JP6533297B2 - 表皮成長因子とリポソームのハイブリッド型多層ナノ構造体及びその製造方法 - Google Patents
表皮成長因子とリポソームのハイブリッド型多層ナノ構造体及びその製造方法 Download PDFInfo
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- 102000009024 Epidermal Growth Factor Human genes 0.000 title claims description 62
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/14—Liposomes; Vesicles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/55—Phosphorus compounds
- A61K8/553—Phospholipids, e.g. lecithin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
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- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
- A61K9/1272—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids
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- A—HUMAN NECESSITIES
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- 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
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/56—Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
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- Chemical & Material Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Organic Chemistry (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
本発明は、
(a)陽イオン性脂質二重膜構造で構成された、内部が空である球−単一層リポソーム;
(b)前記球−単一層リポソームを囲み、陽イオン性脂質二重膜構造で構成された、一つ以上の単一層リポソーム;及び
(c)表皮成長因子;
を含み、前記表皮成長因子は、前記単一層リポソームの間に静電気的相互作用によって結合して位置することを特徴とする表皮成長因子とリポソームのハイブリッド型多層ナノ構造体(hybrid multi-lamellar nanostructures)に関するものである。
1,2−ジオレオイル−sn−グリセロ−3−エチルホスホコリン(1,2-dioleoyl-sn-glycero-3-ethylphosphocholine、EDOPC)、
1−パルミトイル−2−オレオイル−sn−グリセロ−3−エチルホスホコリン(1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine、EPOPC)、
1,2−ジミリストイル−sn−グリセロ−3−エチルホスホコリン(1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine、EDMPC)、
1,2−ジステアロイル−sn−グリセロ−3−エチルホスホコリン(1,2-distearoyl-sn-glycero-3-ethylphosphocholine、SPC)、
1,2−ジパルミトイル−sn−グリセロ−3−エチルホスホコリン(1-dipalmitoyl-sn-glycero-3-ethylphosphocholine、EDPPC)、
1,2−ジオレオイル−3−トリメチルアンモニウム−プロパン(1,2-dioleoyl-3-trimethylammonium-propane、DOTAP)、
N−[1−(2,3−ジオレイルオキシ)プロピル]ーN,N,N−トリメチルアンモニウムクロリド(N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride、DOTMA)、
3β−[N−(N’,N’−ジメチルアミノエタン)−カルバモイル]コレステロール(3β[N−(N',N'-dimethylaminoethane)-carbamoyl]cholesterol、DC−Cholesterol)、ジオレオイルグルタミド(dioleoyl glutamide)、ジステアロイルグルタミド(distearoyl glutamide)、ジパルミトイルグルタミド(dipalmitoyl glutamide)、ジオレオイルアスパルタミド(dioleoyl aspartamide)及びジメチルジオクタデシルアンモニウムブロミド(dimethyldioctadecylammonium bromide、DDAB)からなる群より選択された単独または2種以上であり得るが、これに限定されるものではない。
(1)陽イオン性脂質からなり、粒子サイズが均一な、内部が空いている球−単一層リポソーム含有溶液を製造するステップ;
(2)表皮成長因子含有水溶液を製造するステップ;及び
(3)前記ステップ(1)で得られた球−単一層リポソーム含有溶液と、前記ステップ(2)で得られた表皮成長因子含有水溶液とを混合するステップ;
を含むハイブリッド型多層ナノ構造体の製造方法に関するものである。
1,2−ジオレオイル−sn−グリセロ−3−エチルホスホコリン(1,2-dioleoyl-sn-glycero-3-ethylphosphocholine、EDOPC)、
1−パルミトイル−2−オレオイル−sn−グリセロ−3−エチルホスホコリン(1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine、EPOPC)、
1,2−ジミリストイル−sn−グリセロ−3−エチルホスホコリン(1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine、EDMPC)、
1,2−ジステアロイル−sn−グリセロ−3−エチルホスホコリン(1,2-distearoyl-sn-glycero-3-ethylphosphocholine、SPC)、
1,2−ジパルミトイル−sn−グリセロ−3−エチルホスホコリン(1-dipalmitoyl-sn-glycero-3-ethylphosphocholine、EDPPC)、
1,2−ジオレオイル−3−トリメチルアンモニウム−プロパン(1,2-dioleoyl-3-trimethylammonium-propane、DOTAP)、
N−[1−(2,3−ジオレイルオキシ)プロピル]ーN,N,N−トリメチルアンモニウムクロリド(N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride、DOTMA)、
3β−[N−(N’,N’−ジメチルアミノエタン)−カルバモイル]コレステロール(3β[N−(N',N'-dimethylaminoethane)-carbamoyl]cholesterol、DC−Cholesterol)、ジオレオイルグルタミド(dioleoyl glutamide)、ジステアロイルグルタミド(distearoyl glutamide)、ジパルミトイルグルタミド(dipalmitoyl glutamide)、ジオレオイルアスパルタミド(dioleoyl aspartamide)及びジメチルジオクタデシルアンモニウムブロミド(dimethyldioctadecylammonium bromide、DDAB)からなる群より選択された単独または2種以上であり得るが、これに限定されるものではない。
(a)陽イオン性脂質二重膜構造で構成された、内部が空いている球−単一層リポソーム;
(b)前記球−単一層リポソームを囲み、かつ陽イオン性脂質二重膜構造で構成された一つ以上の単一層リポソーム;及び
(c)表皮成長因子;
を含み、前記表皮成長因子は前記単一層リポソームの間に位置する。
1.1 DOTAPを含む陽イオン性球−単一層リポソームの製造
回転蒸留濃縮装置(rotary evaporator)で、低速で脂質溶液に窒素ガスを流し込んでクロロフォルムを除去して乾燥し、薄い脂質フィルム膜を形成した。
形成された脂質フィルム膜を12時間真空でさらに乾燥し、残余クロロフォルムを完全に除去した。得られた脂質フィルム膜に精製水1mlを加え、37℃で2時間攪拌して脂質球−小胞体を製造した。得られた脂質球−小胞体を孔サイズが100nmであるポリカーボネート膜(policarbonate membrain)(Avanti Polar Lipid, Inc.)を用いて押出法で数回繰り返し透過させ、粒子サイズが均一なDOTAPを含む陽イオン性球−単一層リポソームを製造した。
1.1.陽イオン性球−単一層リポソーム形成の確認
Claims (2)
- (a)陽イオン性脂質二重膜構造で構成された、内部が空である球−単一層リポソーム;
(b)前記球−単一層リポソームを囲み、陽イオン性脂質二重膜構造で構成された、一つ以上の単一層リポソーム;及び
(c)表皮成長因子;
を含み、前記表皮成長因子は、前記単一層リポソームの間に静電気的相互作用によって結合して位置することを特徴とし、粒子サイズが100〜200nmであり、前記表皮成長因子と陽イオン性脂質との重量比(w/w)(表皮成長因子:陽イオン性脂質)が、0.001〜2.5:1である、表皮成長因子とリポソームのハイブリッド型多層ナノ構造体(hybrid multi-lamellar nanostructure)。 - 請求項1に記載のハイブリッド型多層ナノ構造体を有効成分として含む化粧料組成物。
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