JPS60232243A - Adsorbent comprising crosslinked high-molecular polymer - Google Patents

Abstract

PURPOSE:To obtain an adsorbent comprising a crosslinked high-molecular polymer having a high intermolecular complex forming component capable of adsorbing and separating a wide range of substances, having adsorbing capacity especially excellent to protein and enzyme and easily enabled in adsorption and desorption by pH-adjustment. CONSTITUTION:A compound having a polyoxyethylene chain and polymerizable double bond in the molecule thereof such as methoxy polyoxyethylene (meth) acrylate, carboxyic acid having polymerizable double bond forming a high intermolecular complex after the polymerization with the polyoxyethylene unit of said compound such as methacrylic acid or maleic anhydride or a derivative thereof and a crosslinking agent having two or more of redical polymerizable double bonds in the molecule thereof are reacted to obtain a crosslinked high molecular polymer containing a high intermolecular complex forming component represented by the formula [wherein Rs are same or different and H or an org. group and (l),(m), and (n) are an integer of 1 or more].

Description

[Detailed Description of the Invention] JLIL Hikari 1 The present invention is a novel adsorbent, particularly a crosslinked polymer containing a component having excellent inter-polymer complex formation performance as a constituent component. Regarding adsorbents.

High molecular weight polymers are used as adsorbents, especially ion exchange resins, which absorb and desorb specific ionic substances.
It is well known that it is used for the separation and purification of substances, and the interpolymer complex formed by hydrogen bonding undergoes reversible interpolymer complex formation and dissociation depending on the pH, and as a result, large It is well known that physical properties change,
At present, it has not yet been possible to separate substances by utilizing this change in physical properties.

The present inventors have recently discovered that this change in physical properties of inter-polymer complexes can be utilized for substance separation, and in order to obtain a carrier that easily adsorbs and desorbs substances to be separated, the inter-polymer complex structure can be cross-linked. We have obtained the knowledge that it is essential to introduce such an intermolecular complex-forming component into a polymer, and have obtained an adsorbent made of a crosslinked polymer containing such an inter-polymer complex-forming component.

Up until now, polymers in which interpolymer complex-forming components have been introduced into crosslinked polymers have so-called interpenetrating network structures in which polyoxyethylene is crosslinked with triisocyanate and then polymerized by adding acrylic acid and a crosslinking agent. IPN) [Kodaka, Polymer Journal, Joushi + P985 ('82)].

However, in this IPN structure, polyoxyethylene (
POE) Since the silver end is fixed, there is little dynamic change in the mobility of the POE chain, and the inter-polymer complex formation-dissociation phenomenon that occurs here is due to the physics of the separation carrier (adsorbent),
The difference was not sufficient to be used as a chemical property difference.

As a result of intensive research into the introduction of inter-polymer complex-forming components into cross-linked polymers for the purpose of using them as separation carriers (adsorbents), the inventors have discovered (A. ) Polyoxyethylene (POE)
A compound having both a chain and a polymerizable double bond in the molecule, (B) a carboxylic acid having a polymerizable double bond (
It is possible to introduce an inter-polymer complex-forming component into the crosslinked polymer by polymerizing the derivatives) and the crosslinking agent (C), and the obtained crosslinked polymer is P.
The present invention was achieved by discovering that it has a novel chemical structure in which OE chains are grafted and is an excellent adsorbent never seen before.

That is, the present invention provides (1) general formula (I), (wherein each R may be the same or different and represents H or an organic group,
1. m and p are integers of 1 or more. ), and (2) A, a compound having simultaneously a polyoxyethylene chain and a polymerizable double bond in the molecule, B0 polymerization. General formula (I), 4- (wherein R may be the same or different, H or The present invention relates to a method for producing an adsorbent made of a crosslinked polymer containing an interpolymer complex-forming component represented by 1.m and p are integers of 1 or more.

■The polymerization reaction in the present invention involves A, a compound having a polyoxyethylene chain and a polymerizable double bond at the same time in the molecule, and B0 a carboxylic acid (derivative) having a polymerizable double bond. The process proceeds through matrix polymerization that forms an intermolecular complex with the POE chain while polymerizing, producing blocks derived from carboxylic acid (derivatives) containing double bonds corresponding to the POE chain, and these blocks form a crosslinking agent. For example, a crosslinked polymer containing the following structure can be obtained.

(1, m, n, p are integers of 1 or more.) As described above, in the crosslinked polymer obtained by the present invention, POE
It is a graft type in which only one end of the chain is fixed and the other end is free, and this graft type POE chain and the carboxyl group based on the double bond-containing carboxylic acid (derivative) of (B) In addition to constituting an inter-polymer complex-forming component, the graft-type POE chain has remarkable mobility as the inter-polymer complex is formed and dissociated due to pH changes, compared to those in which both ends are fixed. This makes it effective for adsorption and separation of substances.

Regarding the compounds used in the present invention to introduce an inter-polymer complex-forming structure into a crosslinked polymer, compounds having a polyoxyethylene chain and a polymerizable double bond in the molecule ( It is a compound (B) that forms an inter-polymer complex after polymerization with A) and its polyoxyethylene unit, and theoretically any such compound can be used, but (A) As methoxypolyoxyethylene (meth)acrylate methoxypolyoxyethylene vinyl ether polyoxyethylene (meth)acrylate n = 2 to 9 (NOF; Bremmer PE90.PE200.PE350
), etc. Examples of (B) include carboxylic acids such as acrylic acid and methacrylic acid lylic acid, as well as carboxylic acid derivatives such as polyitaconic acid methyl ester, maleic anhydride, and itaconic acid methyl ester.

In particular, methoxypolyoxyethylene methacrylate (acrylate) having an oxyethylene unit (p) of 100 or less, and methacrylic acid or acrylic acid that forms an interpolymer complex with the polyoxyethylene unit after polymerization are preferably used.

The ratio of addition of (A) and (B) is determined by the addition ratio of oxyethylene units and carboxylic acids (derivatives) having polymerizable double bonds that have the ability to form inter-polymer complexes after polymerization with the oxyethylene units such as methacrylic acid or acrylic acid. ) with a molar ratio of 0.
1 to 10, preferably 1.

Depending on the types of (A) and (B) above, R and R' in the polymer complex forming component 8- of the following general formula contained in the absorbent of the present invention may be H, an alkyl group such as methyl or ethyl, or an aryl group. R'' may be combined with 0 0 to represent an acid anhydride residue.

As for the crosslinking agent (C), the following compounds having two or more radically polymerizable double bonds in the molecule can be used. That is, ethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, divinylbenzene, triallyl isocyanate, etc. are added in an amount of 0.1 to 50%, preferably 0.1 to 50%, based on the monomer ratio.
It is 5-30%.

Examples of radical polymerization initiators include azoisobutyronitrile, t-butyl hydroperoxide, cumene hydroperoxide, benzoyl peroxide, acetyl peroxide, and -
di-t-butyl, azodicyclohexylcarbonitrile,
Those commonly used in this type of polymerization reaction, such as dimethyl azodiisobutyrate, succinic peroxide, and dicumene peroxide, can be used, and the amount of these added is from 0.1 to 10% by weight.

The crosslinked polymer of the present invention can be produced by any polymerization method such as solution polymerization, bulk polymerization, suspension polymerization, etc., and the polymerization reaction is preferably carried out under an atmosphere of an inert gas such as nitrogen.
The polymerization is carried out by heating to ~100°C, preferably from 60 to 80°C, for a polymerization time of 3 to 20 hours.

The diluent used in the suspension polymerization reaction is not particularly limited, but for example, the following can be used alone or as a mixture. That is, aromatic hydrocarbons such as benzene, toluene and xylene, aliphatic hydrocarbons such as n-octane, alcohols such as cyclohexanol and lauryl alcohol, etc., and the amount added is 10% to the monomer mixture.
~100%. In addition, a monomer mixture, a polymerization initiator,
The diluent mixture can be subjected to a conventional suspension polymerization reaction with a dispersion medium containing a suitable protective colloid salt. That is, a suitable diluent such as water is added to a monomer mixture capable of introducing an inter-polymer complex structure into a crosslinked polymer, a crosslinking agent and a radical polymerization initiator, and cyclohexanol, which is immiscible with the monomers and diluent, is prepared. Polymerization can also be carried out using liquid paraffin or the like as a dispersion medium in the presence of a suitable protective colloid or surfactant.

The crosslinked polymer obtained by the method described above is separated from the reaction solution by passing through the mouth, and after washing with a solvent such as pure water, methanol, or acetone, it is washed with an alkali, acid aqueous solution, or pure water. It is washed repeatedly and dried under reduced pressure at 40 to 80°C.

Adsorption and separation of substances using the crosslinked polymer of the present invention can be carried out by commonly used batch methods, column methods, etc., and they can be suitably selected as necessary to carry out the adsorption and separation.

ltl! 11 Items The cross-linked polymer containing the inter-polymer complex-forming component of the present invention can adsorb and separate a wide range of substances such as metal ions, basic amino acids, antibiotics, proteins, and enzymes, and in particular It has excellent adsorption ability for proteins and enzymes, and can be easily adsorbed and desorbed by adjusting the pH, making it an industrially useful adsorbent that is easy to operate and requires less equipment. It is a drug.

(H) For adhesive use The crosslinked polymer obtained in the present invention is specifically a crosslinked polymer containing an interpolymer complex-forming component consisting of polyoxyethylene, polymethacrylic acid, polyacrylic acid, etc. It is a type in which POE chains are grafted, and one end of the POE chain is free, so the PO accompanying the formation of a complex between polymers and dissociation.
The E chain has remarkable mobility and is effective for adsorption and separation of substances.
It is a highly practical compound that can be applied as an adsorption carrier or as an immobilized enzyme carrier.

To further explain the range of application, this crosslinked polymer is originally a weakly acidic cation exchange resin, and it can be used to separate substances related to general weakly acidic cation exchange resins, such as calcium ions (Ca++) and magnesium ions (Mg++). ), basic amino acids such as arginine, histidine, lysine, ornithine, antibiotics such as streptomycin, Beni-12-syrin, chloramphenicol, chlorotetracycline, basic dyes such as methylene blue, etc. It is possible to apply both adsorption and separation.

In addition, this crosslinked polymer contains polyoxyethylene chains, which are synthetic polymers that exhibit only mild interactions with biological components, and exhibits adsorption and desorption properties through changes in the mobility of these chains due to pH. Separates or adsorbs proteins and enzymes such as globulin, serum albumin, lactalbumin, β-lactoglobulin, chymotrypsinogen, chymotrypsin, and human leukocyte interferon, as well as biological substances such as red blood cells, granulocytes, and lymphocytes. It is suitable for use in

The present invention will be specifically explained with reference to the following examples, but the present invention is of course not limited to these examples.

Example 1) A 100 ml three-meter flask equipped with a stirrer and a cooling tube was charged with the following raw materials so that the molar ratio of acrylic acid and oxyethylene units was 1. i.e. acrylic acid 10
．． 44g, ethylene glycol dimethacrylate 3.0
2 g of methoxypolyoxyethylene methacrylate (oxyethylene unit: 90), 0.30 g of azoisobutyronitrile, and 30 g of toluene were added, and polymerization was carried out at a polymerization temperature of 60° C. for 3 hours under a nitrogen atmosphere.

The obtained white blocky crosslinked polymer was separated daily, washed with pure water, methanol, and acetone, then washed with alkali, acid aqueous solution, and pure water, dried at a reduced pressure of 80°C, and ground in a mortar to form a white powder 17 .88g was obtained.

The infrared absorption spectrum of this crosslinked polymer is 110
It had absorption bands near 0 cm', 1710 cm-', and 3450 cm'', and the presence of carboxyl groups derived from acrylic acid and ether bonds derived from methoxypolyoxyethylene methacrylate was confirmed.

The percentage composition of this crosslinked high molecular weight polymer according to elemental analysis was as follows.

c; 52.77 H; 6.85 Also, the degree of crosslinking is ethylene glycol dimethacrylate 9
It was 42 mol%.

The polymerization reaction progresses through matrix polymerization in which acrylic acid forms an intermolecular complex with polyoxyethylene chains while polymerizing, so acrylic acid blocks corresponding to polyoxyethylene chains are generated, and these blocks form ethylene glycol, which is a crosslinking agent. It is crosslinked with dimethacrylate, and from the above analysis results, this crosslinked polymer contains the following structure, and the ratio of each block is 1:m:n = 14500:161:1
It is 520.

Note that this crosslinked high molecular weight polymer was insoluble in ordinary organic solvents.

151 Example 2) A 500 ml decomposition flask equipped with a stirring device and a cooling tube was charged with the following raw materials so that the molar ratio of methacrylic acid and oxyethylene units was 1. That is, methacrylic acid 2
1.25g, ethylene glycol dimethacrylate5.
15g, methoxypolyoxyethylene methacrylate (
Oxyethylene units are 9) 13.60g, azoisobutyronitrile 0.60g, toluene 5. 1°3g containing mixed and dissolved OOg and 1% polyvinyl alcohol
200 ml of calcium chloride aqueous solution was added thereto, and suspension polymerization was carried out under a nitrogen atmosphere at a polymerization temperature of 70° C. and a stirring speed of 300 rpm for 8 hours.

The obtained porous white crosslinked polymer was separated daily, washed with pure water, methanol, and acetone, then washed with alkali, acid aqueous solution, and pure water, and dried under reduced pressure at 80°C. Diameter approximately 100. - 36.24 g of white spherical powder was obtained.

The infrared absorption spectrum of this crosslinked polymer is 110
It has absorption bands near 0cm→, 1720cm-', and 3450cm''1, and the presence of carboxyl groups derived from methacrylic acid and ether bonds derived from methoxypolyoxyethylene methacrylate was confirmed, and elemental analysis revealed that this crosslinked polymer The percentage composition of the polymer was as follows.

C; 55.67 H;, 7.48 A 'CNMR spectrum was also measured as follows. A predetermined amount of heavy water was added as a magnetic field locking agent under predetermined pH conditions, the crosslinked polymer was immersed, and a 'CNMR spectrum was measured at room temperature. By integrating 3,000 to 30,000 times, a signal of ether carbon originating from the oxyethylene chain in the crosslinked polymer was observed at around 70 ppm based on tetramethylsilane (this indicates that the weight of the crosslinked polymer This proves that ether carbon derived from methoxypolyoxyethylene methacrylate is introduced into the coalescence).

Table 1 shows the relationship between the half width of the signal of this ether carbon and the pH.

Table 1 and degree of crosslinking is ethylene glycol dimethacrylate 8
．． It was 65 mol%. This crosslinked polymer also has methacrylic acid blocks corresponding to polyoxyethylene chains produced for the same reason as described in Example 1), and these are crosslinked with the crosslinking agent ethylene glycol dimethacrylate 1. Therefore, when the analysis results described above are combined, this crosslinked polymer contains the following structure, and the ratio of each block is 1:m:n=2470:274:26.
It is 0.

Note that this crosslinked high molecular weight polymer was insoluble in ordinary organic solvents.

Furthermore, as shown in Table 1, it can be seen that by changing the pH, the properties of the crosslinked polymer, that is, the mobility of the polyoxyethylene chains in the present crosslinked polymer, change greatly.

Next, using this crosslinked polymer, bovine serum albumin (
The adsorption capacity of BSA) was measured. That is, 1 g of crosslinked polymer and 20 m of a 50 mg/dlBsA solution at a predetermined pH.
After reaching the unbalanced adsorption amount of 1 at room temperature, the amount of BSA in the supernatant was determined by the microbiulet method. The results are shown in Table 2.

Table 2 As shown in Table 2, it can be seen that by changing the pH, the adsorption characteristics of the crosslinked polymer change significantly = 19-.

The reason why this cross-linked polymer showed the maximum adsorption capacity at pH 4.9 is that the carboxyl group does not dissociate in the cross-linked polymer, and moreover, it forms a stable polymer adsorbent with polyoxyethylene chains. However, since it is near the isoelectric point of the BSA molecule, the BSA molecule has no charge and has a compact molecular shape, so the crosslinked polymer was stably adsorbed mainly due to hydrophobic interactions. This is thought to be due to the In any case, as is clear from Table 2, the crosslinked polymer of the present invention can easily adsorb and desorb BSA by changing the pH, making it an excellent adsorbent.

Therefore, by using this crosslinked polymer, p
It can be seen that the target substance can be easily adsorbed and separated simply by adjusting the H content, and that it is a very useful polymer adsorbent industrially.

Example 3) A 500 ml decomposition flask equipped with a stirring device and a cooling tube was charged with the following raw materials so that the molar ratio of methacrylic acid and oxy-20-ethylene units was 1. That is, 22.65 g of methacrylic acid, 5.49 g of ethylene glycol dimethacrylate, and 11.87 g of methoxypolyoxyethylene methacrylate (oxyethylene units are 90).
g, 75% benzoyl peroxide 1.20 g, toluene 4.
200ml of a 1.3g/ml calcium chloride aqueous solution containing a mixed solution of oog and 1% polyvinyl alcohol
1, and suspension polymerization was carried out under a nitrogen atmosphere at a polymerization temperature of 70° C. and a stirring speed of 300 rpm for 8 hours.

The obtained porous white crosslinked polymer was separated into pure water.

After washing with methanol and acetone, alkali and acid aqueous solutions,
It was washed with pure water and dried under reduced pressure at 80°C. Approximately 100P in diameter
34.08 g of white spherical powder was obtained.

The infrared absorption spectrum of this crosslinked polymer is 110
0 cm', 1'710 cm-', 3450 cm-1
There was an absorption band nearby, and the presence of a carboxyl group derived from methacrylic acid and an ether bond derived from methoxypolyoxyethylene methacrylate was confirmed. The percentage composition of this crosslinked high molecular weight polymer according to elemental analysis was as follows.

C: 55.79 H: 7.52 In addition, the 'J'CN MR spectrum was measured in the same manner as in Example 2). In this crosslinked polymer, a signal of ether carbon derived from oxyethylene chains was observed at around 70 ppm based on tetramethylsilane. This shows that ether carbon derived from methoxypolyoxyethylene methacrylate has been introduced into the crosslinked polymer.

Next, Table 3 shows the relationship between the half width of the signal of this ether carbon and the pH.

Table 3 also shows the degree of crosslinking for ethylene glycol dimethacrylate: 9.
It was 43 mol%. This crosslinked polymer was also used in Example 1.
), methacrylic acid blocks corresponding to polyoxyethylene chains are generated, and these are crosslinked by the crosslinking agent ethylene glycol dimethacrylate. The crosslinked polymer contains the following structure, and the ratio of each block is 17m:n=26300:292
: 2770.

Note that this crosslinked high molecular weight polymer was insoluble in ordinary organic solvents.

Furthermore, as shown in Table 3, it can be seen that the properties of the crosslinked polymer, that is, the mobility of the polyoxyethylene chains in the present crosslinked polymer, change greatly by changing the pH. Moreover, this rate of change is larger than the change shown in Example 2). This shows that a larger difference in adsorption characteristics can be expressed by changing the pH, and shows that it is effective in separating and adsorbing substances.

Next, using this crosslinked polymer, the BSA adsorption ability was measured in the same manner as in Example 2). The results are shown in Table 4.

Table 4 As shown in Table 4, it can be seen that by changing the pH, the adsorption characteristics of the crosslinked polymer change greatly. Further, the adsorption behavior can be understood for the same reason as described in Example 2).

As is clear from Table 4, the crosslinked polymer of the present invention can easily adsorb and desorb substances to be separated by changing the pH. Therefore, by using the crosslinked polymer of the present invention, the pH It can be seen that the target substance can be easily adsorbed and separated by simply adjusting the amount, making it a useful polymeric adsorbent.

24- In addition to BSA, similar separation and adsorption of proteins and enzymes such as sea globulin, melactalbumin, and chymotrypsinogen, as well as red blood cells, granulocytes, and lymphocytes, could be performed using this crosslinked polymer. .

pot Agent Akitoshi Ogiri

Claims (2)

[Claims] (1) An interpolymer complex represented by the general formula CI), (wherein each R may be the same or different and represents H or an organic group, and 1.m and p are integers of 1 or more.) An adsorbent made of a crosslinked polymer containing forming components. (2) A, a compound having simultaneously a polyoxyethylene chain and a polymerizable double bond in the molecule, B9 a carboxylic acid or a derivative thereof having a polymerizable double bond, and a C0 crosslinking agent are reacted. An interpolymer complex represented by the general formula (I), (wherein each R may be the same or different and represents H or an organic group, and 1.m and p are integers of 1 or more.) A method for producing an adsorbent comprising a crosslinked polymer containing a forming component.