JPS6125633A - Nylon capsule responding to ph - Google Patents

Abstract

PURPOSE:To change membrane permeability reversibly according to a delicate change of pH by forming a nylon capsule that responds the pH by filling dedodecyl sodium phsphate in fine pores of a nylon capsule membrane. CONSTITUTION:The nylon capsule 1 is forme from a nylon capsule membrane 2. This membrane 2 is porous and the inside thereof is communicated with the outside through fine pores 3. This fine pore part 3 is filled with a bimolecular membrane forming compound 4 comprised of dodecyl phosphate. This bimolecular membrane forming compound 4 forms a bimolecular membrane, and a fluorescence probe 5 trapped in inner water phase is confined in the capsule and hardly scattered to the outside. However, when pH of the outside of the capsule changes to 2.5-2, the compound 4 forms and maintains hardly the bimolecular membrane, and the fluorescence probes 5 are scattered to the outer water phase as shown by the arrow A.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to nylon capsules, and more particularly to nylon capsules.
Concerning a nylon capsule with a completely new structure that reversibly changes membrane permeability in response to a subtle change in pH.A capsule equipped with a membrane that can reversibly change membrane permeability in response to changes in external pH. The development of this is strongly desired in technical fields such as science, biology, medicine, etc., for the purpose of using it as a pl+ indicator, a drug carrier, an in-vivo reaction model, etc.

The present invention was made in response to these demands in the industry, and as a result of intensive research from various fields, it was discovered that nylon is a porous material and that capsules with a nylon membrane can be easily manufactured. After further investigation, we discovered that not only could a fluorescent probe be housed within this nylon capsule, but unexpectedly, didodecyl phosphate was not only appropriated within the pores of the nylon membrane. We have discovered a new phenomenon of bilayer membrane formation.

What is even more surprising is that this bilayer membrane structure is
We have obtained a novel and extremely useful finding that the membrane changes reversibly in response to changes in external pH, resulting in a change in membrane permeability and allowing the fluorescent probe housed inside to permeate to the outside.

The present invention was made based on this new knowledge.

This invention relates to a nylon capsule that responds to p)I, which is prepared by coating the nylon capsule with a bipartite membrane-forming compound represented by: .

The nylon capsule, which is the basis of the present invention, can be easily produced according to conventional methods such as interfacial polymerization. For example, an acid chloride of a dibasic acid is dissolved in an organic solvent that does not mix with water, and an alkaline aqueous solution of a diamine is added to this.
Nylon capsules can be instantaneously formed at the interface between both liquid phases, and the size of the capsules can be adjusted by changing the size of the droplets of the diamine alkaline solution using conventional methods. This can be accomplished by a conventional method of dialyzing the capsule in a phosphate buffer containing the fluorescent probe. If this is placed in a solution of the bilayer membrane compound dissolved in an organic solvent such as dodecane and left to stand, the desired nylon capsule filled with the bilayer membrane compound will be present in the pores of the nylon capsule. easily obtained.

The nylon capsule according to the present invention obtained in this manner is schematically and partially enlarged.
It is a diagram.

The nylon capsule 1 consists of a nylon capsule membrane 2, which is porous and communicates between the inside and outside through pores 3. The pores 3 are filled with a bilayer membrane-forming compound 4 made of sodium didodecyl phosphate. A partially enlarged view of this is shown in the circle, and the compound forms a monomolecular membrane, and the fluorescent probe 5 trapped in the internal aqueous phase is confined within the capsule and comes out. Never. However, the pH outside the capsule is 2.
．． When the compound 4 changes from 5 to 2, it is no longer able to form and maintain a bilayer membrane, and the fluorescent probe 5 exits into the external aqueous phase as shown by arrow A.

At 60°C, which is higher than the gel-liquid crystal phase transition temperature Tc (50'C) of the bilayer membrane, the nylon capsule according to the present invention was placed in a quartz cell, and O, IN) ICIII and 0. The external pH was alternately changed to 7#2 using 1NNaOH, and the transmission coefficient P (cm/5ec) was measured by the time course of the emission intensity at 340 nm (excitation 290 nm), and the results shown in FIG. 2 were obtained.

When Tc is 60℃, external p+
It is clearly seen that the transmission coefficient changes reversibly by a factor of 10 or more due to a change in +. On the other hand, at temperatures below Tc (30°C), this capsule has a pH of
No response indicated.

The details of its mechanism of action will have to be studied in the future, but it is estimated as follows. Please refer to Figure 3. The bilayer membrane-forming substance 4 coating the pores 3 of the capsule membrane 2 forms a bilayer membrane below Tc and does not allow the fluorescent probe 5 to pass through (I).

Even when the temperature rises above Tc, the p of the external aqueous phase
) When I is 7, the phosphoric acid is in the form of an anion, so it forms a bilayer membrane with high barrier ability and does not allow the fluorescent probe 5 to pass through (II). When the temperature decreases, the polar groups are partially neutralized, and then compound 4 is no longer able to form a bilayer membrane.
It is thought that a disordered area is formed, and the passage of the fluorescent probe 5 becomes faster (Ill). Such a mechanism of action changes reversibly with changes in pH.

Nylon capsules coated with bilayer-forming compounds in this way not only trap fluorescent probes in the aqueous phase within the capsule, but also other substances, and are expected to be used for a variety of applications. be done. for example,
As shown above, measurement of membrane permeability using fluorescent probes; missile therapy or sustained release microcapsules using anticancer drugs and other various drugs; fermentation production using enzymes or microorganisms; production of antibodies and other immune substances using antigens; tissue The present invention is expected to be used for various physiological models using the present invention, as well as for industrial, biological, medical, agricultural chemical, and pharmaceutical applications.

EXAMPLE A nylon capsule was manufactured in the following manner using a conventional method. That is, 1Illmol of 1,10-bis(chlorocarbonyl)decane and 0.03-0.0.
]m mol of trymesoil chloride
is dissolved in a mixed solvent of 100IIIQ, and the 80IIQ
was placed in a Petri dish with a diameter of 15 cm. 2 mQ of an aqueous solution containing ethylenediamine (0.38M) and Na0)1 (0.8M) was dropped into the acid chloride solution mentioned above using a glass syringe equipped with a No. 1 stainless steel needle. During this process, the Petri dish was kept in constant vibration.

After dropping, add the remaining acid chloride solution (20wQ) and
The reaction was allowed to occur while shaking the Petri dish for 0 minutes. After the reaction, the solution was decanted and the capsules were washed with a mixed organic solvent.
Washed twice. With this method, the diameter is 2-2.5 mm, the film thickness is 1
-Nylon capsules with a uniform particle size of 10 μm were obtained.

Nylon capsules with a diameter of 2 mm and a film thickness of 1 μm were collected and dialyzed in a 0.01 M phosphate buffer containing 1X10-3 M of fluorescent probe 03Na according to a conventional method to encapsulate the fluorescent probe in the inner space.

This was added to a solution in which 10 mg of an amphipathic compound having the ability to form a bilayer membrane consisting of didodecyl phosphate sodium salt represented by the following formula was dissolved in dodecane IIIQ while heating at 60° C. according to a conventional method. Then let it cool to room temperature,
Thereafter, it was left to stand for 1 hour to obtain the desired nylon capsule.

[Brief explanation of drawings]

FIG. 1 is a schematic cross-sectional view of a nylon capsule according to the present invention, with a portion thereof being exaggerated and enlarged. Figure 2 shows the external p
It is a diagram illustrating a change in transmission coefficient due to a change in H. FIG. 3 is a schematic diagram illustrating the membrane permeability mechanism of a nylon capsule. 1... Nylon capsule 4 ・Bilayer membrane 5... Fluorescent probe representative Patent attorney Door 1) Parent Male O H

Claims (1)

[Claims] A nylon capsule responsive to pH, characterized in that the pores of a nylon capsule membrane are filled with sodium didodecyl phosphate.