JP5864615B2 - リポソーム及びそれを含むパーソナルケア組成物 - Google Patents
リポソーム及びそれを含むパーソナルケア組成物 Download PDFInfo
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- JP5864615B2 JP5864615B2 JP2013550723A JP2013550723A JP5864615B2 JP 5864615 B2 JP5864615 B2 JP 5864615B2 JP 2013550723 A JP2013550723 A JP 2013550723A JP 2013550723 A JP2013550723 A JP 2013550723A JP 5864615 B2 JP5864615 B2 JP 5864615B2
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- Prior art keywords
- liposome
- liposomes
- phospholipid
- aqueous
- dispersion
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- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000011093 media selection Methods 0.000 description 1
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 150000002993 phenylalanine derivatives Chemical class 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000008103 phosphatidic acids Chemical class 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003017 phosphorus Chemical class 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920003217 poly(methylsilsesquioxane) Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 210000003370 receptor cell Anatomy 0.000 description 1
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 230000008591 skin barrier function Effects 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
- ALPWRKFXEOAUDR-GKEJWYBXSA-M sodium;[(2r)-2,3-di(octadecanoyloxy)propyl] hydrogen phosphate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)([O-])=O)OC(=O)CCCCCCCCCCCCCCCCC ALPWRKFXEOAUDR-GKEJWYBXSA-M 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940012831 stearyl alcohol Drugs 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 239000004563 wettable powder Substances 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
Images
Classifications
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Description
本発明のリポソームはリン脂質を含む。リン脂質は、天然リン脂質、合成リン脂質、及びこれらの組み合わせからなる群から選択してもよい。レシチンは、天然リン脂質源の1つである。レシチンは、卵黄及び大豆などに含まれる混合物である。これは、ホスファチジルコリン(PC)、ホスファチジルエタノールアミン(PE)、及びホスファチジルイノシトール(PI)などの多くのリン脂質を含む。天然リン脂質として、例えば、水素添加大豆PC(HSPC)、スフィンゴミエリン、及びホスファチジルグリセロール(PG)も挙げられる。
本発明のリポソームは、カルボキシレート基を含む疎水性有効成分を含む。
リポソームは、正帯電基を含む親水性アジュバントを含む。正帯電基は、疎水性有効成分のカルボキシレート基と相互作用して、複合体を形成できる。正帯電基は、好ましくは正帯電アンモニウム基(−NH3 +)である。一実施形態では、本発明のリポソームの親水性アジュバントは、一方の末端部に正帯電基を含み、正帯電末端部と反対のもう一方の末端部にカルボキシレート基を含む。本発明の別の実施形態では、親水性アジュバントは、リシン(式I)、アルギニン(式II)、ヒスチジン(式III)、及びこれらの組み合わせからなる群から選択される。
本発明のリポソームは、好ましくは弾性エンハンサを含む弾性リポソームである。弾性エンハンサは、コール酸ナトリウム、デオキシコール酸ナトリウム、ポリソルベート80(Tween 80)、モノオレイン酸ソルビタン(Span 80)、オレイン酸、グリチルリチン酸二カリウム(KG)、及びコレステリルエーテル、並びにこれらの組み合わせからなる群から選択してもよい。一実施形態では、弾性エンハンサは、界面活性剤、例えば、アニオン性界面活性剤、非イオン性界面活性剤、又は双極性界面活性剤、好ましくは非イオン性界面活性剤である。好ましくは、非イオン性界面活性剤は、Tween 80、Span−80及び/又は、式C27H45O(CH2CH2O)nH(式中、nは5〜15、例えば5、10、又は15である)のポリオキシエチレンコレステリルエーテルである。
本発明のリポソームは、水性リポソーム分散液の約0.01重量%又は0.1重量%から約2重量%又は5重量%の酸化防止剤を、任意に含んでよい。酸化防止剤は、ビタミンE、ビタミンEエステル、ビタミンC、ビタミンCエステル、及びこれらの組み合わせからなる群から選択してもよい。好ましい実施形態では、リポソームはビタミンEアセテートを含む。
本発明のリポソームを、以下に記載する工程に沿って、水性リポソーム分散液として作製してもよい。第1に、容器中で70℃において、化粧品業界及び製薬業界でリポソーム作製に許容できる適切な有機溶媒、例えば、エタノール中に、リン脂質及び疎水性有効成分を含むすべての疎水性材料を完全に溶解することにより、プレミックスを形成する。室温において一晩真空下で、微量の溶媒を除去できる。続いて、例えば、回転真空蒸発により、有機溶媒をプレミックスから除去する。次に、溶媒除去後、容器の底部に付着したリン脂質フィルムが形成される。親水性アジュバントを含む水性媒体、例えば、リン酸緩衝液(PBS)を用いて、フィルムを水和する。水和後、水性媒体をホモジナイズして水性リポソーム分散液を形成する。ホモジナイズは、連続的に攪拌した後の超音波処理により、又は市販のホモジナイザー、例えば、Emulsiflex C5(Avestin,Canada)により、達成できる。水和媒体の選択、水和方法、及びリポソーム形成に用いられるホモジナイズは、当該技術分野において周知である。水性リポソーム分散液を形成し、室温で保存できる。
封入率
水性リポソーム分散液の作製において、最初に有機溶媒内に投入された疎水性有効成分の総量に対する、リポソーム内にきちんと封入された疎水性有効成分の割合の測定には、封入率を用いる。封入率は、封入効率(EE %)=CS/CU×100%として算出する。
透過効率を用いて、特定の皮膚表面積を透過して、真皮層に達する疎水性有効成分の量を測定する。Franz−Diffusionチャンバとも呼ばれるFranz拡散セルシステムは、当該業界において有効成分の皮膚透過効率の測定に一般に使用される。
この残留量を用いて、皮膚中の全透過深度にわたって、皮膚中に残存する有効成分の総量を測定する。上記透過試験後、ドナー区画中のすべてのサンプルがバリアを通って排出されたときに、バリアを取り外して表面を5回純水でリンスした後に、Franz−Diffusionチャンバに戻した。次に、レセプター区画を50% v/vエタノール−PBSで満たし、バリアの様々な層中に残存するGAをすべて溶解するために、Franz Diffusionチャンバを更に12時間放置する。続いて、サンプルをレセプター区画のサンプリングポートから採取してもよく、サンプル中有効成分濃度をHPLCで測定してもよい。
本発明のリポソームを、疎水性有効成分の経皮的送達を改善する目的で、化粧品組成物及び医薬組成物などのパーソナルケア組成物に組み込んでもよい。化粧品組成物は、クリーム、エマルション、ジェル、ローション、拭き取り用ローション、及びこれらの組み合わせの形態であってもよい。
2.Nihon Emulsion Co.Ltdのポリオキシエチレン(10)コレステリルエーテル
3.Xinjiang Tianshan Pharmaceutical Ltd.のグリチルレチン酸
4.Solarbio Science & Technology Co.,LtdのL−リシン、バイオテクグレード
1.封入率測定
本発明の実施例1〜4のリポソーム及び比較実施例1のリポソームの封入率を、上記測定方法の項に記載の測定方法に従って測定する。比較実施例2のクリーム中のグリチルレチン酸はクリームの油相中に完全に取り込まれているため、その封入率を100%とする。
Franz Diffusionチャンバを純水で1時間平衡化し、サンプルをドナー区画内に添加する。Franz Diffusionチャンバの有効拡散面積に相当する好適な表面積のラット皮膚調製物を、レセプターとドナー区画との間に配置されるバリアとして用いる。この測定には、有効拡散面積0.66cm2を有するFranz拡散チャンバ、及び2.5mLのレシーバーセル容量を用いた。
ドナー区画中のすべてのサンプルがラット皮膚を通って排出された、透過試験の終了時点で、先の測定方法の項に記載の方法に従って、残留物測定に向けて皮膚を取り出す。
Claims (15)
- a)リン脂質と、
b)グリチルレチン酸と、
c)リシン、前記グリチルレチン酸と前記リシンとの複合体、及びこれらの組み合わせからなる群から選択される構成成分と、
を含むリポソーム。 - 前記グリチルレチン酸が、リン脂質の1重量%〜20重量%の量で存在する、請求項1に記載のリポソーム。
- 前記リシンが、リン脂質の1重量%〜20重量%の量で存在する、請求項1に記載のリポソーム。
- 前記グリチルレチン酸と前記リシンのモル比が1:10〜10:1である、請求項1に記載のリポソーム。
- 前記リン脂質が水素添加リン脂質である、請求項1に記載のリポソーム。
- 非イオン性界面活性剤、ポリオキシエチレンコレステリルエーテル、及びこれらの組み合わせからなる群から選択される弾性エンハンサを更に含む、請求項1に記載のリポソーム。
- 前記非イオン性界面活性剤がポリソルベート80又はモノオレイン酸ソルビタンである、請求項6に記載のリポソーム。
- 前記ポリオキシエチレンコレステリルエーテルが、C27H45O(CH2CH2O)nHであり、式中nが5〜15である、請求項6に記載のリポソーム。
- ビタミンE、ビタミンEエステル、ビタミンC、ビタミンCエステル、及びこれらの組み合わせからなる群から選択される酸化防止剤を更に含む、請求項1に記載のリポソーム。
- 前記リン脂質が、水性分散液の1重量%〜20重量%の量で存在する、請求項1〜9のいずれか一項に記載のリポソームを含む、水性リポソーム分散液。
- 前記弾性エンハンサが、水性分散液の0.01重量%〜10重量%の量で存在する、請求項6に記載のリポソームを含む、水性リポソーム分散液。
- 前記酸化防止剤が、水性分散液の0.01重量%〜5重量%の量で存在する、請求項9に記載のリポソームを含む、水性リポソーム分散液。
- 請求項1〜9のいずれか一項に記載のリポソームを含むパーソナルケア組成物であって、クリーム、エマルション、ジェル、ローション、拭き取り用ローション、及びこれらの組み合わせからなる群から選択される形態である、パーソナルケア組成物。
- 請求項10〜12のいずれか一項に記載の水性リポソーム分散液を用いて作製されるパーソナルケア組成物であって、クリーム、エマルション、ジェル、ローション、拭き取り用ローション、及びこれらの組み合わせからなる群から選択される形態である、パーソナルケア組成物。
- a)リン脂質及びグリチルレチン酸を有機溶媒中に溶解し、プレミックスを形成する工程と、
b)前記有機溶媒を前記プレミックスから蒸発させ、リン脂質フィルムを形成する工程と、
c)リシンを含む水和媒体で前記フィルムを水和する工程と、
d)水和媒体をホモジナイズし、水性リポソーム分散液を形成する工程と、
を含むリポソームの作製プロセス。
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PCT/CN2011/000111 WO2012100366A1 (en) | 2011-01-25 | 2011-01-25 | Liposome and personal care composition comprising thereof |
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JP (1) | JP5864615B2 (ja) |
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CA2825417A1 (en) | 2012-08-02 |
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WO2012100366A8 (en) | 2013-09-12 |
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