KRF043B-1
`Laboratory, Main office/Team leader, theme leader
`
`Research and Development Activity Report
`May 28, 1999
`Hisato Senda, Pharmacology Research Division, (seal) Senda
`
`Theme name (code number): KP-103 (062A0)
`Term: April 1999 to May 1999
`Responsible parties (energy allocation): Yoshiyuki Tatsumi (30%), Mamoru Yokoo (30%)
`
`Progress status (results, problems):
`1) Establishment of guinea pig onychomycosis model and treatment efficacy of KP-103 (End)
`
`After licensing KP-103 to Pola Chemical Industries, it is necessary to acquire a use patent for
`onychomycosis, in order to extend the term of the contract and authorize onychomycosis indication. Until
`now, the onychomycosis model was not established in any research term, so this time, establishment of the
`onychomycosis model for guinea pigs was tested using T. mentagrophytes SM-110 strain, for which
`infection in toenails is already confirmed, and the efficacy of KP-103 was investigated. The efficacy on
`onychomycosis was evaluated with a new method that we devised because evaluation was not possible with
`existing methods.
`
`Group
`
`Base control
`KP-103
`Lanoconazole
`Terbinafine
`Base control
`KP-103
`Lanoconazole
`Terbinafine
`
`Treatment frequency
`
`15
`15
`15
`15
`20
`20
`20
`20
`
`Fungus-negative
`toenails
`0/10
`0/10
`0/10
`1/10
`0/10
`3/10
`0/10
`1/10
`
`Average number of
`fungi in nails (Log CFU
`± SD/foot)
`3.00 ± 0.54
`2.86 ± 0.67
`2.23 ± 0.31
`2.25 ± 0.83
`3.23 ± 0.74
`1.82 ± 0.91 a
`2.70 ± 0.63
`2.03 ± 0.75
`
`a P < 0.05 vs base control
`
`Although with the 15-time application treatment all of the drugs exhibited a decline in number of
`fungi in the nail, a significant fungus elimination efficacy was not confirmed. When KP-103 was applied
`20 times, the number of fungi in the nail significantly declined, and complete curing was confirmed in the
`nails of 3 of 10 feet. On the other hand, a significant fungus elimination efficacy was not confirmed with 20
`applications of lanoconazole or terbinafine. Because existing topical agents have poor penetration into the
`nail plate and do not exhibit efficacy, for onychomycosis, oral treatments with terbinafine and itraconazole
`were done. From these results, it is suggested that KP-103 is effective against onychomycosis in local
`administration. It is conjectured that because KP-103 as low affinity with keratin, it exhibited good
`penetration in the nail plate and demonstrated excellent efficacy.
`This time, the world's first in vivo evaluation system for onychomycosis was established,
`suggesting extreme intractability in correlation with onychomycosis in humans. This method is extremely
`useful as a drug efficacy evaluation method for onychomycosis.
`
`2) Conference presentations and paper preparation
`
`Abstract submitted to the Interscience Conference on Antimicrobial Agents and Chemotherapy.
`
`

`

`Preparing paper for submission.
`
`Changes in plans, timing forecast, issues:
`
`1) Confirming consistency with raw data for efficacy tests with an eye on publishing a report after
`the current agreement in August.
`
`2) Based on these results, we will investigate plans for acquiring a use patent for KP-103 on nails,
`with the Intellectual Property Division.
`
`Items of special note:
`
`Affiliated chief's comments:
`
`