JP4499554B2 - 少なくとも1つの二本鎖RNAオリゴヌクレオチド(dsRNA)の局所的使用 - Google Patents
少なくとも1つの二本鎖RNAオリゴヌクレオチド(dsRNA)の局所的使用 Download PDFInfo
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- JP4499554B2 JP4499554B2 JP2004508734A JP2004508734A JP4499554B2 JP 4499554 B2 JP4499554 B2 JP 4499554B2 JP 2004508734 A JP2004508734 A JP 2004508734A JP 2004508734 A JP2004508734 A JP 2004508734A JP 4499554 B2 JP4499554 B2 JP 4499554B2
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- FWFUWXVFYKCSQA-UHFFFAOYSA-M sodium;2-methyl-2-(prop-2-enoylamino)propane-1-sulfonate Chemical compound [Na+].[O-]S(=O)(=O)CC(C)(C)NC(=O)C=C FWFUWXVFYKCSQA-UHFFFAOYSA-M 0.000 description 1
- KJCLYACXIWMFCC-UHFFFAOYSA-M sodium;5-benzoyl-4-hydroxy-2-methoxybenzenesulfonate Chemical compound [Na+].C1=C(S([O-])(=O)=O)C(OC)=CC(O)=C1C(=O)C1=CC=CC=C1 KJCLYACXIWMFCC-UHFFFAOYSA-M 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
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- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
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- 230000009885 systemic effect Effects 0.000 description 1
- 206010052366 systemic mycosis Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
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- 229940104261 taurate Drugs 0.000 description 1
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 1
- 108010093297 tetrapeptide carbamate Proteins 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
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- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
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- 150000003918 triazines Chemical class 0.000 description 1
- LINXHFKHZLOLEI-UHFFFAOYSA-N trimethyl-[phenyl-bis(trimethylsilyloxy)silyl]oxysilane Chemical compound C[Si](C)(C)O[Si](O[Si](C)(C)C)(O[Si](C)(C)C)C1=CC=CC=C1 LINXHFKHZLOLEI-UHFFFAOYSA-N 0.000 description 1
- COXJMKGEQAWXNP-UHFFFAOYSA-N tris(14-methylpentadecyl) 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound CC(C)CCCCCCCCCCCCCOC(=O)CC(O)(C(=O)OCCCCCCCCCCCCCC(C)C)CC(=O)OCCCCCCCCCCCCCC(C)C COXJMKGEQAWXNP-UHFFFAOYSA-N 0.000 description 1
- ZQTYRTSKQFQYPQ-UHFFFAOYSA-N trisiloxane Chemical compound [SiH3]O[SiH2]O[SiH3] ZQTYRTSKQFQYPQ-UHFFFAOYSA-N 0.000 description 1
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- 229910001928 zirconium oxide Inorganic materials 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
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Description
- 皮膚表面の真核微生物内のタンパク質または真皮および表皮細胞内のタンパク質の発現を特異的に目的とする。特に、二本鎖RNAオリゴヌクレオチドが標的細胞内で広がることを可能にする被覆物を選択することによって、細胞のターゲッティングを行うことが可能になる。
- 二本鎖RNAオリゴヌクレオチドによって、1つの遺伝子(または、異なる配列を有し、異なるタンパク質をコードするmRNAを標的とする複数の二本鎖RNAオリゴヌクレオチドを組み合わせた組成物の場合は、複数の遺伝子)を特異的に阻害することが可能になる。
- その二重鎖構造のため、二本鎖RNAオリゴヌクレオチドは、リボヌクレアーゼ(RNAを分解する酵素)に対して耐性を有する。上記オリゴヌクレオチドは皮膚表面では破壊されない。
- その二重鎖構造のため、二本鎖RNAオリゴヌクレオチドは、折りたたみと自己対形成が不可能である。
このようにして、活性産物のバイオアベイラビリティ(すなわち、求める効果を発揮する、細胞内で生ずる二本鎖RNAオリゴヌクレオチドの量)が顕著に改善され、二本鎖RNAオリゴヌクレオチドの使用量を減らすことが可能になる。
- 成長因子EGF、TNF-α、TGF、エンドセリン、NGF、HGF、IGF、およびVEGF;
- サイトカイン、例えば、IL1、IL6、IL8などの型の;
- 受容体、EGFr、TGFr、PAR、PPAR、FXR、RXR、CB1R、CB2R、VR1、CRAB2などの型の;
- カルモジュリン、CLPおよびCLSP型のカルシウム結合タンパク質、ならびにS100A8、Sl00A9、S100A7などS100タンパク質ファミリーのカルシウム結合タンパク質;
- カルシニュリン;
- トランスグルタミナーゼ、例えば、トランスグルタミナーゼ1、3または5;
- 細胞間合着/結合を確実にするタンパク質(オクルディン、ラミニン、カベオリン、デスモグレイン、デスモコリン、コルネオデスモシン、プラコグロビン、デスモプラキン、など);
- ホスファターゼまたはプロテインホスファターゼなどタンパク質の翻訳後修飾に関与する酵素、例えば、カルシニュリン、ホスホリラーゼ、プロテインキナーゼ(例えば、PKC)、グルコシルトランスフェラーゼ、ペプチジルアルギニンデイミナーゼ、など;
- プロテアーゼ(MMP、例えば1、2、3および9、エラスターゼ、アスパラギン酸プロテアーゼ(カテプシンEおよびカテプシンDなど)、カテプシンL、BまたはH型のシステインプロテアーゼ、カテプシンL2、SCCL、キモトリプシン等価物、例えば、SCCE(カリクレイン7)型の、トリプシン様、例えば、SCTE(カリクレイン5)型の、ウロキナーゼ、SASPアーゼ、カスパーゼ、とりわけカスパーゼ14、カルパイン、フィラグリンの加水分解に関与するサブチリシン様プロタンパク質コンバターゼ型のプロテアーゼ(フューリン、PACE4、PC5/6およびPC7/8など)、膜内外型セリンプロテアーゼファミリーのプロテアーゼ[例えば、マトリプターゼおよび/またはそれらの内因性インヒビター(TIMP、PAI1、PAI2、アンチロイコプロテアーゼ、エラフィン、LEKTI、シスタチンA、シスタチンM/E、その他など)];
- エキソグリコシダーゼおよびエンドグリコシダーゼ、(例えば、へパラナーゼ型、ヒアルロニダーゼ、コンドロイチン分解酵素、アスパルチルグルコサミニダーゼ、Bグリコシダーゼ、グリコシダーゼ、その他、およびそれらの内因性インヒビター);
- 脂質代謝酵素(HMGCoA還元酵素、コレステロールスルファターゼまたはスルホトランスフェラーゼ、スフィンゴミエリナーゼ、セラミダーゼ、その他など);
- チロシナーゼ、TRP-1またはTRP-2;
- エイコサノイド代謝酵素(シクロオキシゲナーゼ、リポキシゲナーゼ、ホスホリパーゼ、15-PGDH、その他など);
- I型またはII型5α還元酵素などホルモン代謝酵素;
- エラスチン、コラーゲンなどの型のマトリックスタンパク質;
- サイトケラチン型のケラチノサイト分化タンパク質 ;
- フィラグリン、水チャネルなど皮膚の水分補給に関与するタンパク質;
- 皮膚の抗菌防御に関与するタンパク質、hBD2、hBD3、ダームシディン、リボヌクレアーゼ7、など;
発現および/または活性が阻害されることが意図されるタンパク質またはペプチドの、他の限定されない例は、「Textbook of dermatology」、RH Champion、JL Burton、DA Burns、SM Breathnach編、第6版、1998、Blackwell Science LtD ISBN 0-632-037962で挙げられている。
- 成長因子EGF、TGF、エンドセリン、NGF、HGFおよびFGF、など;
- ホスファターゼ;
- トランスグルタミナーゼ;
- ホスホリラーゼ;
- 細胞外マトリックスの更新に関与するタンパク質(プロテアーゼ:MMPメタロプロテアーゼ、ウロキナーゼなどのセリンプロテアーゼ、tPA、ヒアルロニダーゼ);
- コラーゲンなど真皮の構造タンパク質、またはプロテオグリカンタンパク質などアモルファス基質の構造タンパク質;
- リジルオキシダーゼおよびリジルヒドロキシラーゼなど、真皮の成熟に関与するタンパク質。
- 抗成長:例えば、細胞周期に関与するタンパク質、ならびに/またはIGF受容体および/もしくはT4甲状腺受容体;
- 抗損傷:例えば、サイトカインIL1、IL6、TNFアルファ、ならびにMCP1および/またはMMPプロテアーゼに対して向かうsiRNA、ウロキナーゼおよび/またはリポキシゲナーゼ;
- 再成長:例えば、PGF2アルファおよび/または5アルファ還元酵素の分解に関与するタンパク質;アルファ3ベータ1インテグリン、ベータカテニン、ラミニン10およびLEF-1など形態形成に関与するタンパク質;
- 毛幹の形成(カーリングまたはアンカーリングなど):例えば、毛幹の分化に関与するタンパク質(酸性または塩基性毛角質など)、および毛幹タンパク質のクロスリンクに関連する酵素(例:チオール酸化還元酵素、ならびにトランスグルタミナーゼ3および5)。この型のタンパク質の非限定的リストとして、「Jamora C、DasGupta R、Kocieniewski P、Fuchs E.Nature 2003 Mar 20;422(6929):317-22」を参照してもよい。
- 真菌症を引き起こす病原因子である皮膚糸状菌(紅色白癬菌および毛瘡白癬菌を含むトリコフィートン種)。皮膚糸状菌は好ケラチン性の糸状菌であり、すなわち毛および爪ならびに角膜層に対して優先的親和性を有する。
1.ヒト寄生性皮膚糸状菌(これらは厳密にヒト起源である)。病原菌の例は以下の通りである。紅色白癬菌(Trichophyton rubrum)、趾間白癬菌(Trichophyton interdigitale)、菫色白癬菌(Trichophyton Violaceum)、T.Rosaceeum、断髪性白癬菌(T.Tonsurans)、スーダン白癬菌(T.Soudanensae)、シェンライン白癬菌(Trichophyton Schoenleinii)、有毛表皮糸状菌(Epidermophyton Floccosum)Microsporum Audouinii。
2.動物によって人に伝播される動物好性皮膚糸状菌。原因菌の例は、イヌ小胞子菌(Microsporum canis)、毛瘡白癬菌(Trichophyton Mentagrophytes)、およびTrichophyton Ochraceumである。
3.土によって人に伝播される好地性皮膚糸状菌。主な病原菌は、石膏状小胞子菌(microsporum gypseum)である。
- 非皮膚糸状菌[カンジダアルビカンス(C.albicans)などのカンジダ属種、S.brevicaulisなどのスコプラリオプシス属種、およびマラセジア属種]。これらは、カンジダ属によって、および癜風菌(Malassezia furfur)[以前は、pityrosporonと呼ばれた]によって代表されるイースト菌である。カンジダ属は、皮膚、爪および毛ならびに粘膜に影響を及ぼす。癜風菌(頻出する、皮膚、特に脂漏皮膚の腐生菌)は、癜風の病原因子である。死んだ皮膚の小片が、皮膚の残部から分離するように頭皮から分離するのは、全く正常であるが、一生続くこの表皮更新プロセスは、時々厄介な程度を呈することがある。見苦しいことの他、フケはまた、時に、過敏、発赤およびそう痒などのより深刻な頭皮の問題を伴うこともある。その場合、これは脂漏性皮膚炎と呼ばれる。Pityrosporum ovale菌によって促進される皮膚愁訴である。
- カビ類(角膜層の状態への関与は比較的少ない)。これらはある種の爪甲真菌症および侵襲性真菌症の原因となる。
- IL1(敏感な皮膚の領域における適用のため)、
- 5α還元酵素(脂肪質の皮膚の領域における適用のため)、
- 細菌性リパーゼ(フケ形成の抑制を目的とする適用のため)、あるいは、
- lox12 および/またはcox2および/またはIL1および/またはTGFβ1(毛の喪失を抑制することを目的とする適用のため)。
- ポリカチオン(例えば、親水性PEIまたはキトサン)によって複合化する;
例えば、以下のものを選択することが可能である。ポリ(4-ビニルピリジン)由来ポリカチオン(「Modulation of interaction of polycations with negative unilamellar lipid vesicles」、Yaroslavovら、Colloids and surfaces B:Biointerfaces 16(1999)29-43);リジンの重合体および共重合体(Wardら「Turbidometric analysis of polyelectrolyte complexes formed between poly(Llysine)and DNA」に引用、Colloids and surfaces B:Biointerfaces 16(1999)253-260);BASFのLuviquatsなど、四級化ビニルイミダゾールおよびビニルピロリジンの共重合体(1000〜1000000 mw);BASFのMerquatsなどジアリルジメチルアンモニウムの塩化物ベースの共重合体(10000〜10000000 mw);キトサンおよびその誘導体などポリグルコースアミン;疎水性または非疎水性のポリエチレンイミンなどポリアミン;RhodiaのJaguarsなどグアー誘導体;National StarchのCelquats、またはAmercholのQuarisoftsなど陽イオンセルロース誘導体;ISPのGafquatsなどビニルピロリドンおよびジメチルアミノプロピルメタクリルアミドの共重合体;KingstonのHYPAN QT 100などアクリル酸の陽イオン誘導体;Allied ColloideのSalcare SC92、SC95および96、ならびにRohm GmbhのP1ex4739L;ジウレタンおよびポリウレタンの誘導体(AlzoのPolyderme PPI-SA、Foamox PPI-SA、Foamtaine PPI-SA15およびFoamquat PPI-SAなど)、ならびにコポリアミン(Henkelのpolyquart H-81など);
- この複合体は、その後、リポソーム、特にニオソームなど水性コアを有する粒子内に被包することができる(特許出願EP 0582503または米国特許第5439672号を参照);
- 重合体または陽イオン脂肪親和性界面活性剤を含有する層状表面を有する小胞の表面上で複合化する。
- EP特許0 582 503に記載されたニオソーム。
- 合成の方法が米国特許5021200に記載された脂質小球。
- 米国特許5489426に記載された水中油滴ニオソーム。
- EP特許0 879 589で提案されたナノエマルジョン。
- パラアミノ安息香酸の誘導体:PABA、エチルPABA、エチルジヒドロキシプロピルPABA、エチルヘキシルジメチルPABA(特に、「ESCALOL 507」の名称でISPによって市販されている)、グリセリルPABA、PEG-25 PABA(「UVINUL P25」の名称でBASFによって市販されている)
- サリチル酸誘導体:ホモサラート(「EUSOLEX HMS」の名称でRONA/EM INDUSTRIESによって市販)、エチルヘキシルサリチル酸塩(「NEO HELIOPAN OS」の名称でHAARMANN and REIMERによって市販)、ジプロピレングリコールサリチル酸塩(「DIPSALに」の名称でSCHERによって市販)、TEAサリチル酸塩(「NEO HELIOPAN TS」の名称でHAARMANN and REIMERによって市販)、
- ジベンゾイルメタンの誘導体:ブチルメトキシジベンゾイルメタン(特に、商品名「PARSOL 1789」でHOFFMANN LA ROCHEによって市販)、イソプロピルジベンゾイルメタン、
- ケイ皮の誘導体:メトキシケイ皮酸エチルヘキシル(特に、商品名「PARSOL MCX」でHOFFMANN LA ROCHEによって市販)、メトキシケイ皮酸イソプロピル、メトキシケイ皮酸イソアミル(商品名「NEO HELIOPAN E 1000」でHAARMANN and REIMERによって市販)、シノキセート、メトキシケイ皮酸DEA、メチルケイ皮酸ジイソプロピル、ジメトキシケイ皮酸エチルヘキサン酸グリセリル、
- β,β'-ジフェニルアクリル酸塩の誘導体:オクトクリレン(特に、商品名「UVINUL N539」でBASFによって市販)、エトクリレン(商品名「UVINUL N35」でBASFによって市販)、
- ベンゾフェノンの誘導体:ベンゾフェノン-1(商品名「UVINUL 400」でBASFによって市販)、ベンゾフェノン-2(商品名「UVINUL D50」でBASFによって市販)、ベンゾフェノン-3またはオキシベンゾン(商品名「UVINUL M40」でBASFによって市販)、ベンゾフェノン-4(商品名「UVINUL MS40」でBASFによって市販)、ベンゾフェノン-5、ベンゾフェノン-6(商品名「HELISORB 11」でNORQUAYによって市販)、ベンゾフェノン-8(商品名「SPECTRA-SORB UV-24」でAMERICAN CYANAMIDによって市販)、ベンゾフェノン-9(商品名「UVINUL DS-49」でBASFによって市販)、およびベンゾフェノン12、
- ベンジリデンカンフルの誘導体:3-ベンジリデンカンフル、4-メチルベンジリデンカンフル(「EUSOLEX 6300」の名称でMERCKによって市販)、ベンジリデンカンフルスルホン酸、カンフルベンザルコニウムメトサルフェート、テレフタリリデンジカンフルスルホン酸、およびポリアクリルアミドメチルベンジリデンカンフル、
- フェニルベンゾイミダゾールの誘導体:フェニルベンゾイミダゾールスルホン酸(特に、商品名「EUSOLEX 232」でMERCKによって市販)、およびベンゾイミダジラート(benzimidazilate)(商品名「NEOHELIOPAN AP」でHAARMANN and REIMERによって市販)、
- トリアジンの誘導体:アニソトリアジン(商品名「TINOSORB S」でCIBA GEIGYによって市販)、エチルヘキシルトリアゾン(特に、商品名「UVINUL T150」でBASFによって市販)、およびジエチルヘキシルブタミドトリアゾン(商品名「UVASORB HEB」でSIGMA 3Vによって市販)
- フェニルベンゾトリアゾールの誘導体:
ドロメトリゾールトリシロキサン(「SILATRIZOLE」の名称でRHODIA CHIMIEによって市販)
- アントラニル誘導体:メンチルアントラニル酸塩(商品名「NEO HELIOPAN MA」でHAARMANN and REIMERによって市販)
- イミダゾリン誘導体:プロピオン酸エチルヘキシルジメトキシベンジリデンジオキソイミダゾリン、
- ベンザルマロン酸の誘導体:ベンザルマロン酸官能基を有するポリオルガノシロキサン(商品名「PARSOL SLX」でHOFFMANN LA ROCHEによって市販)、
- およびそれらの混合物。
- サリチル酸エチルヘキシル、
- ブチルメトキシジベンゾイルメタン、
- メトキシケイ皮酸エチルヘキシル、
- オクトクリレン、
- フェニルベンゾイミダゾールスルホン酸、
- テレフタリリデンジカンフルスルホン酸、
- ベンゾフェノン-3、
- ベンゾフェノン-4、
- ベンゾフェノン-5、
- 4-メチルベンジリデンカンフル、
- ベンゾイミダジラート(benzimidazilate)、
- アニソトリアジン、
- エチルヘキシルトリアゾン、
- ジエチルヘキシルブタミドトリアゾン、
- メチレンビス-ベンゾトリアゾイルテトラメチルブチルフェノール、
- ドロメトリゾールトリシロキサン、
- およびそれらの混合物。
- 動物起源の炭化水素油(ペルヒドロスクアレンなど);
- 野菜起源の炭化水素油(4〜10個の炭素原子を含む液体脂肪酸トリグリセリドおよびカリテバターの液体留分など);
- 合成エステルおよびエーテル(特に脂肪酸の)。例えば、化学式R1COOR2およびR1OR2の油(式中、R1は8〜29個の炭素原子を有する脂肪酸の残基を表し、R2は3〜30個の炭素原子を有する分岐状または非分岐状の炭化水素鎖を表す)。パーセリン油、イソノナン酸イソノニル、ミリスチン酸イソプロピル、パルミチン酸エチル-2-ヘキシル、ステアリン酸オクチル-2-ドデシル、オクチル-2-ドデシルエルカート、およびイソステアリン酸イソステアリルなどである;ヒドロキシル化エステル(乳酸イソステアリル、ステアリン酸オクチルヒドロキシ、ステアリン酸オクチルドデシルヒドロキシ、リンゴ酸ジイソステアリル、クエン酸トリイソセチル、ヘプタノエートなど)、ならびに脂肪アルコールのオクタノアートおよびデカノアート;多価アルコールエステル(プロピレングリコールジオクタノアート、ネオペンチルグリコールジヘプタノエート、およびジエチレングリコールジイソノナノアートなど);およびペンタエリスリトールエステル(テトライソステアリン酸ペンタエリスリチルなど);
- 鉱物起源または合成起源の直鎖状または分岐状炭化水素(揮発性または不揮発性パラフィン油およびそれらの誘導体、ペトロラタム、ポリデセン、ならびにパーリーム(parleam)油などの水添ポリイソブテンなど);
- 8〜26個の炭素原子を有する脂肪アルコール。セチルアルコールおよびステアリルアルコールならびにそれらの混合物(セチルステアリルアルコール)、オクチルドデカノール、2ブチルオクタノール、2-ヘキシルデカノール、2-ウンデシルペンタデカノール、オレイン(oleic)アルコール、またはリノール(linoleic)アルコールなど;
- 部分的に炭化水素質(hydrocarbonaceous)および/またはケイ素質(siliconaceous)であるフッ化油(文書JP-A-2-295912に記載されているものなど);
- 直鎖状または環状ケイ素質鎖を有し、周囲温度で液状または糊状である、揮発性または不揮発性ポリメチルシロキサン(PDMS)などのシリコーン油、特に、シクロヘキサシロキサンなどのシクロポリジメチルシロキサン(シクロメチコン);垂下したまたはケイ素質鎖の末端に、アルキル基、アルコキシル基またはフェニル基を含むポリジメチルシロキサン(基は2〜24個の炭素原子を有する);フェニルトリメチコン、フェニルジメチコン、フェニルトリメチルシロキシジフェニルシロキサン、ジフェニルジメチコン、ジフェニルメチルジフェニルトリシロキサン、2-フェニルエチルトリメチルシロキシシリカート、およびポリメチルフェニルシロキサンなどのフェニル化シリコーン;
- それらの混合。
材料と方法:
実験の条件は、Tuschlら(Journal of Cell Science 2001、114、4557-4565)によって記載されたものである。
・siRNA-TYR266 duplex:
siRNA 5'センス鎖(配列番号1):UGCACCACUUGGGCCUCAAdTdT
siRNA 5'アンチセンス鎖(配列番号2):UUGAGGCCCAAGUGGUGCAdTdT
・siRNA-TYR359 duplex:
siRNA 5'センス鎖(配列番号11):AAGUGUUUGAUGCUGGAGGdTdT
siRNA 5'アンチセンス鎖(配列番号12):CCUCCAGCAUCAAACACUUdTdT
・siRNA-TYR690 duplex:
siRNA 5'センス鎖(配列番号13)::GCACCAGCUUUUCUGCCUUdTdT
siRNA 5'アンチセンス鎖(配列番号14):AAGGCAGAAAAGCUGGUGCdTdT
・siRNA TYR832 duplex:
siRNA5'センス鎖(配列番号15):ACUGCACAGAGAGACGACUdTdT
siRNA 5'およびセンス鎖、(配列番号16):AGUCGUCUCUCUGUGCAGUdTdT
・siRNA-TYR1110 duplex:
siRNA 5'センス鎖(配列番号17):GCACCAGCUUUUCUGCCUUdTdT
siRNA 5'アンチセンス鎖(配列番号18):AAGGCAGAAAAGCUGGUGCdTdT
・siRNA-TYR1578 duplex:
siRNA 5'センス鎖(配列番号19):AGCAGCAUGCACAAUGCCUdTdT
siRNA 5'アンチセンス鎖(配列番号20):AGGCAUUGUGCAUGCUGCUdTdT
・siRNA-TYR2120 duplex:
siRNA 5'センス鎖(配列番号21):AGCCUGACCUCACUCUAACdTdT
siRNA 5'アンチセンス鎖(配列番号22):GUUAGAGUGAGGUCAGGCUdTdT
L:分子量ラダー(ladder)
C:MeWo対照(control)
1:MeWo+TYR266 siRNA、0.84μg
2:MeWo+TYR266 siRNA、2.52μg
3:MeWo+TYR359 siRNA、0.84μg
4:MeWo+TYR359 siRNA、2.52μg
5:MeWo+TYR690 siRNA、0.84μg
6:MeWo+TYR690 siRNA、2.52μg
7:MeWo+TYR832 siRNA、0.84μg
8:MeWo+TYR832 siRNA、2.52μg
9:MeWo+TYR1110 siRNA、0.84μg
10:MeWo+TYR1110 siRNA、2.52μg
11:MeWo+TYR1578 siRNA、0.84μg
12:MeWo+TYR1578 siRNA、2.52μg
13:MeWo+TYR2120 siRNA、0.84μg
14:MeWo+TYR2120 siRNA、2.52μg
組成物1:二本鎖RNAオリゴヌクレオチドを、陽イオン小胞の表面で複合化する。
小胞の調製:
イソステアリン酸PEG 400 8%
イソステアリン酸でアミド化したポリエチレンイミン(200〜100000MWのPEI) 2%
蒸留水 100%にメスアップ
- メタノール/クロロホルム混合物内で、脂質を可溶化する;
- 脂質フィルムを得るために、減圧下の回転式蒸発器内で溶媒を蒸発させる;
- 超音波処理をしながら、上記フィルムを水和させる;
- 小胞の直径を確認する(1μm未満、好ましくは200nm);
- 二本鎖RNAオリゴヌクレオチド溶液を追加する。
その後、小胞を、局所適用に適した化粧用製剤に組み込む。
A)ポリカチオン/二本鎖RNAオリゴヌクレオチド複合体を被包する:
ステアリン酸POE(8) 5.5%
コレステロール 4%
イソステアリン酸でアミド化したポリエチレンイミン(200〜100000MW) 0.5%
水溶液A:蒸留水、30%、PEI(200〜100000MW)、1%、および二本鎖RNAオリゴヌクレオチド、(補うためにメスアップ)。
水溶液B:蒸留水、100%にメスアップ
組成物1の製法を参照。この場合、水和工程は、超音波処理によって、上記脂質混合物に適した温度で、溶液Aで行われ、その後、水溶液Bで希釈する工程が行われる。
小胞を、その後、局所適用に適した化粧用製剤に組み込む。
グリセロール 5%
防腐剤 1%
EDTA二ナトリウム 0.2%
カルボマー 0.5%
トリエタノールアミン 0.25%
ポリアクリロイルジメチルタウリン酸アンモニウム* 0.3%
ヒアルロン酸ナトリウム 0.1%
植物油 3%
アクリルアミド/アクリロイルジメチルタウリン酸ナトリウム、
ならびにイソドデカンおよびポリソルベート-80** 2%
シクロペンタシロキサンおよびジメチコノール 3%
例1または2による小胞懸濁液 1〜25%
水 100%にメスアップ
* CLARIANTによって供給されるHostacerin AMPS
** SEPPICによって供給されるSimulgel 600
Claims (7)
- センス鎖およびアンチセンス鎖の配列が、配列番号1および2、配列番号13および14、配列番号15および16、配列番号17および18、配列番号19および20、ならびに、配列番号21および22で規定されたsiRNA二重鎖からなる群から選択される、二本鎖RNAオリゴヌクレオチド。
- 皮膚または毛および爪を色素脱失かつ/または漂白することを意図する薬剤を作製するための、少なくとも1つの請求項1に記載の二本鎖RNAオリゴヌクレオチドの使用。
- 生理学的に許容される媒体内に、少なくとも1つの請求項1に記載の二本鎖RNAオリゴヌクレオチドを含む、皮膚または毛および爪を色素脱失かつ/または漂白するための局所用組成物。
- 前記二本鎖RNAオリゴヌクレオチドが、被膜中に被包された、請求項3に記載の局所用組成物。
- 前記被膜が、マイクロスフィア、ナノスフィア、オレオソーム、およびナノカプセルから選択されることを特徴とする、請求項4に記載の組成物。
- 前記被膜の直径が2μm以下であることを特徴とする、請求項4または5に記載の組成物。
- 前記二本鎖RNAオリゴヌクレオチドが、前記組成物の合計重量に基づき5×10-7〜5重量%を示すことを特徴とする、請求項3から6のいずれか一項に記載の組成物。
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PCT/FR2003/001648 WO2003101376A2 (fr) | 2002-06-03 | 2003-06-02 | Utilisation par voie topique d'au moins un oligonucleotide d'arn double brin (ds rna) |
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GB0307914D0 (en) * | 2003-04-07 | 2003-05-14 | Univ Dundee | Cytochrome p450 |
EP1689864A2 (en) * | 2003-10-21 | 2006-08-16 | Dyad Pharmaceutical Corporation | Method and compositions for treating 5alpha-reductase type 1 and type 2 dependent conditions |
DE102004025881A1 (de) | 2004-05-19 | 2006-01-05 | Beiersdorf Ag | Oligoribonukleotide zur Beeinflussung des Haarwachstums |
WO2006040446A1 (fr) * | 2004-10-07 | 2006-04-20 | L'oreal | Procédé de mise en forme de fibres kératiniques |
WO2006040447A1 (fr) * | 2004-10-07 | 2006-04-20 | L'oreal | Procédé de traitement cosmétique des fibres kératiniques et utilisation d'un inhibiteur de transglutaminase |
US9139850B2 (en) | 2005-05-19 | 2015-09-22 | L'oreal | Vectorization of dsRNA by cationic particles and topical use |
FR2885808B1 (fr) * | 2005-05-19 | 2007-07-06 | Oreal | Vectorisation de dsrna par des particules cationiques et utilisation topique. |
FR2885813B1 (fr) * | 2005-05-19 | 2008-01-11 | Oreal | Vectorisation de dsrna par des particules cationiques et leur utilisation sur modele de peau. |
FR2890859B1 (fr) * | 2005-09-21 | 2012-12-21 | Oreal | Oligonucleotide d'arn double brin inhibant l'expression de la tyrosinase |
JP4981381B2 (ja) * | 2006-08-04 | 2012-07-18 | 株式会社ナリス化粧品 | 美白用皮膚外用剤 |
JP2008115101A (ja) * | 2006-11-02 | 2008-05-22 | Naris Cosmetics Co Ltd | 美白用皮膚組成物 |
TWI382849B (zh) * | 2007-10-29 | 2013-01-21 | Mello Biotech Taiwan Co Ltd | 產生藉由基因靜默效應以用於皮膚維護之化妝品的方法以及編碼基因靜默效應物之基因重組核苷酸 |
FR2940977B1 (fr) * | 2009-01-13 | 2016-11-18 | Oreal | Utilisation de formes complexes de la proteine de type calmodulin-like skin protein clsp |
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FR3043695B1 (fr) * | 2015-11-17 | 2019-10-25 | ISP Investments LLC. | Procede d'obtention d'un extrait aqueux enrichi en petits arn a partir d'une matiere vegetal et extraits issus du procede |
FR3106754B1 (fr) | 2020-02-04 | 2022-01-07 | Isp Investments Llc | Procede d’obtention d’un extrait aqueux de lavande, compositions comprenant un tel extrait et leurs utilisations cosmetiques |
JPWO2021201276A1 (ja) * | 2020-04-03 | 2021-10-07 | ||
FR3116438B1 (fr) | 2020-11-23 | 2022-10-14 | Isp Investments Llc | Procede d’obtention d’extraits aqueux de feuilles de thes, compositions comprenant de tels extraits et leurs utilisations cosmetiques |
FR3125425B1 (fr) | 2021-07-22 | 2024-09-13 | Isp Invest Llc | Extrait de feuilles de the noir, compositions le comprenant et ses utilisations cosmetiques |
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GB9927444D0 (en) * | 1999-11-19 | 2000-01-19 | Cancer Res Campaign Tech | Inhibiting gene expression |
FR2804960B1 (fr) * | 2000-02-11 | 2005-06-24 | Lvmh Rech | Nouveaux oligonucleotides et utilisation d'oligonucleotides modulant l'expression de la tyrosinase et de la tyrosinase- related-protein 1 comme agents depigmentants |
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2003
- 2003-06-02 CA CA002485111A patent/CA2485111A1/fr not_active Abandoned
- 2003-06-02 ES ES03756039T patent/ES2342826T3/es not_active Expired - Lifetime
- 2003-06-02 JP JP2004508734A patent/JP4499554B2/ja not_active Expired - Fee Related
- 2003-06-02 AU AU2003255621A patent/AU2003255621A1/en not_active Abandoned
- 2003-06-02 AT AT03756039T patent/ATE464038T1/de not_active IP Right Cessation
- 2003-06-02 WO PCT/FR2003/001648 patent/WO2003101376A2/fr active Application Filing
- 2003-06-02 DE DE60332112T patent/DE60332112D1/de not_active Expired - Lifetime
- 2003-06-02 EP EP03756039A patent/EP1513482B1/fr not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
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ES2342826T3 (es) | 2010-07-15 |
DE60332112D1 (de) | 2010-05-27 |
WO2003101376A2 (fr) | 2003-12-11 |
ATE464038T1 (de) | 2010-04-15 |
EP1513482B1 (fr) | 2010-04-14 |
CA2485111A1 (fr) | 2003-12-11 |
AU2003255621A8 (en) | 2003-12-19 |
AU2003255621A1 (en) | 2003-12-19 |
EP1513482A2 (fr) | 2005-03-16 |
JP2005530812A (ja) | 2005-10-13 |
WO2003101376A3 (fr) | 2004-05-06 |
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