine
`degree of polymerization (number of
`monomeric units in the polymer)
`
`I
`
`XlV
`
`0004
`
`FAD (FADHZ)
`
`rCA
`
`Pd
`EDA.
`
`FD&C
`
`(Deutsches ReichS—Patentheman
`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/l); dielectric constant
`equation
`equilibrium
`equivalent
`especially
`electrostatic units of electrical charge
`ethyl (321—13—
`viscosity
`(et alii) and others
`et cetera
`ether
`ethyl alcohol
`European patent application
`electron volt
`evacuated
`evaporation
`stereochemical descriptor, see
`Glossary
`experimentalfly)
`extract, extracted
`externally
`Fahrenheit degrees: also Fourneau
`fructose l-phosphate
`fructose 6—phosphate
`fatty acid
`fast atom bombardment
`fiavin adenine dinucleotide (reduced
`form)
`Freund’s complete adjuvant (same as
`CPA)
`ferredoxin
`Food and Drug Administration
`(U.S.A.)
`.
`Food, Drug and Cosmetic (USA).
`
`0004
`
`

`

`GVH
`habit.
`Har
`Hb
`HbCO
`
`Hb02
`HCG
`Hey
`HDL
`HeLa
`
`HGG
`HGH
`His
`HIV
`Hiv
`HLA
`l-lMG—CoA
`
`Houben
`
`Houben Weyl
`
`HPLC
`
`hr
`HSA
`Hse
`HSV
`HT
`‘ HTLV
`
`IARC
`
`ZARC Monographs
`
`ibid.
`l.C.C.
`ICFA
`
`lCSH
`
`EDDM
`idem
`
`
`
`FDNB
`FD
`ff
`FFA
`PFC
`FIA
`
`FIAT
`
`FMN (PNINHZ)
`
`Fmoc
`Forrschr. Chem.
`Org. Natursz‘.
`
`fp
`FP
`PPLC
`Fr. pat.
`Frdl.
`
`l—fluoro—2,4—dinitrobenzene
`fructose l,6-diphosphate
`following
`free fatty acid
`free from chlorine
`Freund’s incomplete adjuvant (same
`as ICFA)
`Field Information Agency, Technical
`(U.S. reports)
`fiavin mononucleotide (reduced
`form); same as riboflavin
`phosphate
`9-fluorenylmethoxycarbonyl
`Forfschrine der Chemie Organischer
`Natursrofi‘e (Progress in the
`Chemistry of Organic Natural
`Products)
`freezing point
`flavoprotein
`fast protein liquid chromatography
`French patent
`P. Fn’edlander Fortschrizre der Teer—
`farbenfabrikarion, a collection of
`patents
`fructose
`
`GLC
`Gch
`GlcN
`GlcNAc
`GlcUA
`Gin
`Gin
`GluA
`Gly
`Glycerol—34D
`Gmelz’n ’s
`
`follicle—stimulating hormone
`Fourier transform
`gram(s)
`guanine; guanosine
`glucose l—phosphate
`glyceraldehyde 3—phosphate
`glucose 6—phosphate
`y—aminobutyric acid
`gallon(s)
`galactose
`N-acetyl—D—galactosarmne
`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—acetyl—D-glucosamine
`glucuronic acid
`glutamine
`glutamic acid
`glucuronic acid
`glycine
`glycerol 3—phosphate
`Gmelin’s Handbuch der
`Anorganischen Chemic, a
`comprehensive German
`encyclopedia of inorganic
`chemisny
`guanosine 5 ’~monophosphate
`(guanylic acid)
`cyclic GMP
`granulocyte macrophage colony
`stimulating factor
`government
`glycoprotein
`growth hormone releasing factor
`glutathione (reduced)
`glutathione (oxidized)
`guanosine triphosphate
`genitourinary
`guanine
`
`0005
`
`incl
`incompat
`.INN
`
`XV
`
`graft—versus—host
`habitat
`homoarginine
`hemoglobin
`carbon monom'de hemoglobin;
`carboxyhemoglobin
`oxyhemoglobin
`human chorionic gonadotropin
`homocysteine
`high density lipoproteins
`cells of the first continuously
`cultured (human cervical)
`carcinoma strain
`human gamma globulin
`human growth hormone
`histidine
`
`human immunodeficiency virus
`a—hydroxyisovahne
`human leukocyte antigen
`3—hydroxy-3—methylglutaryl
`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
`I'ARC Monographs on the Evaluation
`of Carcinogenic Risk of Chemicals
`to Man
`
`(i’oidem) at the same place
`Interstate Commerce Commission
`incomplete Freund’s adjuvant (same
`as PIA)
`interstitial cell—stimulating hormone
`(same as Ll—l)
`insulin dependent diabetes mellitis
`the same (author); plural: eidem, the
`same (authors)
`inosine diphosphate
`(id est) that is
`lsoelecnic focusing
`interferon
`intragastric
`immunoglobulin
`Interessengemeinschafz der
`Forbenz’ndusm'e, Akfiengesellschqfi~
`the German dye trust
`insulin—like growth factor 1
`interleukin
`isoleucine
`intramuscular
`inosine 5’—monophosphate (inosinic
`acid)
`including
`incompatibility
`International Nonproprietary Name
`
`0005
`
`

`

`mcg
`mCi
`
`MD
`
`MDH
`Me
`MeZCO—
`MeOH
`Mellor’s
`
`mEq
`
`Met
`fMet
`MetHb
`meV
`mfg, manur"
`mfr
`mg
`MHC
`mCi
`mg
`microcryst
`MEmm
`MIS
`misc
`mixt
`ml
`NILD
`MLR
`mm
`
`mpu
`mol wt
`Monatsh.
`mOsrn
`mp
`
`Mr
`NIRi
`ms-
`MS
`MSH
`
`7L
`
`N
`
`NAcneu
`NAD+ (NADI-I)
`
`NADP+ (NADPl-l)
`
`NANSAIDS
`
`NBS
`NCTC
`NDP
`Neth. pat. Appl.
`NF.
`Hg
`NGF
`NioDM
`
`MOSH
`
`nm L
`NW '
`
`(ll—NINE)
`
`inorganic
`insoluble
`internal
`International
`intraperitoneal
`infrared
`immune responsegenes
`Internal Organization for
`Standardization
`
`_
`_
`isolation
`inosine triphosphate; idiopathic
`thrombocytopenic purpura
`international unit
`International Union of Chemistry
`International Union of Pure and
`Applied Chemistry
`intravenous
`apanesel patent (unexamined)
`Japanese patent
`dissociation constant; equilibrium
`constant
`degrees Kelvin
`kilobase
`kilocalories(s)
`killer cell
`kilogram(s)
`oc—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 that is
`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
`lysme
`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
`(USA)
`
`
`
`u
`Ym
`
`0006
`
`microgram
`milhcune
`
`at D X mol wt
`100
`
`,
`molecular rotation
`malate dehydrogenase
`methyl CH3—
`acetone
`
`methyl alcohol
`Mellor’s Comprehensive Treatise on
`Inorganic and Theoretical
`Chemistry
`milli—equivalent (0.001 of an
`equivalent)
`methionine
`N—formylrnethionine
`methemoglobin
`millielectron volts
`manufacturing
`manufacture
`
`milligram
`major histocompatibility complex
`microcurie
`
`micrograrn
`microcrystalline
`migration inhibition factor
`minimum; minute(s)
`Mullerian inhibiting substance
`miscible
`mixture
`milliliter (cubic centimeter)
`minimum lethal dose
`mixed lymphocyte reaction
`millimeter
`millimicron(s), 11m
`molecular weight
`Monatshefte flir 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 (n? for 20° and
`sodium light); normal as n—propyl
`normal (equivalents per liter, as
`applied to concentration); nitrogen
`(asin N~methylpyridine)
`N-acetylneuraminic acid
`nicotinamide adenine dinucleotide
`(reduced form)
`nicotinarmde 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 (10—9 grams)
`nerve growth ractor
`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 Nonofiicial Drugs
`(Lippincott, 1959-1964)
`
`inorg
`insol
`intern
`Intl
`
`i.p.
`IR
`Ir genes
`ISO
`
`isoln
`IT?
`
`LU.
`I.U.C.
`I.U.P.A.C.
`
`i.v.
`Japan. Kokai
`Japan. pat.
`
`K °
`
`K
`
`Lac
`LAD
`)1 (lambda)
`LAMMA
`LATS
`lb
`LC
`
`LCso
`
`LCM
`LD
`LDso
`
`LDH
`LDL
`Leu
`LH
`ln
`loc. cit.
`log
`I oi
`LPS
`Lysm
`
`m-
`
`M M
`
`ab, mAb
`MAC
`MAP
`MAO
`MAOI
`mass spec
`max
`Mb
`Mb02
`M.C.A.
`
`0006
`
`

`

`N.N.R.
`
`110.
`7107‘-
`
`PAGE
`passim
`pat.
`PB report
`
`PCA
`PCT
`PEP
`PET
`petr, etrol
`PFC p
`3PG
`PG
`PGA
`' GP
`pH
`
`FHA
`Phe
`physiol
`
`New and Nonofficial Remedies
`(Lippincott, 1933-1958)
`number
`chemical nomenclature descriptor,
`see Glossary
`National Research Development
`Corporation
`nonsteroidal anti-inflammatory
`drugs
`National Service Center
`nucleoside 5’—uiphosphate; National
`Toxicology Program (US)
`ortho chemical locant for ring
`substituents
`denoting attachment to oxygen, as in
`0- acetylhydroxylamine
`ovalbumin
`oxaloacetate
`optical density
`(opera ciraro) in the work cited
`organic
`Occupational Safety and Health Act
`osmolar
`ounce(s)
`concentration by weight (after optical
`rotations only)
`page(s)
`para chemical locant for ring
`substituents
`inorganic phosphate
`pascal
`p-aminobenzoic acid
`platelet—activating factor
`polyacrylamide gel electrophoresis
`here and there, scattered
`patent
`Publication Board Report (United
`States Department of Commerce,
`Scientific and Industrial Reports)
`passive cutaneous anaphylaXis
`Patent Co-operation Treaty
`phosphoenolpyruvate
`positron emission tomography
`petroleum
`plaque—forming cell
`3-phosphoglycerate
`prostaglandin
`pteroylglutarnic acid (folic acid)
`3—phosphoglyceroyl phosphate
`acid-base scale; log of reciprocal of
`hydrogen ion concentration
`phytohemagglutin
`phenylalanine
`physiological
`log of the reciprocal of the
`dissociation constant, l/log K
`phenylketonuria
`polymorphonuclear leukocyte
`inorganic pyrophosphate
`parts per million
`precipitate, precipitating
`precipitated
`plastoquinone
`propyl (normal)
`prepared
`preparation
`pressure
`proline
`5-phosphoribosyl l-pyrophosphate
`pseudo
`point
`parathyroid hormone
`coenzyme Q (ubiquinone)
`(quae vide) which see, plural
`(quad vide) which see
`“roentgen” unit of radiation
`racemic
`
`R
`
`(R)—
`
`RAST
`rbc
`RCO—
`recryst(n)
`ref
`rep [REP]
`
`resp
`Rf or RF
`
`RIA
`Rib
`RIST
`RNA
`hnRNA
`mRNA
`nRNA
`rRNA
`snRNA
`tRNA
`RNase
`RTECS
`
`s-
`S
`
`(S)—
`
`S.A.E.
`SAM
`sapon(if)
`at
`satd
`- s.c.
`SDS
`sec
`sec—
`sepn
`Ser
`SI
`SLE
`SNRI
`
`
`
`sol; soly
`solidif
`soln
`sp.
`spec
`SPECT
`
`sp gr
`spp.
`sq
`sag
`SRBC
`SRS-A
`
`~ss
`SSPE
`SSRI
`S.T.P.
`subl
`SUPP1
`sym-
`syn-
`
`T
`t1,2
`tabl
`
`xvii
`
`0007
`
`alkyl, univalent hydrocarbon radical
`(or hydrogen)
`rectus (right), stereodescriptor see
`Glossary
`radioallergosorbent test
`red blood cell; red blood count
`aliphatic acyl radical
`recrystallize, recrystallization
`reference
`
`‘ ‘roentgen equivalent physical”
`means a dose of ionizing radiation
`capable of producing energy
`absorption of 93 ergs per gram of
`tissue
`respectively
`(in paper chromatography) ratio of
`movement of the band to the front
`of the solvent
`radioimrnunoassay
`D—ribose
`radioimmunosorbent test
`ribonucleic acid
`heterogeneous nuclear RNA
`messenger RNA
`nuclear RNA
`ribosomal RNA
`small nuclear RNA
`transfer (soluble) RNA
`ribonuclease
`
`Registry of Toxic Eflects of Chemical
`Substances
`symmetrical
`denoting attachment to sulfur as in
`S-methylcysteine
`sinister (left), stereodescriptor see
`Glossary
`Society of Automotive Engineers
`S—adenosylmethionjne
`saponification
`sarcosine
`saturated
`subcutaneous
`sodium dodecyl sulfate
`second(s)
`secondary
`separation
`serine
`
`International System of Units
`systemic lupus erythematosus
`serotonin—noradrenaline reuptake
`inhibitor
`soluble; solubility
`solidifies, solidification
`solution
`species; specific
`spectroscopy
`single photon emission computed
`tomography
`specific gravity
`species (plural)
`square
`(sequentia) and following
`sheep red blood cells
`slow reacting substance of
`anaphylaxis
`single stranded
`subacute sclerosing panencephalitis
`selective serotonin reuptake inhibitor
`standard temperature and pressure
`sublimes
`supplement
`symmetrical
`stereochernical descriptor see
`Glossary
`thymine; thymidine
`half—life
`tablet(s)
`
`0007
`
`

`

`tuberculosis
`trichloroacetic acid; tricarboxylic
`acid
`thymus derived cell
`thoracic duct lymphocyte
`thyrnidine diphosphate
`0—(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(hydroxymethyl)aminomethane;
`2—anuno—Z—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.
`U.S.D.A.
`
`U.S.P.
`U.S. pat.
`UTP
`uv
`v
`1/-
`Val
`var
`viz.
`VLDL
`vol
`vs
`v/v
`
`Wbc
`WHO
`wks
`wt
`w/v
`
`w/w
`
`XMP
`yr(s)
`Z
`(2)-
`
`Z. Physiol.
`
`~
`2
`
`>
`<
`
`United States Dispensaz‘ory
`United States Department of
`Agriculture
`United States Pharmacopeia
`United States patent
`uridine triphosphate
`ultraviolet
`volt(s)
`vicinal (adjacent)
`valine
`variety
`(videlicet) that is to say; namely
`very low density lipoproteins
`volume
`versus
`
`percent “volume in volume”
`expresses the number of 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 or"
`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
`Kanthosine monophosphate
`year(s)
`carbobenzoxy
`zusammen stereodescriptor see
`Glossary
`Hoppe-Seyler’s Zeitschn'ftfi'ir
`Physiologische Chemie
`approximately
`approximately equal
`greater than
`less than
`
`xviii
`
`0008
`
`TB, tb
`TCA
`
`T cell
`TDL
`TDP
`TEAE cellulose
`tech
`
`temp
`tert—
`TH
`THF
`THZFA
`Thr
`Thy
`TLC
`TMP
`lM V
`TN?
`TN?
`TPA
`TPP, ThI-‘P
`trans—
`Tris
`
`Tr?
`rsn
`TSTA
`
`TTP, dTTP
`Tyr
`
`UU
`
`DP
`UDP—gal
`UDP—glc
`U. K.
`UMP
`
`uncor{r)
`uns—, unsym—
`Ura
`U.S.A.E.C.
`
`USAN
`
`0008
`
`

`

`I 2384
`
`Citramalic Acid
`
`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 Essenv
`tial Oils, VOL II, 326-336 (1949); Gildemeister-Hoffmann,
`Die Aetherischen 0219, vol. IV, 307-356 (4th ed., 1956).
`
`ago
`
`CH3
`
`l
`
`0,2
`
`|
`
`CH3
`
`H3C
`
`CH3
`
`H30
`
`CH3
`
`Geranial (Citral a)
`
`Neral (Citral b)
`
`Geranial, light oily liquid. Strong lemon odor. bP2.5 92-
`93°.
`dfio 0.8888.
`nfl’ 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. hp” 91-92“. d5” 0.8869. ng’ 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. C5H305; mol wt 148.12. C
`40.55%, H 5.44%, O 54.01%. Enzymatic synthesis: Barker,
`Blair, Biachem. 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).
`H0
`CH3
`
`COOH
`
`HOOC
`
`.
`
`mg! _23.4° (c
`
`[0412} +23.6° (c = 3 in
`=3in
`
`til-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-Forrn, crystals, mp 112.2-112.8°.
`H20).
`I-Forrn, crystals, mp 112-113“.
`H20).
`3-Hydroxy-8’—apo-fi,xl/-car0tenal;
`2385. B-Citraul‘in.
`citraurin. CmeOZ; 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.
`‘4,
`.4..- v c...
`Freely sol in acetone ethanol, ether, benzene, and ”firm
`disulfide. Sparingly sol in petr ether.
`
`
`
`
`
`
`1,2-Dihydm-6—hydrox_y.2~
`2386. Citrazinic Acid.
`,'
`pyridinecarboxylic acid; 2,6—dihydroxyisonicatinic acidlfxoq
`
`1
`dihydroxy-4-pyridinecarboxylic acid. C6H5N04; m;
`1 w
`155.11. C 46.46%, H 3.25%. N 9.03%, 0 41.26%.
`from citric acid with aq NH3 at 140-160° under pregrfl!
`
`Bavley, Hamilton, U.S. pat. 2,729,647 (1956 to Print) “hr
`rification: Bavley et al., US. pat. 2,738,352 (1955 to P};tr) [3'
`OH
`HO
`N
`/
`
`
`\
`
`l
`
`COOH
`
`Yellowish powder with a greenish tinge; carboniZes 31$ ,
`300° without melting. Ultrapure material which is Whiteove’01"
`. colorless, has been prepared. Almost insol in water; 3“
`ghtly,
`sol in hot HCl; sol in alkali hydroxide or carbonate sol“ _
`Alkaline solns turn blue on standing.
`
`‘
`
`
`2—Hydroxy-1,2,3-prapanetrimrba1" .
`2387. Citric Acid.
`ylic acid; B-hydroxytricarballylic acid. C6H807; mOlfw ;
`192.13. c 37.51%, H 4.20%, 0 58.29%. Widely distribfif’t",'
`
`in plants and in animal tissues and fluids. Producediid‘
`mycological fermentation on an industrial scale using (£de
`sugar solns, such as molasses and strains of Aspergm
`niger: See review by Von Loesecke, Chem. & Eng. News 1
`
`1952 (1945); Schweiger, U.S. pat. 2,970,084 (1961 to Mil
`Labs); Faith, Keyes & Clark’s Industrial Chemicals, F_‘
`
`Lowenheim, M. K. Moran, Eds. (Wiley-Interscience,‘ Ne
`
`York, 4th ed., 1975) pp 275-279. Also extracted from citrus
`fruits (lemon juice contains 5 to 8%) and from pi'neap
`
`waste. Reviews: Wilson, Chem. & Met. Eng. 29, 787 (1923).
`Browne, Ind. Eng. Chem. 13, 81 (1921); Warneford, Hardy":
`ibid. 17, 1283 (1925); E. F. Bouchard, E. G. Merrittjh;
`
`Kirk—Othmer Encyclopedia of Chemical Technology vol. “5
`(Wiley-Interscience, New York, 3rd ed., 1979) pp 150-5179.
`
`Toxicity: Gruber, Halbeisen, J. Pharmacol. Exp. Ther. 9
`65 (1948).
`
`
`COOH
`
`HO—C—COOH
`
`COOH
`
`
`
`Anhydr form, mp 153°. Crystals are monoclinic holoi
`_
`hedra and crystallize from hot concd aq soln. d 1.665., At
`
`25°, pKl 3.128; pK2 4.761; sz 6.396, Bates, Pinching,IJ. ,
`
`Am. Chem. Soc. 71, 1274 (1949). Soly in water: 54.0% W/
`1‘
`at 10°; 59.2% at 20°; 64.3% at 30°; 68.6% at 40°; 70.9% at'5 ._
`
`73.5% at 60°; 76.2% at 70°; 78.8% at 80°; 81.4% at 90°; 84.0%."
`at 100°.
`,
`_.
`Monohydrate, orthorhombic crystals from cold aq schist
`Pleasant, sour taste. d 1.542. Monohydrate crystals 1059.
`water of crystn in dry air or when heated at about 40 to 503”
`slightly deliquescent in moist air.
`Softens at 75°-
`13113.”-
`~100°. pH of 0.1N soln = 2.2. Densities of aqueous 50111
`(15°/15°):
`10% = 1.0392; 20% = 1.0805; 30% = 1.124le
`40% = 1.1709; 50% = 1.2204; 60% = 1.2738.
`Soly 1.11,
`g/ 100 g satd soln:
`ether 2.17; chloroform 0.007; 2111131
`alcohol 15.43; amyl acetate 5.98; ethyl acetate 5.28. Soly at}
`19° in g/ 100 g solvent: methanol 197; propanol 62.8. 111359,
`i.p. in rats: 975 mg/kg (Gruber, Halbeisen).
`’.
`-
`Pharmaceutical Incompatibilities: Potassium tartrate, 31'
`kali and alkaline earth carbonates and bicarbonates, 355'
`tates, sulfides. Dilute aq solns may ferment on standing-
`Barium salt heptahydrate, CnHmBasouflHZO, barium
`citrate. Powder. Loses all H20 at 150°. Sol in 1750 PM."S
`water; freely sol in dil HCl or HNOa; practically ins01 in
`alcohol.
`.
`.
`Ethyl ester, 012132007, ethyl citrate, triethyl citrate. Bittelz
`oily liq. d” 1.137. bp76° 294°; pr0 127°. Viscosity at 25:
`35.2 cps. Pour pt ~10°.
`nZD” 1.4455. Soly: water ~6-9%’
`peanut oil 0.8%. Misc with alc, ether.
`t
`USE: Acidulant in beverages, confectionery, effervesce”
`salts, in pharmaceutical syrups, elixirs, in effervescent poW'
`ders and tablets, to adjust the pH of foods and as Syner',
`
`Page 392
`
`Consult the Name Index before using this section.
`
`0009
`
`0009
`
`

`

`
`
`fl-Citronellol
`
`2391
`
`antioxidant, in processing cheese. Used in beverages,
`gistlc
`’eS: jams, preserves and candy to provide tartness. In the
`jelll 11f of alkyd reSins; in esterified form as plasticizer, foam
`whitor-
`In the manuf of citric acid salts. As sequestering
`ill111 t to remove trace metals. As mordant to brighten
`gen 5. in electroplating; in special inks; in analytical chem-
`1:010r for determining citrate—soluble P205; as reagent for
`15‘” in, mucin, glucose, bile pigments.
`”117 ERA? CAT: Component of anticoagulant citrate solns
`(agate dextrose soln; citrate phosphate dextrose soln; citric
`acid syrup)-
`(3R-trans)-4,6-Dihydro-8-hydroxy-3,4,5—
`2338, Citrinill.
`. ethyl—6—0xa—3H-2-benz0pyran-7-carbaxylic acid; Antimy-
`W” C13H1405; mol Wt 250.25. c 62.39%, H 5.64%, o
`C‘n'97%_ Antibiotic substance produced by a White spore
`31’ rgfllus which has been placed under the species name
`aspergillus niveus (Thorn and Raper). Also produced in
`ASP?“ quantities by Penicillium citrinum: Hetherington,
`szmck, Trans. Roy. Soc. London 3220, 269 (1931); Rais-
`R?‘k Smith, Chem. & Ind (London) 60, 828 (1941); Timo-
`‘r-‘C :Science 96, 494 (1942); Timonin, Rovatt, Can. J. Pub.
`Innlilth 35, 80 (1944).
`Identity with antimycin: Haese,
`frem Pharm. 296, 227 (1963). Structure: Brown et al., J.
`Chem- Soc. 1949, 867; Warren et al., J. Am. Chem. Soc. 79,
`3812 (1957); Kovac et (11., Nature 190, 1104 (1961). Synthe-
`iS' Cartwright et al., J. Chem. Soc. 1949, 1563; J. A. Bar-
`f”; e, 41,, J. Chem. Soc. Perkin Trans. I 1986, 2101. Stereo-
`chemiStryi Cram, J. Am. Chem. Soc. 72, 1001 (1950); Meh-
`ta Whalley’ J. Chem. Soc. 1963, 3777; Mathieson, Whalley,
`ibia'. 1964, 4640. Physical characteristics and toxicity:
`Nagai 81‘ £11., Chem. Zentr. 1958, 8088', CA. 55, 1914 (1961).
`' Crystal and molecular structure: Rodig, Chem. Commun.
`1971, 1553. Biosynthesis:
`J. Barber et aI., J. Chem. Soc.
`Perkin Trans. I 1981, 2577; L. Colombo et 11]., nibid. 2594.
`Physicochemical data: A. E. Pohland et (11., Pure Appl.
`Chem. 54, 2219 (1982). Toxicology: A. M. Ambrose, F. De
`Eds, J. Pharmacol. Exp. Ther. 88, 173 (1946). Review: Saito
`let (1]., “Yellowed Rice Toxins” in Microbial Toxins, A. Cieg-
`153-, S. Kadis, A. Ajl, Eds. (Academic Press. New York,
`{1971) vol. VI, pp 357-367.
`
`HOOC
`
`o
`
`OH
`
`~CH3
`
`CH,
`
`CH,
`
`[0433
`Lemon-yellow needles from alcohol, dec 175°.
`—37.4° (c = 1.15 in alc.). uv max: 250, 331 nm (E1211. 370,
`413). Strong acid. Practically insol in water. Sol in alco-
`1101, dioxane, dilute alkali. Solns change color with changes
`111 PH. from lemon-yellow at pH 4.6 to cherry-red at pH
`9.9. Poisonous!
`LDSO in mice, rats (mg/kg):
`35, 67 i.p.
`(Ambrose, De Eds).
`Igethyl citrinin, CHI-I160? plates from benzene, dec 139°.
`la] +217.1° (c = 0.38 in acetone). uv max: 260, 334 nm
`E161. 520, 151.6).
`Sol
`in hot alcohol; moderately sol in
`chloroform. Practically insol in petr ether.
`Dlhydrocitrinin, C13H1605’ prisms from benzene, dec
`3;};
`[00138 ~18.8° (c = 4.148 in chloroform).
`uv max:
`rofi; 330 nm (E13; 400, 100). So] in alcohol, acetone, chlo—
`rm; sparingly sol in benzene, petr ether.
`4112:189- Citromycetin.
`8,9-Dihydr0xy-2-methyl-4-axo-
`qufi’tnt' ‘Pyrqtto[3,2-c][1]benz0pyran-10-carbaxylic acid; fre-
`347‘710 acid. C14H1007; mol Wt 290.23. C 57.94%, H
`Gilli“; 0 38.59%. Antibiotic substance produced by Peni-
`y Cir frequentans Westling and P. vesiculosum Bainier and
`0y. S’Omyces Spp: Hetherington, Raistrick, Phil. Trans.
`Natureoc. London, Ser. B, 220, 209 (1931); Grove, Brian,
`Chem 5357, 995 (1951). Structure: Robertson et al., J.
`1958 '45°C~ 1951, 2013. Biosynthesis: Birch et al.,
`ibid.
`Sis:
`in ‘76; Money, Nature 199, 592 (1963). Total synthe-
`395'“. {amaUChi et al., J. Chem. Soc. Perkin Trans. I 1987,
`
`
`
`HO
`
`HO
`
`HOOC
`
`0
`
`0
`
`/
`o /
`
`CH,
`
`Dihydrate, 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°.
`
`C10H130§
`3, 7-Dimethyl-6-octenal.
`2390. Citronellal.
`mol wt 154.25. C 77.87%, H 11.76%, 0 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,
`
`HC§
`
`H,C
`
`CH,
`
`d 0.848-
`[04E5 +11.50°.
`n}? 1.4460.
`bp1 47°.
`Liquid.
`0856. Soluble in alcohols; very slightly sol in Water.
`a-citranellal, 3,7-Di