JPS58136351A - Cellulose molded product containing anionic polymer and production thereof - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The Ij1 of the present invention is a molded product with less contamination due to blood clots,
□The present invention also relates to a molded product in which the ionic components in the molded product gradually migrate into the blood upon contact with blood, thereby imparting anticoagulant properties to blood as well, and a method for producing the same.

More generally, molded products made of anionic water- or alkali-soluble polymers arranged in water-insoluble polymers,
This invention relates to a wet manufacturing method for molded products with molded parts and wrinkles.

With the spread of hemodialysis therapy, it has become desirable for dialysis M to be made of a material with higher anticoagulant properties. The conditions that anticoagulant materials must meet include surface smoothness and the presence of anionic substances. Among blood coagulation factors, these seem to correspond to a decrease in the activity of contact factors, inhibition of extrinsic mechanisms, and a decrease in the activity of thrombin formation-promoting factors, that is, inhibition of endogenous mechanisms. be. On the other hand, during hemodialysis, substances that prevent blood from coagulating, i.e.
Due to the complexity of having to mechanically inject a heparin solution into the blood, there is hope for the development of a membrane that allows such substances to be transferred into the blood more gradually than a dialysis membrane during dialysis.

As membranes meeting the above-mentioned objectives, membranes in which heparin is grafted onto synthetic polymers or cellulose, gel-like membranes in which heparin is encapsulated in a polymer gel, and the like are known. Although heparin-grafted membranes are excellent against blood clots caused by contact with blood membranes and non-contaminating due to blood clots, they are ineffective against blood clots caused by endogenous mechanisms and require heparin infusion during hemodialysis. On the other hand, Panocrin placed in a gel-like membrane can certainly migrate into the blood and prevent endogenous blood coagulation; There are problems with strength.

Also, heparin itself is quite expensive, so the quality of the drug, the efficiency with which heparin penetrates into the gel, and the efficiency with which it transfers into the blood greatly influences economic efficiency.

The present inventors investigated the shortcomings of the conventional technology and discovered an inexpensive anticoagulant to replace heparin, and also developed a group of substances that have excellent mechanical strength and are widely used as hemodialysis membranes. After intensive study on a method for temporarily fixing it in a cellulose membrane, the present invention was finally completed.

According to the present invention 111, it is possible to obtain the above-mentioned anticoagulant and anticoagulant sequential release membrane, but in addition to this, 41
1. Ion exchange membranes with excellent mechanical strength, ion exchange fibers,
It is also possible to manufacture water absorbers, water-based liquid absorbers, etc.hh.

To explain the present invention in detail, the molded article of the present invention is produced by mixing and dissolving cellulose and an anionic polymer in the form of a free acid or a sodium salt in an own solvent during the cellulose regeneration process,
It is produced by soaking the mixture in a solution containing selected metal salts to reduce the solubility of the anionic polymer and immobilize it in regenerated cellulose.

As the cellulose used in the present invention, natural wood bulbs, cotton linters, cotton lint, and in some cases regenerated cellulose such as rayon or ammonium rayon are preferably used. In order to obtain a cellulose molded article with excellent mechanical strength, it is sufficient if the degree of polymerization is 100 or more. Regenerated cellulose is the material of the molded product of the present invention.) In order to make IJ Lux, the raw material cellulose can be dissolved and regenerated with a simple operation.
A solvent is required that can also dissolve the anionic polymer reservoir, which is one of the constituent elements of the molded article of the present invention.

Many methods are known for dissolving cellulose, but in most cases cellulose is dissolved in the form of derivatives, so in order to obtain the molded article of the present invention, regeneration by the simple operation described above is necessary. This is an advantage in order to minimize possible spillage of the anionic polymer in the molded article during the cellulose regeneration process.

Solvents used in this reaction include metal-containing alkaline solutions such as copper ammonia solution, viscose solution, Kadoki Ryuun, Jinkosen, Niokiryuun, iron-tartaric acid-caustic soda mixture (IWNN), and dimethyl sulfoxide/Pal2* solution. maldehyde,
Dimethylformamide/N2O2, H-oxide, N-ethylpyridi9mutarolide, 8-helamine-based solvents, dimethylformamide/chlorine, so-called cellulose organic solution #II can be used. However, with a good cellulose solution using 1W and solvent, there is a problem with the amperage of the anionic polymer added, and the MSF effect is small in terms of reusing the solvent. Among the metal-containing alkaline solutions, copper ammonia solution or viscose solution is preferred from the viewpoint of stability and industrial operability. Although the concentration of cellulose is not limited, it is preferable to use it at 12% by weight or less in terms of defoaming and transportation.

The anionic polymers used in this invention are polymers with carboxyl groups such as polyacrylic acid, carboxymethyl cellulose, carboxyethyl cellulose, carboxyethyl-carbamoylethyl cellulose, and their salts, cellulose sulfate, chondroitin sulfate, amylose sulfate, amylopectin sulfate, and mucopolysaccharides. Sulfated polymers such as sulfates, polyvinyl alcohol sulfates and their salts, cellulose phosphates and their salts are used.

The number of substituents is 0.1 to 1 per monomer unit for non-cellulose derivatives, and 0.1 to 1 for cellulose derivatives.
3.0 is used. □Generally, in cellulose derivatives, when the number of substituents defined above is 0.1 to 50 and s5, it is alkali soluble and insoluble in water.

When it is 0.35 or more, it becomes soluble in alkali and water.

The degree of polymerization of these polymers can be selected depending on the purpose. Among the above polymers, sulfated derivatives are preferably used in terms of anticoagulant properties and release of anticoagulant components, and cellulose sulfate is more preferred in terms of toxicity and economy.Incidentally, LD can be administered intravenously to rats. The values are 2 sq/hour for carboxymethyl cellulase, 1 sq/hour for heparif
, 200 to 1,700 ml/kl, number average molecular weight is 60,000 or less and the number of substituents is 1.6 to 1.6 to 1,700 ml/kl.
Cellulose sulfate of 2.4 has an extremely low toxicity of 5,200-S and 400 damas, and in order to obtain a strong ion-exchange molded product, it is desirable that the anionic polymer be substantially insoluble in water. .

The above nine polymers can be dissolved and mixed in a cellulose solution by directly dissolving the polymer in the cellulose solution, or by adding, mixing and dissolving the polymer in the form of an aqueous solution or an alkaline solution. The anionic polymer used in the present invention is generally difficult to dissolve in organic solvents, but even if the cellulose solution used is an organic solvent-based one, it can be used, for example, with monomer N-oxide, methyl sulfoxide/baraformaldehyde, N-
- A solution of ethylpyridium chloride has 11
The anionic polymer can be added and mixed in the form of an aqueous solvent. Furthermore, since polyacrylate can be dissolved in dioxins, etc., it can be mixed with most organic solvent-based cellulose solutions. However, since Ktj is molded using the actual method, it is desirable to use an aqueous solvent, that is, an alkaline solvent, for both the cellulose and the anionic polymer in terms of economy, as described above.

At this mixing stage, it is usually advisable to supply the anionic polymer in the form of a sodium salt from an economical point of view, but the invention is not limited to this. Metal salts other than those used in the immersion step can also be supplied as other metal salts. On the other hand, supplying wrinkled anionic polymers in free acid form may have to be avoided depending on the type of anionic polymer. Examples include carboxymethyl cellulose, carboxyethyl cellulose, and carboxyethyl-carbamoylethyl cellulose.

However, in this case, if the cellulose to be mixed is dissolved in the metal-containing alkaline solution, it may be supplied as an acid type anionic polymer.

The mixing ratio of cellulose and the anionic polymer is appropriately selected depending on the use of the final molded product. However, from the viewpoint of mechanical strength of the molded article, it is preferable that the weight ratio of cellulose/wrinkled anionic polymer is Fi1 or more, that is, the weight of the wrinkled anionic polymer in the molded article is sos or less. In addition, in order for the molded article to be sufficiently usable for the intended purpose, it is necessary that the molded article contains at least 40.25% by weight of the anionic polymer.

In order to mold the cellulose/anionic polymer maple mixture obtained in this way by a wet method and to fix the anionic polymer in the regenerated cellulose matrix, it is necessary to Education
It is necessary to prevent the water from flowing into the coagulation regeneration bath. In the case of a mixture containing an anionic polymer that is insoluble in water and soluble in alkali, by using the acid bath as a regeneration bath, a large portion of the Kll anionic polymer in the cellulose matrix can be temporarily fixed, and the thus obtained The molded article is stable in media other than alkali. However, in a mixed solution that essentially contains a water-soluble anionic polymer, if the cellulose portion is directly regenerated with an acid or alkali without undergoing a temporary insolubilization process, the water-soluble anionic polymer easily flows out into the regeneration bath. However, it is difficult to obtain the desired molded product, and therefore it is necessary to prevent the water-soluble anionic polymer from flowing out during cellulose regeneration.

A unique feature of the production of the molded article of the present invention is that the above-mentioned purpose can be accomplished with extremely simple operations. This is achieved by treating the cellulose/anionic polymer mixture with an aqueous solution containing metal salts before introducing it into the regeneration bath. In some cases, regeneration can also be carried out at the same time using an acid bath or an alkaline bath containing a metal salt. Theoretically, this consists in converting the anionic polymer into a more water-soluble salt or forming partial ionic crosslinks. This method is a very effective means for reducing V in the case of anionic polymers that are soluble only in alkali.

The metal salt that insolubilizes the anionic polymer in this way should naturally be selected according to the species 1 [IK] of the anionic polymer. For example, potassium salts, zirconium salts, and titanium salts are used for sulfated polymers, and polyvalent metal salts such as aluminum, copper, nickel, iron, lead, zirconium, and titanium are used for anionic polymers with four carboxyl groups. used.

The aqueous solution concentration of these metal salts is 0 in terms of the metal cation.
．． Used between 05 mot/t and 8 mot/l. It is also possible to use acidic or alkaline aqueous solutions containing the single range salts. In this case, temporary insolubilization of the anionic polymer and regeneration of cellulose can be performed simultaneously. During molding, the cellulose/anionic polymer mixture is abraded or extruded through a nozzle to form a fiber, which is then immersed in the treatment tower. Surprisingly, the mixture becomes insolubilized in a few seconds of contact with the metal salt bath and is easily incorporated into the wrinkle matrix with coagulation of cellulose.

The cellulose portion ′ in the semi-molded product thus obtained is
Acids are regenerated by alkalis. It is desirable to select an acid or alkali concentration of the wound so that cell fight O regeneration is completed within 60 seconds. Generally, an acid of 5 or less and an alkali of 15 or less are used. As the acid, sulfuric acid, hydrochloric acid, phosphoric acid, nitric acid, etc. are used. As the alkali, caustic sorter and caustic potash are preferably used. If the coagulation of cellulose is not completed within 50 to 60 seconds, the semi-molded product is immersed in metal salt again, the regeneration method is repeated, and finally, after washing with water, dehydrate with methanol, acetone, etc. and dry. Alternatively, the desired molded product can be obtained by drying directly.

The resulting molded products can be obtained in the form of membranes, fibers, and hollow fibers, and are less likely to be contaminated by blood clots, and can be used as membranes that release anticoagulants into blood, hollow fibers, etc. It is not just an ordinary material; it can also be used as a highly hygroscopic material, an ion exchanger, a body fluid absorber, etc., and has an extremely wide range of uses.

In addition, the manufacturing method is extremely simple, workability is good, and the molded product is inexpensive and has high mechanical strength.

Hereinafter, the present embodiment will be explained.

Example 1 This example provides an example in which an alkali-soluble anionic polymer is effectively identified in regenerated cellulose.

One part by weight of an alkali-soluble cellulose conductor consisting of a carboxyl group with a degree of substitution of 0.25 and a carbamoylethyl group with a degree of substitution of 0.07 was dissolved in 100 parts by weight of a steel ammonia solution containing 10 parts by weight of cellulose.

After spreading this solution on a glass plate, AlC15.6H
5 in an aqueous solution containing tO,5- (usually the solution is acidic).
After dipping for seconds, dipping in 2% HC1KSQ for seconds, washing with water, replacing the solvent with acetone, and air drying to obtain the desired membrane A.

On the other hand, as a comparison, mu! ct, 4H, Q solution treatment with 211 HCl! Comparison films B and C1- were obtained by processing for 5 seconds and 30 seconds at 14 $ full blast.

The presence of an anionic polymer was confirmed by IR in Am, but not in lI[c. On the other hand, the obtained 6
The ion exchange capacity of the membrane was measured after 1ffi of drying.
M is 0.15 meq/f, B is o, o a meq
/l, C is o, o o meq7t, and it has been found that the anionic polymer obtained by the production method of the present invention can be most efficiently immobilized in regenerated cellulose, and the membrane AFi of the present invention, It exhibited water absorption 5 times higher than that of membrane CK.

Example 2 This example shows an example of a molded article and a method for producing the same, which has little contamination with blood coagulation, releases an anticoagulant into the blood, and imparts anticoagulant properties to the blood itself.

A 10 weight aqueous solution tube of cellulose sulfate Na salt having a number average molecular weight of 19,000 and a degree of substitution of 2.2 was prepared, and 5 parts by weight of the cellulose solution used in Example 1 was mixed with 1 part by weight of the tube. This solution was used as a coagulation regeneration bath using a normal hollow fiber manufacturing method and using a halogenated organic filtrate as a hollowing agent.
- Using 14q & caustic soda aqueous solution containing KCl, 8
The yarn was spun at a speed of 0.011/min.

The hollow fibers were washed with water, neutralized with acid, washed with water, and then drained of water and dried. This hollow fiber has an inner diameter of 200μ and a membrane thickness of 13μ.
Met.

On the other hand, as a comparative example, hollow fibers were obtained under the same conditions except for KCl during doffing.

The obtained hollow fibers (109 each) were bundled into a bundle with an inner diameter of 5 and a height of 10 a.
A hemodialysis module III was created. Using a dog as a specimen, a hemodialysis tube was run for 2 hours under normal conditions using Solita, etc. as the dialysate. After hemodialysis was completed, the blood remaining in the hollow fiber was collected and its coagulation rate was observed. However, in the case of the comparative example, it took about 14 to 20 minutes to solidify, whereas in the case of the hollow fiber obtained by the technique of the present invention, it took about 40 to 90 minutes to solidify.
It had extremely high anticoagulant properties in minutes. On the other hand, after leaving the remaining blood in the hollow fiber in the module for 40Q, the inside of the hollow fiber was washed with a certain amount of physiological saline at a certain speed.
In the comparative example, there was severe coagulation and holes in the hollow fibers, but in the case of the present invention, most of them were removed by washing.

Theoretical Example Shimamoto's example illustrates that various water-soluble anionic polymers can be effectively temporarily fixed by selected good metal salts.

Preparation of the warming dope K11k uses an aqueous solution of an anionic polymer (supplied as a Na salt) and an ammonium solution of cellulose, both with a polymer concentration of 10 wt. This mixed dope with a weight ratio of cellulose and anionic polymer of 9/1 was poured onto a glass plate, and 1/2 of each metal salt was poured onto a glass plate.
5. Reference solution [after immersion for 20 seconds, 2 @ Hcz K s
o Soak for ~60 seconds, rinse with water Ll.

These immersion solutions were combined, electrodialysis was performed, the dialysate was concentrated to dryness using an evaporator, and the amount of anionic polymer that was not temporarily fixed in the regenerated cellulose that flowed out was measured. Immobilization rate [(amount of polymer fixed in regenerated cellulose/initial amount used)
xloo(1)) was calculated, and the metal types used for each of the 7 ionic polymers were listed in Table 1 to give the above effective immobilization rate.

Table 1 Cu"" 95 Ni" 95 Carboxymethyen Luulose (DB■0.4)
Muta + y B~10OI
Cu heavy + 90#
Fm”
90～! 2 polyacrylic acid
zr4+40mu48+40
~70 I C + 50 or less Blade J-Ki-C V Reggie I; Ko [, Chill Chiroki J/Shichimoi A Kushi wo Island → U Rerose pba+
97# 1t
a+ 97~100 sulfur 7 (a-s(M-~1.4
) K+ 7o ~ 80m 1m
+ 5 (1 to 55 polyvinyl alcohol sulfate (scream β7!-) K
+, o~8゜'
In addition, as a comparison, when the above anionic polymer (containing Rulose) was prepared without salt treatment, the effective nitridation rate was less than S11.

Example 4 In this example, cellulose was dissolved in an organic solvent, a water-soluble anionic polymer was also dissolved in an organic solvent, and the anionic polymer was effectively fixed in regenerated cellulose from a mixture of the two. Here is an example of what can happen.

Cellulose was added to a solvent consisting of N-ethylpyridium prid and dimethylformamide at a weight ratio of 1/1 in an amount of 8% by weight, and the mixture was heated to 80°C to form a cellulose solution of 1
Obtained. Thread obtained by mixing 5 parts by weight of this solution with 1 part of a formamide solution of sodium salt of carboxyethyl cellulose with substitution f0.8, prepared in advance to 8 parts by weight, was extruded from a syringe into a 5-solution of MutC14.6H10. After washing with water, the strips were dried. When this was dyed with methylene blue, it was dyed more deeply than cotton. The effective identification rate of anionic poly 1- was estimated from the exhaustion amount of methylene blue. It turned out to be more than 〇- friend.

As shown in the examples above, the molded products obtained by the technology of the present invention can be used not only in the medical field, but also in a wide range of fields such as clothing textiles, ion exchange, and fields that require water absorption. In addition, the above-mentioned new molded product can be obtained by adding only a few improvement steps to the conventional molding technology, which is extremely effective.

Claims (3)

[Claims] 1.50～? 9.75 wt cellulose and 50-0
．． A molded article with anticoagulant and ion exchange properties composed of a 25% by weight anionic polymer. 2.7 Cellulose derivatives in which the ionic polymer has a carboxyl residue t, cellulose derivatives such as cellulose sulfate and cellulose phosphate, and their salts, amylose sulfate, amylopectin sulfate and their salts, mucopolysaccharide sulfates and their salts, polyacrylic acid The molded article according to claim 1, which is selected from polyvinyl alcohol sulfates and salts thereof, polyvinyl alcohol sulfates, and salts thereof. 3.7 The anionic polymer is cellulose sulfate, which is a salt thereof, has little contaminating property against blood coagulation, and the anionic polymer can be transferred into the blood upon contact with blood, as described in claim 18, paragraph 1. @O dignified item. An anticoagulant and anionic polymer characterized by immobilizing the anionic polymer in regenerated luulose by immersing a solution prepared by dissolving cellulose and a 7-ionic polymer in a neutral, acidic or alkaline aqueous solution containing a metal salt. Ion exchange property 4
A method for manufacturing molded products. - The process according to claim S4a, wherein the metal salt is selected from salts of potassium, alkenium, copper, aluminum, iron, lead, zirconium, titanium, calcium and zinc.