JP2008264897A - Hollow fiber type organic nanotube intercalated with low-molecular organic compound and method for producing the same - Google Patents
Hollow fiber type organic nanotube intercalated with low-molecular organic compound and method for producing the same Download PDFInfo
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- JP2008264897A JP2008264897A JP2007107999A JP2007107999A JP2008264897A JP 2008264897 A JP2008264897 A JP 2008264897A JP 2007107999 A JP2007107999 A JP 2007107999A JP 2007107999 A JP2007107999 A JP 2007107999A JP 2008264897 A JP2008264897 A JP 2008264897A
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- Prior art keywords
- organic compound
- hollow fiber
- organic
- low molecular
- intercalated
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- 239000002071 nanotube Substances 0.000 title claims abstract description 111
- 239000012510 hollow fiber Substances 0.000 title claims abstract description 65
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- 150000002632 lipids Chemical class 0.000 claims abstract description 32
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 claims abstract description 26
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- 239000002904 solvent Substances 0.000 claims abstract description 21
- 239000012528 membrane Substances 0.000 claims abstract description 12
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- 150000002430 hydrocarbons Chemical group 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/10—Phosphatides, e.g. lecithin
- C07F9/106—Adducts, complexes, salts of phosphatides
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Abstract
Description
本発明は、医薬、化成品分野などにおける包接・分離用材料、薬剤徐放材料として、あるいは高機能性材料として有用な低分子有機化合物インターカレート型中空繊維状有機ナノチューブとその製造方法に関するものである。 The present invention relates to a low-molecular-weight organic compound intercalated hollow fiber organic nanotube useful as an inclusion / separation material, a drug sustained-release material, or a high-functional material in the fields of medicine and chemicals, and a method for producing the same. Is.
ナノテクノロジーを代表する材料として０．５〜５００ナノメートル（以下ｎｍと記す）の細孔を有するナノチューブ状材料が注目を集めている。そのなかでも人工的に初めて合成された無機系ナノチューブであるカーボンナノチューブは良く知られており（非特許文献１）、そのサイズ、形状、化学構造、等に由来する特性への期待から、ナノスケールの電子デバイス、高強度材料、電子放出、及びガス貯蔵等への用途開発とともに、実用化への要望から精力的に量産化に関する研究が進められている（特許文献１、非特許文献２）。 As a material representative of nanotechnology, a nanotube-like material having pores of 0.5 to 500 nanometers (hereinafter referred to as nm) has attracted attention. Among them, carbon nanotubes, which are inorganic nanotubes synthesized artificially for the first time, are well known (Non-Patent Document 1). From the expectation of characteristics derived from their size, shape, chemical structure, etc., nanoscale In addition to development of applications for electronic devices, high-strength materials, electron emission, gas storage, etc., research on mass production has been vigorously pursued from the demand for practical application (Patent Document 1, Non-Patent Document 2).
また、１ｎｍ以下の細孔を有する有機環状化合物としてシクロデキストリンが有名である。シクロデキストリンは、種々の低分子有機化合物をその環状中空部に内包できることから、健康食品分野、化粧品分野、抗菌消臭・家庭品分野、工業・農業・環境分野への貢献を目的に、様々なシクロデキストリン包接品が研究開発され、既に事業化されているものも多い（特許文献２〜４）。このようなシクロデキストリンの広範な用途開発の実施は、シクロデキストリンの量産化が実現していることと、シクロデキストリンの構造がブドウ糖６〜８単位を環状に連ねたものであり、生体への安全性が確保されていることが大きな要因である。 Cyclodextrin is well known as an organic cyclic compound having pores of 1 nm or less. Cyclodextrins can encapsulate various low-molecular-weight organic compounds in their annular hollow parts. Many cyclodextrin inclusion products have been researched and developed and are already commercialized (Patent Documents 2 to 4). The development of a wide range of applications for such cyclodextrins is realized by the mass production of cyclodextrins and the structure of cyclodextrins in which 6 to 8 units of glucose are linked in a ring, which is safe for the living body. The main factor is that it is secured.
本発明者らは無機系ナノチューブとは違った分野での応用が見込まれ、またシクロデキストリンよりも大きな内孔サイズの中空構造を有する長鎖炭化水素基に糖残基を結合させた糖脂質又はペプチド脂質を自己集合させることにより形成される中空繊維状有機ナノチューブを合成することに成功している（特許文献５、６、非特許文献３）。この中空繊維状有機ナノチューブは、中空シリンダー部の内孔サイズが１０〜５００ｎｍであり、シクロデキストリンよりも一桁以上大きいため、シクロデキストリンでは包接が不可能である３〜５００ｎｍのタンパク質、ウイルス、金属微粒子やその他の無機微粒子等をその中空シリンダー内部に捕捉できるため、その用途開発が行われている。 The present inventors are expected to be applied in a field different from inorganic nanotubes, and are glycolipids in which sugar residues are bonded to long-chain hydrocarbon groups having a hollow structure having a larger inner pore size than cyclodextrins or It has succeeded in synthesizing hollow fiber-like organic nanotubes formed by self-assembling peptide lipids (Patent Documents 5 and 6, Non-Patent Document 3). This hollow fiber-like organic nanotube has a hollow cylinder part with an inner pore size of 10 to 500 nm, which is larger by one digit or more than cyclodextrin, so that it can not be included in cyclodextrin from 3 to 500 nm of proteins, viruses, Since metal fine particles and other inorganic fine particles can be trapped inside the hollow cylinder, their use has been developed.
１ｎｍ以下の細孔を有するシクロデキストリンが包接することの出来る低分子有機化合物は、１ｎｍ以下のシクロデキストリン細孔に入ることが出来るものに限られている。すなわち、１ｎｍ以下のサイズを有する低分子有機化合物であり、１ｎｍより大きなサイズを有する有機化合物は、包接することが出来ない。また、シクロデキストリンの低分子有機化合物に対する包接は、溶液中において包接状態と解離状態が共存する平衡状態にあり、一般的にシクロデキストリン−低分子有機化合物包接体の安定性は高くはないことから、より安定性の高い包接体が求められている。 Low molecular weight organic compounds that can be included by cyclodextrins having pores of 1 nm or less are limited to those that can enter cyclodextrin pores of 1 nm or less. That is, it is a low molecular organic compound having a size of 1 nm or less, and an organic compound having a size larger than 1 nm cannot be included. In addition, the inclusion of cyclodextrin with a low molecular organic compound is in an equilibrium state in which the inclusion state and the dissociation state coexist in the solution, and the stability of the cyclodextrin-low molecular organic compound inclusion is generally high. Therefore, a more stable clathrate is required.
一方、本発明者らの開発した中空繊維状有機ナノチューブは中空構造を有し、その内孔サイズは、１０〜５００ｎｍであるため、その内孔サイズより小さい３〜５００ｎｍのタンパク質、ウイルス、金属微粒子やその他の無機微粒子等をその中空シリンダー内部に捕捉できる。しかしながら、３ｎｍより小さい有機化合物を安定に包接することは、困難であった。
本発明は、上記従来の課題に鑑みなされたものであり、その目的は、シクロデキストリン包接体に不足する、安定性のある低分子有機化合物の包接体及びその製造方法を提供することにある。また、本発明のもう１つの目的は、シクロデキストリンが包接することの出来ない１ｎｍより大きなサイズであって、中空繊維状有機ナノチューブが安定に包接することの出来ない３ｎｍより小さいサイズの有機化合物の包接体及びその製造方法を提供することにある。 The present invention has been made in view of the above-described conventional problems, and an object of the present invention is to provide a stable inclusion body of a low-molecular-weight organic compound that is deficient in a cyclodextrin inclusion body and a method for producing the same. is there. Another object of the present invention is to provide an organic compound having a size larger than 1 nm in which cyclodextrin cannot be included and a hollow fiber-like organic nanotube cannot be stably included in a size smaller than 3 nm. It is in providing a clathrate and a manufacturing method thereof.
発明者らは、上記課題を解決するため、鋭意検討した結果、糖脂質又はペプチド脂質と組み合わせた低分子有機化合物を、溶媒単独もしくは何種類かの溶媒を組み合わせた混合溶媒に溶解し、その溶液を室温下に静置するか或いは濃縮することにより自己集合させると、低分子有機化合物が中空繊維状有機ナノチューブを構成する脂質二分子膜内にインターカレートした低分子有機化合物インターカレート型中空繊維状有機ナノチューブを形成することを見出し、本発明を完成させるに至った。 As a result of intensive studies to solve the above problems, the inventors have dissolved a low-molecular-weight organic compound combined with a glycolipid or peptide lipid in a solvent alone or a mixed solvent combined with several solvents, and the solution Low-molecular-weight organic compound intercalated hollow intercalated into lipid bilayers constituting hollow-fiber organic nanotubes when allowed to stand at room temperature or self-assemble by concentrating The present inventors have found that a fibrous organic nanotube is formed, and have completed the present invention.
すなわち本発明は、医薬、化成品分野などにおける包接・分離用材料、薬剤徐放材料として、あるいは高機能性材料として有用な、糖脂質又はペプチド脂質と組み合わせた炭化水素化合物の使用を特徴とする、以下の（１）ないし（１０）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブを提供するものである。
（１）糖脂質又はペプチド脂質から合成される中空繊維状有機ナノチューブの脂質膜中に低分子有機化合物がインターカートされていることを特徴とする低分子有機化合物インターカレート型中空繊維状有機ナノチューブ。
（２）前記糖脂質が、下記一般式（１）
Ｇ−ＮＨＣＯ−Ｒ （１）
（式中、Ｇは糖のアノマー炭素原子に結合するヘミアセタール水酸基を除いた糖残基を表し、Ｒは炭素数が１０〜２４の不飽和炭化水素基を表す。）で表わされるＮ−グリコシド型糖脂質である前記（１）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブ。
（３）前記糖がグルコースである前記（２）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブ。
（４）前記糖脂質が下記一般式（２）
Ｇ−ＮＨＣＯ−（ＣＨ２）ｎＣＯＯＨ （２）
（式中、Ｇは糖のアノマー炭素原子に結合するヘミアセタール水酸基を除いた糖残基を表し、ｎは６〜２０の整数を表す。）で表わされる非対称双頭型糖脂質である前記（１）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブ。
（５）前記糖がグルコースである前記（４）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブ。
（６）前記ペプチド脂質が下記一般式（３）
ＱＣＯ（ＮＨＣＨ２ＣＯ）ｍＯＨ （３）
（式中、Ｑは炭素数６〜１８の炭化水素基、ｍは１〜３の整数を表す。）で表わされるペプチド脂質である前記（１）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブ。
（７）前記ペプチドがグリシルグリシン（ｍ＝２）である前記（６）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブ。
（８）前記低分子有機化合物が、脂肪族炭化水素及び芳香族炭化水素から選ばれるものであり、中空繊維状有機ナノチューブを構成する脂質二分子膜内にインターカレート出来る構造を有する３ｎｍ以下の大きさを持つ炭化水素化合物である前記（１）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブ。
（９）前記低分子有機化合物が、機能性化合物である前記（１）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブ。
（１０）前記低分子有機化合物が、蛍光性を有する化合物である前記（１）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブ。
That is, the present invention is characterized by the use of a hydrocarbon compound in combination with a glycolipid or peptide lipid, which is useful as an inclusion / separation material, a drug sustained-release material, or a highly functional material in the fields of medicine and chemicals. The following (1) to (10) low molecular organic compound intercalated hollow fiber organic nanotubes are provided.
(1) A low-molecular-weight organic compound intercalated hollow-fibrous organic nanotube characterized in that a low-molecular-weight organic compound is intercarted in a lipid membrane of a hollow-fibrous organic nanotube synthesized from glycolipid or peptide lipid .
(2) The glycolipid is represented by the following general formula (1)
G-NHCO-R (1)
(In the formula, G represents a sugar residue excluding the hemiacetal hydroxyl group bonded to the anomeric carbon atom of the sugar, and R represents an unsaturated hydrocarbon group having 10 to 24 carbon atoms). (1) The low-molecular-weight organic compound intercalated hollow fiber organic nanotube of the above (1) which is a type glycolipid.
(3) The low-molecular-weight organic compound intercalated hollow fiber organic nanotube according to (2), wherein the sugar is glucose.
(4) The glycolipid is represented by the following general formula (2)
G-NHCO- (CH 2) n COOH (2)
(Wherein G represents a sugar residue excluding the hemiacetal hydroxyl group bonded to the anomeric carbon atom of the sugar, and n represents an integer of 6 to 20). ) Low molecular organic compound intercalated hollow fiber organic nanotube.
(5) The low-molecular-weight organic compound intercalated hollow fiber organic nanotube according to (4), wherein the sugar is glucose.
(6) The peptide lipid is represented by the following general formula (3)
QCO (NHCH 2 CO) m OH (3)
(Wherein Q represents a hydrocarbon group having 6 to 18 carbon atoms, and m represents an integer of 1 to 3). The low molecular weight organic compound intercalated hollow fiber of (1), which is a peptide lipid represented by Organic nanotube.
(7) The low molecular organic compound intercalated hollow fiber organic nanotube according to (6), wherein the peptide is glycylglycine (m = 2).
(8) The low-molecular organic compound is selected from aliphatic hydrocarbons and aromatic hydrocarbons, and has a structure capable of intercalating in a lipid bilayer membrane constituting a hollow fiber-like organic nanotube. The low molecular weight organic compound intercalated hollow fiber organic nanotube according to (1), which is a hydrocarbon compound having a size.
(9) The low molecular organic compound intercalated hollow fiber organic nanotube of (1), wherein the low molecular organic compound is a functional compound.
(10) The low molecular organic compound intercalated hollow fiber organic nanotube according to (1), wherein the low molecular organic compound is a fluorescent compound.
また本発明は、以下の（１１）ないし（１９）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブの製造方法を提供するものである
（１１）糖脂質又はペプチド脂質と低分子有機化合物を溶媒に溶解させる工程、その溶液を室温下に静置するか或いは濃縮することにより、溶液中で自己集合させて、低分子有機化合物インターカレート型中空繊維状有機ナノチューブを生成させる工程、生成した低分子有機化合物インターカレート型中空繊維状有機ナノチューブを溶液から回収し、室温で風乾又は減圧加熱乾燥させる工程からなる、低分子有機化合物インターカレート型中空繊維状有機ナノチューブの製造方法。
（１２）前記糖脂質が下記一般式（１）
Ｇ−ＮＨＣＯ−Ｒ （１）
（式中、Ｇは糖のアノマー炭素原子に結合するヘミアセタール水酸基を除いた糖残基を表し、Ｒは炭素数が１０〜２４の不飽和炭化水素基を表す。）で表わされるＮ−グリコシド型糖脂質である前記（１１）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブの製造方法。
（１３）前記糖がグルコースである前記（１２）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブの製造方法。
（１４）前記糖脂質が下記一般式（２）
Ｇ−ＮＨＣＯ−（ＣＨ２）ｎＣＯＯＨ （２）
（式中、Ｇは糖のアノマー炭素原子に結合するヘミアセタール水酸基を除いた糖残基を表し、ｎは６〜２０の整数を表す。）で表わされる非対称双頭型糖脂質である前記（１１）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブの製造方法。
（１５）前記糖がグルコースである前記（１４）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブの製造方法。
（１６）前記ペプチド脂質が下記一般式（３）
ＱＣＯ（ＮＨＣＨ２ＣＯ）ｍＯＨ （３）
（式中、Ｑは炭素数６〜１８の炭化水素基、ｍは１〜３の整数を表す。）で表わされるペプチド脂質である前記（１１）に記載の低分子有機化合物インターカレート型中空繊維状有機ナノチューブの製造方法。
（１７）前記ペプチドがグリシルグリシン（ｍ＝２）である前記（１６）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブの製造方法。
（１８）前記低分子有機化合物が、脂肪族炭化水素及び芳香族炭化水素から選ばれるものであり、中空繊維状有機ナノチューブを構成する脂質二分子膜内にインターカレート出来る構造を有する３ｎｍ以下の大きさを持つ炭化水素化合物である前記（１１）の低分子有機化合物インターカレート型中空繊維状有機ナノチューブの製造方法。
（１９）前記溶媒が、沸点が１２０℃以下のアルコール類を少なくとも１０容積％含む前記１１〜１８の低分子有機化合物インターカレート型中空繊維状有機ナノチューブの製造方法。
The present invention also provides a method for producing the following low molecular organic compound intercalated hollow fiber organic nanotubes (11) to (19): (11) Glycolipid or peptide lipid and low molecular organic compound A step of dissolving a solution in a solvent, a step of generating a low-molecular-weight organic compound intercalated hollow fiber organic nanotube by allowing the solution to stand at room temperature or concentrating it to self-assemble in the solution. A method for producing a low molecular weight organic compound intercalated hollow fiber-like organic nanotube comprising a step of recovering the low molecular weight organic compound intercalated hollow fiber shaped organic nanotube from a solution and air drying or drying under reduced pressure at room temperature.
(12) The glycolipid is represented by the following general formula (1)
G-NHCO-R (1)
(In the formula, G represents a sugar residue excluding the hemiacetal hydroxyl group bonded to the anomeric carbon atom of the sugar, and R represents an unsaturated hydrocarbon group having 10 to 24 carbon atoms). (11) The manufacturing method of the low molecular weight organic compound intercalation type | mold hollow fiber organic nanotube which is a type | mold glycolipid.
(13) The method for producing a low molecular weight organic compound intercalated hollow fiber organic nanotube according to (12), wherein the sugar is glucose.
(14) The glycolipid is represented by the following general formula (2)
G-NHCO- (CH 2) n COOH (2)
(Wherein G represents a sugar residue excluding the hemiacetal hydroxyl group bonded to the anomeric carbon atom of the sugar, and n represents an integer of 6 to 20). ) For producing low-molecular-weight organic compound intercalated hollow fiber organic nanotubes.
(15) The method for producing a low-molecular-weight organic compound intercalated hollow fiber organic nanotube according to (14), wherein the sugar is glucose.
(16) The peptide lipid is represented by the following general formula (3):
QCO (NHCH 2 CO) m OH (3)
(In the formula, Q is a hydrocarbon group having 6 to 18 carbon atoms, and m is an integer of 1 to 3). A method for producing fibrous organic nanotubes.
(17) The method for producing a low-molecular organic compound intercalated hollow fiber organic nanotube according to (16), wherein the peptide is glycylglycine (m = 2).
(18) The low molecular organic compound is selected from aliphatic hydrocarbons and aromatic hydrocarbons, and has a structure capable of intercalating in a lipid bilayer membrane constituting a hollow fiber-like organic nanotube of 3 nm or less (11) The method for producing a low molecular weight organic compound intercalated hollow fiber organic nanotube according to the above (11), which is a hydrocarbon compound having a size.
(19) The method for producing a low molecular weight organic compound intercalated hollow fiber organic nanotube according to the above 11 to 18, wherein the solvent contains at least 10% by volume of an alcohol having a boiling point of 120 ° C. or less.
本発明の低分子有機化合物インターカレート型中空繊維状有機ナノチューブは、３ｎｍより小さい低分子有機化合物を安定に微細中空繊維状有機ナノチューブの膜中に分散含有しているため、微細中空繊維状有機ナノチューブが元来有するその中空内部への３ｎｍ未満並びに３ｎｍ以上のサイズを有する薬剤や生体分子の包接能力と、その膜中に３ｎｍより小さい低分子有機化合物を安定に分散含有する能力を併せ持つ、新規な複合材料を作成し、提供できるものである。 Since the low molecular organic compound intercalated hollow fiber organic nanotube of the present invention contains a low molecular organic compound smaller than 3 nm stably dispersed in the fine hollow fiber organic nanotube film, the fine hollow fiber organic nanotube The ability of inclusion of drugs and biomolecules having a size of less than 3 nm and a size of 3 nm or more into the hollow interior of nanotubes and the ability to stably disperse low molecular organic compounds smaller than 3 nm in the membrane, New composite materials can be created and provided.
また、本発明の中空繊維状有機ナノチューブは、例えば、ファインケミカル工業分野、医薬、化粧品分野などにおいて薬剤や有用生体分子の包接・分離用材料、ドラッグデリバリ材料として利用可能である。その際、膜中に安定に分散含有された有機化合物は、中空内部へ包接された薬剤等と環境が異なるため、薬剤等を包接した低分子有機化合物インターカレート型中空繊維状有機ナノチューブを溶媒中に分散した場合、包接された薬剤は溶媒に運ばれ徐放されるが、膜中に分散含有された低分子有機化合物は安定に存在し続けることができる。
すなわち、膜中に分散含有される低分子有機化合物として蛍光性を有する化合物を使用すれば、微細中空繊維状有機ナノチューブの生体内での直接蛍光顕微鏡観察が可能になり、薬剤等を包接した微細中空繊維状有機ナノチューブがどの様な挙動を示すか明らかにすることができる。
Further, the hollow fibrous organic nanotube of the present invention can be used as a material for inclusion / separation of drugs and useful biomolecules and a drug delivery material, for example, in the fields of fine chemical industry, medicine, cosmetics and the like. At that time, since the organic compound stably dispersed in the membrane has a different environment from the drug encapsulated in the hollow interior, the low molecular organic compound intercalated hollow fiber organic nanotubes encapsulating the drug etc. Is dispersed in a solvent, the encapsulated drug is carried to the solvent and released slowly, but the low molecular weight organic compound dispersed and contained in the film can continue to exist stably.
That is, if a fluorescent compound is used as the low molecular weight organic compound dispersed and contained in the membrane, it becomes possible to directly observe the hollow fiber-like organic nanotube in the living body with a fluorescence microscope, and include a drug or the like. It is possible to clarify how the fine hollow fiber-like organic nanotubes behave.
さらには、微小なチューブ構造を利用した人工血管、ナノチューブキャピラリ、ナノリアクターとして医療、分析、化学品製造分野などで有用であり、工業的利用価値が高いため、これら様々な分野へ貢献することができる。 In addition, it is useful as an artificial blood vessel, nanotube capillary, and nanoreactor using a micro tube structure in the fields of medicine, analysis, and chemical production, and has high industrial utility value, so it can contribute to these various fields. it can.
本発明の低分子有機化合物インターカレート型中空繊維状有機ナノチューブは、一般式（１）Ｇ−ＮＨＣＯ−Ｒ並びに一般式（２）Ｇ−ＮＨＣＯ−（ＣＨ２）ｎＣＯＯＨで表される糖脂質、もしくは一般式（３）ＱＣＯ（ＮＨＣＨ２ＣＯ）ｍＯＨで表されるペプチド脂質と、低分子有機化合物を原料とすることによって製造することができる。
この一般式（１）及び一般式（２）中、Ｇは糖のアノマー炭素原子に結合するヘミアセタール水酸基を除いた糖残基、好ましくはグルコースである。
上記一般式（１）中、Ｒは炭素数が１０〜２４の不飽和炭化水素基、好ましくは１個の二重結合を含む不飽和炭化水素基である。またＲの炭素数は６〜２４、好ましくは１０〜１６である。
上記一般式（２）中、ｎは６〜２０の整数であり、好ましくは１０〜１６である。
上記一般式（３）中、Ｑは炭素数６〜１８の炭化水素基、好ましくは１０〜１６である。また上記一般式（３）中、ｍは１〜３の整数であり、好ましくは２である。
The low molecular weight organic compound intercalated hollow fiber organic nanotube of the present invention is a glycolipid represented by general formula (1) G-NHCO-R and general formula (2) G-NHCO- (CH 2 ) n COOH. Or a peptide lipid represented by general formula (3) QCO (NHCH 2 CO) m OH and a low molecular organic compound as raw materials.
In general formulas (1) and (2), G is a sugar residue, preferably glucose, excluding the hemiacetal hydroxyl group bonded to the anomeric carbon atom of the sugar.
In the above general formula (1), R is an unsaturated hydrocarbon group having 10 to 24 carbon atoms, preferably an unsaturated hydrocarbon group containing one double bond. R has 6 to 24 carbon atoms, preferably 10 to 16 carbon atoms.
In said general formula (2), n is an integer of 6-20, Preferably it is 10-16.
In said general formula (3), Q is a C6-C18 hydrocarbon group, Preferably it is 10-16. Moreover, in said general formula (3), m is an integer of 1-3, Preferably it is 2.
図１は、前記糖脂質又はペプチド脂質と、前記低分子有機化合物とから合成される、本発明の低分子有機化合物インターカレート型中空繊維状有機ナノチューブを模式的に示すものである。
図１に示すとおり、本発明の低分子有機化合物インターカレート型中空繊維状有機ナノチューブは、中空繊維状有機ナノチューブを構成する脂質二分子膜内に、低分子有機化合物がインターカレートした構造を有するものである。
FIG. 1 schematically shows a low molecular organic compound intercalated hollow fiber organic nanotube of the present invention synthesized from the glycolipid or peptide lipid and the low molecular organic compound.
As shown in FIG. 1, the low molecular organic compound intercalated hollow fiber organic nanotube of the present invention has a structure in which a low molecular organic compound is intercalated in a lipid bilayer membrane constituting the hollow fiber organic nanotube. It is what you have.
本発明においてインターカレートされる低分子有機化合物は、脂肪族炭化水素及び芳香族炭化水素から選ばれるものであり、中空繊維状有機ナノチューブを構成する脂質二分子膜内にインターカレート出来る構造を有する３ｎｍ以下の大きさを持つ炭化水素化合物である。
具体的には、クロロフィル色素、ナフトキノン類、アントラキノン類、カテキン類、フラボノイド類、スチルベノイド類、フェニルプロパノイド類、カロテノイド系色素、テルペン類、ステロイド、トリテルペンアルコール類、脂溶性ビタミン類、脂肪酸類、アルカロイド、ポルフィリン誘導体、フタロシアニン誘導体、ナフタレン誘導体、アントラセン誘導体、ピレン誘導体、ペリレン誘導体、等の低分子有機化合物が挙げられる。
The low molecular weight organic compound intercalated in the present invention is selected from aliphatic hydrocarbons and aromatic hydrocarbons, and has a structure capable of intercalating in the lipid bilayer membrane constituting the hollow fiber organic nanotube. It is a hydrocarbon compound having a size of 3 nm or less.
Specifically, chlorophyll pigments, naphthoquinones, anthraquinones, catechins, flavonoids, stilbenoids, phenylpropanoids, carotenoid pigments, terpenes, steroids, triterpene alcohols, fat-soluble vitamins, fatty acids, alkaloids , Low molecular organic compounds such as porphyrin derivatives, phthalocyanine derivatives, naphthalene derivatives, anthracene derivatives, pyrene derivatives, perylene derivatives, and the like.
また、本発明における前記低分子有機化合物は、所望の機能を有する機能性化合物であることが好ましい。
例えば、前記低分子有機化合物として蛍光性を有する化合物を用いた場合には、微細中空繊維状有機ナノチューブの生体内での直接蛍光顕微鏡観察が可能になり、薬剤等を包接した微細中空繊維状有機ナノチューブがどの様な挙動を示すか明らかにすることができる。
このような蛍光性を有する低分子有機化合物としては、具体的には、８−アミノ−１−ナフタレンスルホン酸塩類、フタロシアニン誘導体、ポルフィリン誘導体、アントラセン誘導体、フルオレセイン誘導体、クマリン誘導体、ピレン誘導体、等を挙げることができる。
Moreover, it is preferable that the said low molecular organic compound in this invention is a functional compound which has a desired function.
For example, when a compound having fluorescence is used as the low molecular weight organic compound, it becomes possible to directly observe a fine hollow fiber-like organic nanotube in a living body with a fluorescence microscope, and a fine hollow fiber shape in which a drug or the like is included. It is possible to clarify how organic nanotubes behave.
Specific examples of such low-molecular organic compounds having fluorescence include 8-amino-1-naphthalene sulfonates, phthalocyanine derivatives, porphyrin derivatives, anthracene derivatives, fluorescein derivatives, coumarin derivatives, pyrene derivatives, and the like. Can be mentioned.
次に、一般式（１）もしくは一般式（２）で表される糖脂質もしくは一般式（３）で表されるペプチド脂質と組み合わせた低分子有機化合物を用いて低分子有機化合物インターカレート型中空繊維状有機ナノチューブを製造する方法について述べる。 Next, a low molecular organic compound intercalation type using a low molecular organic compound combined with a glycolipid represented by the general formula (1) or the general formula (2) or a peptide lipid represented by the general formula (3) A method for producing hollow fiber-like organic nanotubes will be described.
（１）まず、以下の（１ａ）又は（１ｂ）の方法により、低分子有機化合物がインターカレートされた有機ナノチューブを溶液中に生成させる。
（１ａ）溶媒に一般式（１）もしくは一般式（２）で表される糖脂質もしくは一般式（３）で表されるペプチド脂質を溶解させて溶液を調製する。この溶媒は沸点以下に加温する。そのため脂質の溶解量を多くすることができる。この溶液中の脂質の濃度は高いほど好ましく、飽和であることが最も好ましい。
(1) First, organic nanotubes intercalated with a low molecular weight organic compound are produced in a solution by the following method (1a) or (1b).
(1a) A solution is prepared by dissolving the glycolipid represented by the general formula (1) or the general formula (2) or the peptide lipid represented by the general formula (3) in a solvent. This solvent is heated below the boiling point. Therefore, the amount of lipid dissolution can be increased. The lipid concentration in this solution is preferably as high as possible, and most preferably saturated.
この溶媒としては、沸点が１２０℃以下であるアルコール類を用いることができる。この溶媒は単独でもよいし、２種以上の混合溶媒であってもよい。
このようなアルコール類としては、１−ブタノール、２−ブタノール、エタノール、メタノール、２−メトキシエタノール、イソブチルアルコール、三級ブチルアルコール、２−ペンタノール、１−プロパノール、２−プロパノール、アミルアルコール、アリルアルコール、を挙げることができる。
As this solvent, alcohols having a boiling point of 120 ° C. or lower can be used. This solvent may be used alone or in combination of two or more.
Examples of such alcohols include 1-butanol, 2-butanol, ethanol, methanol, 2-methoxyethanol, isobutyl alcohol, tertiary butyl alcohol, 2-pentanol, 1-propanol, 2-propanol, amyl alcohol, and allyl. Alcohol can be mentioned.
更に、このアルコール類に、芳香族炭化水素類、パラフィン類、塩化パラフィン類、塩化オレフィン類、塩化芳香族炭化水素類、エーテル類、ケトン類、エステル類、含窒素化合物及び水の１種以上を混合した混合溶媒を用いてもよい。この混合溶媒はこのアルコール類を好ましくは少なくとも１０容積％、より好ましくは少なくとも５０容積％含む。
前記芳香族炭化水素類としては、ベンゼン、トルエン、メシチレン、テトラリン、キシレン、を挙げることができる。
前記パラフィン類としては、シクロヘキサン、ヘプタン、ヘキサン、リグロイン、ペンタン、エチルシクロペンタン、石油エーテル、イソオクタン、イソヘキサン、イソヘプタン、イソペンタン、デカリン、デカン、ドデカン、オクタン、ノナン、を挙げることができる。
前記塩化パラフィン類としては、四塩化炭素、クロロホルム、１，１−ジクロロエタン、１，２−ジクロロエタン、塩化メチレン、塩化エチル、塩化ブチル、塩化プロピルを挙げることができる。
前記塩化オレフィン類としては、テトラクロロエチレン、トリクロロエチレン、1,1-ジクロロエチレン、1,2-ジクロロエチレンを挙げることができる。
前記塩化芳香族炭化水素類としては、1-クロロナフタレン、o-ジクロロベンゼン、m-ジクロロベンゼン、を挙げることができる。
前記エーテル類としては、ジエチルエーテル、ジイソプロピルエーテル、１，２−ジメトキシエタン、ジメトキシメタン、エチルメチルエーテル、ジベンジルエーテル、ジフェニルエーテル、トリグリム、ジオキサン、テトラヒドロフラン、を挙げることができる。
ケトン類としては、アセトン、メチルエチルケトン、アセタール、アセトアルデヒド、シクロヘキサノン、メチルイソブチルケトン、ジメチルスルホキシド、を挙げることができる。
前記エステル類としては、酢酸エチル、ギ酸エチル、酢酸メチル、ギ酸メチル、ギ酸ブチル、ギ酸プロピル、ギ酸イソプロピル、酢酸プロピル、プロピオン酸エチル、プロピオン酸メチル、酪酸エチル、酪酸メチルを挙げることができる。
前記含窒素化合物としては、アセトアミド、アセトニトリル、ジエチルアミン、ジイソプロピルアミン、エチルアミン、エチレンジアミン、ヒドラジン、ニトロメタン、ピペリジン、プロピルアミン、ピリジン、N,N,N’,N’-テトラメチルエチレンジアミン、トリエチルアミン、アクリロニトリル、アニリン、ジイソプロピルエチルアミン、ジメチルアセトアミド、ジメチルアニリン、N,N-ジメチルホルムアミド、ホルムアミド、N-メチルピロリドン、モルホリン、ニトロベンゼン、キノリン、を挙げることができる。
Further, to this alcohol, one or more aromatic hydrocarbons, paraffins, chlorinated paraffins, chlorinated olefins, chlorinated aromatic hydrocarbons, ethers, ketones, esters, nitrogen-containing compounds and water are added. You may use the mixed solvent which mixed. The mixed solvent preferably contains at least 10% by volume, more preferably at least 50% by volume of the alcohol.
Examples of the aromatic hydrocarbons include benzene, toluene, mesitylene, tetralin, and xylene.
Examples of the paraffins include cyclohexane, heptane, hexane, ligroin, pentane, ethylcyclopentane, petroleum ether, isooctane, isohexane, isoheptane, isopentane, decalin, decane, dodecane, octane, and nonane.
Examples of the chlorinated paraffins include carbon tetrachloride, chloroform, 1,1-dichloroethane, 1,2-dichloroethane, methylene chloride, ethyl chloride, butyl chloride, and propyl chloride.
Examples of the chlorinated olefins include tetrachloroethylene, trichloroethylene, 1,1-dichloroethylene, and 1,2-dichloroethylene.
Examples of the chlorinated aromatic hydrocarbons include 1-chloronaphthalene, o-dichlorobenzene, and m-dichlorobenzene.
Examples of the ethers include diethyl ether, diisopropyl ether, 1,2-dimethoxyethane, dimethoxymethane, ethyl methyl ether, dibenzyl ether, diphenyl ether, triglyme, dioxane, and tetrahydrofuran.
Examples of ketones include acetone, methyl ethyl ketone, acetal, acetaldehyde, cyclohexanone, methyl isobutyl ketone, and dimethyl sulfoxide.
Examples of the esters include ethyl acetate, ethyl formate, methyl acetate, methyl formate, butyl formate, propyl formate, isopropyl formate, propyl acetate, ethyl propionate, methyl propionate, ethyl butyrate, and methyl butyrate.
Examples of the nitrogen-containing compound include acetamide, acetonitrile, diethylamine, diisopropylamine, ethylamine, ethylenediamine, hydrazine, nitromethane, piperidine, propylamine, pyridine, N, N, N ′, N′-tetramethylethylenediamine, triethylamine, acrylonitrile, aniline. , Diisopropylethylamine, dimethylacetamide, dimethylaniline, N, N-dimethylformamide, formamide, N-methylpyrrolidone, morpholine, nitrobenzene, quinoline.
このようにして調製した脂質溶液に低分子有機化合物をそのまま、もしくは溶媒に溶解した溶液を加えることにより、脂質−低分子有機化合物混合溶液を調整する。
この際、低分子有機化合物をそのまま脂質溶液に加えるのは、低分子有機化合物が脂質溶液に溶解する場合である。低分子有機化合物が脂質溶液に溶解しない場合には、脂質溶液に良く混ざる溶媒を選択し、その溶媒に低分子有機化合物を溶解した後に、脂質溶液に加えることにより脂質−低分子有機化合物混合溶液を調整する。
The lipid-low molecular weight organic compound mixed solution is prepared by adding the low molecular weight organic compound as it is or a solution in which the low molecular weight organic compound is dissolved in the solvent to the lipid solution thus prepared.
At this time, the low molecular organic compound is added to the lipid solution as it is when the low molecular organic compound is dissolved in the lipid solution. If the low-molecular-weight organic compound does not dissolve in the lipid solution, select a solvent that mixes well with the lipid solution, dissolve the low-molecular-weight organic compound in the solvent, and then add the lipid-low-molecular-weight organic compound mixed solution to the lipid solution. Adjust.
このようにして調製した脂質−低分子有機化合物混合溶液を徐冷して、室温下に静置して低分子有機化合物インターカレート型中空繊維状有機ナノチューブを生成させる。この「徐冷」とは、特に加熱や冷却操作を行わないで温度を下げるという意味と、加熱や冷却操作を行い温度制御しながらゆっくり下げるという２つの意味がある。従って、徐冷時の温度は、周囲の温度や装置の熱容量などによって異なる場合と、温度をコントロールする装置の設定に依存する場合がある。また「室温」とは特に過剰な加熱や冷却を行わない温度という意味であり、具体的には０〜４０℃、好ましくは２０℃付近の温度をいう。このようにして、徐冷十数時間〜数日間経過後、溶液から低分子有機化合物インターカレート型中空繊維状有機ナノチューブが析出してくる。 The lipid-low molecular organic compound mixed solution thus prepared is slowly cooled and allowed to stand at room temperature to produce low molecular organic compound intercalated hollow fiber organic nanotubes. This “slow cooling” has two meanings, in particular, that the temperature is lowered without performing heating and cooling operations and that the temperature is slowly lowered while performing heating and cooling operations and temperature control. Therefore, the temperature at the time of slow cooling may vary depending on the ambient temperature, the heat capacity of the apparatus, or the like, and may depend on the setting of the apparatus that controls the temperature. Further, “room temperature” means a temperature at which excessive heating and cooling are not performed, and specifically refers to a temperature of 0 to 40 ° C., preferably around 20 ° C. In this way, low-molecular-weight organic compound intercalated hollow fiber-like organic nanotubes are precipitated from the solution after gradual cooling for 10 hours to several days.
（１ｂ）上記と同様の溶媒に脂質と低分子有機化合物を溶解させて脂質−低分子有機化合物混合溶液を調製する。この溶媒を使用するにあたっては特に加温を要しない。この溶液中の脂質の濃度は高いほど好ましく、飽和であることが最も好ましい。
次に、この溶液を濃縮する。例えば、エバポレーターを用いて、蒸発温度は好ましくは室温〜低圧力下での沸点以下、圧力５〜１０ＫＰａで濃縮乾固する。
その結果、各溶媒に対する溶解度に依存して、溶液から低分子有機化合物インターカレート型中空繊維状有機ナノチューブが析出してくる。
(1b) A lipid-low molecular organic compound mixed solution is prepared by dissolving a lipid and a low molecular organic compound in a solvent similar to the above. When using this solvent, no particular heating is required. The lipid concentration in this solution is preferably as high as possible, and most preferably saturated.
The solution is then concentrated. For example, using an evaporator, the evaporation temperature is preferably from room temperature to the boiling point under low pressure, and concentrated to dryness at a pressure of 5 to 10 KPa.
As a result, depending on the solubility in each solvent, low molecular weight organic compound intercalated hollow fiber organic nanotubes are precipitated from the solution.
（２）次に、溶液から低分子有機化合物インターカレート型中空繊維状有機ナノチューブを回収し、風乾又は減圧加熱乾燥することにより、空気中で安定な、平均外径が２０〜７００ｎｍ、好ましくは４０〜４００ｎｍであり、平均内径（中空の平均径）が１０〜５００ｎｍ、好ましくは２０〜２００ｎｍであり、長さが数百ｎｍ〜数百μｍのサイズを有する低分子有機化合物インターカレート型中空繊維状有機ナノチューブが得られる。
風乾の条件は、回収した低分子有機化合物インターカレート型中空繊維状有機ナノチューブを空気の流れのある場所で室温、大気圧下で乾燥することである。乾燥時間は２時間〜４８時間であり、好ましくは２４時間以上である。
減圧加熱乾燥の条件は、室温から６０℃の温度範囲において減圧度２０Ｐａ以下で、２時間以上乾燥することである。加熱温度は６０℃以下であれば高いほど乾燥時間が短くて済むが、脂質の熱安定性に与える影響を考慮すると４０℃以下が好ましい。より好ましい乾燥条件は、３０℃で２４〜４８時間である。
(2) Next, the low molecular weight organic compound intercalated hollow fiber organic nanotube is recovered from the solution, and air-dried or heat-dried under reduced pressure, so that the average outer diameter is 20 to 700 nm, which is stable in the air, preferably Low molecular organic compound intercalated hollow having a size of 40 to 400 nm, an average inner diameter (hollow average diameter) of 10 to 500 nm, preferably 20 to 200 nm, and a length of several hundred nm to several hundred μm A fibrous organic nanotube is obtained.
The air-drying condition is to dry the collected low-molecular-weight organic compound intercalated hollow fiber-like organic nanotubes at a room with air flow at room temperature and atmospheric pressure. The drying time is 2 to 48 hours, preferably 24 hours or more.
The conditions for heat drying under reduced pressure are to dry for 2 hours or more at a reduced pressure of 20 Pa or less in a temperature range from room temperature to 60 ° C. The higher the heating temperature is 60 ° C. or less, the shorter the drying time is. However, in consideration of the influence on the thermal stability of lipids, 40 ° C. or less is preferable. More preferable drying conditions are 24 to 48 hours at 30 ° C.
低分子有機化合物インターカレート型中空繊維状有機ナノチューブの形態やサイズ次元の確認のためには、走査電子顕微鏡、透過電子顕微鏡、などが用いられる。走査電子顕微鏡は繊維状構造体の表面観察、形態観察には非常に有効な観察手段である。繊維構造体の配向状態によっては、中空シリンダー構造の直接確認は可能であるが、万能とは言えない。透過電子顕微鏡は、中空シリンダー構造を濃淡のコントラストの差で表現できるため、中空シリンダー構造の確認は可能であるが、リボン状の構造体の横幅両端が単に少し巻き上がった状態でも同様なコントラスト像を与えるため、単独使用では、中空シリンダー構造と断定するには少し危険である。そのため、中空繊維状形態の存在確認のためには、走査電子顕微鏡と透過電子顕微鏡を併用して使用することが望ましい。また、低分子有機化合物インターカレート型中空繊維状有機ナノチューブに分子有機化合物が含まれていることの確認のためには、蛍光顕微鏡、核磁気共鳴装置、などが用いられる。蛍光顕微鏡は低分子有機化合物が蛍光性を持つ場合、有機ナノチューブの膜中に低分子有機化合物の存在を直接確認するための非常に有効な観察手段である。核磁気共鳴装置は、低分子有機化合物インターカレート型中空繊維状有機ナノチューブを溶媒に溶解した後、核磁気共鳴スペクトル測定によって、低分子有機化合物が有機ナノチューブの膜中に含まれているがどうかを確認することができる手段である。蛍光性を持つか持たないかに関わらず、低分子有機化合物の膜中での存在は、核磁気共鳴スペクトルを測定することによって、確認できる。 In order to confirm the form and size dimension of the low molecular organic compound intercalated hollow fiber organic nanotube, a scanning electron microscope, a transmission electron microscope, or the like is used. The scanning electron microscope is a very effective observation means for observing the surface and morphology of the fibrous structure. Depending on the orientation of the fiber structure, the hollow cylinder structure can be confirmed directly, but it is not universal. The transmission electron microscope can express the hollow cylinder structure with the contrast of light and shade, so the hollow cylinder structure can be confirmed, but the same contrast image can be obtained even when the widthwise ends of the ribbon-like structure are slightly rolled up. Therefore, when used alone, it is a little dangerous to conclude with a hollow cylinder structure. Therefore, it is desirable to use a scanning electron microscope and a transmission electron microscope in combination in order to confirm the presence of the hollow fiber form. In order to confirm that the low molecular weight organic compound intercalated hollow fiber organic nanotube contains a molecular organic compound, a fluorescence microscope, a nuclear magnetic resonance apparatus, or the like is used. The fluorescence microscope is a very effective observation means for directly confirming the presence of the low molecular weight organic compound in the organic nanotube film when the low molecular weight organic compound has fluorescence. The nuclear magnetic resonance apparatus uses a low molecular weight organic compound intercalated hollow fiber-like organic nanotube dissolved in a solvent, and then whether or not the low molecular weight organic compound is contained in the organic nanotube film by nuclear magnetic resonance spectrum measurement. It is means that can be confirmed. Regardless of whether it has fluorescence or not, the presence of the low molecular weight organic compound in the film can be confirmed by measuring a nuclear magnetic resonance spectrum.
次に、本発明を実施例によりさらに詳細に説明するが、本発明は、これらの例によって何ら限定されるものではない。
（実施例１）
［８−アニリノ−１−ナフタレンスルホン酸／Ｎ−テトラデカノイル−グリシルグリシン低分子有機化合物インターカレート型中空繊維状有機ナノチューブの合成］
Ｎ−テトラデカノイル−グリシルグリシン２０ｍｇと８−アニリノ−１−ナフタレンスルホン酸アンモニウム塩４ｍｇを４０℃に加温したエタノール２０ｍｌに溶解し、その後、ロータリーエバポレーター（圧力１０ＫＰａ、蒸発温度４０℃）を用いて濃縮乾固すると白色粉末が析出する。得られた白色粉末を更に２４時間風乾することにより、８−アニリノ−１−ナフタレンスルホン酸／Ｎ−テトラデカノイル−グリシルグリシン低分子有機化合物インターカレート型中空繊維状有機ナノチューブ（収量：２４ｍｇ）を得た。透過電子顕微鏡と走査電子顕微鏡観察により平均内径６０ｎｍ、平均外径１５０ｎｍの中空繊維状有機ナノチューブが形成していることがわかった（図１）。また、蛍光顕微鏡観察により８−アニリノ−１−ナフタレンスルホン酸が有機ナノチューブの膜中にインターカレートしていることが確かめられた（図２）。
EXAMPLES Next, although an Example demonstrates this invention still in detail, this invention is not limited at all by these examples.
Example 1
[Synthesis of 8-anilino-1-naphthalenesulfonic acid / N-tetradecanoyl-glycylglycine low molecular weight organic compound intercalated hollow fiber organic nanotube]
20 mg of N-tetradecanoyl-glycylglycine and 4 mg of 8-anilino-1-naphthalenesulfonic acid ammonium salt are dissolved in 20 ml of ethanol heated to 40 ° C., and then a rotary evaporator (pressure 10 KPa, evaporation temperature 40 ° C.) is used. When used and concentrated to dryness, a white powder precipitates. The obtained white powder was further air-dried for 24 hours to obtain 8-anilino-1-naphthalenesulfonic acid / N-tetradecanoyl-glycylglycine low molecular organic compound intercalated hollow fiber organic nanotube (yield: 24 mg ) Observation with a transmission electron microscope and a scanning electron microscope revealed that hollow fiber-like organic nanotubes having an average inner diameter of 60 nm and an average outer diameter of 150 nm were formed (FIG. 1). Further, it was confirmed by observation with a fluorescence microscope that 8-anilino-1-naphthalenesulfonic acid was intercalated in the organic nanotube film (FIG. 2).
（実施例２）
［８−アニリノ−１−ナフタレンスルホン酸／Ｎ−（１１−ｃｉｓ−オクタデセノイル）−β−Ｄ−グルコピラノシルアミン低分子有機化合物インターカレート型中空繊維状有機ナノチューブの合成］
Ｎ−（１１−ｃｉｓ−オクタデセノイル）−β−Ｄ−グルコピラノシルアミン１ｍｇをメタノール−酢酸エチル１対１混合溶液０．４ｍｌに溶解した。この溶液に８−アニリノ−１−ナフタレンスルホン酸アンモニウム塩０．２ｍｇを溶解した水溶液２０ｍｌを加え、室温で２４時間放置すると白色粉末が析出する。得られた白色粉末を濾過により集め、更に２４時間風乾することにより、８−アニリノ−１−ナフタレンスルホン酸／Ｎ−（１１−ｃｉｓ−オクタデセノイル）−β−Ｄ−グルコピラノシルアミン低分子有機化合物インターカレート型中空繊維状有機ナノチューブ（収量：１ｍｇ）を得た。透過電子顕微鏡と走査電子顕微鏡観察により平均内径６０ｎｍ、平均外径１２０ｎｍの中空繊維状有機ナノチューブが形成していることがわかった（図３）。また、蛍光顕微鏡観察により８−アニリノ−１−ナフタレンスルホン酸が有機ナノチューブの膜中にインターカレートしていることが確かめられた（図４）。
(Example 2)
[Synthesis of 8-anilino-1-naphthalenesulfonic acid / N- (11-cis-octadecenoyl) -β-D-glucopyranosylamine low molecular weight organic compound intercalated hollow fiber organic nanotube]
1 mg of N- (11-cis-octadecenoyl) -β-D-glucopyranosylamine was dissolved in 0.4 ml of a methanol-ethyl acetate 1: 1 mixture. To this solution is added 20 ml of an aqueous solution in which 0.2 mg of 8-anilino-1-naphthalenesulfonic acid ammonium salt is dissolved, and when left at room temperature for 24 hours, a white powder precipitates. The obtained white powder was collected by filtration and further air-dried for 24 hours, whereby 8-anilino-1-naphthalenesulfonic acid / N- (11-cis-octadecenoyl) -β-D-glucopyranosylamine low molecular organic compound Intercalated hollow organic nanotubes (yield: 1 mg) were obtained. Observation by transmission electron microscope and scanning electron microscope revealed that hollow fiber-like organic nanotubes having an average inner diameter of 60 nm and an average outer diameter of 120 nm were formed (FIG. 3). Further, it was confirmed by observation with a fluorescence microscope that 8-anilino-1-naphthalenesulfonic acid was intercalated in the organic nanotube film (FIG. 4).
（実施例３）
［８−アニリノ−１−ナフタレンスルホン酸／Ｎ−（９−ｃｉｓ−オクタデセノイル）−β−Ｄ−グルコピラノシルアミン低分子有機化合物インターカレート型中空繊維状有機ナノチューブの合成］
Ｎ−（９−ｃｉｓ−オクタデセノイル）−β−Ｄ−グルコピラノシルアミン１０ｍｇと８−アニリノ−１−ナフタレンスルホン酸アンモニウム塩２ｍｇを５０℃に加温したメタノール−酢酸エチル１：５混合溶媒５ｍｌに溶解し、その後、放冷すると白色粉末が析出する。得られた白色粉末を更に２４時間風乾することにより、８−アニリノ−１−ナフタレンスルホン酸／Ｎ−（９−ｃｉｓ−オクタデセノイル）−β−Ｄ−グルコピラノシルアミン低分子有機化合物インターカレート型中空繊維状有機ナノチューブ（収量：１５ｍｇ）を得た。透過電子顕微鏡と走査電子顕微鏡観察により平均内径６０ｎｍ、平均外径６０ｎｍの中空繊維状有機ナノチューブが形成していることがわかった（図５）。また、蛍光顕微鏡観察により８−アニリノ−１−ナフタレンスルホン酸が有機ナノチューブの膜中にインターカレートしていることが確かめられた（図６）。
(Example 3)
[Synthesis of 8-anilino-1-naphthalenesulfonic acid / N- (9-cis-octadecenoyl) -β-D-glucopyranosylamine low molecular weight organic compound intercalated hollow fiber organic nanotube]
N- (9-cis-octadecenoyl) -β-D-glucopyranosylamine 10 mg and 8-anilino-1-naphthalenesulfonic acid ammonium salt 2 mg were heated to 50 ° C. in methanol-ethyl acetate 1: 5 mixed solvent 5 ml. Dissolve and then leave to cool to precipitate white powder. The obtained white powder was further air-dried for 24 hours, whereby 8-anilino-1-naphthalenesulfonic acid / N- (9-cis-octadecenoyl) -β-D-glucopyranosylamine low molecular organic compound intercalated type Hollow fibrous organic nanotubes (yield: 15 mg) were obtained. Observation with a transmission electron microscope and a scanning electron microscope revealed that hollow fiber-like organic nanotubes having an average inner diameter of 60 nm and an average outer diameter of 60 nm were formed (FIG. 5). Further, it was confirmed by observation with a fluorescence microscope that 8-anilino-1-naphthalenesulfonic acid was intercalated in the organic nanotube film (FIG. 6).
（実施例４）
［８−アニリノ−１−ナフタレンスルホン酸／１９−[（β−Ｄ−グルコピラノシル）カルバモイル]ノナデカン酸低分子有機化合物インターカレート型中空繊維状有機ナノチューブの合成］
１９−[（β−Ｄ−グルコピラノシル）カルバモイル]ノナデカン酸１ｍｇと８−アニリノ−１−ナフタレンスルホン酸アンモニウム塩０．２ｍｇを７０℃に加温したエタノール−水１対１混合溶媒３０ｍｌに溶解し、その後、アルゴンガス気流中に放置することによって濃縮すると白色粉末が析出する。得られた白色粉末を更に２４時間風乾することにより、８−アニリノ−１−ナフタレンスルホン酸／１９−[（β−Ｄ−グルコピラノシル）カルバモイル]ノナデカン酸低分子有機化合物インターカレート型中空繊維状有機ナノチューブ（収量：１．２ｍｇ）を得た。透過電子顕微鏡と走査電子顕微鏡観察により平均内径２０ｎｍ、平均外径２７ｎｍの中空繊維状有機ナノチューブが形成していることがわかった（図７）。また、蛍光顕微鏡観察により８−アニリノ−１−ナフタレンスルホン酸が有機ナノチューブの膜中にインターカレートしていることが確かめられた（図８）。
Example 4
[Synthesis of 8-anilino-1-naphthalenesulfonic acid / 19-[(β-D-glucopyranosyl) carbamoyl] nonadecanoic acid low molecular weight organic compound intercalated hollow fiber organic nanotube]
19 mg of 19-[(β-D-glucopyranosyl) carbamoyl] nonadecanoic acid and 0.2 mg of 8-anilino-1-naphthalenesulfonic acid ammonium salt were dissolved in 30 ml of ethanol-water 1: 1 mixed solvent heated to 70 ° C., Then, when it is concentrated by leaving it in an argon gas stream, a white powder precipitates. The obtained white powder was further air-dried for 24 hours, whereby 8-anilino-1-naphthalenesulfonic acid / 19-[(β-D-glucopyranosyl) carbamoyl] nonadecanoic acid low molecular organic compound intercalated hollow fiber organic Nanotubes (yield: 1.2 mg) were obtained. Observation by transmission electron microscope and scanning electron microscope revealed that hollow fiber-like organic nanotubes having an average inner diameter of 20 nm and an average outer diameter of 27 nm were formed (FIG. 7). Further, it was confirmed by observation with a fluorescence microscope that 8-anilino-1-naphthalenesulfonic acid was intercalated in the organic nanotube film (FIG. 8).
本発明によれば、３ｎｍ以下の低分子有機化合物をインターカレートした中空繊維状有機ナノチューブが得られるため、微小なチューブ構造を利用した人工血管、ナノチューブキャピラリ、ナノリアクターとして医療、分析、化学品製造分野などで有用であり、工業的利用価値が高いため、これら様々な分野への貢献が期待できる。 According to the present invention, hollow fiber-like organic nanotubes intercalated with a low molecular weight organic compound of 3 nm or less can be obtained, so that medical, analytical, and chemical products can be used as artificial blood vessels, nanotube capillaries, and nanoreactors using a minute tube structure. Since it is useful in the manufacturing field and has high industrial utility value, it can be expected to contribute to these various fields.
Claims (19)
Ｇ−ＮＨＣＯ−Ｒ （１）
（式中、Ｇは糖のアノマー炭素原子に結合するヘミアセタール水酸基を除いた糖残基を表し、Ｒは炭素数が１０〜２４の不飽和炭化水素基を表す。）で表わされるＮ−グリコシド型糖脂質である請求項１に記載の低分子有機化合物インターカレート型中空繊維状有機ナノチューブ。 The glycolipid is represented by the following general formula (1)
G-NHCO-R (1)
(In the formula, G represents a sugar residue excluding the hemiacetal hydroxyl group bonded to the anomeric carbon atom of the sugar, and R represents an unsaturated hydrocarbon group having 10 to 24 carbon atoms). The low molecular weight organic compound intercalated hollow fiber organic nanotube according to claim 1, which is a type glycolipid.
Ｇ−ＮＨＣＯ−（ＣＨ２）ｎＣＯＯＨ （２）
（式中、Ｇは糖のアノマー炭素原子に結合するヘミアセタール水酸基を除いた糖残基を表し、ｎは６〜２０の整数を表す。）で表わされる非対称双頭型糖脂質である請求項１に記載の低分子有機化合物インターカレート型中空繊維状有機ナノチューブ。 The glycolipid is represented by the following general formula (2)
G-NHCO- (CH 2) n COOH (2)
(Wherein G represents a sugar residue excluding the hemiacetal hydroxyl group bonded to the anomeric carbon atom of the sugar, and n represents an integer of 6 to 20). The low-molecular-weight organic compound intercalated hollow fiber organic nanotube described in 1.
ＱＣＯ（ＮＨＣＨ２ＣＯ）ｍＯＨ （３）
（式中、Ｑは炭素数６〜１８の炭化水素基、ｍは１〜３の整数を表す。）で表わされるペプチド脂質である請求項１に記載の低分子有機化合物インターカレート型中空繊維状有機ナノチューブ。 The peptide lipid is represented by the following general formula (3)
QCO (NHCH 2 CO) m OH (3)
The low-molecular-weight organic compound intercalated hollow fiber according to claim 1, which is a peptide lipid represented by the formula (wherein Q represents a hydrocarbon group having 6 to 18 carbon atoms, and m represents an integer of 1 to 3). Organic nanotubes.
Ｇ−ＮＨＣＯ−Ｒ （１）
（式中、Ｇは糖のアノマー炭素原子に結合するヘミアセタール水酸基を除いた糖残基を表し、Ｒは炭素数が１０〜２４の不飽和炭化水素基を表す。）で表わされるＮ−グリコシド型糖脂質である請求項１１に記載の低分子有機化合物インターカレート型中空繊維状有機ナノチューブの製造方法。 The glycolipid is represented by the following general formula (1)
G-NHCO-R (1)
(In the formula, G represents a sugar residue excluding the hemiacetal hydroxyl group bonded to the anomeric carbon atom of the sugar, and R represents an unsaturated hydrocarbon group having 10 to 24 carbon atoms). The method for producing a low-molecular-weight organic compound intercalated hollow fiber-like organic nanotube according to claim 11, which is a type glycolipid.
Ｇ−ＮＨＣＯ−（ＣＨ２）ｎＣＯＯＨ （２）
（式中、Ｇは糖のアノマー炭素原子に結合するヘミアセタール水酸基を除いた糖残基を表し、ｎは６〜２０の整数を表す。）で表わされる非対称双頭型糖脂質である請求項１１に記載の低分子有機化合物インターカレート型中空繊維状有機ナノチューブの製造方法。 The glycolipid is represented by the following general formula (2)
G-NHCO- (CH 2) n COOH (2)
12. In the formula, G represents a sugar residue excluding a hemiacetal hydroxyl group bonded to an anomeric carbon atom of a sugar, and n represents an integer of 6 to 20. The manufacturing method of the low molecular weight organic compound intercalation type | mold hollow fiber organic nanotube as described in 2 above.
ＱＣＯ（ＮＨＣＨ２ＣＯ）ｍＯＨ （３）
（式中、Ｑは炭素数６〜１８の炭化水素基、ｍは１〜３の整数を表す。）で表わされるペプチド脂質である請求項１１に記載の低分子有機化合物インターカレート型中空繊維状有機ナノチューブの製造方法。 The peptide lipid is represented by the following general formula (3)
QCO (NHCH 2 CO) m OH (3)
The low-molecular-weight organic compound intercalated hollow fiber according to claim 11, which is a peptide lipid represented by the formula (wherein Q represents a hydrocarbon group having 6 to 18 carbon atoms, and m represents an integer of 1 to 3). For producing organic organic nanotubes.
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| JP2007107999A JP5339399B2 (en) | 2007-04-17 | 2007-04-17 | Low molecular organic compound intercalated hollow fiber organic nanotube and method for producing the same |
| PCT/JP2008/057279 WO2008129973A1 (en) | 2007-04-17 | 2008-04-14 | Hollow fiber-shaped organic nanotube having low-molecular organic compound intercalated therein and method of producing the same |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011184391A (en) * | 2010-03-10 | 2011-09-22 | National Institute Of Advanced Industrial Science & Technology | Nucleic acid introducing agent made of organic nanotube |
| JP2011184365A (en) * | 2010-03-09 | 2011-09-22 | National Institute Of Advanced Industrial Science & Technology | Organic nanotube formed with boronic acid derivative having aromatic group and glycolipid, and method for producing the same |
| US9018156B2 (en) | 2011-05-09 | 2015-04-28 | National Institute Of Advanced Industrial Science And Technology | Organic nanotube having hydrophobized inner surface, and encapsulated medicinal agent prepared using the nanotube |
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| CN102040193B (en) * | 2009-10-23 | 2013-05-08 | 中国科学院理化技术研究所 | Method for preparing organic micromolecule nano ring and nano tube |
| JP6875725B2 (en) * | 2017-02-02 | 2021-05-26 | 国立研究開発法人産業技術総合研究所 | Manufacturing methods for asymmetric bilayer lipid molecules, asymmetric organic nanotubes, and asymmetric organic nanotubes |
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| SE0003506D0 (en) * | 2000-09-28 | 2000-09-28 | Daniel Chiu | Microscopic networks of containers and nanotubes |
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| JPH04270218A (en) * | 1991-02-25 | 1992-09-25 | Taisho Pharmaceut Co Ltd | Water suspension of vitamin a-containing liposome |
| JPH069336A (en) * | 1992-04-15 | 1994-01-18 | Unilever Nv | Composition for make-up good |
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| JP2011184365A (en) * | 2010-03-09 | 2011-09-22 | National Institute Of Advanced Industrial Science & Technology | Organic nanotube formed with boronic acid derivative having aromatic group and glycolipid, and method for producing the same |
| JP2011184391A (en) * | 2010-03-10 | 2011-09-22 | National Institute Of Advanced Industrial Science & Technology | Nucleic acid introducing agent made of organic nanotube |
| US9018156B2 (en) | 2011-05-09 | 2015-04-28 | National Institute Of Advanced Industrial Science And Technology | Organic nanotube having hydrophobized inner surface, and encapsulated medicinal agent prepared using the nanotube |
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