JPS6129773B2 - - Google Patents
Info
- Publication number
- JPS6129773B2 JPS6129773B2 JP51135421A JP13542176A JPS6129773B2 JP S6129773 B2 JPS6129773 B2 JP S6129773B2 JP 51135421 A JP51135421 A JP 51135421A JP 13542176 A JP13542176 A JP 13542176A JP S6129773 B2 JPS6129773 B2 JP S6129773B2
- Authority
- JP
- Japan
- Prior art keywords
- membrane
- group
- double
- double layer
- present
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 239000012528 membrane Substances 0.000 claims description 56
- 125000002091 cationic group Chemical group 0.000 claims description 23
- 210000002472 endoplasmic reticulum Anatomy 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 12
- 230000002209 hydrophobic effect Effects 0.000 claims description 9
- 125000001165 hydrophobic group Chemical group 0.000 claims description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
- 239000003012 bilayer membrane Substances 0.000 description 18
- 239000000243 solution Substances 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- 239000000693 micelle Substances 0.000 description 7
- 230000009102 absorption Effects 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 150000003904 phospholipids Chemical class 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 4
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 4
- 229940012189 methyl orange Drugs 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000000635 electron micrograph Methods 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound 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 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- WLCFKPHMRNPAFZ-UHFFFAOYSA-M didodecyl(dimethyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCC WLCFKPHMRNPAFZ-UHFFFAOYSA-M 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 150000002314 glycerols Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 150000004668 long chain fatty acids Chemical class 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 125000005496 phosphonium group Chemical group 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- HISNRBVYBOVKMB-UHFFFAOYSA-N stibonium Chemical group [SbH4+] HISNRBVYBOVKMB-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium group Chemical group [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
Description
本発明は、新規な二重層ないし多重層構造膜お
よびその小胞体に関するものである。すなわち、
本発明は、従来全く知られていない、表面にカチ
オン性親水性基を有する合成二重層膜および該二
重層膜より構成された多重層構造膜、さらにそれ
らより成る小胞体を提供するものである。
本発明でいう表面にカチオン性親水性基を有す
るとは、カチオン性親水性基が共有結合で膜本体
に結合し、対アニオンは遊離の状態あるいはベタ
イン型で、該カチオン近傍の非疎水側に存在する
ことを意味する。
従来、二重層膜としては、生体膜がその典型的
な例としてよく知られているが、生体膜を形成し
ている成分は、リン脂質と蛋白質がほとんどであ
り、その他若干の糖脂質などを含んでいる。この
うち、二重層膜の骨格を形成するのはリン脂質で
あり、これはリン酸と長鎖脂肪酸のグリセリンエ
ステルを主要成分とする。生体膜のモデルとして
現在広くうけいれられている流動的モザイクモデ
ルによれば、生体膜はリン脂質の親水性の部分で
あるリン酸基が膜の両面に整列し、膜の内部に向
つて二本の疎水性の脂肪酸部分を突き出して向い
あうことによつて二重層膜を形成している。した
がつて、膜の表面には、アニオン性の親水基が並
んでいることになる。
このような生体膜は、一般に、蛋白質等と複合
化されて、それぞれの生体特有の膜機能を発現し
ているわけであるが、生化学的見地から、これら
の膜より蛋白その他を除去して、比較的純粋なリ
ン脂質とし、生体膜機能解析が行われ、さらには
脂肪酸部分を入為的に置換して種々の検討が成さ
れ、生体膜の本質解明への努力が積み重ねられて
いる。しかしながら、このような生体膜に特長的
な安定な二重層膜は、現在までリン脂質を中心と
したグリセライドに特徴的なものであり、これら
と構造的に異なる脂質類似物質では、類似膜構造
は構成しえないものと考えられていた。
本発明者らは、酵素類似の触媒反応の研究を進
めている過程において、特殊な挙動を示す電解質
集合体の存在を見出し、鋭意検討を重ねた結果、
本発明に到達したものである。
すなわち、本発明における二重層膜は、膜表面
にカチオン性親水性基を有し、従来知られている
生体膜の二重層膜が、膜表面にアニオン性の親水
性基を有しているのに対して著しく異なつてい
る。本発明のカチオン性二重層膜は、実質的に層
間隔が20〜200Åであり、濃度、温度、溶解方
法、添加物、系のイオン強度などの製造条件によ
り膜状物、多層状構造体あるいはこれらが閉じた
小胞体の形態で存在しうるもので、その製造初期
状態は、一般には膜状物、多層状構造体である
が、時間とともに小胞体の形態になる。積極的に
小胞体を製造する場合は、本発明の化合物を低濃
度にし、必要があれば温度を上げ、撹拌を強める
等により容易に得られる。これらの二重層膜、多
重層構造膜および小胞体は、驚くべきことには、
稀薄な水溶液中あるいはさらに乾燥状態において
も、その形態を保持していることが判明した。
また、膜状物、多層状構造体を支持体の上に塗
布し、乾燥することにより、二重層ないし二重層
を基本骨格とする多重層構造膜を得ることができ
る。
本発明になるカチオン性二重層膜が安定な二重
層膜であることは、生体膜二重層膜の諸挙動との
酷似性において認識されるが、最も直接的な形態
観察法である電止顕微鏡観察によれば、生体膜二
重層膜類似の二重層膜の存在が確認されると同時
に、水溶液中に安定な構造体である二重層膜とし
て存在していることが、NMRスペクトルの生体
膜NMRスペクトルとの対比から立証された。
本発明によるカチオン性二重層膜の特徴の若干
について説明を加えると、本発明の二重層膜
は、一般の界面活性剤が濃厚状態でのみ形成する
不安定な構造体となり、一般界面活性剤の限界ミ
セル濃度（CMC）より低い濃度領域（10-2〜
10-7M）で安定した二重層膜あるいは小胞体を形
成保持し、さらにこれらは、濃縮状態あるいはさ
らに乾燥状態においてさえも、安定にその構造、
形態を保持する。本発明の二重層膜は、一般の
界面活性剤がそのCMC以上で形成する単純ミセ
ルと異なり、構成要素化合物の束縛度の大きい強
固な構造物より成つている。二重層膜において
形成された小胞体は、胞内外の物質透過の制御が
可能で、表面荷電が生体膜と逆である点において
物質透過特性も異なり、また前述の膜の安定性あ
るいは構成要素化合物の束縛度が大きい故に、一
般の単純ミセルにおける物質透過特性とも異な
る。溶液中の二重層膜構造は電気的特異層を形
成しているため二重層内外の化学反応を正あるい
は負に加速する。
上述の如く、本発明によるカチオン性二重層膜
の特徴は、従来の生体膜二重層膜と際立つた対比
をなし、また公知の単純ミセルのそれとは著しく
異なつている。これらの諸特徴を認識した上で、
本発明のカチオン性二重層膜の用途の一例を列挙
すれば、小胞体としてはマイクロカプセル、主と
して小胞体としては相間移動触媒担体、選択加水
分解触媒共触媒、膜としては選択透過膜、選択吸
着膜等があり、本発明のカチオン性二重層膜の有
用性ならびに工業的利用価値の巾は著しく広いも
のである。
本発明のカチオン性二重層膜の構成としては、
表面にカチオン性親水性基を有する二重層膜であ
るが、具体的に本発明の二重層膜を構成する化合
物としては、カチオン性親水性基と長鎖疎水性基
とを有し、好ましくはハイドロフイリツク・リポ
フイリツクバランス（HLB）が７以下であり、
さらに具体的には、長鎖疎水性基とは実質的に鎖
長10Å以上を有し、単位鎖長当りの平均疎水性パ
ラメータが0.3／Å以上である疎水性長鎖置換基
であることが好ましい。
疎水性長鎖置換基を構成する単位としては、た
とえば、−CH2−、−CH＝、
The present invention relates to a novel double-layered or multilayered membrane and its endoplasmic reticulum. That is,
The present invention provides a synthetic bilayer membrane having a cationic hydrophilic group on its surface, which has not been known in the past, a multilayer structure membrane composed of the bilayer membrane, and a endoplasmic reticulum composed of the same. . In the present invention, having a cationic hydrophilic group on the surface means that the cationic hydrophilic group is covalently bonded to the membrane body, and the counter anion is in a free state or betaine type and is located on the non-hydrophobic side near the cation. means to exist. Conventionally, biomembranes are well known as a typical example of bilayer membranes, but the components that make up biomembranes are mostly phospholipids and proteins, with some other substances such as glycolipids. Contains. Among these, phospholipids form the skeleton of the bilayer membrane, and the main components are phosphoric acid and glycerin esters of long-chain fatty acids. According to the fluid mosaic model, which is currently widely accepted as a model for biological membranes, in biological membranes, phosphate groups, which are the hydrophilic parts of phospholipids, are aligned on both sides of the membrane, with two groups extending toward the inside of the membrane. A double layer membrane is formed by protruding the hydrophobic fatty acid portions of the two and facing each other. Therefore, anionic hydrophilic groups are lined up on the surface of the membrane. Such biological membranes are generally complexed with proteins, etc., and express membrane functions unique to each organism, but from a biochemical standpoint, it is necessary to remove proteins and other substances from these membranes. , relatively pure phospholipids have been used to analyze biomembrane functions, and various studies have also been conducted by artificially replacing fatty acid moieties, and efforts are being made to elucidate the essence of biomembranes. However, the stable bilayer membrane characteristic of biological membranes has so far been characteristic of glycerides, mainly phospholipids, and lipid-like substances that are structurally different from these have similar membrane structures. It was thought that it could not be constructed. In the process of researching enzyme-like catalytic reactions, the present inventors discovered the existence of electrolyte aggregates that exhibit special behavior, and as a result of extensive investigation,
This has led to the present invention. That is, the double-layer membrane of the present invention has a cationic hydrophilic group on the membrane surface, which is different from the conventional double-layer membrane of biological membranes, which has an anionic hydrophilic group on the membrane surface. There is a marked difference between The cationic double layer membrane of the present invention has a layer spacing of 20 to 200 Å, and depending on manufacturing conditions such as concentration, temperature, dissolution method, additives, and ionic strength of the system, it can be formed into a membrane, multilayer structure, or These can exist in the form of closed endoplasmic reticulum, and the initial state of production is generally a membranous or multilayered structure, but over time it changes to the form of endoplasmic reticulum. When actively producing endoplasmic reticulum, it can be easily obtained by lowering the concentration of the compound of the present invention, raising the temperature if necessary, increasing stirring, etc. Surprisingly, these bilayer membranes, multilayer membranes and endoplasmic reticulum
It was found that it retains its shape even in dilute aqueous solutions or even in dry conditions. Further, by applying a film-like material or a multilayer structure onto a support and drying it, a double layer or a multilayer structure film having a double layer as a basic skeleton can be obtained. The fact that the cationic bilayer membrane of the present invention is a stable bilayer membrane is recognized from its close resemblance to various behaviors of biological membrane bilayer membranes, but the most direct method for morphological observation is electrostatic microscopy. According to the observation, the existence of a double-layer membrane similar to a biological membrane double-layer membrane was confirmed, and at the same time, the existence of a double-layer membrane that is a stable structure in an aqueous solution was confirmed by the biological membrane NMR spectrum. This was proven by comparison with the spectrum. To explain some of the characteristics of the cationic double layer membrane according to the present invention, the double layer membrane according to the present invention is an unstable structure that is formed only in a concentrated state of a general surfactant. Concentration region lower than critical micelle concentration (CMC) (10 -2 ~
10 -7 M) and maintain stable bilayer membranes or endoplasmic reticulum, which maintain their structure stably even in concentrated or even dry conditions.
Retains form. The double-layer membrane of the present invention is different from simple micelles formed by general surfactants with a CMC or higher, and is composed of a strong structure in which the component compounds are highly constrained. The endoplasmic reticulum formed in a bilayer membrane can control the permeation of substances inside and outside the cell, and has different substance permeation characteristics in that the surface charge is opposite to that of biological membranes. Because the degree of restriction is large, the material permeation characteristics are different from those of ordinary simple micelles. The double layer membrane structure in solution forms an electrically specific layer, which accelerates chemical reactions inside and outside the double layer, either positively or negatively. As mentioned above, the characteristics of the cationic bilayer membrane according to the present invention are in marked contrast to conventional biological membrane bilayer membranes, and are also markedly different from those of known simple micelles. After recognizing these characteristics,
Examples of uses of the cationic double-layer membrane of the present invention include microcapsules as endoplasmic reticulum, phase transfer catalyst carriers and selective hydrolysis catalyst cocatalysts as endoplasmic reticulum, and selectively permeable membranes and selective adsorption as membranes. The cationic double layer membrane of the present invention has a significantly wide range of usefulness and industrial utility value. The structure of the cationic double layer membrane of the present invention is as follows:
The double-layer membrane has a cationic hydrophilic group on the surface, and the compound specifically constituting the double-layer membrane of the present invention has a cationic hydrophilic group and a long-chain hydrophobic group, and is preferably The hydrophilic lipophilic balance (HLB) is 7 or less,
More specifically, a long-chain hydrophobic group is a hydrophobic long-chain substituent having a substantially chain length of 10 Å or more and an average hydrophobicity parameter per unit chain length of 0.3/Å or more. preferable. Examples of units constituting the hydrophobic long-chain substituent include -CH 2 -, -CH=,
【式】【formula】
【式】−CF2−、−Si−Ｏ−、−CO−
NH2−、エーテルなどがあり、これらの１種また
は２種以上の組合せによつて、上記条件を満足す
るものであればよい。また１個の化合物に存在す
る疎水性長鎖基は、必ずしも同一である必要はな
く、異種の構造の疎水基でもよい。
本発明のカチオン性親水性基とは、一例をあげ
ると、アンモニウム基、スルホニウム基、ホスホ
ニウム基、アルゼニウム基、スチボニウム基等の
オニウム基であり、対イオンは一般のアニオンで
あれば特に制限はないが、用途によつては、反応
試薬、反応物等との対比によつて選択の必要が生
ずる場合もあり、一例をあげれば、クロライド、
ブロマイド、アセテーテ、サルフエート等が用い
られる。
これらの構成要素化合物の１種または２種以上
を、一般には水溶媒あるいは各種の溶剤さらには
混合系に溶解し、必要があれば超音波照射等の物
理的手段を駆使して、本発明のカチオン性二重層
膜ないし多重層構造膜およびその小胞体分散溶液
を得ることができる。
本発明の二重層膜の性状確認するために行つた
試験結果を示すと次のとおりである。
試験 １
表面に存在するカチオン性親水性基が第４級ア
ンモニウム基であるカチオン性二重層膜の10ｍＭ
水溶液を、銅メツシユに炭素を蒸着させたカーボ
ン膜の上にのせ、デシケータ内で乾燥させた後、
その上に適当な染色剤の２％水溶液をのせて、再
びデシケータ内で乾燥させて試料とした。
これを日立電子顕微鏡Ｈ−500及びHU−11Bで
加速電圧75〜100KV、倍率５〜30万の条件で写真
を得た。
第１〜３図に電顕写真を示す。第１図には明確
なラメラ構造とその多重層構造が観察され、第２
図には直径100〜500Åの小胞体が、また第３図に
は直径1000〜3000Åの多重層小胞体の存在が見ら
れる。さらによく分散された直径100〜500Åの本
発明二重層膜小胞体の見掛の分子量を、光散乱法
によつて求めると約70万であつた。これは生体膜
構成の主要脂質であるレシチンのリポソームの分
子量100万、直径200〜500Åの小胞体とほぼ同程
度の大きさと対比される。
試験 ２
試験１の二重層膜溶液を４×10-5Mに稀釈して
メチルオレンジ（5.34×10-6M）を加え、メチル
オレンジの極大吸収波長を測定した。本発明の二
重層膜溶液では400nｍに吸収が見られ、同濃度
のトリメチルセチルアンモニウムブロミドは
CMC以下であり、メチルオレンジの吸収は水中
と同様の465nｍを示し、単純ミセルは存在しな
いことを示す一方、前述の本件二重層膜溶液では
400nｍ以下の短波長にシフトし、メチルオレン
ジが疎水性媒体中に存在している時の吸収波長
420nｍ（ベンゼン中）に近いことから、本発明
の二重層膜は稀薄溶液状態でも安定な疎水性構造
を示していることが判明した。
試験 ３
試験１の本件二重層膜溶液の7.7×10-3M濃度
のＨ−NMRスペクトルを第４図に示した。参照
として単純ミセルを形成する濃度のセチルトリメ
チルアンモニウムブロミド（1.1×10-2M）のス
ペクトルも示した。メチレンおよびＮ−メチルの
吸収は、本発明の二重層膜において著しく広巾化
しているのが認められる。この事実は、生体膜二
重層膜において脂質が極度に固定化され、交換速
度が著しく小さい事実と合致し、本発明のカチオ
ン性二重層膜が、ここに安定に存在することが認
められた。
次に本発明の実施例を挙げて説明する。
実施例 １
ジドデシルジメチルアンモニウムクロリド184
mgに蒸留水40mlを加え、懸濁液をBransonic卓上
型超音波洗浄器（水浴型）で50℃で30分間超音波
処理を行い溶解する。溶解物は透明な溶液を保ち
濃縮可能であり、これらの溶液中には、試験１〜
３において示される二重層膜ないしはそれらの構
造物が形成されていた。これらの二重層膜は室温
において長期間安定に存在する。
これらの二重層膜を構成する化合物は、単一あ
るいは構造類似体の混合物であり、また溶解方法
としては、溶媒混和法、昇温冷却法、強制撹拌
法、稀薄溶解濃縮法等も用いられる。さらに二重
層膜においてしばしば登場する各種の添加物、た
とえば、コレステロール、コール酸、蛋白質等を
加えて製造することも可能である。
実施例 ２〜８
下表に示す構成化合物において、実施例１と同
様に溶解してカチオン性二重層膜を形成せしめ、
その結果を次表に示した。[Formula] -CF 2 -, -Si-O-, -CO- NH 2 -, ether, etc. One type or a combination of two or more of these may be used as long as the above conditions are satisfied. . Further, the hydrophobic long chain groups present in one compound do not necessarily have to be the same, and may have different structures. The cationic hydrophilic group of the present invention is, for example, an onium group such as an ammonium group, a sulfonium group, a phosphonium group, an arzenium group, or a stibonium group, and the counter ion is not particularly limited as long as it is a general anion. However, depending on the application, it may be necessary to make a selection based on comparison with reaction reagents, reactants, etc. For example, chloride,
Bromide, acetate, sulfate, etc. are used. One or more of these component compounds are generally dissolved in an aqueous solvent or various solvents or a mixed system, and if necessary, physical means such as ultrasonic irradiation are used to prepare the present invention. A cationic bilayer membrane or multilayer structure membrane and a vesicle-dispersed solution thereof can be obtained. The results of tests conducted to confirm the properties of the double layer membrane of the present invention are as follows. Test 1 10mM of a cationic double layer membrane in which the cationic hydrophilic groups present on the surface are quaternary ammonium groups.
After placing the aqueous solution on a carbon film made by depositing carbon on a copper mesh and drying it in a desiccator,
A 2% aqueous solution of an appropriate staining agent was placed thereon, and the sample was dried again in a desiccator. Photographs were taken of this using a Hitachi electron microscope H-500 and HU-11B at an acceleration voltage of 75 to 100 KV and a magnification of 50,000 to 300,000. Electron micrographs are shown in Figures 1-3. A clear lamellar structure and its multilayer structure are observed in Figure 1, and the second
The figure shows endoplasmic reticulum with a diameter of 100 to 500 Å, and Figure 3 shows the presence of multilayered endoplasmic reticulum with a diameter of 1000 to 3000 Å. Furthermore, the apparent molecular weight of the well-dispersed double-layer membrane vesicles of the present invention having a diameter of 100 to 500 Å was determined by a light scattering method to be about 700,000. This is in contrast to the molecular weight of lecithin liposomes, a major lipid in biological membranes, with a molecular weight of 1 million and a diameter of 200 to 500 Å, which is about the same size as the endoplasmic reticulum. Test 2 The double layer membrane solution from Test 1 was diluted to 4×10 −5 M, methyl orange (5.34×10 −6 M) was added, and the maximum absorption wavelength of methyl orange was measured. In the double layer membrane solution of the present invention, absorption is seen at 400 nm, and the same concentration of trimethylcetylammonium bromide
CMC or below, and the absorption of methyl orange is 465 nm, which is similar to that in water, indicating that simple micelles do not exist.
Absorption wavelength shifted to shorter wavelengths below 400 nm and when methyl orange is present in a hydrophobic medium
Since it is close to 420 nm (in benzene), it was found that the double layer membrane of the present invention exhibits a stable hydrophobic structure even in a dilute solution state. Test 3 The H-NMR spectrum of the present double layer membrane solution of Test 1 at a concentration of 7.7×10 -3 M is shown in FIG. As a reference, the spectrum of cetyltrimethylammonium bromide (1.1×10 -2 M) at a concentration that forms simple micelles is also shown. It is observed that the methylene and N-methyl absorptions are significantly broadened in the bilayer membrane of the present invention. This fact is consistent with the fact that lipids are extremely immobilized in biological bilayer membranes and the exchange rate is extremely low, and it was confirmed that the cationic bilayer membrane of the present invention exists stably here. Next, examples of the present invention will be described. Example 1 Didodecyldimethylammonium chloride 184
Add 40 ml of distilled water to 1.0 mg, and dissolve the suspension by sonicating at 50°C for 30 minutes in a Bransonic tabletop ultrasonic cleaner (water bath type). The lysate remains a clear solution and can be concentrated.
A double layer film or a structure thereof as shown in No. 3 was formed. These double layer films remain stable for long periods of time at room temperature. The compound constituting these double-layer membranes may be a single compound or a mixture of structural analogues, and methods for dissolving include a solvent mixing method, a heating and cooling method, a forced stirring method, a diluted dissolution and concentration method, and the like. Furthermore, it is also possible to manufacture the film by adding various additives that often appear in bilayer membranes, such as cholesterol, cholic acid, and protein. Examples 2 to 8 The constituent compounds shown in the table below were dissolved in the same manner as in Example 1 to form a cationic double layer membrane,
The results are shown in the table below.
第１図ないし第３図は試験１による試料の電子
顕微鏡写真で、第１図はネガ倍率５万倍、加速電
圧100KV、第２図はネガ倍率３万倍、加速電圧
100KV、第３図はネガ倍率５万倍、加速電圧
100KVのものであり、第４図イは単純ミセルを形
成する濃度のセチルトリメチルアンモニウムブロ
ミドのNMRスペクトル、第４図ロは試験１の本
発明二重層膜溶液のNMRスペクトルである。
Figures 1 to 3 are electron micrographs of the samples from Test 1. Figure 1 is a negative magnification of 50,000 times and an accelerating voltage of 100 KV, and Figure 2 is a negative magnification of 30,000 times and an accelerating voltage.
100KV, Figure 3 shows negative magnification 50,000 times, acceleration voltage
100KV, and FIG. 4A shows the NMR spectrum of cetyltrimethylammonium bromide at a concentration that forms simple micelles, and FIG. 4B shows the NMR spectrum of the double layer membrane solution of the present invention in Test 1.
Claims (1)
長鎖疎水性基の鎖長が10Å以上、単位鎖長当りの
平均疎水性パラメータが0.3／Å以上であつて、
ハイドロフイリツク・リポフイリツクバランスが
７以下の化合物で構成される二重層ないし二重層
を基本骨格とする多重層構造膜。 ２ カチオン性親水性基がオニウム基または第４
級アンモニウム基を有する化合物で構成される特
許請求の範囲第１項記載の二重層ないし多重層構
造膜。 ３ カチオン性親水性基と長鎖疎水性基を有し、
長鎖疎水性基の鎖長が10Å以上、単位鎖長当りの
平均疎水性パラメータが0.3／Å以上であつて、
ハイドロフイリツク・リポフイリツクバランスが
７以下の化合物で構成される二重層ないし二重層
を基本骨格とする多重層構造膜よりなる小胞体。 ４ カチオン性親水性基がオニウム基または第４
級アンモニウム基を有する化合物で構成される特
許請求の範囲第５項記載の二重層ないし多重層構
造膜よりなる小胞体。[Claims] 1 Having a cationic hydrophilic group and a long-chain hydrophobic group,
The chain length of the long-chain hydrophobic group is 10 Å or more, and the average hydrophobic parameter per unit chain length is 0.3/Å or more,
A double layer composed of a compound with a hydrophilic-lipophilic balance of 7 or less, or a multilayer structure membrane with a double layer as its basic skeleton. 2 The cationic hydrophilic group is an onium group or a quaternary
2. The double-layer or multilayer structure film according to claim 1, which is composed of a compound having an ammonium group. 3 has a cationic hydrophilic group and a long-chain hydrophobic group,
The chain length of the long-chain hydrophobic group is 10 Å or more, and the average hydrophobic parameter per unit chain length is 0.3/Å or more,
The endoplasmic reticulum consists of a double layer composed of compounds with a hydrophilic-lipophilic balance of 7 or less, or a multilayered membrane with a double layer as its basic skeleton. 4 The cationic hydrophilic group is an onium group or
6. The endoplasmic reticulum comprising a double-layered or multi-layered membrane according to claim 5, comprising a compound having an ammonium group.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP13542176A JPS5360883A (en) | 1976-11-12 | 1976-11-12 | Artificial membrane having structure of double layers or multiple layersand its vesicular substance |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP13542176A JPS5360883A (en) | 1976-11-12 | 1976-11-12 | Artificial membrane having structure of double layers or multiple layersand its vesicular substance |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5360883A JPS5360883A (en) | 1978-05-31 |
| JPS6129773B2 true JPS6129773B2 (en) | 1986-07-09 |
Family
ID=15151329
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP13542176A Granted JPS5360883A (en) | 1976-11-12 | 1976-11-12 | Artificial membrane having structure of double layers or multiple layersand its vesicular substance |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5360883A (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5858104A (en) * | 1981-09-30 | 1983-04-06 | Kuraray Co Ltd | Separation membrane for mixed liquid |
| US4707266A (en) * | 1982-02-05 | 1987-11-17 | Pall Corporation | Polyamide membrane with controlled surface properties |
| US4919804A (en) * | 1988-03-01 | 1990-04-24 | University Of Florida | Ultrasound driven synthesis of reversed and normal phase stationary phases for liquid chromatography |
-
1976
- 1976-11-12 JP JP13542176A patent/JPS5360883A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5360883A (en) | 1978-05-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Fuhrhop et al. | Membranes and molecular assemblies: the synkinetic approach | |
| Wang et al. | Assembly behaviors of calixarene-based amphiphile and supra-amphiphile and the applications in drug delivery and protein recognition | |
| Arnold et al. | Effect of poly (ethylene glycol) on phospholipid hydration and polarity of the external phase | |
| JPS63182029A (en) | Liposome | |
| Guilbot et al. | Efficient synthesis of unsymmetrical bolaamphiphiles for spontaneous formation of vesicles and disks with a transmembrane organization | |
| Rendón et al. | Model systems of precursor cellular membranes: long-chain alcohols stabilize spontaneously formed oleic acid vesicles | |
| DE10010264A1 (en) | Production of nano- or micro-capsules used in the production of liposomes coated with polyelectrolytes comprises electrically recharging template particles with polyelectrolytes | |
| Lioi et al. | Catanionic surfactant vesicles for electrostatic molecular sequestration and separation | |
| Simon et al. | Increased adhesion between neutral lipid bilayers: interbilayer bridges formed by tannic acid | |
| CN113292608B (en) | Exosome drug delivery system and preparation method and application thereof | |
| Yang et al. | Bioorganometallic ferrocene-tripeptide nanoemulsions | |
| US5165994A (en) | Spontaneous equilbrium surfactant vesicles | |
| Bolard et al. | Transfer of the polyene antibiotic amphotericin B between single-walled vesicles of dipalmitoylphosphatidylcholine and egg-yolk phosphatidylcholine | |
| JPS6129773B2 (en) | ||
| Fendler | Photochemistry in organized media | |
| Natal'ya et al. | Synthesis, properties and self-organization of meso-arylporphyrins with higher alkyl substituents | |
| Gugliuzza | Smart Membranes and Sensors: Synthesis, Characterization, and Applications | |
| WO1997031927A1 (en) | Tetraether lipids and liposomes containing said lipids, and use of the same | |
| Munoz et al. | Redox-switched vesicle formation from two novel, structurally distinct metalloamphiphiles | |
| JPWO2017150705A1 (en) | Selective permeable membrane, method for producing the same, and water treatment method using the selective permeable membrane | |
| Jadhav et al. | Mimicking the Natural World with Nanoarchitectonics for Self‐Assembled Superstructures | |
| Ishii et al. | Preparation conditions and evaluation of the stability of lipid vesicles (liposomes) using the microencapsulation technique | |
| Michaelis et al. | Location of ubiquinone-10 (CoQ-10) in phospholipid vesicles | |
| Papahadjopoulos | Phospholipid membranes as experimental models for biological membranes | |
| Nostro et al. | Structural properties of vesicles produced from a new bipolar lipid |