JP2021514940A - 化粧料および医薬に使用するためのペプチドおよび組成物 - Google Patents
化粧料および医薬に使用するためのペプチドおよび組成物 Download PDFInfo
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Abstract
Description
ボツリヌス毒素:特に血清型A(BOTOX(登録商標)Cosmetic、Allergan Inc.)は表情のしわを減少および/または排除する目的で広く使用されてきた。前記ボツリヌス毒素は局所的に注射され、それらの麻痺効果は平均期間6ヶ月の可逆的な効果であり、従って、反復注射が必要となる。ボツリヌス製剤に対する免疫反応を引き起こし、治療効果を失うという危険性が知られている。B、F、Eのようなボツリヌス毒素の他の血清型もこの問題を克服すると考えられていたが、前記血清型も免疫応答を引き起こす危険性を有する。分子レベルでは、ボツリヌス毒素は、カルシウムイオン活性化エキソサイトーシス機構に関与する、ニューロンタンパク質を分解するプロテアーゼである。例えば、ボツリヌス毒素Aは、ニューロンSNAP−25タンパク質を切断する。
R1−AA1−AA2−AA3−AA4−AA5−AA6−R2
(I)
ここで:
AA1は、正の電荷を有する側鎖または電荷を有さない極性の側鎖を有するアミノ酸の群から選択され;
AA2は、非極性の疎水性側鎖を有するアミノ酸の群から選択され;
AA3は、非極性の疎水性側鎖を有するアミノ酸の群から選択され;
AA4は、電荷を有する側鎖を有するアミノ酸の群から選択され;
AA5は、非極性の疎水性側鎖または芳香族側鎖を有するアミノ酸の群から選択され;
AA6は、Trpであり;
R1はH、置換されたもしくは非置換の非環式脂肪族、置換されたもしくは非置換のアリシクリル、置換されたもしくは非置換のヘテロシクリル、置換されたもしくは非置換のヘテロアリールアルキル、置換されたもしくは非置換のアリール、置換されたもしくは非置換のアラルキル、およびR5−CO−から選択され、ここでR5は置換されたもしくは非置換のC1−C24アルキルラジカル、置換されたもしくは非置換のC2−C24アルケニル、置換されたもしくは非置換のC2−C24アルキニル、置換されたもしくは非置換のC3−C24シクロアルキル、置換されたもしくは非置換のC5−C24シクロアルケニル、置換されたもしくは非置換のC8−C24シクロアルキニル、置換されたもしくは非置換のC6−C30アリール、置換されたもしくは非置換のC7−C24アラルキル、置換されたもしくは非置換の3〜10員のヘテロシクリル環、および2〜24個の炭素原子と1〜3個の炭素原子以外の原子と1〜6個の炭素原子のアルキル鎖とを有する置換されたもしくは非置換のヘテロアリールアルキルによって形成された群から選択され;および、
R2はH、−NR3R4−、−OR3および−SR3から選択され、ここで、R3およびR4はH、置換されたまたは非置換の非環式脂肪族基、置換されたまたは非置換のアリシクリル、置換されたまたは非置換のヘテロシクリル、置換されたまたは非置換のヘテロアリールアルキル、置換されたまたは非置換のアリール、および置換されたまたは非置換のアラルキルから独立して選択される。
AA1は、Hisであり;
AA2は、非極性の疎水性側鎖を有するアミノ酸の群から選択され;
AA3は、非極性の疎水性側鎖を有するアミノ酸の群から選択され;
AA4は、電荷を有する側鎖を有するアミノ酸の群から選択され;
AA5は、Metまたは芳香族側鎖を有するアミノ酸の群から選択され;および、
AA6は、Trpである。
AA1は、Hisであり;
AA2は、Gly、Ala、Val、Leu、MetおよびIleの群から選択され;
AA3は、Gly、Ala、Val、Leu、MetおよびIleの群から選択され;
AA4は、Lys、Arg、His、AspおよびGluの群から選択され;
AA5は、Met、Phe、TyrおよびTrpから選択され;および、
AA6はTrpである。
AA1は、Hisであり;
AA2は、AlaおよびIleの群から選択され;
AA3は、LeuおよびMetの群から選択され;
AA4は、ArgおよびAspの群から選択され;
AA5は、Met、PheおよびTrpの群からから選択され;および、
AA6は、Trpである。
R1−His−Ile−Leu−Asp−Met−Trp−R2(R1−配列番号5−R2);
R1−His−Ile−Met−Asp−Phe−Trp−R2(R1−配列番号6−R2);
R1−His−Ile−Leu−Asp−Trp−Trp−R2(R1−配列番号7−R2);
R1−His−Ala−Leu−Arg−Phe−Trp−R2(R1−配列番号8−R2);および/または、
R1−His−Ile−Met−Asp−Trp−Trp−R2(R1−配列番号9−R2)である。
Ac−His−Ile−Leu−Asp−Met−Trp−NH2(Ac−配列番号5−NH2);
Ac−His−Ile−Met−Asp−Phe−Trp−NH2(Ac−配列番号6−NH2);
Ac−His−Ile−Leu−Asp−Trp−Trp−NH2(Ac−配列番号7−NH2);
Ac−His−Ala−Leu−Arg−Phe−Trp−NH2(Ac−配列番号8−NH2)および/または、
Ac−His−Ile−Met−Asp−Trp−Trp−NH2(Ac−配列番号9−NH2)である。
R1−AA1−AA2−AA3−AA4−R2
(II)
ここで:
AA1は、正の電荷を有する側鎖を有するアミノ酸の群から選択され;
AA2は、任意のアミノ酸であり;
AA3は、正の電荷を有する側鎖を有するアミノ酸の群から選択され;
AA4は、芳香族側鎖を有するアミノ酸の群から選択され;
R1はH、置換されたもしくは非置換の非環式脂肪族、置換されたもしくは非置換のアリシクリル、置換されたもしくは非置換のヘテロシクリル、置換されたもしくは非置換のヘテロアリールアルキル、置換されたもしくは非置換のアリール、置換されたもしくは非置換のアラルキル、およびR5−CO−から選択され、ここでR5は置換されたもしくは非置換のC1−C24アルキルラジカル、置換されたもしくは非置換のC2−C24アルケニル、置換されたもしくは非置換のC2−C24アルキニル、置換されたもしくは非置換のC3−C24シクロアルキル、置換されたもしくは非置換のC5−C24シクロアルケニル、置換されたもしくは非置換のC8−C24シクロアルキニル、置換されたもしくは非置換のC6−C30アリール、置換されたもしくは非置換のC7−C24アラルキル、置換されたもしくは非置換の3〜10員のヘテロシクリル環、および2〜24個の炭素原子と1〜3個の炭素原子以外の原子と1〜6個の炭素原子のアルキル鎖とを有する置換されたまたは非置換のヘテロアリールアルキルによって形成される群から選択され;および、
R2はH、−NR3R4−、−OR3および−SR3から選択され、ここで、R3およびR4はH、置換されたまたは非置換の非環式脂肪族基、置換されたまたは非置換のアリシクリル、置換されたまたは非置換のヘテロシクリル、置換されたまたは非置換のヘテロアリールアルキル、置換されたまたは非置換のアリール、および置換されたまたは非置換のアラルキルから独立して選択される。
AA1は、Lys、ArgおよびHisの群から選択され;
AA2は、任意のアミノ酸であり;
AA3は、Lys、ArgおよびHisの群から選択され;および、
AA4は、Phe、TyrおよびTrpの群から選択される。
AA1は、Argの群から選択され;
AA2は、任意のアミノ酸であり;
AA3は、Argの群から選択され;および、
AA4は、Pheの群から選択される。
R1−Arg−Arg−Arg−Phe−R2(R1−配列番号10−R2);および/または、
R1−Arg−Met−Arg−Phe−R2(R1−配列番号11−R2)である。
Ac−Arg−Arg−Arg−Phe−NH2(Ac−配列番号10−NH2);および/または、
Ac−Arg−Met−Arg−Phe−NH2(Ac−配列番号11−NH2)である。
省略形:
アミノ酸に使用される略語は、1983 IUPAC-IUB Joint Commission on Biochemical Nomenclature recommendations outlined in Eur. J. Biochem. (1984) 138:937に従う。
この実験における目的は、Munc18およびシンタキシン−1の相互作用領域に対して親和性および/または特異性を有し、したがって、前記2つのタンパク質間の相互作用および/または結合に対して競合、干渉および妨害可能であるインシリコペプチドを生成することであった。
Fmoc−AA1−AA2−AA3−AA4−AA5−AA6−Rink−MBHA−樹脂の取得。式中、AA1がL−Hisであり、AA2がL−IleまたはL−Alaであり、AA3がL−LeuまたはL−Metであり、AA4がL−AspまたはL−Argであり、AA5がL−Met、L−TrpまたはL−Pheであり、およびAA6がL−Trpである。
His−Ile−Leu−Asp−Met−Trp(配列番号5);
His−Ile−Met−Asp−Phe−Trp(配列番号6);
His−Ile−Leu−Asp−Trp−Trp(配列番号7);
His−Ala−Leu−Arg−Phe−Trp(配列番号8);
His−Ile−Met−Asp−Trp−Trp(配列番号9);
Arg−Arg−Arg−Phe(配列番号10);
Arg−Met−Arg−Phe(配列番号11);
Glu−Arg−Ile−Asn−Lys−Arg−Arg−Trp(配列番号13);および、
Glu−Arg−Ile−Asn−Lys−Met−Arg−Tyr(配列番号14)。
以下のペプチドを、実施例1のインシリコ研究および、実施例2〜6に従って合成した:
Ac−配列番号5−NH2
Ac−配列番号8−NH2
SNARE複合体タンパク質であるシンタキシン‐1と、Munc18とのタンパク質‐タンパク質相互作用を阻害するペプチドの能力を、ELISA−ベースインビトロMunc18/シンタキシン‐1結合アッセイによって機能的に評価した。簡潔に述べると、0.1、0.5および1mMの前記ペプチドを、当該ペプチドの標的タンパク質である10および5nMのシンタキシン−1(GSTタグ化)と共に、バッファ(20mM Hepes、150mM NaCl、2mM MgCl2、2mM DTT、0.5% Triton−X100および0.5%脱脂乳)中で、室温で3時間、前培養した。一方、100nMのHis標識Munc18をニッケル被覆96ウェルプレートに結合させ、室温で1.5時間培養した。続いて、非結合タンパク質を洗浄除去した後、洗浄バッファ(PBS+0.02% Triton−X100)中の脱脂乳でウェルをさらに30分間ブロックした。次いで、ペプチドと前培養した10および5nMのGSTタグ付きシンタキシン−1をプレートに添加し、室温で2時間培養した。ウェルを洗浄バッファで3回洗浄した後、一次抗体(GSTタグポリクローナル抗体−Thermofisher Scientific、Massachusetts、USA)と共に45分間培養した。最後に、再び洗浄した後、HRP共役二次抗体(Anti−Rabbit−IgG−HRP−Sigma、Missouri、USA)を添加し、室温で培養した。TMB基質(3,3’,5,5’−テトラメチルベンジジン)を用いてシグナルを発現させた。停止試薬を添加して、反応を停止させた。シンタキシン−1タンパク質のMunc18タンパク質への結合量を、450nmにおける吸光度の測定によって分析した。
Ac−配列番号5−NH2
Ac−配列番号8−NH2
Ac−配列番号10−NH2
ヒト骨格筋ミオサイトにおける筋収縮および弛緩に関連するいくつかの遺伝子の発現を調節する能力を評価するために、前記ペプチドを試験した(Lodish H, Berk A, Zipursky SL, et al. (2000), Molecular Cell Biology, 4th edition; Section 18.3 Myosin: The Actin Motor Protein, Nueva York, W. H. Freeman; Kuo, IY, & Ehrlich, BE (2015), Signaling in Muscle Contraction, Cold Spring Harbor Perspectives in Biology, 7(2); RAPSN receptor associated protein of the synapse [ Homo sapiens (human) ], Gene ID in NCBI 5913; Blake DJ, Tinsley JM, Davies KE (1996), Utrophin: a structural and functional comparison to dystrophin, Brain Pathol., 6(1):37-47; Barik A, Lu Y, Sathyamurthy A, et.al. (2014), LRP4 Is Critical for Neuromuscular Junction Maintenance, The Journal of Neuroscience, 34(42), 13892−13905; Kim N, Stiegler AL, Cameron TO, Hallock PT, et.al. (2008), Lrp4 is a Receptor for Agrin and Forms a Complex with MuSK, Cell, 135(2), 334−342; Mahavadi S, Nalli A, Kumar D, et.al. (2014), Increased expression of caveolin-1 is associated with upregulation of the RhoA/Rho kinase pathway and smooth muscle contraction in diabetes (1110.11), The FASEB Journal, 28:1_supplement)。そのために、収縮スマートデータ遺伝子パネルを設計した。前記収縮スマートデータ遺伝子パネルは、表5に含まれる筋収縮および弛緩に関連する遺伝子の発現を分析する。
ペプチドAc−配列番号8−NH2を、実施例2〜6に従って合成した。
ヒト骨格筋細胞におけるミオシン重鎖タンパク質の発現を低下させる前記ペプチドAc−配列番号8−NH2の能力を、このタンパク質に対する特異的抗体(Biotechne、USA)、続いて二次蛍光抗体(Thermofisher、USA)を用いた免疫蛍光によって、インビトロで評価した。簡潔に述べると、ヒト骨格筋芽細胞を、3×104細胞/cm2の濃度でSKM−M培地(Tebu−Bio、France)中のカバーガラス上に播種し、標準的な培養条件下(37℃、95%湿度、5% CO2)で一晩培養した。次にミオサイトへの筋芽細胞の分化を特異的分化培地(Skeletal Muscle Cell Differentiation Medium、SKM−D培地)で誘導し、さらに7日間モニターした。分化した細胞を、細胞毒性を有さない濃度のペプチドAc−配列番号8−NH2(0.05mg/mLおよび0.5mg/mL)でさらに48時間処理した。
収縮頻度を調節する前記ペプチドAc−配列番号8−NH2の能力を、ヒト筋細胞およびhiPSC共培養由来の運動ニューロンを用いて、60秒間、処理の前と後(処理後は、それぞれ規定された時点)におけるInCell 2200自動顕微鏡で記録された局在化収縮筋線維のライブイメージングビデオによってインビトロで評価した。
神経芽細胞腫細胞株由来の神経伝達物質を含む小胞のエキソサイトーシスを調節する、前記ペプチドAc−配列番号8−NH2の能力を、20x対物レンズおよびキセノンランプを備えたZeiss axiovert 200倒立落射蛍光顕微鏡を用いた蛍光イメージングによって、SH−SY5Y細胞を用いてインビトロで評価した。
エキソサイトーシスレベル:個々の細胞について、AUC分析から総ピーク面積を得て、イオノマイシンを注射する前の3サイクルにおける蛍光強度として定義される基準線によって正規化した。
皮膚硬化の潜在的な改善剤としてのI型コラーゲンの産生を調節する、前記ペプチドAc−配列番号8−NH2の能力を、ヒト皮膚線維芽細胞を用いてインビトロで評価した。
Claims (18)
- 配列番号3および/または配列番号4と競合することを特徴とする、Munc18−シンタキシン−1複合体相互作用に干渉可能なペプチド、その許容可能な異性体、塩、溶媒和物および/または誘導体および/またはそれらの混合物。
- 配列が配列番号3および/または配列番号4であることを特徴とする、請求項1に記載のペプチド。
- 式(I):
R1−AA1−AA2−AA3−AA4−AA5−AA6−R2
に記載の配列を有することを特徴とする請求項1に記載のペプチド、その美容的および薬学的に許容可能な異性体、塩、溶媒和物および/または誘導体ならびにそれらの混合物
ここで:
AA1は、正の電荷を有する側鎖または電荷を有さない極性の側鎖を有するアミノ酸の群から選択され;
AA2は、非極性の疎水性側鎖を有するアミノ酸の群から選択され;
AA3は、非極性の疎水性側鎖を有するアミノ酸の群から選択され;
AA4は、電荷を有する側鎖を有するアミノ酸の群から選択され;
AA5は、非極性の疎水性側鎖または芳香族側鎖を有するアミノ酸の群から選択され;
AA6は、Wであり;
R1はH、置換されたもしくは非置換の非環式脂肪族、置換されたもしくは非置換のアリシクリル、置換されたもしくは非置換のヘテロシクリル、置換されたもしくは非置換のヘテロアリールアルキル、置換されたもしくは非置換のアリール、置換されたもしくは非置換のアラルキル、およびR5−CO−から選択され、ここでR5は置換されたもしくは非置換のC1−C24アルキルラジカル、置換されたもしくは非置換のC2−C24アルケニル、置換されたもしくは非置換のC2−C24アルキニル、置換されたもしくは非置換のC3−C24シクロアルキル、置換されたもしくは非置換のC5−C24シクロアルケニル、置換されたもしくは非置換のC8−C24シクロアルキニル、置換されたもしくは非置換のC6−C30アリール、置換されたもしくは非置換のC7−C24アラルキル、置換されたもしくは非置換の3〜10員のヘテロシクリル環、および2〜24個の炭素原子と1〜3個の炭素原子以外の原子と1〜6個の炭素原子のアルキル鎖とを有する置換されたまたは非置換のヘテロアリールアルキルによって形成される群から選択され;および、
R2はH、−NR3R4−、−OR3および−SR3から選択され、ここで、R3およびR4はH、置換されたまたは非置換の非環式脂肪族基、置換されたまたは非置換のアリシクリル、置換されたまたは非置換のヘテロシクリル、置換されたまたは非置換のヘテロアリールアルキル、置換されたまたは非置換のアリール、および置換されたまたは非置換のアラルキルから独立して選択される。 - AA1は、Hであり;
AA2は、非極性の疎水性側鎖を有するアミノ酸の群から選択され;
AA3は、非極性の疎水性側鎖を有するアミノ酸の群から選択され;
AA4は、電荷を有する側鎖を有するアミノ酸の群から選択され;
AA5は、Mまたは芳香族側鎖を有するアミノ酸の群から選択され;および、
AA6は、Trpであることを特徴とする、請求項3に記載のペプチド。 - AA1はHisであり;
AA2はAlaおよびIleの群から選択され;
AA3はLeuおよびMetの群から選択され;
AA4はArgおよびAspの群から選択され;
AA5はMet、Phe、およびTrpの群からから選択され;および、
AA6は、Trpであることを特徴とする、請求項3または4に記載のペプチド。 - 式(I)のペプチドが、
R1−His−Ile−Leu−Asp−Met−Trp−R2(R1−配列番号5−R2);
R1−His−Ile−Met−Asp−Phe−Trp−R2(R1−配列番号6−R2);
R1−His−Ile−Leu−Asp−Trp−Trp−R2(R1−配列番号7−R2);
R1−His−Ala−Leu−Arg−Phe−Trp−R2(R1−配列番号8−R2);および/または、
R1−His−Ile−Met−Asp−Trp−Trp−R2(R1−配列番号9−R2)であることを特徴とする、請求項3〜5のいずれか1項に記載のペプチド。 - 式(I)のペプチドが、
Ac−His−Ile−Leu−Asp−Met−Trp−NH2(Ac−配列番号5−NH2);
Ac−His−Ile−Met−Asp−Phe−Trp−NH2(Ac−配列番号6−NH2);
Ac−His−Ile−Leu−Asp−Trp−Trp−NH2(Ac−配列番号7−NH2);
Ac−His−Ala−Leu−Arg−Phe−Trp−NH2(Ac−配列番号8−NH2)および/または、
Ac−His−Ile−Met−Asp−Trp−Trp−NH2(Ac−配列番号9−NH2)であることを特徴とする、請求項3〜6のいずれか1項に記載のペプチド。 - 式(II):
R1−AA1−AA2−AA3−AA4−R2
に記載の配列を有することを特徴とする、請求項1に記載のペプチド、その美容的および薬学的に許容可能な異性体、塩、溶媒和物および/または誘導体ならびにそれらの混合物
ここで:
AA1は、正に電荷を有する側鎖を有するアミノ酸の群から選択され;
AA2は、任意のアミノ酸であり;
AA3は、正の電荷を有する側鎖を有するアミノ酸の群から選択され;
AA4は、芳香族側鎖を有するアミノ酸群から選択され;
R1はHis、置換されたもしくは非置換の非環式脂肪族、置換されたもしくは非置換のアリシクリル、置換されたもしくは非置換のヘテロシクリル、置換されたもしくは非置換のヘテロアリールアルキル、置換されたもしくは非置換のアリール、置換されたもしくは非置換のアラルキル、およびR5−CO−から選択され、ここでR5は置換されたもしくは非置換のC1−C24アルキルラジカル、置換されたもしくは非置換のC2−C24アルケニル、置換されたもしくは非置換のC2−C24アルキニル、置換されたもしくは非置換のC3−C24シクロアルキル、置換されたもしくは非置換のC5−C24シクロアルケニル、置換されたもしくは非置換のC8−C24シクロアルキニル、置換されたもしくは非置換のC6−C30アリール、置換されたもしくは非置換のC7−C24アラルキル、置換されたもしくは非置換の3〜10員のヘテロシクリル環、および2〜24個の炭素原子と1〜3個の炭素原子以外の原子と1〜6個の炭素原子のアルキル鎖とを有する置換されたまたは非置換のヘテロアリールアルキルによって形成される群から選択され;および、
R2はH、−NR3R4−、−OR3および−SR3から選択され、ここで、R3およびR4はH、置換されたまたは非置換の非環式脂肪族基、置換されたまたは非置換のアリシクリル、置換されたまたは非置換のヘテロシクリル、置換されたまたは非置換のヘテロアリールアルキル、置換されたまたは非置換のアリール、および置換されたまたは非置換のアラルキルから独立して選択される。 - AA1は、Lys、ArgおよびHisの群から選択され;
AA2は、任意のアミノ酸であり;
AA3は、Lys、ArgおよびHisの群から選択され;および、
AA4は、Phe、TyrおよびTrpの群から選択されることを特徴とする、請求項8に記載のペプチド。 - AA1は、Argの群から選択され;
AA2は、任意のアミノ酸であり;
AA3は、Argの群から選択され、および、
AA4は、Pheの群から選択されることを特徴とする、請求項8または9に記載のペプチド。 - 式(II)のペプチドが、
R1−Arg−Arg−Arg−Phe−R2(R1−配列番号10−R2);および/または、
R1−Arg−Met−Arg−Phe−R2(R1−配列番号11−R2)であることを特徴とする、請求項8〜10のいずれか1項に記載のペプチド。 - 式(II)のペプチドが、
Ac−Arg−Arg−Arg−Phe−NH2(Ac−配列番号10−NH2);および/または、
Ac−Arg−Met−Arg−Phe−NH2(Ac−配列番号11−NH2)であることを特徴とする、請求項8〜11のいずれか1項に記載のペプチド。 - 請求項1〜12のいずれか1項に記載のペプチドを含む組成物。
- 薬剤として使用するための、請求項1〜12のいずれか1項に記載のペプチドまたは請求項13に記載の組成物。
- ニューロンのエキソサイトーシス障害および/または筋収縮性障害の予防および/または治療に使用するための、請求項1〜12のいずれか1項に記載のペプチドまたは請求項13に記載の組成物。
- ニューロンのエキソサイトーシス障害および/または筋収縮性障害が、老人性認知症、アルツハイマー関連認知症、エイズ関連認知症、てんかん、筋萎縮性硬化症、多発性/側索硬化症、肥満細胞症、慢性片頭痛、ジストニアおよび/または不安障害であることを特徴とする、請求項15に記載の使用するためのペプチドまたは組成物。
- 筋収縮性障害が、筋強直症、筋強直性ジストロフィー、先天性筋強直症、パーキンソン病、二次性パーキンソニズム、ハンチントン病、痙縮または遅発性ジスキネジア(TD)であることを特徴とする、請求項15に記載の使用するためのペプチドまたは組成物。
- 被験体における皮膚の老化および/または表情による徴候を予防、減少および/または排除するための、請求項1〜12のいずれか1項に記載のペプチドまたは請求項13に記載の組成物の化粧料としての使用。
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EP (1) | EP3758730B1 (ja) |
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WO2023161264A1 (en) | 2022-02-23 | 2023-08-31 | Prospera Biotech, S.L. | Compositions for treating hyperhidrosis |
EP4249498A1 (en) * | 2022-03-23 | 2023-09-27 | Lipotrue, S.L. | Peptides and compositions for use in cosmetics, food and medicine |
AU2022202825B1 (en) * | 2022-04-28 | 2023-09-07 | AUSTRALIAN HEALTH INDUSTRY Co. PTY LTD | Polypeptide, polypeptide composition and application, and prepared anti-wrinkle lotion thereof |
CN114917139B (zh) * | 2022-05-09 | 2023-10-13 | 珀莱雅化妆品股份有限公司 | 一种复合乙酰基六肽-1及其透皮制剂和应用 |
CN114990089B (zh) * | 2022-05-26 | 2023-01-17 | 广州市乾相生物科技有限公司 | 微型内含肽Ssa DnaH及其在表达分离六肽-8中的应用 |
CN117017874B (zh) * | 2023-10-08 | 2023-12-05 | 铂臻(广州)生物科技有限公司 | 一种抗皱紧致面霜及其制备方法 |
Citations (3)
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JPH10251296A (ja) * | 1997-03-06 | 1998-09-22 | American Cyanamid Co | ソマトスタチン拮抗薬として有用なペプチド |
WO2014036198A1 (en) * | 2012-08-28 | 2014-03-06 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for specific inhibition of leishmania receptor for activated c-kinase (lack) |
WO2020028515A1 (en) * | 2018-07-31 | 2020-02-06 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Neuroprotective disruption of kv2.1/syntaxin interaction by small molecules |
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WO1997034620A1 (en) | 1996-03-18 | 1997-09-25 | The Regents Of The University Of California | Peptide inhibitors of neurotransmitter secretion by neuronal cells |
WO1999021879A1 (en) * | 1997-10-27 | 1999-05-06 | Intrabiotics Pharmaceuticals, Inc. | Cyclic peptides having broad spectrum antimicrobial activity |
ES2160485B1 (es) | 1999-04-23 | 2002-05-16 | Lipotec Sa | Peptidos inhibidores de la exocitosis neuronal, composiciones cosmeticas y farmaceuticas que los contienen. |
EP1809652B1 (de) | 2004-11-02 | 2010-05-05 | DSM IP Assets B.V. | Neue topisch anwendbare wirkstoffe gegen mimische und alterabedingt falten |
US20100256041A1 (en) * | 2004-11-12 | 2010-10-07 | Christophe Bonny | Conjugate Molecule Compounds With Enhanced Cell Uptake Activity |
EP1656951A1 (en) * | 2004-11-12 | 2006-05-17 | Xigen S.A. | Conjugates with enhanced cell uptake activity |
ES2259928B1 (es) * | 2005-04-08 | 2007-11-01 | Lipotec, S.A. | Composicion cosmetica o dermofarmaceutica que comprende peptidos derivados de encefalinas para reducir y/o eliminar arrugas faciales. |
ES2322882B1 (es) | 2006-10-25 | 2010-04-22 | Lipotec Sa | Peptidos inhibidores de la exocitosis neuronal. |
CA2892134C (en) * | 2012-11-21 | 2022-10-04 | University Of Cincinnati | Skin care compositions and methods comprising selective agonists of melanocortin 1 receptor |
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Patent Citations (3)
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JPH10251296A (ja) * | 1997-03-06 | 1998-09-22 | American Cyanamid Co | ソマトスタチン拮抗薬として有用なペプチド |
WO2014036198A1 (en) * | 2012-08-28 | 2014-03-06 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for specific inhibition of leishmania receptor for activated c-kinase (lack) |
WO2020028515A1 (en) * | 2018-07-31 | 2020-02-06 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Neuroprotective disruption of kv2.1/syntaxin interaction by small molecules |
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KR20200124218A (ko) | 2020-11-02 |
TW201941783A (zh) | 2019-11-01 |
EP3758730A1 (en) | 2021-01-06 |
AU2019228281B2 (en) | 2024-06-13 |
US20210032287A1 (en) | 2021-02-04 |
US11634458B2 (en) | 2023-04-25 |
EP3758730B1 (en) | 2022-11-02 |
CA3090060A1 (en) | 2019-09-06 |
ES2937382T3 (es) | 2023-03-28 |
WO2019166347A1 (en) | 2019-09-06 |
CN112040969A (zh) | 2020-12-04 |
AU2019228281A1 (en) | 2020-08-13 |
PL3758730T3 (pl) | 2023-03-20 |
CN112040969B (zh) | 2023-03-14 |
JP7296642B2 (ja) | 2023-06-23 |
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