Format 1
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`
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`
`
`
`Research Lab · Head Office/ Group Leader ·Theme Leader
`
`Research/Development Activity Report
`
` Pharmacological Research Department, Yoshiyuki Tatsumi seal
`KP-103 (062A0)
`April 1999 to May 1999
`Yoshiyuki Tatsumi (30 %), Mamoru Yokoo (30 %)
`
`
`
`
`
`May 26, 1999
`
`
`Theme Name (Code Number):
`
`
`Period:
`
`
`Assigned Person(s) (Energy Allocation):
`
`Progress Status (Results, Issue Points):
`Establishment of tinea unguium guinea pig model in order to obtain use patent for KP-103 for tinea unguium, and study
`effect of KP-103 on tinea unguium
`After KP-103 was licensed to Pola Chemical Industries, there has been, as a means by which to extend the
`contract period and secure the rights for use for tinea unguium, the need to obtain a use patent for tinea unguium. This
`time, because no tinea unguium model has been established up until now during any research term, the effect of KP-103
`was studied by trying to establish a tinea unguium model with guinea pigs using the T. mentagrophytes SM-110 strain,
`which has already been confirmed to infect nails. Because the effect on tinea unguium cannot be evaluated with existing
`methods, evaluation was by means of a new evaluation method that we devised.
`
`
`Group
`
`Number of
`Treatments
`
`15
`15
`15
`15
`
`20
`20
`20
`20
`
`Fungal-
`Negative
`Toenails
`0/10
`0/10
`0/10
`1/10
`
`0/10
`3/10
`0/10
`1/10
`
`Mean Fungi Count Within the
`Toenails
`(LogCFU ± SD/foot)
`3.00 ± 0.54
`2.86 ± 0.67
`2.25 ± 0.31
`2.25 ± 0.83
`
`3.23 ± 0.74
`1.82 ± 0.91*
`2.70 ± 0.63
`2.03 ± 0.75
`
`Substrate
`Control
`KP-103
`Lanoconazole
`Terbinafine
`Substrate
`Control
`KP-103
`Lanoconazole
`Terbinafine
`*, P < 0.05 vs. substrate control
`
`Although with 15-application courses of treatment, all of the drug substances decreased the fungal count within
`the nails, significant fungal eradication effect was not confirmed. With a 20-application course of treatment with KP-103,
`there was significant decrease in the fungal count within the nails; complete cure was confirmed with the nails with 3 feet
`out of 10 feet. On the other hand, 20-application courses of treatment with laconazole and terbinafine, significant fungal
`eradication effect was not confirmed. Because with the existing topical preparations, permeability into the nail plate is
`poor and it is not possible to be effective, per os treatment is being used. It was suggested from these results that topically
`administered KP-103 is effective against tinea unguium. It is surmised that because of the low affinity of KP-103 to
`keratin, it penetrates well into the nail plate and shows excellent effect.
`
`Based on these results, a study with the Intellectual Property Department as to whether or not it is possible to
`obtain a use patent for KP-103 for nails is scheduled.
`This time, for the first time in the world, in vivo evaluation of KP-103 for nails has been established, and it has been
`
`made clear that there is a correlation between guinea pig tinea unguium and human tinea unguium in that they are very
`difficult to treat with topical preparations. It is thought that this method is very useful as a method for evaluating drug
`efficacy against tinea unguium.
`
`Plan Change(s), Scheduled Duration, Topics:
`Confirm consistency with raw data for disclosure of reports after the official entry into an agreement in August.
`Special Instruction:
`
`Manager’s Comments:
`
`
`
`
`
`
`
`
`

`

`Format 1
`
`
`
`
`Research Lab · Head Office/ Group Leader ·Theme Leader
`
`Research/Development Activity Report
`May 28, 1999 Pharmacological Research Department, Hisato Senda seal Senda
`Theme Name (Code Number):
` KP-103 (062A0)
`Period: April 1999 to May 1999
`Assigned Person(s) (Energy Allocation): Yoshiyuki Tatsumi (30 %), Mamoru Yokoo (30 %)
`
`Progress Status (Results, Issue Points):
`1) Establish tinea unguium guinea pig model and therapeutic effect of KP-103 (final)
`After KP-103 was licensed to Pola Chemical Industries, there has been, as a means by which to extend the
`contract period and secure the rights for use for tinea unguium, the need to obtain a use patent for tinea unguium. This
`time, because no tinea unguium model has been established up until now during any research term, the effect of KP-103
`was studied by trying to establish a tinea unguium model with guinea pigs using the T. mentagrophytes SM-110 strain,
`which has already been confirmed to infect nails. Because the effect on tinea unguium cannot be evaluated with existing
`methods, evaluation was by means of a new evaluation method that we devised.
`
`
`Group
`
`Number of
`Treatments
`
`15
`15
`15
`15
`
`20
`20
`20
`20
`
`Fungal-
`Negative
`Toenails
`0/10
`0/10
`0/10
`1/10
`
`0/10
`3/10
`0/10
`1/10
`
`Mean Fungi Count Within the
`Toenails
`(LogCFU ± SD/foot)
`3.00 ± 0.54
`2.86 ± 0.67
`2.25 ± 0.31
`2.25 ± 0.83
`
`3.23 ± 0.74
`1.82 ± 0.91*
`2.70 ± 0.63
`2.03 ± 0.75
`
`Substrate
`Control
`KP-103
`Lanoconazole
`Terbinafine
`Substrate
`Control
`KP-103
`Lanoconazole
`Terbinafine
`*, P < 0.05 vs. substrate control
`
`Although with 15-application courses of treatment, all of the drug substances decreased the fungal count within
`
`the nails, significant fungal eradication effect was not confirmed. With a 20-application course of treatment with KP-103,
`there was significant decrease in the fungal count within the nails; complete cure was confirmed with the nails with 3 feet
`out of 10 feet. On the other hand, 20-application courses of treatment with laconazole and terbinafine, significant fungal
`eradication effect was not confirmed. Because with the existing topical preparations, permeability into the nail plate is
`poor and it is not possible to be effective, per os treatment is being used. It was suggested from these results that topically
`administered KP-103 is effective against tinea unguium. It is surmised that because of the low affinity of KP-103 to
`keratin, it penetrates well into the nail plate and shows excellent effect.
`This time, for the first time in the world, in vivo evaluation of KP-103 for nails has been established, and it has
`
`been suggested that there is a correlated extreme difficulty in treating tinea unguium in humans. It is thought that this
`method is very useful as a method for evaluating drug efficacy against tinea unguium.
`
`2. Presentations at Academic Conferences, and Submission Preparations
`
`Submission of abstract to Interscience Conference on Antimicrobial Agents and Chemotherapy. Paper to be
`submitted under preparation.
`
`Plan Change(s), Scheduled Duration, Topics:
`1) Confirm consistency with raw data for disclosure of reports after the official entry into an agreement in August. (~July)
`2) Based on these results, study with the Intellectual Property Department the policy regarding obtaining a use patent for
`KP-103 for nails.
`Special Instruction:
`
`Manager’s Comments:
`
`
`
`