JP7171611B2 - 網膜症を治療するための組成物及び方法 - Google Patents
網膜症を治療するための組成物及び方法 Download PDFInfo
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- JP7171611B2 JP7171611B2 JP2019557486A JP2019557486A JP7171611B2 JP 7171611 B2 JP7171611 B2 JP 7171611B2 JP 2019557486 A JP2019557486 A JP 2019557486A JP 2019557486 A JP2019557486 A JP 2019557486A JP 7171611 B2 JP7171611 B2 JP 7171611B2
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Description
[0001]本願は、2017年4月21日出願の米国仮特許出願第62/488,161号に基づく優先権の利益を主張し、その全文を引用によって本明細書に援用する。
[0002]本発明は、一般的に、糖尿病性網膜症及び黄斑変性を含む網膜症を治療するための組成物、キット、及び方法に関する。
[0013]本開示において、文脈上明白に他の意味を示していない限り、単数形の“a”、“an”及び“the”はその複数形の指示対象も含み、特定の数値への言及は少なくともその特定の値を含む。従って、例えば、“ある一つの化合物”への言及は、一つ又は複数のそのような化合物及び当業者に公知のその等価物への言及でもあるといったことなどである。“複数”という用語は、本明細書においては、一つより多いことを意味する。値の範囲が表現されている場合、別の態様は、一つの特定値から及び/又は他の特定値までを含む。同様に、値が“約”という先行詞の使用によって近似値として表されている場合、その特定の値は別の態様を形成することは理解されるであろう。全ての範囲は包括的であり且つ結合可能である。
[0041]100人の糖尿病性網膜症患者を対照群(n=50)と試験群(n=50)に分ける。両群のベースライン網膜血流と血管新生をドップラー光コヒーレンス断層法(Doppler Optical Coherence Tomography)と光干渉断層血管造影法(Optical Coherence Tomography Angioagraphy)を用いて評価する。Gao SSら、Optical Coherence Tomography Angiography,Invest Ophthalmol Vis Sci.2016,57:OCT27-OCT36参照;また、Leitgeb,RAら、Doppler Optical Coherence Tomography,Progress in Retinal and Eye Research 2014,41,26-43も参照。試験群の患者には日用量のチロシンヒドロキシラーゼ阻害剤が投与される。30日後、対照群及び試験群の網膜血流と網膜血管系を再度評価する。試験群は、対照群と比べて網膜血流の改良と異常網膜血管系の低減を示す。
[0042]100人の黄斑変性患者を対照群(n=50)と試験群(n=50)に分ける。
両群のベースライン網膜血流と血管新生をドップラー光コヒーレンス断層法と光干渉断層
血管造影法を用いて評価する。Gao SSら、Optical Coherence
Tomography Angiography,Invest Ophthalmol
Vis Sci.2016,57:OCT27-OCT36参照;また、Leitge
b,RAら、Doppler Optical Coherence Tomograp
hy,Progress in Retinal and Eye Research
2014,41,26-43も参照。試験群の患者には日用量のチロシンヒドロキシラー
ゼ阻害剤が投与される。30日後、対照群及び試験群の網膜血流と網膜血管系を再度評価
する。試験群は、対照群と比べて網膜血流の改良と異常網膜血管系の低減を示す。
以下に、出願時の特許請求の範囲の記載を示す。
[請求項1]
対象における網膜症の治療法であって、それを必要とする対象に有効量のチロシンヒド
ロキシラーゼ阻害剤を投与することを含み、前記チロシンヒドロキシラーゼ阻害剤は、メ
チル (2R)-2-アミノ-3-(2-クロロ-4-ヒドロキシフェニル)プロパノエ
ート、D-チロシンエチルエステル ヒドロクロリド、メチル (2R)-2-アミノ-
3-(2,6-ジクロロ-3,4-ジメトキシフェニル)プロパノエート、H-D-チロ
シン(tBu)-アリルエステル ヒドロクロリド、メチル (2R)-2-アミノ-3
-(3-クロロ-4,5-ジメトキシフェニル)プロパノエート、メチル (2R)-2
-アミノ-3-(2-クロロ-3-ヒドロキシ-4-メトキシフェニル)プロパノエート
、メチル (2R)-2-アミノ-3-(4-[(2-クロロ-6-フルオロフェニル)
メトキシ]フェニル)プロパノエート、メチル (2R)-2-アミノ-3-(2-クロ
ロ-3,4-ジメトキシフェニル)プロパノエート、メチル (2R)-2-アミノ-3
-(3-クロロ-5-フルオロ-4-ヒドロキシフェニル)プロパノエート、ジエチル
2-(アセチルアミノ)-2-(4-[(2-クロロ-6-フルオロベンジル)オキシ]
ベンジルマロネート、メチル (2R)-2-アミノ-3-(3-クロロ-4-メトキシ
フェニル)プロパノエート、メチル (2R)-2-アミノ-3-(3-クロロ-4-ヒ
ドロキシ-5-メトキシフェニル)プロパノエート、メチル (2R)-2-アミノ-3
-(2,6-ジクロロ-3-ヒドロキシ-4-メトキシフェニル)プロパノエート、メチ
ル (2R)-2-アミノ-3-(3-クロロ-4-ヒドロキシフェニル)プロパノエー
ト、H-DL-チロシンメチルエステル ヒドロクロリド、H-3,5-ジヨード-チロ
シンメチルエステル ヒドロクロリド、H-D-3,5-ジヨード-チロシンメチルエス
テル ヒドロクロリド、H-D-チロシンメチルエステル ヒドロクロリド、D-チロシ
ンメチルエステル ヒドロクロリド、D-チロシン-メチルエステル ヒドロクロリド、
メチル D-チロシネート ヒドロクロリド、H-D-チロシンメチルエステル・ヒドロ
クロリド、D-チロシンメチルエステル ヒドロクロリド、H-D-チロシンメチルエス
テル ヒドロクロリド、(2R)-2-アミノ-3-(4-ヒドロキシフェニル)プロピ
オン酸、(2R)-2-アミノ-3-(4-ヒドロキシフェニル)メチルエステル ヒド
ロクロリド、メチル (2R)-2-アミノ-3-(4-ヒドロキシフェニル)プロパノ
エート ヒドロクロリド、メチル (2R)-2-アザニル-3-(4-ヒドロキシフェ
ニル)プロパノエート ヒドロクロリド、3-クロロ-L-チロシン、3-ニトロ-L-
チロシン、3-ニトロ-L-チロシンエチルエステル ヒドロクロリド、DL-m-チロ
シン、DL-o-チロシン、Boc-チロシン(3,5-I2)-OSu、Fmoc-チ
ロシン(3-NO2)-OH、α-メチル-L-チロシン、α-メチル-D-チロシン、
及びα-メチル-DL-チロシンの内の少なくとも一つである方法。
[請求項2]
前記チロシンヒドロキシラーゼ阻害剤が、経口、皮下、静脈内、経皮、経膣、直腸又は
それらの任意の組合せで投与される、請求項1に記載の方法。
[請求項3]
経皮投与が、オレイン酸、1-メチル-2-ピロリドン、又はドデシルノナオキシエチ
レングリコールモノエーテルと組み合わせて実施される、請求項2に記載の方法。
[請求項4]
前記対象にp450 3A4プロモーターを投与することをさらに含む、請求項1に記
載の方法。
[請求項5]
p450 3A4プロモーターが5,5-ジフェニルヒダントインである、請求項4に
記載の方法。
[請求項6]
p450 3A4プロモーターがバルプロ酸又はカルバマゼピンである、請求項4に記
載の方法。
[請求項7]
前記チロシンヒドロキシラーゼ阻害剤とp450 3A4プロモーターが同時に投与さ
れる、請求項4に記載の方法。
[請求項8]
前記チロシンヒドロキシラーゼ阻害剤とp450 3A4プロモーターが、経口、皮下
、静脈内、経皮、経膣、直腸又はそれらの任意の組合せで投与される、請求項4に記載の
方法。
[請求項9]
経皮投与が、オレイン酸、1-メチル-2-ピロリドン、又はドデシルノナオキシエチ
レングリコールモノエーテルと組み合わせて実施される、請求項8に記載の方法。
[請求項10]
前記チロシンヒドロキシラーゼ阻害剤がα-メチル-D-チロシンである、請求項1に
記載の方法。
[請求項11]
前記チロシンヒドロキシラーゼ阻害剤がα-メチル-L-チロシンである、請求項1に
記載の方法。
[請求項12]
前記チロシンヒドロキシラーゼ阻害剤がα-メチル-D-チロシン及びα-メチル-L
-チロシンである、請求項1に記載の方法。
[請求項13]
前記チロシンヒドロキシラーゼ阻害剤がラセミ体のα-メチル-DL-チロシンである
、請求項1に記載の方法。
[請求項14]
前記対象がヒトである、請求項1に記載の方法。
[請求項15]
前記網膜症が糖尿病性網膜症である、請求項1に記載の方法。
[請求項16]
前記対象における前記糖尿病性網膜症の進行を評価することをさらに含む、請求項15
に記載の方法。
[請求項17]
前記網膜症が黄斑変性である、請求項1に記載の方法。
[請求項18]
前記黄斑変性が滲出型黄斑変性である、請求項17に記載の方法。
[請求項19]
前記黄斑変性が萎縮型黄斑変性である、請求項17に記載の方法。
[請求項20]
前記対象における前記黄斑変性の進行を評価することをさらに含む、請求項17に記載
の方法。
Claims (7)
- 対象における網膜症の治療のための医薬組成物であって、当該治療が、それを必要とする対象に当該組成物を投与することを含み、当該医薬組成物が、有効量の、α-メチル-DL-チロシン又は薬学的に許容可能なその塩であるチロシンヒドロキシラーゼ阻害剤を含み、そして前記網膜症が、糖尿病性網膜症又は黄斑変性である、前記組成物。
- 前記治療において、前記組成物が、経口、皮下、静脈内、経皮、経膣、直腸又はそれらの任意の組合せで投与される、請求項1に記載の組成物。
- 経皮投与が、オレイン酸、1-メチル-2-ピロリドン、又はドデシルノナオキシエチレングリコールモノエーテルと組み合わせて実施される、請求項2に記載の組成物。
- 前記治療が、前記対象に、5,5-ジフェニルヒダントイン、バルプロ酸又はカルバマゼピン、又は薬学的に許容可能なその塩であるp450 3A4プロモーターを投与することをさらに含む、請求項1に記載の組成物。
- 前記対象がヒトである、請求項1に記載の組成物。
- 前記治療が、前記対象における前記糖尿病性網膜症の進行を評価することをさらに含む、請求項1に記載の組成物。
- 前記治療が、前記対象における前記黄斑変性の進行を評価することをさらに含む、請求項1に記載の組成物。
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EP3612225A1 (en) | 2020-02-26 |
AU2018254556A1 (en) | 2019-11-14 |
US20220288003A1 (en) | 2022-09-15 |
CA3060417A1 (en) | 2018-10-25 |
KR20190138683A (ko) | 2019-12-13 |
EA201992515A1 (ru) | 2020-04-09 |
US20180303783A1 (en) | 2018-10-25 |
CN110769855A (zh) | 2020-02-07 |
MX2019012476A (es) | 2020-02-12 |
WO2018195411A1 (en) | 2018-10-25 |
JP2020517663A (ja) | 2020-06-18 |
PH12019502380A1 (en) | 2020-09-14 |
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