JP4712285B2 - Blood filtration filter and method for producing the same - Google Patents

Description

【表２】

【００２４】
実施例１と比較例１の比較及び実施例２と比較例２の比較から、親水性高分子をポリプロピレン樹脂に直接コーティングするよりも、ポリアミドのコーティングを事前に施すことで、溶出物が減少していることが確認できた。
【００２５】
実施例１、２と比較例１、２、３の比較から、ポリアミドのコーティング上に親水性高分子をコーティングすることで熱処理後も親水性が維持され、ポリアミドまたは親水性高分子のいずれか単体をコーティングするのみでは本発明の目的が達成できないことが確認された。
以上の結果により、本発明は、簡易な方法より、耐熱性（オートクレーブ滅菌、熱水の濾過等の熱的に過酷な環境に耐え得る）を有しかつ親水性高分子に由来する溶出物が少ない血液濾過用フィルターおよび血液濾過用フィルターの製造方法を確立することができた。
【００２６】
【発明の作用効果】
以上説明したように、
〈１〉簡易な方法より、優れた耐熱性（１２１℃ ２０分のオートクレーブ滅菌、熱水の濾過等の熱的に過酷な環境に耐え得る）を有しかつ親水性高分子に由来する溶出物が少ない血液濾過用フィルターおよび血液濾過用フィルターの製造方法を提供することができる。
〈２〉本発明の血液濾過用フィルターの製造方法は、第一の工程で、ポリアミド系高分子を溶媒に溶解し、これを疎水性材料（ポリオレフィン樹脂）をコーティングするという、極めて簡便な操作をした後に、二次工程で水不溶性の親水性高分子（ポリヒドロキシエチルメタクリレート、またはエチレンビニルアルコール）をコーティングするという簡便なものであるから、エネルギー線を照射するような専用装置の導入が不要である為、大幅なコスト削減が可能である。また、架橋反応を行う場合と比較して、作業効率が極めて良い上、未架橋のモノマーに由来する毒性も問題とならない。
〈３〉溶出物の面でも極めて良好で、疎水性材料（ポリオレフィン樹脂）に直接親水性高分子をコーティングした場合よりも溶出物を低く抑えることができる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a blood filtration filter in which a hydrophobic material is coated with a hydrophilic polymer (also referred to as a coating) and a method for producing the blood filtration filter , and more specifically, heat resistance (autoclave sterilization, hot water filtration, etc.). The present invention relates to an improved blood filtration filter and a method for producing a blood filtration filter that can withstand thermally severe environments) and has a small amount of eluate derived from a hydrophilic polymer. In particular, it can be suitably used for a substrate that is in direct contact with a body fluid containing blood, such as a filter for blood filtration in which an eluate is regarded as a problem. In particular, it is suitably used for polyolefin resins, which are said to have a relatively large amount of eluate among hydrophobic materials.
[0002]
[Prior Art and Problems to be Solved by the Invention]
For example, polyolefin resins are used for a very wide range of uses in terms of their physical properties, processability, cost, and the like. However, since the surface is hydrophobic, it cannot be used for applications such as filtration filters, and its use has been limited. Therefore, in order to impart hydrophilicity, various hydrophilic methods have been studied in the past.
Conventionally, as a method most commonly used for imparting hydrophilicity to the hydrophobic surface of a polyolefin resin, a method of coating the surface with a hydrophilic substance and hydrophilizing the surface is known. Although this method is simple, when the hydrophilic substance used for coating is a low molecular weight substance such as alcohol, it has a drawback that it is easily detached from the surface.
For example, hydrophobic polyolefin resins do not accept water, but can be wetted (hydrophilized) with water by first treating with alcohol and then substituting the alcohol with water. However, the method using a low molecular weight substance (hydrophilic substance) such as alcohol has a short-term effect, and once the surface is dried, it returns to its original hydrophobicity.
[0003]
There is also a method of coating a polyolefin resin with a hydrophilic polymer. As an example, many techniques such as JP-A-06-296841 (Patent Document 1) are disclosed. The polyolefin resin hydrophilized by these methods maintains its hydrophilicity even after its surface is dried. However, polyolefin resins, particularly polypropylene resins, made hydrophilic by these methods lose their hydrophilicity and become hydrophobic when subjected to severe heat conditions such as autoclave sterilization and hot water filtration. This is because the thermally unstable hydrophilic polymer adheres to the base material that does not have an affinity called polyolefin resin without having a covalent bond, and thus shrinks and separates due to heat. Guessed.
In order to solve this, an attempt has been made to insolubilize the hydrophilic polymer coated on the surface of the hydrophobic material. The most effective as these means is a method of crosslinking a hydrophilic polymer, particularly a three-dimensional crosslinking method. It is well known that a hydrophilic polymer is insoluble in any solvent including water if it is crosslinked three-dimensionally.
For example, JP-A-05-103831 (Patent Document 2), JP-A 09-507154 (Patent Document 3) and the like are chemical methods using a crosslinking agent. As physical methods using radiation, electron beam, or ultraviolet irradiation, there are JP-A No. 2002-201297 (Patent Document 4), No. 2566548 (Patent Document 5), and No. 2992566 (Patent Document 6). Any of these can reliably fix the hydrophilic polymer to the surface of the hydrophobic material. However, when irradiating energy rays, it is necessary to introduce a dedicated device, which is a big problem in terms of cost. In addition, when a crosslinking reaction is performed, there are many reaction steps, the working efficiency is extremely complicated, and uncrosslinked monomers are generally toxic and become a big problem.
[0004]
As a method for solving these problems, a technique has been developed in which a polyolefin resin is coated with polyvinyl ether, and then a coating with nylon or the like is applied to easily perform a thermally stable hydrophilic treatment (Japanese Patent Laid-Open No. 06-2006). 296840) (Patent Document 7). However, there is still room for improvement in terms of eluate.
[0005]
As described above, a hydrophilic treatment base material that has heat resistance (can withstand harsh thermal environments such as autoclave sterilization and filtration of hot water) by a simple method and has few eluates derived from hydrophilic polymers. As for the invention of the method for producing a hydrophilic treatment substrate, its appearance has been eagerly desired for many years, but no specific invention has yet been proposed that can sufficiently solve these problems of heat resistance and eluate. When the hydrophilization technology of these hydrophobic materials is completed, it can be expected to develop a large application in the medical field in particular.
[0006]
For example, a blood filtration filter can be cited as a medical use of a nonwoven fabric made of a hydrophobic material such as polyolefin (polypropylene, polyethylene).
For example, leukocyte removal filters and apheresis filters used for the treatment of ulcerative colitis are currently used. These filters remove a large amount of white blood cells by passing blood through a polyolefin nonwoven fabric having a fiber diameter of about 1 μm. However, untreated (non-hydrophilized) polyolefin non-woven fabric is hydrophobic and does not allow blood to pass through. Therefore, the non-woven fabric is usually coated with a hydrophilic polymer such as hydroxyethyl methacrylate. High hydrophilicity can be imparted to the nonwoven fabric by coating with these hydrophilic polymers, but after autoclave sterilization, the hydrophilicity is lost and the nonwoven fabric is converted to hydrophobicity. Moreover, although it depends on the kind of hydrophilic polymer, there is still room for improvement so that the amount of eluate derived from these still remains.
[0007]
[Patent Document 1]
JP-A-06-296841
[Patent Document 2]
JP 05-103831 (Example 1)
[Patent Document 3]
Special table 09-507154 (Example 1)
[Patent Document 4]
JP-A-2002-201297 (Example 1)
[Patent Document 5]
No. 2566548 (Example 1)
[Patent Document 6]
No. 299556 (Example 1)
[Patent Document 7]
Japanese Patent Laid-Open No. 06-296840 (Example 1)
[0008]
[Means for Solving the Problems]
In the present invention, a hydrophobic material (polyolefin resin) is coated with a polyamide polymer, and then the surface thereof is further coated with a water-insoluble hydrophilic polymer, thereby improving heat resistance (autoclave sterilization, hot water filtration, etc.). reaches the thermally harsh environments withstand) a has and the eluate is less blood filtration filter and a manufacturing method of a blood filtration filter is derived from a hydrophilic polymer present invention.
[1] The present invention covers a hydrophobic material with a polyamide polymer,
Provided is a blood filtration filter in which the polyamide polymer is coated with polyhydroxyethyl methacrylate or ethylene vinyl alcohol.
[2] The present invention provides the blood filtration filter according to [1], wherein the polyamide polymer is polyamide 6, polyamide 66, polyamide 12, polyamide 11, copolymer polyamide, or polyamide elastomer.
[3] The blood according to [1] or [2], wherein the hydrophobic material is a polyolefin resin in which the hydrophobic material is any one of polypropylene, polyethylene, polyethylene terephthalate, polybutylene terephthalate, or a copolymer thereof. A filter for filtration is provided.
[4] The present invention provides the blood filtration filter according to any one of [1] to [3], which is a base material used by being temporarily or permanently treated in an environment of 70 ° C. or higher. To do.
[5] The present invention provides:
(1) A step of coating a hydrophobic material with a polyamide polymer,
(2) a step of coating the polyamide polymer with polyhydroxyethyl methacrylate or ethylene vinyl alcohol;
The method for producing a blood filtration filter according to any one of [1] to [4], including the steps (1) and (2).
[0009]
DETAILED DESCRIPTION OF THE INVENTION
The filter for blood filtration of the present invention is obtained by coating a hydrophobic material (polyolefin resin) with a polyamide polymer, and coating the polyamide polymer with a water-insoluble hydrophilic polymer.
[Polyamide polymer]
In the present invention, polyamide 6, polyamide 66, polyamide 12, polyamide 11, copolymer polyamide, polyamide elastomer and the like are preferably used as the polyamide polymer, but have a bonding group (amide group) with the hydrophilic polymer. Any polyamide-based polymer that can be coated on the hydrophobic material can be used.
The polyamide polymer is preferably adjusted to a concentration of 0.1 (weight / volume)% to 5 (weight / volume)% in the solvent, depending on the type of polymer. If the concentration is too low (for example, less than 0.1 (weight / volume)), sufficient hydrophilicity cannot be obtained, and if the concentration is too high (for example, exceeding 5 (weight / volume)), it is applied to a hydrophobic material. Since it becomes easy to produce spots, it is not preferable.
The solvent for the polyamide polymer is not particularly limited, but a 5% (weight / volume)% methanol solution of calcium chloride is suitable. If the concentration of calcium chloride is too low (for example, 5 (weight / volume)% or less), the polyamide polymer is difficult to dissolve, and if the concentration is too high (for example, exceeds 20 (weight / volume)%), it causes coating spots. Therefore, it is not preferable.
[Water-insoluble hydrophilic polymer]
As the hydrophilic polymer of the present invention, polyhydroxyethyl methacrylate, ethylene vinyl alcohol or the like is preferably used. However, the hydrophilic polymer has a bonding group (hydroxyl group) with a polyamide-based polymer and is insoluble in water. Any material that can be coated and exhibits high hydrophilicity can be used.
[Hydrophobic material]
The hydrophobic material of the present invention may be anything as long as it can coat the polyamide-based polymer and the water-insoluble hydrophilic polymer. For example, polypropylene, polyethylene, polyethylene terephthalate, polybutylene terephthalate, or a copolymer thereof can be used. Any such polyolefin resin is preferred. In particular, in the case of medical use, any material having good biocompatibility (physical properties that are difficult to induce a foreign body reaction when contacting a body fluid containing blood) may be used.
[0010]
[Method for producing filter for blood filtration ]
The blood filtration filter of the present invention can be produced by the following method.
(1) A step of coating a hydrophobic material (polyolefin resin) with a polyamide polymer,
(2) a step of coating a polyamide polymer with a water-insoluble hydrophilic polymer;
The present invention is produced by coating a hydrophobic material (polyolefin resin) with a polyamide polymer and then coating the surface with a water-insoluble hydrophilic polymer.
The filter for blood filtration of the present invention is a base material that is used temporarily or permanently in an environment of 70 ° C. or more, and is sufficient for a severe heat environment such as autoclave sterilization and hot water filtration. I can stand it.
[0011]
[Knowledge of the present invention]
The blood filtration filter according to the present invention has the heat resistance (can withstand heat-harsh environments such as autoclave sterilization and hot water filtration) and has few effluents derived from hydrophilic polymers. Although not restricted, the hydrophilic polymer is strongly bonded to the polyamide polymer by the bond (ionic bond) of the bond group (amide group) of the polyamide polymer and the bond group (hydroxyl group) of the hydrophilic polymer. It is presumed that the molecular weight is increased and the stability against hot water is improved.
In the present invention, “bond” includes polycondensation and the like in addition to ionic bond.
The “bonding group” is not limited to an amide group and a hydroxyl group, and includes a carboxyl group and the like.
[0012]
【Example】
Example 1
This hydrophilic treatment was attempted on a polypropylene nonwoven fabric having a fiber diameter of 1.2 μm produced by the melt blown method. Polyamide 6 (nylon 6: Unitika) was dissolved in a calcium chloride / methanol solution (5% weight / volume) to a concentration of 0.3% (weight / volume). A polypropylene non-woven fabric was immersed in this solution for 20 minutes and allowed to air dry at room temperature. Thereafter, it was washed with running water for 5 minutes and dried to remove calcium chloride. This nonwoven fabric was coated with polyhydroxyethyl methacrylate (pHEMA) (Mn = ˜20,000: POLYSCIENCES, INC.). The coating was completed by dissolving pHEMA at 0.2% (weight / volume) in a mixed solvent of isopropyl alcohol: water = 50:50, immersing a polypropylene nonwoven fabric in this solution for 5 minutes, and then air-drying at room temperature. .
[0013]
The polypropylene nonwoven fabric subjected to the hydrophilization treatment shown in Example 1 was subjected to autoclave sterilization at 121 ° C. for 20 minutes. When 100 μl of water droplets were dropped there, the water droplets were completely absorbed by the nonwoven fabric after 120 seconds.
[0014]
Example 2
This hydrophilic treatment was attempted on a polypropylene nonwoven fabric having a fiber diameter of 1.2 μm produced by the melt blown method. Polyamide 6 (nylon 6: Unitika) was dissolved in a calcium chloride / methanol solution (5% weight / volume) to a concentration of 0.3% (weight / volume). A polypropylene non-woven fabric was immersed in this solution for 20 minutes and allowed to air dry at room temperature. Thereafter, it was washed with running water for 5 minutes and dried to remove calcium chloride. This non-woven fabric was coated with a solution of ethylene vinyl alcohol (Soarnol D2908: Nippon Synthetic Chemical) dissolved in a mixed solvent of (isopropyl alcohol: water = 30: 70) so as to be 0.2% (weight / volume). A polypropylene non-woven fabric was immersed in this solution for 5 minutes and then air-dried at room temperature.
[0015]
The polypropylene non-woven fabric subjected to the hydrophilization treatment shown in Example 2 was subjected to autoclave sterilization at 121 ° C. for 20 minutes. When 100 μl of water droplets were dropped there, the water droplets were completely absorbed by the nonwoven fabric after 170 seconds.
[0016]
Comparative Example 1
An attempt was made to hydrophilic treatment with a hydrophilic polymer on a polypropylene nonwoven fabric having a fiber diameter of 1.2 μm produced by the melt blown method. Hydroxyethyl methacrylate (Mn = ˜20,000: POLYSCIENCES, INC.) Is dissolved in a mixed solvent of (isopropyl alcohol: water = 30: 70) so as to be 0.2% (weight / volume). A polypropylene nonwoven fabric was immersed in this solution for 5 minutes and then allowed to air dry at room temperature.
[0017]
Autoclave sterilization at 121 ° C. for 20 minutes was performed on the non-woven polypropylene fabric subjected to the hydrophilization treatment shown in Comparative Example 1. When 100 μl of water drops were dropped there, the water drops remained spherical on the nonwoven fabric and were not absorbed.
[0018]
Comparative Example 2
An attempt was made to hydrophilic treatment with a hydrophilic polymer on a polypropylene nonwoven fabric having a fiber diameter of 1.2 μm produced by the melt blown method. Ethylene vinyl alcohol (Soarnol D2908: Nippon Synthetic Chemical) was dissolved in a mixed solvent of (isopropyl alcohol: water = 30: 70) so as to be 0.2% (weight / volume). A polypropylene nonwoven fabric was immersed in this solution for 5 minutes and then allowed to air dry at room temperature.
[0019]
Autoclave sterilization at 121 ° C. for 20 minutes was performed on the nonwoven fabric made of polypropylene subjected to the hydrophilization treatment shown in Comparative Example 2. When 100 μl of water drops were dropped there, the water drops remained spherical on the nonwoven fabric and were not absorbed.
[0020]
Comparative Example 3
An attempt was made to make the nonwoven fabric made of polypropylene having a fiber diameter of 1.2 μm made by the melt blown method hydrophilic with a hydrophilic polymer. Polyamide 6 (nylon 6: Unitika) was dissolved in a calcium chloride / methanol solution (5% weight / volume) to a concentration of 0.3% (weight / volume). A polypropylene non-woven fabric was immersed in this solution for 20 minutes and allowed to air dry at room temperature. Thereafter, it was washed with running water for 5 minutes and dried to remove calcium chloride.
[0021]
Autoclave sterilization at 121 ° C. for 20 minutes was performed on the polypropylene non-woven fabric subjected to the hydrophilization treatment shown in Comparative Example 3. When 100 μl of water drops were dropped there, the water drops remained spherical on the nonwoven fabric and were not absorbed.
[0022]
Table 1 shows the results of the eluate test performed on the samples of Examples 1 and 2 and Comparative Examples 1 to 3 under elution conditions based on the sterilized blood set criteria. Each numerical value is the difference in the amount of eluate between the hydrophilized and untreated polypropylene nonwoven fabric. In other words, it can be said that the larger the difference (numerical value), the larger the amount of the eluate.
[0023]
[Table 1]

[Table 2]

[0024]
From the comparison between Example 1 and Comparative Example 1 and the comparison between Example 2 and Comparative Example 2, the elution is reduced by applying the polyamide coating in advance rather than directly coating the hydrophilic polymer on the polypropylene resin. It was confirmed that
[0025]
From the comparison between Examples 1 and 2 and Comparative Examples 1, 2, and 3, the hydrophilicity is maintained after the heat treatment by coating the hydrophilic coating on the polyamide coating, and either the polyamide or the hydrophilic polymer alone. It was confirmed that the object of the present invention could not be achieved only by coating the film.
Based on the above results, the present invention has an elution product derived from a hydrophilic polymer that has heat resistance (can withstand heat-harsh environments such as autoclave sterilization and hot water filtration) and a simple method. A few blood filtration filters and methods for producing blood filtration filters could be established.
[0026]
[Effects of the invention]
As explained above,
<1> Eluent derived from a hydrophilic polymer that has superior heat resistance (can withstand harsh environments such as autoclave sterilization at 121 ° C. for 20 minutes and filtration of hot water) over a simple method it is possible to provide a manufacturing method of a small blood filtration filter and a blood filter for filtration.
<2> The method for producing a filter for blood filtration according to the present invention comprises a very simple operation of dissolving a polyamide polymer in a solvent and coating it with a hydrophobic material (polyolefin resin) in the first step. After that, it is easy to coat a water-insoluble hydrophilic polymer (polyhydroxyethyl methacrylate or ethylene vinyl alcohol) in the secondary process, so there is no need to introduce a dedicated device that irradiates energy rays. Therefore, significant cost reduction is possible. In addition, the working efficiency is very good as compared with the case of performing a crosslinking reaction, and toxicity derived from an uncrosslinked monomer is not a problem.
<3> The eluate is extremely good in terms of the eluate, and the eluate can be kept lower than when a hydrophobic polymer (polyolefin resin) is directly coated with a hydrophilic polymer.

Claims (5)

A hydrophobic material is coated with a polyamide polymer,
A filter for blood filtration , wherein the polyamide polymer is coated with polyhydroxyethyl methacrylate or ethylene vinyl alcohol. The blood filtration filter according to claim 1, wherein the polyamide polymer is polyamide 6, polyamide 66, polyamide 12, polyamide 11, copolymer polyamide, or polyamide elastomer. 3. The blood filter according to claim 1, wherein the hydrophobic material is a polyolefin resin that is any one of polypropylene, polyethylene, polyethylene terephthalate, polybutylene terephthalate, or a copolymer thereof . Filter . The blood filtration filter according to any one of claims 1 to 3, wherein the blood filtration filter is a base material that is used temporarily or permanently in an environment of 70 ° C or higher. (1) A step of coating a hydrophobic material with a polyamide polymer,
(2) a step of coating the polyamide polymer with polyhydroxyethyl methacrylate or ethylene vinyl alcohol;
The method for producing a filter for blood filtration according to any one of claims 1 to 4, wherein the steps (1) and (2) are included.