JPS60195455A - Polymer useful as blood treating agent and molding thereof - Google Patents

Abstract

PURPOSE:To remove selectively the cholesterol in blood by a vinyl polymer having the arom. nucleus into which the functional group expressed by the specific formula is incorporated as a side chain and the molding thereof. CONSTITUTION:A vinyl polymer having the arom. nucleus into which the functional group expressed by the formula is incorporated as a side chain and the molding thereof constitute a blood treating agent. The result is much better if the polymer is crosslinked and if the polymer is reinforced by poly alpha-olefin as represented by crystalline PP or PE as the mechanical strength is improved with the latter. The immobilizing density decreases if the surface area is too small in the case of the molding but if the surface area is too large, the liquid passability of the column in which the molding is packed decreases and therefore the preferable surface area is 0.01-50m<2>/g.

Description

DETAILED DESCRIPTION OF THE INVENTION [Technical Field of the Invention] The present invention relates to an m-combination useful as a blood treatment agent that specifically adsorbs lipids such as cholesterol in blood and molded products thereof.

(Prior art and its problems) Cholesterol in the blood is originally necessary for life support, but too much cholesterol promotes arteriosclerosis, leading to strokes and myocardial infarctions. Hyperlipidemia, where ■ increases rapidly, can lead to sudden death. Cholesterol in the blood is bound to globulin proteins and exists as lipoproteins. It is extremely difficult to selectively remove these lipoproteins without using expensive immunological techniques.

(Object of the Invention) The present inventors have arrived at the present invention as a result of intensive studies to find an adsorbent that selectively removes cholesterol in blood, which can be used for clinical analysis and treatment.

[Structure of the invention]

That is, the present invention relates to a vinyl polymer having an aromatic nucleus into which a functional group represented by the following general formula (1) is introduced as a side chain, and a molded product thereof.

In the above formula, R1 represents a 1J alkyl group having a methylene chain length of 10 or more, and R2 and R3 represent a methyl group, an ethyl group, or an n-propyl group. Further, R4 and R5 represent a hydrogen atom or a lower alkyl group. X does not represent the usual anion A represented by chlorine ion.

It is intended to provide the following.

(Summary of Effects) The polymer of the present invention and its molded product can selectively adsorb and remove cholesterol in blood, plasma, or serum. Accordingly, it may be used for the treatment of hyperlipidemia, hyper]leste[1-lipidemia.

[Explanation of composition and effects]

In the present invention, the vinyl polymer having an aromatic nucleus is a homopolymer of a vinyl monomer having an aromatic nucleus such as styrene, α-methylstyrene, vinyltoluene, etc., or a 1 m aggregation of these monomers with 1 blade. It is more preferable if these hand-combined IJ crosslinks. Further, it is more preferable that the polymer is reinforced with a poly-α-olefin such as crystal 171 polypropylene or polyethylene, since the mechanical properties will be improved. for example,
In addition to Jtffi combinations with polyvinyl compounds typified by divinylbenzene or methylenebisacrylamide, examples include those obtained by crosslinking the above-mentioned monovinyl compound polymer molded products with formaldehyde, chlorosulfonic acid, etc. Coalescing during crosslinking has no fluidity and is difficult to mold.
Therefore, when the polymer molded article is lJi Ml, a membrane, etc., a method of crosslinking after molding is preferably employed.

In the above general formula (1), the methylene chain length of alkyl M R1 is long, and it has good affinity with lipids such as cholesterol (11), but
Raw materials for those with a methylene chain length of 24 or more are difficult to obtain. This alkyl too! may be branched, but the original I
It is difficult to obtain I. If the alkyl group of R2 and R3 has a large number of carbon atoms, the hydrophobicity of the polymer of the present invention will become high, so a methyl group having the smallest number of carbon atoms is best. The alkyl groups of R4 and R5 are most often hydrogen atoms!
Easy to build.

If the surface area of the molded article of the present invention is too small, the immobilization density will be low, but if it is too large, the liquid permeability of the column filled with the molded article of the present invention will be poor. The surface area is preferably 0.01 or more and 50 m'7·'Q or less, more preferably 0.05 or more and 10 m'/Q or less.

There is no particular limitation on the amount of functional groups represented by the above general formula (1) in the polymer of the present invention (although there is no particular limitation), if the amount is too small, the affinity of the polymer of the present invention and its molded products with blood will deteriorate. So,
The amount is preferably 0.2 mmol or more, more preferably 1.0 mmol or more per 1Q of the polymer. Furthermore, when a functional group represented by the general formula (2) is present as an aromatic nucleus side chain in the polymer of the present invention in addition to the functional group represented by the general formula (1), 5-/I R81 (the above formula Among them, Re, R7, and R8 represent a lower alkyl group, and represent a group of combination I in which the sum of their carbon numbers is 12 or less.

Even if the number of functional groups represented by the general formula (1) is small, it is preferable because the affinity of the polymer of the present invention and its molded product with blood will not deteriorate. Functional) i↓ (1) and functional group (2)
When coexisting, the functional group (1) is 0 per 1Ω of R polymer.
．． It is preferable that the amount is 0.1 mmol or more, and the sum of both functional groups is preferably 1.0 mmol or more.

The polymer of the present invention and the molded product thereof can be produced by using α-haloacetamidomethylated aromatic vinyl polymer.
12008> and a child molded product by immersing it in a solution of an amine represented by general formula (3), or by immersing it in a mixed solution of the above amine and an amine represented by general formula (4). .

6-R1-N-R2 1 R3 (3) Pa-N-Ra ■ R7 (4) Example 1 Volip [1 Pyrene (Mitsui) 'Noblen'” J 3 H
G) Sea, Peng-type composite with a mixture of 50 parts of island component, 16 parts of Boris Dilene ('Styron' 666), and 4 parts of polypropylene (Sumitomo 'Noblen'' WF-727-F) as sea component.砿腑(,@number 16, single yarn fineness 2.6
Denier, tensile strength 2.9a/d, elongation 50%, number of filaments 42) 100G,
00 g, 98% sulfuric acid aoog, and paraformaldehyde 1.70 g, and reacted at 20° C. for 1 hour. Take out the fibers from the reaction solution and add them to ice water at 0°C.
After the reaction was stopped, the fibers were washed with water, and the nitrobenzene adhering to the fibers was extracted and removed with methanol. These 11 fibers (fiber MA) were vacuum-dried at 50'C to form 41E H14
I got 1q of 09.

Soak 100g of the above (100g of 1lIftA in 2Q of 10% water-containing T-tanol containing potassium acetate),
The mixture was heated at 0° C. for 4 hours to obtain 3-j-doacetic acid 1-amitomedel fiber B).

mlftB100 was immersed in a solution consisting of 20Q N,N-dimethylsudearylamine, 28o1 dimethylformamide and 50ml ethanol and heated at 70"C for 14 hours. Roughly, the string was soaked in a Soxhlet extractor.
After methanol extraction for 10 hours, it was packed into a chromatography column and mixed with IN-Jg 1a, 5f2(7) water, 1[(7
)I N-Caussio'l water, 5Q water and 100 parts of 1M saline solution, washed sequentially to prepare N,N-dimedylene chloride, N-sudearylammonium acidamide methyl synthetic fiber (wooden invention trial). 11) (q. This thing has a neutral salt decomposition ratio of 0.73 μU/9, a weak base bamboo is
in is 0.03 mmffi/Q, and the water content of type C1 is 0.
．． It was 47.

Example 2 The fiber It B 10a, which had been prepared by 1η in Example 1, was immersed in a mixed solution of N,N-dimethyllaurylamine 200 and dimethylformamide 180Q, and heated at 80° C. for 5 hours. This IMM was extracted with methanol for 10 hours using a Soxhlet extractor, and then packed into a chromatography column and
N-hydrochloric acid, 5a water, 10 1N-caustic soda water, 5
The N,N-dimethyl chloride-N-lauryl ammonium acetamidomethyl synthetic fiber string (Sample 2 of the present invention) was washed with water of Q and 1M saline solution of 1072. was 0.73 mm/ffi/G, the weak base was <'K<, and the C1 type water content was 0.71.

Example 3 The following adsorption test was conducted on Inventive Sample 1, Inventive Sample 2, and Comparative Samples 1, J: and 2.

Add 200mg of sample to human blood R101+11 and heat at 37°C.
After shaking for 3 hours, the supernatant was examined for blood components.
were investigated, and the eye sperm rate for each component was determined.

-〇- The results are shown in Table 1. However, I-ID L-cholesterol was determined by the heparin-manganese precipitated enzyme method.

Table 1 However, comparative samples 1 and 2 were treated in exactly the same manner as in Example 1, except that 1-helical n-butylamine and tri-n-octylamine were used instead of N,N-dimethylstearylamine in Example 1. It was made using v4. Comparison sample 1
(Tri n-butylammonium 10-nium ace1-amide methyl synthetic fiber lt> is a neutral salt decomposition chamber ff 11.54 milliequivalents/Q, a weak base attack io,

3mm per ff110. The CI type water content was 1.54.

Comparative sample 2 (tri n-octylammonium acetamitomedelated IJIff) has a neutral salt storage ff10.61
There was no weakly basic group, and the water content of C1 type was 0.46.

Table 1 shows that sample 1.2 of the present invention selectively adsorbs only IDL-cholesterol without adsorbing any useful protein components. On the other hand, Comparative Sample 1.2 does not adsorb 1-ID L-cholesterol at all, even though its functional group has almost the same number of carbon atoms as the sample of the present invention. That is, it can be seen that the specific adsorption ability of the sample of the present invention is derived from the structure of its special functional group.

Patent applicant Higashi Shikikai Co., Ltd. 11- AQ-

Claims (1)

[Scope of Claims] A vinyl polymer having an aromatic nucleus into which a functional group represented by the following general formula (1) is introduced as a side chain, and a molded product thereof. /I R31'' In the above formula, R1 represents an alkyl group having a methylene chain length of 10 or more, and R2 and R3 represent a methyl group, an ethyl group, or an n-propyl group. Further, R4 and R5 represent a hydrogen atom or a lower alkyl group. X represents a normal anion represented by a chlorine ion.