JPS6411042B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a polymer electrolyte complex (hereinafter referred to as PIC) comprising a pullulan derivative. Pullulan is an unbranched linear polysaccharide polymer that consists of maltotriose as a repeating unit and has α(1→6) and α(1→4) bonds, and it easily dissolves in water and forms a stable aqueous solution. crystallization,
Alternatively, almost no abnormal behavior in solution physical properties is observed.

It can be produced industrially at low cost by the fermentation method and has a suitable molecular weight.

Furthermore, PIC is a substance formed by the reaction between an anionic polymer and a cationic polymer, and its utility value is high. For example, it has useful properties such as ion selective permeability, semipermeability, electrical conductivity, and anticoagulability.

On the other hand, polysaccharide PICs other than pullulan are described in Patent Publication 1983-41718, and unlike conventional synthetic compounds, they are close to natural materials, have good affinity with living organisms, and have excellent anticoagulant properties. Moreover, since it is easily decomposed by enzymes, it is a promising biocompatible material and there is no need to worry about it remaining as a foreign substance in the body.

However, in general, polysaccharides have varying molecular weights and higher-order structures, and when these polysaccharides are used as raw materials,
PIC is difficult to design molecularly and is not suitable for industrially producing uniform products. For this reason, dextran, a water-soluble linear polysaccharide that is industrially produced by fermentation and whose molecular weight can be easily controlled and other molecular designs, is used as a starting material.
Invented PIC (Japanese Patent Application Laid-Open No. 1939-1939). The present invention relates to a PIC made of a pullulan derivative that has superior properties comparable to PIC made of a dextran derivative. This invention will be explained in detail below.

The novel PIC of the pullulan derivative of the present invention is an anionic pullulan derivative represented by the following formula (1).

[C ₆ H ₇ O ₂ (OH) ₃ -a・(OX)a]x・H ₂ O (1) [In the formula, X is −SO ⁻ ₃ , −PO ⁻² ₃ , −(CH ₂ )mR ¹ (However, R ¹ is a group selected from the group consisting of -COO ^- , -SO ^- ₃ , -PO ^-2 ₃ , m is an integer from 1 to 3), 0<a≦3
a positive number, an integer of x≧5], and the unit of [C ₆ H ₇ O ₂ (OH) ₃ −b・(OY)b]y・H ₂ O (2) [where Y is −(CH ₂ ) nR ² (R ² is −NH ⁺ ₃ , −NH ⁺
(CH ₃ ) ₂ , −NH ⁺ (C ₂ H ₅ ) ₂ , −N ⁺ (C ₂ H ₅ ) ₃ , −
C ₆ H ₄ .NH ⁺ ₃ , -CO.C ₆ H ₄ .NH ⁺ ₃ (n is an integer from 1 to 3), or -CO.R ³
(R ³ is −CH ₂・NH ⁺ ₃ or −C ₆ H ₄・NH ⁺ ₃ ), or −
CH ₂ CH(OH)・CH ₂ R ⁴ (R ⁴ is −NH ⁺ ₃ , −NH ⁺
(CH ₃ ) ₂ , −NH ⁺ (C ₂ H ₅ ) ₂ , −N ⁺ (C ₂ H ₅ ) ₃ ), a positive number of 0<b≦3, y≧5
[an integer] It consists of a unit of a cationic derivative of pullulan shown by formula (2). Examples of the anionic derivative of pullulan represented by formula (1) above include pullulan sulfate, phosphate, carboxymethyl ether, sulfoethyl ether, sulfopropyl ether, phosphomethyl ether, and phosphoethyl ether. It will be done.

In addition, examples of cationic derivatives of pullulan that produce the structural unit represented by formula (2) above include pullulan aminoethyl ether, dimethylaminoethyl ether, diethylaminoethyl ether, triethylaminoethyl ether chloride,
P-aminobenzyl ether, P-aminophenacyl ether, P-aminophenylethyl ether, diethylaminopropyl ether, α-aminoacetic acid ester, P-aminobenzoic acid ester, 3
-amino-2oxypropyl ether, 3-dimethylamino-2oxypropyl ether, 3-diethylamino-2oxypropyl ether, 3-
Examples include triethylamino-2oxypropyl ether chloride.

These compounds are those in which part or all of the hydroxyl groups of pullulan are substituted with a dissociative group that dissociates in an aqueous solution and becomes negatively or positively charged, or a dissociative group that can carry a negative or positive charge. can be introduced by etherification or esterification of

The PIC of the present invention is obtained by dissolving a cationic derivative of pullulan and an anionic derivative of pullulan in water and reacting them in water.

The concentration, which is one of the reaction conditions, is not particularly limited, but if the concentration is high, it may be difficult to separate the reaction product from the dissolved product, so it is desirable to carry out the reaction at a concentration of 0.01 to 10%.

The reaction temperature can be from 0 to 100°C. Moreover, the reaction time can be selected as appropriate. The resulting precipitate is separated by precipitation, thoroughly washed with water, and then dried under reduced pressure to obtain the desired product.

In the reaction, the ratio of the units of the anionic derivative of pullulan to the units of the cationic derivative of pullulan can be selected as appropriate. That is, the positive charges and negative charges may be completely neutralized, or some positive charges or negative charges may remain.

The resulting pullulan PIC is insoluble or poorly soluble in solvents such as water, alcohols, ketones, and ethers. However, it is soluble in a ternary solvent consisting of water, a water-miscible organic solvent, and an acid/base or salt. Examples of water-miscible organic solvents here include alcohols such as methanol and ethanol, ketones such as acetone and methyl ethyl ketone, and cyclic ethers.

The PIC of this invention can be obtained as a powder, but it can be made into a molded product if necessary. For example, this invention
PIC powder is supplied to the mold of the molding machine, and the pressure is approximately 10t/cm ²
Various PIC molded products can be obtained by vacuum compression.
Further, the PIC of the present invention can be dissolved in the above three-component solvent and used, for example, by coating it on a glass plate. These PICs have properties such as ion selective permeability, semipermeability, electrical conductivity, and anticoagulability.

Therefore, it can be used as an ion exchange membrane, a hypermembrane, an ultramembrane, an electrically conductive coating, an anticoagulant medical material, or an artificial organ material such as an artificial blood vessel or an artificial cornea.

In particular, it has extremely good affinity for living organisms and can be suitably used as a material for artificial organs.

Example 1 0.2% aqueous solution of pullulan sulfate sodium salt with S content 18.3% and molecular weight MW 300000 and DEAE
Equal volumes of 0.4% aqueous solution of pullulan (diethylaminoethyl) hydrochloride (N content 4.8%, molecular weight MW 500000) were mixed to form a water-insoluble white precipitate.

This precipitate was separated from the solution, thoroughly washed with water, and then dried under reduced pressure to obtain the desired product.

Yield was 23%, N content 4.6%, S content 8.3%.

This reaction product was insoluble in water, and no Cl was detected, indicating that it was electrostatically bound by the attractive force between the negative charge of pullulan sulfate sodium salt and the positive charge of DEAE pullulan hydrochloride. This PIC is PIC(1)
It is called. Pullulan sulfate ester (S content 18.3%,
PIC (1b) was prepared by reacting with the same substances and under the same conditions except for the molecular weight (MW 40,000), and the anticoagulant properties of each were compared using the test method described below.

Test method: 100 mg each of PIC (1) and PIC (1b) were fed into the mold of a molding machine and vacuum compressed at 10 t/cm ² to produce tablets. Place 0.1ml of ACD blood on the surface of this tablet,
Further, 0.01 ml of 0.1M calcium chloride is added, and a coagulation reaction is caused on a watch glass in a 37°C water bath for 8 minutes, after which the amount of thrombus formed is measured. If the amount of blood clots formed on the glass surface under the same conditions is taken as 100%, PIC(1): 40% PIC(1b): 80%, and the dependence on molecular weight becomes clear.
In the case of molecular design, the influence of molecular weight is important.

Example 2 Carboxymethyl pullulan sodium salt (carboxymethyl group substitution degree 0.65 mol, average molecular weight
A 0.3% aqueous solution of 1,000,000) and a 0.12% aqueous solution of DEAE pullulan hydrochloride of Example 1 are mixed in equal volumes to form a white precipitate, and the desired product is obtained in the same manner as in Example 1.

Yield is 17%, N content 2.6% -CH ₂ COO ^- content 10.6% Example 3 Carboxymethyl pullulan sodium salt (degree of carboxymethyl group substitution 0.3, average molecular weight MW 8000)
Cation exchange resin (Dowex 50W-X8;
A 0.2% aqueous solution of DEAE pullulan hydrochloride (N content 1.4%, average molecular weight MW 900000) was converted into a base form using an anion exchange resin (Amberlite 400). A precipitate was obtained by mixing the same volume of 0.3% aqueous solution. The target product is obtained in the same manner as in Example 1.

Yield 18%, N content 0.9%, -CH ₂ COO ^- content 4.0 Example 4 Pullulan sulfate ester sodium salt (S content
5.5%, average molecular weight MW800000) and 0.7% aqueous solution
HPTMA-Pullulan (2-hydroxypropyltrimethylammonium) hydrochloride (N content 4.9
%, average molecular weight MW 400000) in equal volumes to form a white precipitate. The desired product was obtained in the same manner as in Example 1.

Yield 20%, N content 4.6%, S content 8.1%.

Claims (1)

[Claims] 1. The formula of the unit of the anionic derivative of pullulan is [C ₆ H ₇ O ₂ (OH) ₃ -a・(OX)a]x・H ₂ O (1) [in the formula is −SO ⁻ ₃ , −PO ⁻² ₃ , −(CH ₂ )m・R ¹
(However, R ¹ is a group selected from the group consisting of -COO ^- , -SO ^- ₃ , -PO ^-2 ₃ , m = an integer of 1 to 3), 0<a≦3
positive number, x is an integer of 5 or more]. It is shown by formula (1), and the formula of the unit of the cationic derivative of pullulan is [C ₆ H ₇ O ₂ (OH) ₃ −b・(OY)b]y・H ₂ O (2) [in the formula Y is −(CH ₂ )nR ² (R ² is −NH ₃ ⁺ , −
NH ⁺ (CH ₃ ) ₂ , −NH ⁺ (C ₂ H ₅ ) ₂ , −N ⁺ (C ₂ H ₅ ) ₃ , −
a group selected from the group consisting of C ₆ H ₄・NH ₃ ⁺ , −CO・C ₆ H ₄・NH ⁺ ₃ , n = an integer of 1 to 3), or −
COR ³ (R ³ is −CH ₂ NH ⁺ ₃ or −C ₆ H ₄・NH ⁺ ₃ ) or −CH ₂ CH(OH)・CH ₂ R ⁴ (R ⁴ is −NH ⁺ ₃ , −NH ⁺
(CH ₃ ) ₂ , -NH ⁺ (C ₂ H ₅ ) ₂ , -N ⁺ (C ₂ H ₅ ) ₃ , an integer of 0<b≦3, an integer of y≧5] Formula (1), which is represented by formula (2) and is formed by combining the above X and Y in an appropriate ratio,
A polymer electrolyte complex composed of formula (2).