JP5006789B2 - 表情皺及び加齢による皺に対する新規な局所適用剤 - Google Patents
表情皺及び加齢による皺に対する新規な局所適用剤 Download PDFInfo
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- JP5006789B2 JP5006789B2 JP2007539437A JP2007539437A JP5006789B2 JP 5006789 B2 JP5006789 B2 JP 5006789B2 JP 2007539437 A JP2007539437 A JP 2007539437A JP 2007539437 A JP2007539437 A JP 2007539437A JP 5006789 B2 JP5006789 B2 JP 5006789B2
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- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- NCYCYZXNIZJOKI-OVSJKPMPSA-N retinal group Chemical group C\C(=C/C=O)\C=C\C=C(\C=C\C1=C(CCCC1(C)C)C)/C NCYCYZXNIZJOKI-OVSJKPMPSA-N 0.000 description 1
- 229940058287 salicylic acid derivative anticestodals Drugs 0.000 description 1
- 150000003872 salicylic acid derivatives Chemical class 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000009759 skin aging Effects 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 210000000273 spinal nerve root Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 210000003699 striated muscle Anatomy 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229960002663 thioctic acid Drugs 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229950009883 tocopheryl nicotinate Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 150000002266 vitamin A derivatives Chemical class 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
-
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0815—Tripeptides with the first amino acid being basic
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- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
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- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Description
Xは、結合又はNH−CH(C=O)−(CH2)3+n−NH−R5を表し、
nは、0、1又は2を表し、
R1、R4及びR5は、相互に独立に、水素、場合により置換されているC1−C6−アルキル、アミジノ又はテトラ−C1−C6−アルキルアミジニウムを表し、
R2は、水素又は場合により置換されているC1−C6−アルキルを表すか、あるいは
R1及びR2は、これらが結合している残基と一緒になって、5〜7員の飽和環を表し、
R3は、C1−C12−アルコキシ、C1−C12−アルキルアミノ、場合により置換されているアリール−C1−C6−アルキルアミノ、場合により置換されているヘテロアリール−C1−C6−アルキルアミノ、場合により置換されているアリール−C1−C6−アルコキシ又は場合により置換されているヘテロアリール−C1−C6−アルコキシを表し、そして
R6は、水素を表すか、あるいはnが1であるとき、アミノも表すか、又はR1及び残基(ここにR6及びR1が結合している)と一緒になって、5〜7員の飽和環をも表す]で示される、ラセミ体又は純粋なエナンチオマーとしての、トリペプチド、トリペプチド様化合物及びその誘導体、並びにその塩に関する。
− H−Ala−Pro−Arg−Arg−NH−ベンジル(配列番号3);
− H−(β−Ala)−Pro−Dab−NH−ベンジル;
− H−Dap−Pro−Arg−NH−ベンジル;
− H−Ala−Pro−Arg−NH−(CH2)2−フェニル;
− H−(β−Ala)−Pro−Gab−NH−ベンジル;
− N−[ビス(ジメチルアミノ)メチレン]−Ala−Pro−Arg−NH−ベンジル;及びこれらの化合物の酸付加塩である。
化合物257は、配列番号3に相当する。
本発明の組成物は、安全かつ有効量のビタミンB3化合物を含むことができる。ビタミンB3化合物は、WO 97/39733 A1(1997年10月30日公開)に記載されているように、皮膚の状態を調節するのに特に有用である。引用されたビタミンB3化合物の誘導体の例は、ニコチン酸の非血管拡張性エステル(例えば、ニコチン酸トコフェリル)、ニコチニルアミノ酸、カルボン酸のニコチニルアルコールエステル、ニコチン酸−N−オキシド及びナイアシンアミド−N−オキシドを含むニコチン酸エステルを含む。
本発明の組成物はまた、レチノイドを含んでいてもよい。この場合の「レチノイド」は、皮膚においてビタミンAの生物学的効力を持つ、ビタミンA又はレチノール様化合物の全ての天然及び/又は合成類似体、並びにこれらの化合物の幾何異性体及び立体異性体を含む。レチノイドは、好ましくはレチノール、レチノールエステル(例えば、パルミチン酸レチニル、酢酸レチニル及びプロピオン酸レチニルを含む、レチノールのC2〜C22アルキルエステル)、レチナール及び/又はレチノイン酸(全transレチノイン酸及び/又は13−cisレチノイン酸を含む)、特にレチノイン酸とは異なるレチノイドである。他の適切なレチノイドは、レチノイン酸トコフェリル[レチノイン酸のトコフェロールエステル(trans又はcis)]、アダプタレン(adaptalen){6−[3−(1−アダマンチル)−4−メトキシフェニル]−2−ナフトエ酸}及びタザロテン(tazaroten)(エチル−6−[2−(4,4−ジメチルチオクロマン−6−イル)−エチニル]ニコチナート)である。好ましいレチノイドは、レチノール、パルミチン酸レチニル、酢酸レチニル、プロピオン酸レチニル、レチナール及びこれらの組合せである。本発明の組成物は、得られる組成物が、角化した皮膚の状態を調節するのに、好ましくは目に見えかつ/又は知覚できる皮膚の不連続を調節するのに、特に皮膚の加齢の徴候を調節するのに、非常に特定して加齢による目に見えかつ/又は知覚できる皮膚の平滑度における不連続を調節するのに安全かつ有効であるような、安全かつ有効量のレチノイドを含んでいてもよい。
本発明の組成物は、安全かつ有効量のヒドロキシ酸を含んでいてもよい。本発明の組成物に使用するのに好ましいヒドロキシ酸は、乳酸及びグリコール酸のようなα−ヒドロキシ酸、又はサリチル酸及びサリチル酸誘導体、例えば、そのオクタノイル誘導体のようなβ−ヒドロキシ酸を含む。
NMR 核磁気共鳴
MS 質量分析
Fmoc 9−フルオレニルメチルオキシカルボニル
Boc tert−ブチルオキシカルボニル
Z ベンジルオキシカルボニル
Dab 2,4−ジアミノ酪酸
Dap 2,3−ジアミノプロピオン酸
Gab 2−アミノ−4−グアニジノ−酪酸
Pro プロリン[(−)−ピロリジン−2−カルボン酸]
β−Ala β−アラニン(3−アミノプロピオン酸)
EtOAc 酢酸エチル
DCM ジクロロメタン
DMF ジメチルホルムアミド
TBTU O−(ベンゾトリアゾール−1−イル)−N,N,N’,N’−テトラメチルウロニウム・テトラフルオロホウ酸塩
DIPEA ジイソプロピルエチルアミン
NMM N−メチルモルホリン
HOBt 1−ヒドロキシベンゾトリアゾール
DCC N,N’−ジシクロヘキシルカルボジイミド
TFA トリフルオロ酢酸
GF/A ガラス繊維マイクロフィルター
ACN アセトニトリル
RT 室温
HPLC 高圧液体クロマトグラフィー
THF テトラヒドロフラン
MEM 最少必須培地
M199 培地199(テコメディカル社(TECOmedical Ltd.))
Bzl ベンジル
下記実施態様1.1により、代表的な本発明の式(I)の化合物及びこのような化合物の塩の製造法を説明する。実施例により得られる溶出液及び生成物の分析は、プロトンNMR分光法、HPLC電子スプレーMS又は微量分析法により実施した。化合物は、本明細書に後述の既知の方法により製造することができる(M. Bodanszky 「ペプチド合成の実践(The Practice of Peptide Synthesis)」 Springer, 第2版, 1994の汎用説明)。P1アミノ酸はカルボキシ末端で相応じて誘導体化し、α−アミノ保護基(例えば、Boc基)を脱離して、所望の配列が完了するまでペプチド合成における通常の試薬を用いてペプチドを段階的に構築し、直ぐに側鎖保護基(例えば、Z又はBoc官能基)を分離する。
1.1.1 Boc−Dab(Z)−NHBzl
Boc−Dab(Z)−OH 1.4gを、ACN 10ml及びDMF 5mlに溶解して、TBTU 1.35g及びDIPEA 1.43mlを加えたら、直ぐにベンジルアミン0.88mlを加え、この混合物をRTで1時間撹拌した。溶媒を留去し、残渣をEtOAcにとり、この溶液をNa2CO3 10%、クエン酸10%及び飽和NaCl溶液で3×洗浄した。Na2SO4で乾燥し、溶媒を留去して40℃で一晩真空乾燥後、油状生成物1.8gを単離した。
化合物(1.1.1)1.8gをDCM 15mlに溶解して、TFA 5mlを加え、この溶液をRTで30分間撹拌した。溶媒の留去後、粗生成物を分取HPLCにより精製して、所望の化合物0.60gを単離した。342の理論質量は、342の結果により確認した。
Boc−Pro−OH 0.42gをTHF 8ml及びACN 16mlに溶解し、TBTU 0.63g及びDIPEA 66mlを加え、この混合物をRTで撹拌した。3分後、THF 10ml及びDMF 2ml中の化合物(1.1.2)0.60g及びNMM 0.143mlからなる溶液を加えた。RTで1時間撹拌後、溶媒を留去して、残渣をEtOAcにとり、Na2CO3溶液10%、クエン酸10%及び飽和NaCl溶液で3×洗浄した。Na2SO4で乾燥し、溶媒を留去して、40℃で一晩真空乾燥後、油状粗生成物0.8gを単離した。
上記化合物(1.1.3)0.8gをジオキサン中の4M HCl溶液6mlに溶解して、RTで1時間撹拌した。溶媒の留去後、粗生成物を分取HPLCによりクロマトグラフィーに付し、そして所望の化合物0.6gを得た。439の理論質量は、439の結果により確認した。
Z−β−Ala−OH 0.34gをTHF 10mlに溶解して、氷浴中で5℃まで冷却し、直ぐにHOBt 0.17g及びDCC 0.31gを加えた。45分後、THF 10ml及びNMM 0.14ml中の化合物(1.1.4)0.6gからなる溶液を加えた。RTで18時間撹拌後、生成した沈殿尿素誘導体を濾別し、溶媒を留去して、残渣をEtOAcにとり、Na2CO3溶液10%、クエン酸10%及び飽和NaCl溶液で3×洗浄した。Na2SO4で乾燥し、溶媒を留去後、粗生成物を分取HPLCによりクロマトグラフィーに付した。所望の化合物の無色の油状物0.5gを単離した。644の理論質量は、644の結果により確認した。
化合物(1.1.5)0.5gを酢酸20ml及びTFA 1mlに溶解して、この溶液を水5ml中のパラジウム担持炭素10% 100mgの懸濁液と混合した。飽和するまで水素ガスを加えると、変換が完了するまで常圧で水和させた(約12時間)。この懸濁液をGF/Aフィルターにより濾過して、溶媒を留去した。得られた粗生成物は、分取HPLCにより精製し、溶媒の留去後、水に溶解して凍結乾燥した。所望の化合物0.34gを得た。376の理論質量は、376の結果により確認した。
化合物4.3は、配列番号3に相当する。
2.1 材料
− 3代継代した正常ヒト筋細胞(筋芽細胞)
− 後根神経節を伴う13日齢ラット胎仔の脊髄外植片
− 培地:2/3 MEM及び1/3 M199、2mM L−グルタミン、ペニシリン50IU/ml、ストレプトマイシン50μg/ml、ウシ胎仔血清5%
培養条件:37℃、5% CO2
本発明の化合物の有効性を試験するために、一方でヒト筋細胞と、もう一方でラット胎仔の脊髄由来のニューロンとの共培養モデルを確立した。
方法: 成分1〜5(A)を70℃に加熱する。成分6〜7(B)を75℃に加熱する。Bを、撹拌しながらAに加え、50℃に冷却し、ホモジナイズして30℃に冷却する。次に、成分8〜9(C)及び成分10(D)を順々に加え、冷却撹拌する。
方法: 成分2〜6を脱イオン水(1)中に続けざまに希釈する(A)。成分7(B)でpHを6.0に調整し、直ぐに成分8(C)を加える。
Claims (31)
- 下記式(I):
Xは、結合;又はNH−CH(C=O)−(CH2)3+n−NH−R5を表し;
nは、0;又は1を表し;
R1は、水素;アミジノ;又はテトラ−C1−C6−アルキルアミジニウムを表し;
R2は、水素;又は場合によりアミノで置換されているC1−C6−アルキルを表し;
R3は、場合によりアリール部分でC1−C6−アルコキシにより置換されているアリール−C1−C6−アルキルアミノを表し;
R4は、水素;又はアミジノを表し;
R5は、アミジノ;又は水素を表し;
R6は、水素を表すか;あるいはnが1であるとき、アミノも表すか;又は−NH−R1及びR6−が一緒になって、−NH−(CH2)3−;又は−NH−(CH2)2−NH−を表す]で示される化合物。 - R1が、水素を意味する、請求項1記載の化合物。
- R2が、水素;又はメチルを意味する、請求項1又は2記載の化合物。
- R3が、アリール−C1−C6−アルキルアミノを意味する、請求項1〜3のいずれか1項記載の化合物。
- 前記化合物が、一価、多価、単一又は混合の酸付加塩の形態で存在する、請求項1〜4のいずれか1項記載の化合物。
- 前記化合物が、無機酸及び/又は有機酸との塩の形態で存在する、請求項5記載の化合物。
- 前記化合物が、脂肪族の飽和もしくは不飽和のモノ−もしくはジカルボン酸との、並びに/又は芳香族カルボン酸、並びに/又は芳香族−脂肪族カルボン酸、並びに/又はヘテロ芳香族カルボン酸、並びに/又は脂肪族もしくは芳香族スルホン酸との塩の形態で存在する、請求項6記載の化合物。
- 前記化合物が、塩化水素、及び/又は臭化水素、及び/又は硫酸、及び/又はリン酸、及び/又はギ酸、及び/又は酢酸、及び/又はトリフルオロ酢酸、及び/又はトリクロロ酢酸、及び/又はプロピオン酸、及び/又はグリコール酸、及び/又はコハク酸、及び/又はフマル酸、及び/又はマロン酸、及び/又はマレイン酸、及び/又はシュウ酸、及び/又はフタル酸、及び/又はクエン酸、及び/又は乳酸、及び/又は酒石酸、及び/又は安息香酸、及び/又はサリチル酸、及び/又はマンデル酸、及び/又はケイ皮酸、及び/又はニコチン酸、及び/又はメタンスルホン酸、及び/又はトルエンスルホン酸との塩の形態で存在する、請求項5〜7のいずれか1項記載の化合物。
- 前記化合物が、酢酸、及び/又はトリフルオロ酢酸、及び/又は乳酸との塩の形態で存在する、請求項8記載の化合物。
- 前記化合物が、光学的に純粋な異性体、又は異なる異性体の混合物、及び/又は回転異性体の混合物の形態で存在する、請求項1〜9のいずれか1項記載の化合物。
- 前記化合物が、H−Ala−Pro−Arg−Arg−NH−ベンジルである、請求項1記載の化合物。
- 前記化合物が、H−(β−Ala)−Pro−Dab−NH−ベンジルである、請求項1記載の化合物。
- 前記化合物が、H−Dap−Pro−Arg−NH−ベンジルである、請求項1記載の化合物。
- 前記化合物が、H−Ala−Pro−Arg−NH−(CH2)2−フェニルである、請求項1記載の化合物。
- 前記化合物が、H−(β−Ala)−Pro−Gab−NH−ベンジルである、請求項1記載の化合物。
- 前記化合物が、N−[ビス(ジメチルアミノ)メチレン]−Ala−Pro−Arg−NH−ベンジルである、請求項1記載の化合物。
- 酸付加塩の形態の、請求項11〜16のいずれか1項記載の化合物。
- 請求項1〜17のいずれか1項記載の化合物の製造方法であって、ペプチド化学においてそれ自体既知の方法を用いることにより、式(I)の化合物を完全に合成すること、及び
アルキル化された又はグアニジノ官能基に変換されたアミノ基を有する対応する式(I)の化合物を製造するために、式(I)の化合物における遊離アミノ基をアルキル化するか又はこれをグアニジノ官能基に変換すること、及び/又は
アミド化されたカルボキシル基を有する対応する式(I)の化合物を製造するために、式(I)の化合物における遊離カルボキシル基をアミド化すること、並びに/又は
酸付加塩の形態の対応する式(I)の化合物を製造するために、得られた式(I)の塩基性化合物を酸付加塩に変換すること、又は
対応する共役塩基もしくは別の塩の形態の対応する式(I)の化合物を製造するために、得られた式(I)の化合物の酸付加塩を対応する共役塩基に、若しくは別の塩に変換することを含む方法。 - それぞれ、局所適用できる組成物の製造のための、請求項1〜17のいずれか1項記載の化合物の使用。
- 前記組成物がスキンケア製品であることを特徴とする、請求項19記載の使用。
- 前記組成物が、ヒトの皮膚における表情皺及び/又は加齢による皺の処置のためのスキンケア製品であることを特徴とする、請求項20記載の使用。
- 請求項1〜17のいずれか1項記載の少なくとも1つの化合物を含む、局所適用できる組成物。
- 請求項1〜17のいずれか1項記載の少なくとも1つの化合物を、0.5ppm〜5,000ppm(w/w)の範囲の量で含む、請求項22記載の組成物。
- 請求項1〜10のいずれか1項記載の少なくとも1つの化合物を、1ppm〜1000ppm(w/w)の範囲の量で含む、請求項23記載の組成物。
- 局所適用できるスキンケア製品としての、請求項22〜24のいずれか1項記載の組成物。
- ヒトの皮膚における表情皺及び/又は加齢による皺の処置のための、請求項25記載の組成物。
- 抽出脂質;合成脂質;ゲル形成性及び粘性の界面活性剤及び乳化性ポリマー;水溶性又は脂溶性有効成分;植物エキス;組織抽出液;海のエキス;合成品;日焼け防止製品;酸化防止剤;保湿剤;遮断物質;及び皮膚再活性化有効成分よりなる群から選択される、局所適用できる組成物において普通に使用される更に別の成分を含む、請求項22〜26のいずれか1項記載の組成物。
- a)請求項1〜17のいずれか1項記載の少なくとも1つの化合物、及び
b)安全かつ有効量の、皺取り有効成分及び抗皮膚萎縮有効成分よりなる群から選択される少なくとも1つの追加のスキンケア有効成分
を含む、局所適用できる組成物。 - 液剤;分散剤;乳剤;ミルク;ローション;軟膏剤;ゲル形成性及び粘性の界面活性剤及び乳化性ポリマー;ポマード;シャンプー;石鹸;ゲル;パウダー;スティック;ペンシル;スプレー又はボディーオイルの形態であるか、あるいは担体中にカプセル化されている、請求項22〜28のいずれか1項記載の組成物。
- マクロ−、マイクロ−若しくはナノカプセルに、リポソーム若しくはキロミクロンにカプセル化されているか;マクロ−、マイクロ−若しくはナノ粒子又はマイクロスポンジに封入されているか;あるいは粉末化有機ポリマー、タルク、ベントナイト及び/又は他の鉱物担体上に吸収されている、請求項29記載の組成物。
- ヒトの皮膚における表情皺及び/又は加齢による皺の化粧法的処置のための方法であって、請求項1〜17のいずれか1項記載の化合物の、又は請求項22〜30のいずれか1項記載の組成物の、皮膚への適用を含む方法。
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WO2010003781A1 (en) * | 2008-07-08 | 2010-01-14 | Unilever Plc | Antiperspirant compositions |
WO2010003861A1 (en) * | 2008-07-08 | 2010-01-14 | Unilever Plc | Antiperspirant products |
MX2012001077A (es) | 2009-07-24 | 2012-06-12 | Lipotec Sa | Compuestos inhibidores de la contraccion muscular. |
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US9566227B2 (en) | 2012-04-13 | 2017-02-14 | Activen | Cosmetic composition comprising a muconopeptide |
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RU2524428C1 (ru) * | 2013-01-21 | 2014-07-27 | Общество с ограниченной ответственностью "Синейро" | Пептиды и их производные, взаимодействующие с никотиновым ацетилхолиновым рецептором и пригодные для использования в косметологии против мимических и возрастных морщин |
CN103570804B (zh) * | 2013-09-11 | 2015-04-15 | 深圳市维琪医药研发有限公司 | 一种具皮肤活性的多肽的合成方法 |
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RU2551276C1 (ru) * | 2014-02-03 | 2015-05-20 | Закрытое Акционерное Общество "Фарм-Синтез" | Способ получения диацетата трипептида |
AU2015252949B2 (en) * | 2014-05-01 | 2020-12-10 | Anterios, Inc. | Methods to treat, prevent, and improve skin conditions |
CN104327155A (zh) * | 2014-10-20 | 2015-02-04 | 张嘎 | 一种含有15n—l—脯氨酸残基的三肽型减皱化合物及其制备方法和应用 |
CN104478991B (zh) * | 2014-12-10 | 2018-06-19 | 深圳市维琪医药研发有限公司 | 一种新型多肽化合物及其制备方法和其医药应用 |
KR101710486B1 (ko) * | 2015-01-05 | 2017-02-28 | 주식회사 앤코스메슈 | 올리고펩타이드 유도체 및 이를 포함하는 주름개선용 조성물 |
CN104592348A (zh) * | 2015-01-16 | 2015-05-06 | 张嘎 | 一种含有3,4-脱氢-l-脯氨酸残基的三肽减皱化合物及其制备方法和应用 |
BR112018011857A2 (pt) * | 2015-12-16 | 2018-11-27 | Dsm Ip Assets Bv | uso de dipeptídeos que contêm prolina |
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BRPI0517917A (pt) | 2008-10-21 |
WO2006047900A3 (de) | 2006-07-27 |
US20090111731A1 (en) | 2009-04-30 |
PL1809652T3 (pl) | 2010-10-29 |
EP1809652B1 (de) | 2010-05-05 |
CN101061134B (zh) | 2011-05-11 |
ATE466867T1 (de) | 2010-05-15 |
KR101227301B1 (ko) | 2013-01-29 |
CN101061134A (zh) | 2007-10-24 |
BRPI0517917B1 (pt) | 2020-11-10 |
JP2008518978A (ja) | 2008-06-05 |
ES2345667T3 (es) | 2010-09-29 |
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