JP2009138131A - Method for chemically decomposing organic nanotube - Google Patents
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Abstract
Description
本発明は、有機ナノチューブに関するものであり、特に、生成された有機ナノチューブを、化学的に、且つ安全に分解する方法に関する。 The present invention relates to an organic nanotube, and more particularly, to a method for chemically and safely decomposing a produced organic nanotube.
医療、健康、食品、衛生、農業分野においては薬剤、香料、風味成分など有効成分の安定保存、放出濃度制御がきわめて重要な課題である。その解決法として種々の基質を無機材料又は有機材料への内包化し、該基質を徐放させる研究がされ、今日までに数多く実用化されている。
例えば、特許文献1では、多孔性アパタイト誘導体にヒト成長ホルモンおよび水溶性2価金属化合物を含有させることにより、生体内分解性および徐放性能を併せ持つヒト成長ホルモンの徐放性微粒子製剤が得られることが報告されている。
また、特許文献2では、難水溶性の抗腫瘍などの医薬化合物を包接したシクロデキストリンをさらに球状分子集合体の内水相に被包したリポソームと、その医薬化合物の徐放性が報告されている。
In the medical, health, food, hygiene, and agricultural fields, stable preservation of active ingredients such as drugs, fragrances, and flavor components, and control of the release concentration are extremely important issues. As a solution to this problem, studies have been made to encapsulate various substrates in inorganic materials or organic materials and to release the substrates slowly, and many have been put to practical use to date.
For example, in Patent Document 1, a sustained-release fine particle preparation of human growth hormone having both biodegradability and sustained-release performance can be obtained by incorporating human growth hormone and a water-soluble divalent metal compound into a porous apatite derivative. It has been reported.
Patent Document 2 reports a liposome in which a cyclodextrin encapsulating a pharmaceutical compound such as a poorly water-soluble antitumor is further encapsulated in the inner aqueous phase of a spherical molecular assembly, and the sustained release of the pharmaceutical compound. ing.
本発明者らは、両親媒性化合物の分子が集合してできる有機ナノチューブについても、その一次元内部空孔へ基質が内包できることを見いだし、すでに出願している。
例えば、特許文献3には、糖脂質を有機溶媒中で再沈殿させることにより、カーボンナノチューブに代表される無機ナノチューブにはない特性を持ち、且つシクロデキストリンより約10倍以上大きい内径と高い軸比を持ち、固相状態にある脂質膜構造からなる中空繊維状有機ナノチューブを簡便且つ大量に合成し、その中空シリンダー内に毛細管現象を利用して金属ナノ粒子やタンパク質を導入したことが記載されている。また、特許文献4では、ペプチド脂質を用いて同様の性質をもつ中空繊維状有機ナノチューブを簡便且つ大量に合成したことが記載されている。
The present inventors have found that an organic nanotube formed by assembling molecules of an amphiphilic compound can contain a substrate in its one-dimensional internal pore, and has already filed an application.
For example, Patent Document 3 discloses that by reprecipitation of glycolipids in an organic solvent, it has characteristics not found in inorganic nanotubes typified by carbon nanotubes, and has an inner diameter and a high axial ratio that are about 10 times more than cyclodextrin. It is described that hollow fiber-like organic nanotubes having a lipid membrane structure in a solid phase state are synthesized easily and in large quantities, and metal nanoparticles and proteins are introduced into the hollow cylinder using capillary action. Yes. Patent Document 4 describes that a hollow fiber-shaped organic nanotube having the same properties was synthesized easily and in large quantities using peptide lipids.
このような有効成分を封入できる材料を分解する場合、シリカやアパタイトなど無機材料からなるナノ多孔質粒子は、物理的、化学的に極めて安定であり、中空構造の分解には強塩基、強酸などの過酷な条件が必要となる。
これに対して、リポソームは、物理的、化学的な刺激による放出が容易に可能であるが、リポソームを構成する脂質膜構造が液晶相にあるため、固相状態にある脂質膜構造からなる有機ナノチューブに比べて安定性が低く、材料としての適用範囲が限定される。
When decomposing materials that can enclose such active ingredients, nanoporous particles made of inorganic materials such as silica and apatite are physically and chemically very stable, and strong bases, strong acids, etc. Harsh conditions are required.
In contrast, liposomes can be easily released by physical and chemical stimuli, but the lipid membrane structure that constitutes the liposome is in the liquid crystal phase, so that the organic membrane consists of a lipid membrane structure in a solid phase. Compared with nanotubes, the stability is low, and the range of application as a material is limited.
一方、特許文献3,4の有機ナノチューブは、1)相転移点温度(水中で60度前後)以上に加熱する、或いは2)超音波を照射する、など物理的な刺激を加える手法により、そのチューブ構造が分解される。
しかしながらこのような物理的な刺激を作用させることが困難な状況下での応用を想定した場合、安全で、かつ広範に利用できる化学的な分解法の開発が望まれる。
However, development of a chemical decomposition method that is safe and can be widely used is desired when an application under a situation where it is difficult to apply such a physical stimulus is desired.
本発明は、以上のような事情に鑑みてなされたものであって、すでに特許文献3、4において提案している両親媒性分子が集合してできる有機ナノチューブにおいて、安全で広範に利用できる化学的な分解法を提供することを目的とするものである。 The present invention has been made in view of the circumstances as described above, and has been proposed in Patent Documents 3 and 4, and the organic nanotubes formed by assembling the amphiphilic molecules can be used safely and widely. The purpose is to provide an effective decomposition method.
これまでに化学物質の添加により、有機ナノチューブを分解できるという報告例がある。
例えば、非特許文献1では、フォスファチジルコリンは、水中で球状分子集合体(リポソーム)を形成するが、コレステロールが混在すると、この球状構造がナノチューブで接続された組織化体を形成すること、ここにβ−シクロデキストリンを加えると、シクロデキストリンがコレステロールを包接し、ナノチューブが消失して、球状分子集合体のみになることが報告されている。
また、非特許文献2では、ピレニル基を含む両親媒性化合物は、水中で自己集合して直径約250nmのベシクルを形成すること、この分散液にγ−シクロデキストリンを加え、超音波を照射するとγ−シクロデキストリンがピレニル基を包接し、集合体構造が内径22nm外径45nmのナノチューブに変化すること、さらにγ−シクロデキストリンとより安定な包接錯体を形成するポリプロピレングリコールをナノチューブ分散液に加えるとゲスト交換が起き、再びベシクル構造へと変化することが報告されている。
しかしながら、これらの文献には、それらのナノチューブの内包化能については報告がされていない。
There have been reports that organic nanotubes can be decomposed by adding chemical substances.
For example, in Non-Patent Document 1, phosphatidylcholine forms a spherical molecular assembly (liposome) in water, but when cholesterol is mixed, this spherical structure forms an organized body connected by nanotubes, It has been reported that when β-cyclodextrin is added here, the cyclodextrin includes cholesterol, the nanotubes disappear, and only spherical molecular aggregates are formed.
In Non-Patent Document 2, an amphiphilic compound containing a pyrenyl group self-assembles in water to form a vesicle having a diameter of about 250 nm, and γ-cyclodextrin is added to this dispersion and irradiated with ultrasonic waves. γ-cyclodextrin clathrates a pyrenyl group, the aggregate structure changes to a nanotube having an inner diameter of 22 nm and an outer diameter of 45 nm, and polypropylene glycol that forms a more stable inclusion complex with γ-cyclodextrin is added to the nanotube dispersion. It has been reported that the guest exchange occurred and changed to the vesicle structure again.
However, these documents do not report the encapsulating ability of these nanotubes.
シクロデキストリンが脂肪酸、コレステロールと包接化合物を作ることは知られている。
例えば、非特許文献3には、α、β、γ−シクロデキストリンによる油性物質の包接を検討したところ、α−シクロデキストリンは直鎖脂肪酸を選択的に包接し、β−シクロデキストリンはコレステロールに対して高い包接選択性を示し、γ−シクロデキストリンは脂肪酸、コレステロールともに包接するが、包接による安定化の寄与が小さく包接量は全体的に少なかったことが報告されている。
Cyclodextrins are known to make inclusion compounds with fatty acids and cholesterol.
For example, in Non-Patent Document 3, the inclusion of an oily substance by α, β, γ-cyclodextrin was examined. Α-cyclodextrin selectively included linear fatty acids, and β-cyclodextrin became cholesterol. It is reported that γ-cyclodextrin is included in both fatty acids and cholesterol, but the contribution of stabilization by inclusion is small and the amount of inclusion is generally small.
本発明者らは、上記目的を達成すべく鋭意研究を重ねた結果、シクロデキストリンの添加により、前記の両親媒性分子が集合してできる有機ナノチューブが分解できることという知見を得た。
本発明は、これらの知見に基づいて完成に至ったものであり、以下のとおりのものである。
(1)両親媒性化合物が集合して形成された有機ナノチューブに、シクロデキストリンを添加することにより、該有機ナノチューブのチューブ構造を化学的に分解する方法。
(2)前記両親媒性化合物が、
下記一般式(1)
G−NHCO−R1 (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、R1は炭素数が10〜39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、又は
下記一般式(2)
R2CO(NH−CHR3−CO)mOH (2)
(式中、R2は炭素数6〜24の炭化水素基、R3はアミノ酸側鎖、mは1〜10の整数を表す。)で表わされるペプチド脂質、又は
下記一般式(3)
H(NH−CHR3−CO)mNHR2 (3)
(式中、R2は炭素数6〜24の炭化水素基、R3はアミノ酸側鎖、mは1〜10の整数を表す。)で表わされるペプチド脂質
のいずれかである(1)に記載の方法。
(3)前記シクロデキストリンが、α−シクロデキストリン、β−シクロデキストリン又はγ−シクロデキストリンのいずれかである(1)又は(2)に記載の方法。
(4)前記シクロデキストリンの添加量が、有機ナノチューブを形成する両親媒性化合物に対して、1当量以上である(1)〜(3)のいずれかに記載の方法。
As a result of intensive studies to achieve the above object, the present inventors have found that the addition of cyclodextrin can decompose organic nanotubes formed by the assembly of the amphiphilic molecules.
The present invention has been completed based on these findings, and is as follows.
(1) A method of chemically decomposing a tube structure of an organic nanotube by adding cyclodextrin to the organic nanotube formed by assembling an amphiphilic compound.
(2) The amphiphilic compound is
The following general formula (1)
G-NHCO-R 1 (1)
(Wherein G represents a sugar residue excluding the hemiacetal hydroxyl group bonded to the anomeric carbon atom of the sugar, and R 1 represents an unsaturated hydrocarbon group having 10 to 39 carbon atoms). Glycoside glycolipid or the following general formula (2)
R 2 CO (NH-CHR 3 -CO) m OH (2)
(Wherein R 2 is a hydrocarbon group having 6 to 24 carbon atoms, R 3 is an amino acid side chain, and m is an integer of 1 to 10), or the following general formula (3)
H (NH—CHR 3 —CO) m NHR 2 (3)
(Wherein R 2 is a hydrocarbon group having 6 to 24 carbon atoms, R 3 is an amino acid side chain, and m is an integer of 1 to 10). the method of.
(3) The method according to (1) or (2), wherein the cyclodextrin is any one of α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin.
(4) The method according to any one of (1) to (3), wherein the addition amount of the cyclodextrin is 1 equivalent or more with respect to the amphiphilic compound forming the organic nanotube.
本発明の方法によれば、有機ナノチューブを熱、超音波など物理的刺激ではなく、化学的に室温で分解、構造変化させることができる。また、本発明の方法により、加熱や超音波照射に耐えない、または困難な条件、例えば皮膚のような生体組織、屋外のような大面積などに存在するナノチューブの分解が可能になる。さらに、非特許文献2に挙げたように、従来のシクロデキストリンを用いた形態変化は、その空孔に適合するためにピレニル基など非天然由来の大きな疎水性官能基をあらかじめ導入する必要があるが、本発明の有機ナノチューブは、天然物を出発原料としており、特殊な官能基を導入することなく、天然物であるシクロデキストリンの添加で分解できることは、環境中や生体組織上にもおいて有利である。 According to the method of the present invention, organic nanotubes can be chemically decomposed and changed in structure at room temperature rather than by physical stimulation such as heat and ultrasonic waves. In addition, the method of the present invention makes it possible to decompose nanotubes that do not endure or are difficult to withstand heating or ultrasonic irradiation, for example, living tissue such as skin, large areas such as outdoors. Furthermore, as mentioned in Non-Patent Document 2, the conventional shape change using cyclodextrin needs to introduce in advance a large non-naturally occurring hydrophobic functional group such as a pyrenyl group in order to adapt to the pores. However, the organic nanotube of the present invention uses natural products as a starting material, and it can be decomposed by adding cyclodextrin, which is a natural product, without introducing a special functional group. It is advantageous.
本発明の方法は、デキストリンを添加することにより、両親媒性化合物からなる有機ナノチューブを、熱、超音波など物理的刺激ではなく、化学的に室温で分解させて、チューブ構造を変化させるものである。
本発明において、シクロデキストリンの添加によりチューブ構造が分解されるのは、本発明の有機ナノチューブが、脂肪酸由来の分子構造を含むため、シクロデキストリンの添加により脂肪酸部位が包接されて、その集合形態が変化することによるものと考えられる。
In the method of the present invention, by adding dextrin, an organic nanotube composed of an amphiphilic compound is chemically decomposed at room temperature instead of physical stimulation such as heat and ultrasonic waves to change the tube structure. is there.
In the present invention, the tube structure is decomposed by the addition of cyclodextrin because the organic nanotube of the present invention contains a molecular structure derived from fatty acid, so that the fatty acid site is included by the addition of cyclodextrin and the aggregated form It is thought that this is due to the change.
本発明において、用いる有機ナノチューブは、疎水基および親水基を有する両親媒性化合物の分子が集合してチューブ構造を形成している。
両親媒性化合物における疎水基としては、直鎖又は分岐型の飽和もしくは不飽和アルキル基が挙げられる。また、親水基としては、単糖、オリゴ糖及びその類縁体、アミノ酸、及びオリゴペプチドやその類縁体などが挙げられるが、特に、両親媒性化合物として、
下記一般式(1)
G−NHCO−R1 (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、R1は炭素数が10〜39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、又は
下記一般式(2)
R2CO(NH−CHR3−CO)mOH (2)
(式中、R2は炭素数6〜24の炭化水素基、R3はアミノ酸側鎖、mは1〜10の整数を表す。)で表わされるペプチド脂質、又は
下記一般式(3)
H(NH−CHR3−CO)mNHR2 (3)
(式中、R2は炭素数6〜24の炭化水素基、R3はアミノ酸側鎖、mは1〜10の整数を表す。)で表わされるペプチド脂質が、好ましく用いられる。
In the present invention, the organic nanotube to be used forms a tube structure by collecting molecules of an amphiphilic compound having a hydrophobic group and a hydrophilic group.
Examples of the hydrophobic group in the amphiphilic compound include a linear or branched saturated or unsaturated alkyl group. In addition, examples of hydrophilic groups include monosaccharides, oligosaccharides and analogs thereof, amino acids, oligopeptides and analogs thereof, etc.
The following general formula (1)
G-NHCO-R 1 (1)
(Wherein G represents a sugar residue excluding the hemiacetal hydroxyl group bonded to the anomeric carbon atom of the sugar, and R 1 represents an unsaturated hydrocarbon group having 10 to 39 carbon atoms). Glycoside glycolipid or the following general formula (2)
R 2 CO (NH-CHR 3 -CO) m OH (2)
(Wherein R 2 is a hydrocarbon group having 6 to 24 carbon atoms, R 3 is an amino acid side chain, and m is an integer of 1 to 10), or the following general formula (3)
H (NH—CHR 3 —CO) m NHR 2 (3)
A peptide lipid represented by the formula (wherein R 2 represents a hydrocarbon group having 6 to 24 carbon atoms, R 3 represents an amino acid side chain, and m represents an integer of 1 to 10) is preferably used.
本発明において用いるシクロデキストリン類は、数分子のD−グルコースが、α−1,4グルコシド結合によって結合して環状構造をとった環状オリゴ糖の一種であって、グルコースが5個以上結合したものが知られている。一般的なものは、グルコースが6個から8個結合したものであり、それぞれ6個結合しているものがα−シクロデキストリン、7個結合しているものがβ−シクロデキストリン、8個結合しているものがγ−シクロデキストリンと呼ばれているが、本発明では、α、β、γのいずれでも良く、また1つ以上の水酸基が他の官能基で修飾されていても良い。 The cyclodextrins used in the present invention are a kind of cyclic oligosaccharides in which several molecules of D-glucose are linked by α-1,4 glucoside bonds to form a cyclic structure, and 5 or more glucoses are bonded. It has been known. In general, 6 to 8 glucoses are bonded, each having 6 bonded α-cyclodextrin, 7 bonded β-cyclodextrin, and 8 bonded. In the present invention, any of α, β and γ may be used, and one or more hydroxyl groups may be modified with other functional groups.
本発明において、両親媒性化合物から形成される有機ナノチューブに添加するシクロデキストリンの量は、多ければ多い程分解に必要な時間が短くなるが、該有機ナノチューブを形成する両親媒性化合物に対して、少なくとも1当量以上のシクロデキストリンを添加することが必要であり、好ましくは、4当量以上のシクロデキストリンを添加する。 In the present invention, the amount of cyclodextrin added to the organic nanotube formed from the amphiphilic compound is shorter as the time required for decomposition is shorter, but with respect to the amphiphilic compound that forms the organic nanotube. It is necessary to add at least 1 equivalent of cyclodextrin, and preferably 4 equivalents or more of cyclodextrin is added.
以下、本発明を実施例によってさらに具体的に説明するが、本発明はこれら実施例により何ら限定されるものではない。
(実施例1)
下記の構造式1に示す糖脂質分子から形成した有機ナノチューブ(I)(22mg、糖脂質0.05mmol)に、それぞれ、1当量(48.6mg)、2当量(97.3mg)、4当量(194.6mg)、及び8当量(389.2mg)のα−シクロデキストリン(α−CD)水溶液を加え、さらに水を最終液量が4mLとなるようにそれぞれ添加し、タッチミキサーで5分間撹拌した。この混合物を異なる時間(10分、24時間、4日)静置した後、遠心処理(4000回転、30分)を行い、残渣に水4mLを加え5分間撹拌した。再度30分間の遠心処理を行い、残渣を凍結乾燥して粉末状のサンプルを得た。このサンプルについて重量を秤量し、電界放出型走査型電子顕微鏡観(FE−SEM)による形態観察をし、プロトン核磁気共鳴(1H−NMR)、粉末X線回折(XRD)測定をおこなった。
EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.
(Example 1)
Each of the organic nanotubes (I) (22 mg, glycolipid 0.05 mmol) formed from the glycolipid molecule represented by the structural formula 1 shown below has 1 equivalent (48.6 mg), 2 equivalents (97.3 mg), 4 equivalents ( 194.6 mg) and 8 equivalents (389.2 mg) of α-cyclodextrin (α-CD) aqueous solution were added, and water was further added so that the final liquid volume became 4 mL, and the mixture was stirred for 5 minutes with a touch mixer. . The mixture was allowed to stand for different times (10 minutes, 24 hours, 4 days), then centrifuged (4000 rpm, 30 minutes), 4 mL of water was added to the residue, and the mixture was stirred for 5 minutes. Centrifugation for 30 minutes was performed again, and the residue was freeze-dried to obtain a powdery sample. The sample was weighed, observed by a field emission scanning electron microscope (FE-SEM), and subjected to proton nuclear magnetic resonance ( 1 H-NMR) and powder X-ray diffraction (XRD) measurements.
各サンプルの回収重量、1H−NMRから算出した組成を下記の表1に示す。
図1ないし図4は、各サンプルの24時間静置で得られた集合体のFE−SEM写真である。
これらの写真から明らかなように、α−CDの添加によってナノチューブ構造から板状構造に変換されていることが観察された。ナノチューブと板状集合体の割合はα−CDの増加にともない板状構造が増加し、4当量以上、24時間でナノチューブが完全に消失した。また板状集合体は、糖脂質とα−CDがおよそ1:2.7の組成を有し、またXRDから複合体固体中の分子配列は、α−CD及び有機ナノチューブ(I)単体とは異なることが分かった。
The recovered weight of each sample and the composition calculated from 1 H-NMR are shown in Table 1 below.
1 to 4 are FE-SEM photographs of aggregates obtained by allowing each sample to stand for 24 hours.
As is apparent from these photographs, it was observed that the nanotube structure was converted to a plate structure by the addition of α-CD. The ratio of the nanotubes to the plate-like aggregates increased with the increase in α-CD, and the nanotubes disappeared completely in 24 hours with 4 equivalents or more. The plate-like aggregate has a composition of glycolipid and α-CD of about 1: 2.7, and the molecular arrangement in the complex solid from XRD is that α-CD and organic nanotube (I) alone are I found it different.
(実施例2)
β−シクロデキストリン(β−CD)水溶液(600mg/40mL)に、40mg、80mg、及び160mgの有機ナノチューブ(I)を加え、タッチミキサーで5分間撹拌した。この混合物を異なる時間(24時間、4日間)静置した。その後遠心処理(4000回転、60分)を行い、上澄み液を除去した後、残渣に水を40mL加え、再度同様の遠心処理を行い、残渣を凍結乾燥して粉末状のサンプルを得た。このサンプルについて重量を秤量し、FE−SEMによる形態観察をし、1H−NMR、XRD測定をおこなった。
(Example 2)
40 mg, 80 mg, and 160 mg of organic nanotube (I) were added to an aqueous β-cyclodextrin (β-CD) solution (600 mg / 40 mL), and the mixture was stirred for 5 minutes with a touch mixer. The mixture was allowed to stand for different times (24 hours, 4 days). Thereafter, centrifugation (4000 rpm, 60 minutes) was performed, the supernatant was removed, 40 mL of water was added to the residue, the same centrifugation was performed again, and the residue was freeze-dried to obtain a powdery sample. The sample was weighed, observed for morphology by FE-SEM, and subjected to 1 H-NMR and XRD measurements.
各サンプルの回収重量、1H−NMRから算出した組成を下記の表2に示す。
図5ないし図7は、各サンプルの、24時間静置で得られた集合体のFE−SEM写真である。
これらの写真から明らかなように、24時間後のサンプルはナノチューブと板状構造の混合物であったが、4日後のサンプル中に残留するナノチューブはわずかであった。また添加する有機ナノチューブ(I)の量の増加とともに残留するナノチューブ構造の割合が減少した。
The recovered weight of each sample and the composition calculated from 1 H-NMR are shown in Table 2 below.
FIG. 5 to FIG. 7 are FE-SEM photographs of the aggregates obtained by allowing the samples to stand for 24 hours.
As is apparent from these photographs, the sample after 24 hours was a mixture of nanotubes and a plate-like structure, but few nanotubes remained in the sample after 4 days. Moreover, the ratio of the remaining nanotube structure decreased with the increase in the amount of added organic nanotube (I).
(実施例3)
γ−シクロデキストリン(γ―CD)水溶液(130mg/4mL、260mg/4mL、520mg/4mL、及び1040mg/5mL)を調製し、有機ナノチューブ(I)(44.4mg)に加えてタッチミキサーで5分間撹拌した。この混合物を10分もしくは24時間静置した。その後遠心処理(4000回転、30分)を行い、上澄み液を除去した後、残渣に水を4mL加え、再度同様の遠心処理を行い、残渣を凍結乾燥して粉末状のサンプルを得た。このサンプルについて重量を秤量し、FE−SEMによる形態観察、1H−NMR、XRD測定をおこなった。
(Example 3)
γ-cyclodextrin (γ-CD) aqueous solution (130 mg / 4 mL, 260 mg / 4 mL, 520 mg / 4 mL, and 1040 mg / 5 mL) was prepared, and added to organic nanotube (I) (44.4 mg) for 5 minutes with a touch mixer Stir. The mixture was allowed to stand for 10 minutes or 24 hours. Thereafter, centrifugation (4000 rpm, 30 minutes) was performed, the supernatant was removed, 4 mL of water was added to the residue, the same centrifugation treatment was performed again, and the residue was freeze-dried to obtain a powdery sample. The sample was weighed and subjected to morphological observation by FE-SEM, 1 H-NMR, and XRD measurement.
各サンプルの回収重量、1H−NMRから算出した組成を下記の表3に示す。
図8ないし図10は、それぞれ、濃度260mg/4mLのサンプルの10分間静置で得られた集合体、濃度520mg/4mLのサンプルの10分間静置で得られた集合体、及び濃度1040mg/5mLのサンプルの24時間静置で得られた集合体のFE−SEM写真である。
これらの写真から明らかなように、γ−CD濃度が130mg/4mL、及び260mg/4mLの場合、回収重量は若干減少し、ほぼナノチューブのみであった。γ−CD濃度が520mg/4mLの場合、回収固体はナノチューブ構造と板状構造体の混合物であった。γ=CD濃度が1040mg/5mL(24時間、4日間静置)の場合は、いずれの回収固体もγ−CDを主成分とするもので、その集合体形態は板状構造であった。すなわち、γ―CDによるナノチューブの分解はγ―CD水溶液の濃度依存性がみられた。
The recovered weight of each sample and the composition calculated from 1 H-NMR are shown in Table 3 below.
8 to 10 show, respectively, an assembly obtained by standing for 10 minutes of a sample having a concentration of 260 mg / 4 mL, an assembly obtained by standing for 10 minutes of a sample having a concentration of 520 mg / 4 mL, and a concentration of 1040 mg / 5 mL. It is a FE-SEM photograph of the aggregate obtained by standing for 24 hours.
As is clear from these photographs, when the γ-CD concentrations were 130 mg / 4 mL and 260 mg / 4 mL, the recovered weight was slightly decreased, and only the nanotubes were obtained. When the γ-CD concentration was 520 mg / 4 mL, the recovered solid was a mixture of a nanotube structure and a plate-like structure. When γ = CD concentration was 1040 mg / 5 mL (24 hours, left for 4 days), all the recovered solids were mainly composed of γ-CD, and the aggregate form was a plate-like structure. That is, the decomposition of the nanotubes by γ-CD was dependent on the concentration of the γ-CD aqueous solution.
(実施例4)
下記の構造式2に示すペプチド脂質から形成した有機ナノチューブ(II)(23.4mg、ペプチド脂質0.068mmol)に265mg(0.27mmol)/4mLのα―CD水溶液を加え、タッチミキサーで5分間撹拌した。この混合物を24時間静置した後、遠心処理(4000回転、20分)を行い、残渣に水4mLを加え5分間撹拌した。再度20分間の遠心処理を行い、残渣を凍結乾燥して粉末状のサンプルを得た。このサンプルについて重量を秤量し、FE−SEMによる形態観察、1H−NMR、XRD測定をおこなった。
Example 4
265 mg (0.27 mmol) / 4 mL of α-CD aqueous solution was added to organic nanotube (II) (23.4 mg, peptide lipid 0.068 mmol) formed from the peptide lipid represented by the following structural formula 2, and the mixture was touched for 5 minutes. Stir. The mixture was allowed to stand for 24 hours, then centrifuged (4000 rpm, 20 minutes), 4 mL of water was added to the residue, and the mixture was stirred for 5 minutes. Centrifugation for 20 minutes was performed again, and the residue was freeze-dried to obtain a powdery sample. The sample was weighed and subjected to morphological observation by FE-SEM, 1 H-NMR, and XRD measurement.
回収重量は98mgで、α−CDとペプチド脂質のモル比は1.83:1であった。電子顕微鏡によりα―CDの添加によってナノチューブ構造からほぼ完全に板状構造に変換されていることが観察された。すなわち有機ナノチューブ(I)の場合とほぼ同様にα−CDの添加によりチューブ構造を分解可能であることが示された。 The recovered weight was 98 mg, and the molar ratio of α-CD to peptide lipid was 1.83: 1. It was observed by electron microscopy that the nanotube structure was almost completely converted into a plate-like structure by the addition of α-CD. That is, it was shown that the tube structure can be decomposed by adding α-CD in the same manner as in the case of the organic nanotube (I).
本発明において、有機ナノチューブ構造の分解に用いるシクロデキストリンは、天然に存在する物質で、食品としての利用もされており、生体組織のみならず環境への負荷も低い化合物であるため、広範な応用が期待できる。 In the present invention, cyclodextrin used for decomposition of the organic nanotube structure is a naturally occurring substance that is also used as a food, and is a compound that has a low impact on the environment as well as living tissues. Can be expected.
Claims (4)
下記一般式(1)
G−NHCO−R1 (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、R1は炭素数が10〜39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、又は
下記一般式(2)
R2CO(NH−CHR3−CO)mOH (2)
(式中、R2は炭素数6〜24の炭化水素基、R3はアミノ酸側鎖、mは1〜10の整数を表す。)で表わされるペプチド脂質、又は
下記一般式(3)
H(NH−CHR3−CO)mNHR2 (3)
(式中、R2は炭素数6〜24の炭化水素基、R3はアミノ酸側鎖、mは1〜10の整数を表す。)で表わされるペプチド脂質
のいずれかである請求項1に記載の方法。 The amphiphilic compound is
The following general formula (1)
G-NHCO-R 1 (1)
(Wherein G represents a sugar residue excluding the hemiacetal hydroxyl group bonded to the anomeric carbon atom of the sugar, and R 1 represents an unsaturated hydrocarbon group having 10 to 39 carbon atoms). Glycoside glycolipid or the following general formula (2)
R 2 CO (NH-CHR 3 -CO) m OH (2)
(Wherein R 2 is a hydrocarbon group having 6 to 24 carbon atoms, R 3 is an amino acid side chain, and m is an integer of 1 to 10), or the following general formula (3)
H (NH—CHR 3 —CO) m NHR 2 (3)
2. The peptide lipid according to claim 1, wherein R 2 is a hydrocarbon group having 6 to 24 carbon atoms, R 3 is an amino acid side chain, and m is an integer of 1 to 10. the method of.
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