`
`BIOMEDICAL LIBRARY
`
`APR 0? 1997
`
`University of California
`Los Angeles
`
`ABSTRACTS
`
`of the 36th
`
`lnterscience Conference
`
`on Antimicrobial Agents
`
`and Chemotherapy
`
`an Annual Meeting
`of the American Society for Microbiology
`
`September 15—18, 1996
`
`Ernest N. Morial Convention Center
`
`New Orleans, Louisiana
`
`Amercan Society for Microbiology
`Washington, DC.
`
`Kaken Exhibit 203 8
`
`Acrux V. Kaken
`
`IPR2017-00190
`
`Page 1 of 4
`
`

`

`©1996 American Society for Microbiology
`1325 Massachusetts Avenue, NW.
`
`Washington, DC 20005—4171
`
`All Rights Reserved
`Printed in the United States of America
`ISBN 1-55581-113-2
`
`Page 2 of 4
`
`

`

`INTRODUCTION
`logical mama having a radium-alumna
`KP—Im la a naval
`moielyjl 1m W 995mm lfigum 11.!" ammo! Ida-792. we remitted
`MKPJN has a hmad nulfungll spam spinal pallych [any
`Including dermal We? 599.. Int! yams The mum-gm
`activity ul'KP—flfl was less mm my fill! and mum and KP—Im
`thW mafianl hit-glam} mlvlly agalrsl Was 91mm on
`ma hnlny layer. suggeslhg that KF—IBB ls refined at a fish mm
`lava! IrI ma hon-qr hum.
`In flab study. as examined lha thampautk sinus? and mphfiacli:
`tallest 01 K9403 an the awed-rental dwmalonrywals modal in W
`MswmmlapsaaMWwammhm-nmmmmw
`figure 2). duhlmazale [811}. mm [NOE].
`and mm; (am.
`MATERIALS AND METHODS
`
`mflmwsralngumeapigaism-fimquadlfldadhmmm
`algnlgmlpsul'w anlmals sash.
`-
`mm
`IMhmfithmmmm
`mmmpmmmammaFujlauat".Ampanam
`{laflmlb'mlfllal unmmwmma
`mtranefinerpwmabalnmmmmarplahwum
`ton-um uao'c under 1m 00,
`mammxw
`_
`amnsmmwnfarzmlnaficmasmm
`
`[Elknn Cflmlcai Ca. Japan]. which mum 4.§ run at yeast—ant:
`perm-l. lumnlmnmm,mmdnmmpfilm&5mfl
`WIMIWI WmmrmLmfimgMaaarparm.mfl Irma-net
`we. Belem umwn In ma :3an phlza m muffled. The mm
`mmeasmplflomnflmfnmmgmwmmdmln
`skin magnate of an anlmai.
`Pmphflluflc “a.
`AhalrlusmalsbyflummmuMonmamdgulnaa
`plusOnhemnawlngday.hakhmnmdwlhc£mmmndm
`“mama-1.4:. H.Nflfihmmgwflumn.asmflm
`arm-mus {3.1 mL ufi was rLflzel um Inn pan-m am ufll'le
`skm.On2-1naflnrmpncafimnfdmmunmbsumad dnmmaswhecl
`on. On any-1? mammal-l, nulluro studies we dawn as deserted
`above.
`mlammtmafiloflt
`[Wand mum Immatiuummswa
`minim Hl: mnmhma mammswm
`m.auMammmmmm—sltmwm-ao
`fimmfiwtmmrmmwmlmquemm
`sommmmmmmplmmmmmww
`mummmwnmm
`
`Flame 2. MINI Mus of Malone drug!
`
`Am
`
`CI
`N")
`
`m:
`
`:5
`N4‘u
`L—J
`Lanomnazola (1.021
`
`5: Q
`
`a
`
`-HC|
`anaflna {EFF}
`
`mm: 1. “crumb «mm d KP-Hla h the Mn pl“ finn-
`urporil mndul
`
`No. or mm: win mama Cm mm
`mum I [an] m at anqu
`“mm”
`1!“!
`10
`0.35% @400 mm
`9"“!
`90
`0.59: KP-‘IGS 6mm
`IWID
`1W
`1% 0-103 8M“
`10110
`100
`2': KP-103 mm
`am
`a
`Nana
`‘I‘laaaflmmappladm BWM1UW.
`
`Tlhll 2. “Ian may! 81' KPwWS and [Ill lllnrlllm dilly!
`In an when my: Malamut- mu
`
`Nu er afllmals mm mm mile mu
`Tmmm
`albums .l mu nu. d mm [361
`10110
`“10
`11!: NIP-103 solublen
`me
`lo
`1% M62 sen-lion
`we
`so
`1% LG: semen
`Tuflfl
`100
`116 B‘I'F solqu
`em
`a
`None
`mmmmwrmlmhrwhq.
`
`Tune 3. Truman": M a! 0493 ll Illa IIIIIl flu "an
`m mm]
`
`0.25% ICE-1m adufion
`Q59. 9—193 film
`196 KP~1CB mlulim
`29a KP-m salmon
`Nam:
`madman wan-mind mu,me lamp,
`
`Tm days'mr the last mmm all salt-ms m swam. and
`Mn rt arms}. mama (1". M53. andmnnlufilgltalrmmn
`HMWmmmmmm.Emhwmmam
`amnmmmmmmWIMmdwmma
`pnrwfl,§0ygdahloramphenlwlparml.1mmafgemfiamrml.
`mummus—nmmoammmanmuanMinoan-um
`wwtmmaummmminuhnwgmmw
`mmamaflsklfibbdtsofanmlmnlufw.
`TmmmrmmmmLauaammmnm,m
`chm wasmcisad ham [In Imamd sin and mammal:
`In sallna
`mnlalnrng 0.0596 green MAmuEpomnofmnmoganateand
`i1:lO-foiflsoflaldfiuliensmmlfladmWriIDfC‘MfliGaBSAam
`
`.I. Mad. w. Myml. mass.
`
`annammhawwmmmdwun".uw
`mflufledwmfinmmmaflsxzsmemmd
`gulnna pigs andlfla sklnmllahw wm‘lnd “handgun”. Each
`.
`mmmmfimawmdxmwm
`Zfl'km Mmmlnharmalal 11mm;
`IManumwasmmmdmmemw
`rummumwam.mmmmapmlfishlulem.la
`mmlwmmnmmutmmmm
`m lnL107‘lanflIppmonlnfl'laplaanmoanhatFot
`mmlgwmmamwammnmmmmmm
`nsmmuwmspurw lin‘m wawflodmlmmgm
`mmmammmmuMMdeMwmamm
`mummmmmmmmqmmmmn
`lummmnMWalnfimmMndmmflmfl
`mammamfimmemsmmmummmm
`lannmbahwmafiormemhflonjmnmdaumd
`mmntmmmmkmsplumhymdhmmwtuw
`ESMmMMdguh-ammmmgsmmma
`gmmammuammmna was].
`m1Mm'amuW in puma! mimmm [75:85;
`Man. one perusal
`soluflens
`of mm mam». mi
`mmnbmwmmssnmm ca..‘run1umcg.
`and MYmm 00. my. 0419 wantbmmrne sumo"
`mama mdmafourmnmv.
`Ilmmmmmumu
`Each gulrlnn pig was MSW mun Mil H3 m1 Effie man
`smmnmalw.msmlmtmfiwmmm—
`spusunlamn and conlhusd hrlflodeays-Tha Wald
`mdflmmmdmmrzmmmmwadma
`QMMMMMWWMB
`Encnloelaraumupgsmuamwuhmmnlmmg
`Mullen mmldfltfia mamms'mmunuay-w p:me
`and Mnmmmmm In days
`
`1w. a. hummus: «flu-q It [fir-103 and tho shunned was In
`an nub-II pip Than Wmdd
`Madleelmm mauve
`mm Hula: m. n! in:
`rm”
`Ml!
`115 1413-139 Damian
`am
`H. N82 Bouillon
`m
`H. La: mum
`m
`196 EITF mu
`man
`None
`mwmmmmnmwwm.
`
`0mm
`[as]
`m:
`an
`m
`1013
`I:
`
`Tuna 5. “mm may all xP—m and m erlm drum h
`if“ uulun ply: hmw ma My madnl
`
`mahenmmgm 6mm
`Wt
`wllulas 1 ma! no. at [Del
`m
`m
`45
`0.25% KP—fln salullun
`1520
`75
`a.“ HIP—103 mm
`_ mm
`__199____
`1% $1er
`8:29
`40
`(16 NW Bouillon
`m
`we
`m m: aolu'flon
`20:20
`100
`1% BTF lalenll
`W
`G
`None
`mam-MW mnmuledm.
`
`filth O. Thu-punk smell?! of "-101! Ind m. III-run:- drug: kl
`an when m: am mm mot
`demmmmmm mm
`Tm mmlmmmfmlm
`1330
`10
`0.2596 KP-IOG solution
`1% RIF—10$ Malian
`W10
`W
`m
`W15
`0
`1% c1: suluunn
`rm
`0
`Isa ch aduflm
`arm
`a
`1-1. LGZ salutlnn
`mo
`0
`Mme
`ma
`0
`Maillnmwmudarham
`
`Tabl- I. mum me at Well" In 1m: nmma pigs mud wltlI
`KP-183 and Bun-ulna!ch alum hr hmlglkl fin" M!
`Na at 1w m positive
`Hume
`alludes ; mat m, of loan
`rate [15;
`«20
`141'?!)
`
`mam“ '1
`1% KP—m “fallen
`1% NH admin“
`
`ll KP-m mums [0.5.]. m 2%] m “9th me la ll'ls
`“Emulation-palsilunnulmamswmaalywmh
`106335.1'hahmnm'lwlll1a'l‘la “Numbnth
`mmmrmmdnmummwmwb
`d1$lflflfihflflfL¢ZMflBTFfiflflles1m2l
`
`wmwmwmmwmm
`mmmmmm
`dwmmmmwummmammwm
`nanuaquaxmmdm ammo!
`4].
`a.) mhlgmanawmhmammmt
`unhammanmmwfllafi
`
`mmmrsm—mmnm
`hnihmmamwmmdmo
`fianW—1mmmmwhdm
`
`8888g
`agno
`
`uni-7. Pmmmmm1mmmmmsh
`nemwnmmpan-m
`Wham Mn. dumm mm
`mum mama alum}
`E!
`am no. d animals
`34
`9'10
`913
`firm
`
`mammal
`1% [05-103 amnion
`1% $4433 89mm!
`1% 9-11! man
`
`“WMWHWMWDH
`
`Tahlulmnkflmhwcanhfllumpmmd with
`[rm—163 IIII IIII lulu-III:- dfll]! Ill! 'l'l'm BOMB
`m. ammmmsm mm
`mrasfmm.ulmrmfl$ rum m
`1m“
`3'10
`N
`H. KP-Il'fl salutlan
`W10
`80
`19¢ [.52 Efil‘lhn
`am
`30
`m BTP mum
`mu:
`Ian
`Mann
`mdmmmfldmammwm.
`nwmmmm
`
`11min. s..1-. mm and v. Saw. 1m. 56% and reliable
`“mm impmdmlnl «We mumm. Jpn.
`J. Med. mm mus—131.
`21 m a. T. Kaela. a Sula. N. Mullahs. and v. Tmaam 1952.
`51mm on mmmm of W Wm.
`1. mum-Ina!
`mm of wagon phenol m. J. Sci. Res. E151. 45:113-117.
`9] Fajita 5., and T. Malawian“.
`1362'. Mental lass pldb by
`Mll-mllim Wu 1:! WWW "mm mm!!!
`nu ma mumdwmmma. Mad. vaL meal. Human.
`a}MaatnsnLlL.T.llnynmI£len.mmanII-L
`W_1W.Amlmflmmamdmhmmwdm
`maximum—m gulnua plus.
`
`

`

`CONCLUSIONS
`
`the treatment of
`in
`A 1% KP—‘IOB eoiution was highly effective
`darmatophytosie in the guinea pigs by once daily topical apptioation. being
`more effective than that of a 1% N02 solution and equal to that of 1%
`aolutioas of LCZ and BTF. A 1% KP—tfl3 solution was also highly effective
`in the treatment of cutaneous oandidiasis in the guinea pigs by once daily
`topical application. while 1% eolutions of CTZ. N62. and LCZ were less
`effective.
`
`Therapeutic Efficacy of KP—103, a Novel Topical Antifungal
`Trlazole, on Experimental Superficial Mycosis
`Y. Tatsumi. M. Yol-(co. T. Arilca, H. OgLIra. K. Nagei. and T. Naito.
`Development Research Laboratories. Kaken Pharmaceutical Co. Ltd. Kyoto. Japan.
`H. Yamaguchi. Teikyo Univ.. Tokyo, Japan.
`
`ABSTRACT
`
`The therapeutic efficacy oi KP—toa on derrnatomycosis models In guinea pigs was compared with
`that at netiwnazoiemCZ}.
`lenooonazoleiLGZl. butenatlneiBTFi. and clotrimazoleiCTZ]. One percent
`solution of each drug was topicaHy applied onoe a day. Two days aler lest application. skin blocks
`or homogenates were cultured. Rate of complete cure was expressed by the percentage at animals
`(nzioi or feet (11:20] with negative cultures.
`
`Myoosis models
`
`Tmee corpora
`Trrrea penis
`lnlerdigital
`tin-ea penis
`Skin oendidiasis
`" Not mined.
`
`Treatment
`duration
`(dyg)
`10
`to
`to
`3
`
`Fiate of complete cure (‘16)
`
`KP—103
`100
`100
`100
`an
`
`NCZ
`10
`30
`40
`0
`
`LCZ
`90
`1'00
`100
`0
`
`BTF
`100
`100
`100
`ND."
`
`Ci?
`ND.
`ND.
`ND.
`
`The otficacy oi KP—toa on dematophytosis models was superior to that of N02 and almost equal
`to that of LCZ and BTF. KPH103 was attentive on skin oandidlasis. while the other rings were not.
`To clarity the duration of retention time 01 the drug in skin after topimt application.
`the prophylactic
`effect of Kenna on dermatophytosis model was examined. KP-tos exerted prophylactic eftect with
`90% cure rate at application of 43 h before infection.
`In summary. the excellent efiicacles of KP-tos on dematophytoeis and skin mndidlasis may be
`attributed to its high activity and long time retention in the homy layer.
`
`A single topical application 01 1% KPetua within 48 h prior to challenge
`with T. menragrophytes almost completely protected the guinea pigs trom
`development of infection. suggesting that an effective concentration of KP~103
`remains in the skin tor at least 48 h after application.
`The relapse rate of infection of the guinea pigs treated with a 1% KP-
`103 solution for interdigltal T. pedis was lower than that of animals treated
`with a 1% solution of N02 or LCZ.
`In summary, the excellent therapeutic efficacy and the low relapse rate
`atter KP—103 therapy may be attributed to the protongecl retention of active
`drug in the skin tissue.
`Accordingly, KP—103 may be a usefui topical antjfungal agent for the
`treatment of all types of dermatophytosie and other superficial mycosis.
`
`i996
`
`Figure 1. Chemical structure of KP—103
`
`For further information. pteeae contact the iollowing.
`MASAO IBHIDA
`Manager
`Licensing Department
`
`KAKEN PHARMACEUTICAL (10., LTD.
`2—28—3. HDNKOMAGOME. BLINKYO—KU. TOKYO. Hit-8650. JAPAN
`FHDNE' 8170375977—5M6
`FAX :81-03—5977—513l
`
`36th Intersoionoe Conterenoe on Antimicrobial Agents and Chemotherapy
`New Orleans. Louisiana
`15—18 September.
`
`