JPS62111736A - Medical flexible vinyl chloride resin molded shape - 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 (Field of Industrial Application) The present invention relates to a soft vinyl chloride resin molded body used for medical treatment.

[Conventional technology]

Soft vinyl chloride resin is widely used as a medical material because of its flexibility and high-pressure steam sterilization, but there is concern that the plasticizer contained in the resin may elute. Tokuko Showa 5
7-1540 and Proceedings of the Society of Polymer Science, Vol. 26, No. 8, 167
0-1673 (1977) proposes a method of treatment with discharge plasma as a method of preventing plasticizer elution. One of the inventors of the present invention has discovered that blood cells stored in bags made of soft polyvinyl chloride sheets treated with discharge plasma (glow discharge treatment), temporarily exhibiting a part of their aggregation ability (ADP aggregation ability).
It has been found that the platelets are higher than those of platelets stored in a conventional bag (Kobunshi Ronsen Vol. 38, No. 10, pp. 709-714 (1981)).

However, the level of its function is still greatly reduced compared to the level before storage, and is not sufficient to significantly extend the shelf life of platelets. In addition, the glow discharge treated sea 1~
has stronger platelet adhesion than conventional polyvinyl chloride sheets.

On the other hand, one of the present inventors reported in Kobunshi Saishu Vol. 39, p. 165 (1982) that on the surface of a soft vinyl chloride resin coated with a polymer obtained by polymerizing polyvinyl chloride to polyethylene glycol monomethacrylate (Graph 1), plasma proteins were absorbed. reported that platelet adhesion was significantly inhibited. When we evaluated the preservation of platelets using a soft vinyl chloride resin laminated with the graft polymer, we found that each function of the preserved platelets was significantly higher than that of platelets preserved using a conventional soft vinyl chloride resin. It was found that the decline was still large compared to the functionality. Furthermore, it has become clear that unless the laminated thickness of the polymers from Graph 1 reaches approximately 20 nm, they do not exhibit the performance and are the same as uncoated soft vinyl chloride resins.

Polymer resins that are generally said to have good blood compatibility are mostly hydrophilic polymers, and when these polymer resins are applied to a thickness of 20 um, the surface becomes sticky, making it difficult to process into bags, etc. If it is made into a bag, it has the disadvantage that the inner surface blocks, making it difficult to inject blood or the like.

[Problem that the invention seeks to solve]

The present inventors have conducted intensive research to develop a medical material that does not have the above-mentioned drawbacks and can preserve blood components for a long time without reducing their functions, and as a result, they have arrived at the present invention. be.

[Means for solving problems]

The present invention is characterized in that a crosslinked layer and a polymer layer (hereinafter referred to as a copolymer layer) made of a copolymer of a hydrophobic monomer and a hydrophilic layer are laminated on the surface of a soft vinyl chloride resin. This is a medical soft vinyl chloride resin molded body.
The soft vinyl chloride resin referred to in the present invention is not particularly limited as long as it is used as a medical soft vinyl chloride resin, but the plasticizers used in the soft vinyl chloride resin molded product of the present invention include phthalate esters, Preferred are limellitic acid esters, epoxidized soybean oil, or mixtures thereof. Among them, di(2-ethylhexyl) phthalate (hereinafter referred to as DEHP), or tos(2-ethylhexyl) trimerite i~ (hereinafter referred to as T).

TM) or mixtures thereof with epoxidized soybean oil are more preferred, and mixtures of di(2-ethylhexyl) phthalate and epoxidized soybean oil are particularly preferred.

The amount of plasticizer added is appropriately determined depending on the type of plasticizer, but in the vinyl chloride resin molded product of the present invention intended for medical materials, in order to obtain appropriate flexibility, vinyl chloride resin 100%
The total amount of plasticizer is preferably 30 to 110 parts by weight, especially di(2-ethylhexyl) phthalate 1
40 to 60 parts by weight of tri(2-ethylhexyl)
For trimellitate, 70 to 100 parts by weight is preferred.

In addition to these plasticizers, the vinyl chloride resin molded product of the present invention may contain small amounts of other plasticizers, stabilizers, lubricants, etc., but of course, tests determined for medical use may be carried out. The substance and amount must meet the standards. As the stabilizer, a Ca--Zn stabilizer is particularly preferred, and as the lubricant, a low molecular weight polyolefin such as low molecular weight polyethylene is particularly preferred.

The molded product as used in the present invention is a product obtained by molding the above-mentioned soft vinyl chloride resin into a sheet, a tube, etc., which has a crosslinked layer on at least a part of the surface of the molded product, and which has a crosslinked layer on at least a part of the surface of the molded product. A copolymer layer is laminated on the top.

The thickness of the crosslinked layer is preferably 1,000 to 1.5 μm, and more preferably 2,000 to 1 μm. The thickness of the crosslinked layer is determined by staining a cross-sectional section of the molded body with osmic acid.
It can be quantified by observation with an electron microscope. The presence or absence of a crosslinked layer can be determined by the appearance of an insoluble gel-like substance or film in the solution when the molded body is dissolved in Te1 to Uzidorofuran. An important feature of the crosslinked layer is that it reduces the amount of plasticizer eluted. For example, when vinyl chloride resin is subjected to plasma treatment, a crosslinked layer is formed under almost all conditions, but there are limited conditions under which a crosslinked layer can be formed that significantly reduces the amount of plasticizer elution. The soft vinyl chloride resin molded article of the present invention is produced by placing 2Qml of n-hexynane in a bag having an inner surface area of 70 cJ, which is made with the surface of the copolymer layer on the crosslinked layer as the inner surface, and leaving it at 40'C for 2 hours. The amount of plasticizer eluted into n-hexynane from the soft vinyl chloride resin molded body forming the bag is preferably 1000 μQ/- or less per unit inner surface area, more preferably 600 μQ/cnf. However, TOTM
When the plasticizer is contained as a plasticizer, the plasticizer is significantly less eluted into blood than n-benzene, so the amount of the plasticizer eluted in the above test method is 5000μQ/
CD or less is preferable, more preferably 3000μΩ/
cmf or less is desirable. Plasticizer concentration is 1000μQ/rA
(5000 μg/i for TOTM), a partial decrease in the ability of stored platelets is observed.

If the molded product is in the shape of a tube, the plasticizer can be added by injecting n-hexane into the tube so that the ratio of the inner surface area of the tube to the amount of n-hexane matches the above. The elution amount can be measured.

The method of forming the crosslinked layer is not particularly limited, but a method of forming a soft vinyl chloride resin sheet or tube by plasma treatment is likely to form a uniform crosslinked layer that efficiently reduces elution of the plasticizer. More preferred. Plasma treatment is a method of treating a substrate by exposing it to glow discharge generated by applying a high voltage under low pressure gas. A general explanation of this method is given in detail in "Low Temperature Plasma Chemistry" (Region of Chemistry, Special Edition No. 111, Nankodo Publishing (1976)), and some specific and practical methods are also described in detail. Kosho 57-1540,
Proceedings of the Society of Polymer Science, Vol. 26, No. 8, pp. 1670-1673 (1
977) and Japanese Patent Application Laid-Open No. 54-80373.

In the present invention, the polymer consisting of a copolymer of a hydrophobic monomer and a hydrophilic monomer has a solubility parameter (Solubil
ity parameter) is 9.5 (cat/c
4>172 or more monomer (hydrophilic monomer) and 9.5 (c
at/ci) "Copolymers of less than 2 monomers (hydrophobic monomers), or solubility parameter 13.0 (cat/c
r+t) 9, 5 to the following polymer (hydrophobic polymer)
(Cal/Ci) “2 or more (7)-E/? Gua 7
Must be 1 to polymerized.

Among the hydrophilic monomers, -○)'' group, -C○OR group (R is H or a halogen atom), -CONH2 group -03
O3R group (R is an alkyl group or halogen atom with H1 carbon atoms of 1 to 3), -C6H4S03R (R is H1 carbon atoms 1
~3 alkyl groups or - (CH2CH20)n R groups (n is 6 to 100, R is H or CH3), and have hydrophilic atom causes such as acrylic groups (methacrylic groups), allyl groups, vinyl groups, etc. Monomers with unsaturated groups are more preferred, and more preferred hydrophilic monomers are vinylpyrrolidone, polyethylene glycol monoacrylate (methacrylate-1-), acrylamide, β-bitroxyethyl acrylate (methacrylate-1-), and B-hydroxypropyl acrylate. (methacrylate-1~), sulfoacrylate-1~, mono(2-hydroxyethyl acrylate-1~)
〉Acid phosphate is necessary.

Among the hydrophobic monomers, alkyl acrylates 1 to 1 (
More preferred monomers are methacrylate-1-), styrene, acrylonitrile, vinyl chloride, and vinyl acetate, and particularly preferred monomers are methyl methacrylate-1-, styrene, acrylonitrile, and vinyl chloride.

Examples of hydrophobic polymers include polymethylmethacrylate-1-, polystyrene, polyacrylyl, polyvinyl chloride, ethylene-vinyl acetate copolymer, and ethylene-vinyl acetate-vinyl alcohol terpolymer. A preferred and particularly preferred polymer is polyvinyl chloride.

Among these copolymers, vinylpyrrolidone, β-hydroxyethyl acrylate-1 (methacrylate), β-
Hydroxypropyl acrylate-1~ (methacrylate-1~
〉or polyethylene glycol monoacrylate (
A polymer obtained by graft copolymerizing polyvinyl chloride (methacrylate) with polyvinyl chloride exhibits excellent performance in the present invention.

In addition, non-grade polyester copolymers containing polyethylene glycol and ethylene glycol as the main alcohol component and dimethyl terephthalate as the main acid component also exhibit excellent performance as the copolymer layer in the present invention. Note that dimethyl isophthalate 1 or more may be added as an acid component to the copolymer.

In the present invention, the method of laminating the copolymer layer is not particularly limited, but a method of dissolving the copolymer layer in a solvent and applying it is more preferable since it can be applied uniformly and easily.

The thickness of the copolymer layer is preferably 0.2 to 10 μm.

If it is less than 0.2 μm, the desired performance cannot be obtained;
If it exceeds m, the surface becomes sticky and Sea 1~ becomes blocking. More preferable copolymer thickness is 0.5 to 5
μm is necessary.

According to experiments conducted by the present inventors, when such a copolymer layer is applied to ordinary vinyl chloride resin, the characteristics of this copolymer cannot be obtained unless the thickness is 20 μm or more, but when it is applied on a crosslinked layer, A surprising synergistic effect was observed in which excellent properties were exhibited even in thin films such as those described above. When a copolymer layer is applied to ordinary vinyl chloride resin, the solvent dissolves in the vinyl chloride resin, and in order to remove the solvent, it is placed in a solvent that is a poor solvent for the vinyl chloride resin and a good solvent for the solvent. It is necessary to remove the solvent by immersing the resin in a polyvinyl chloride resin, but when it is coated on a crosslinked layer, the solvent does not dissolve into the vinyl chloride resin, and there is an advantage that the solvent removal step as described above is not required.

Note that this copolymer layer does not necessarily need to be provided on the entire surface of the crosslinked layer, and may be laminated only on the surface of the crosslinked layer where it is necessary.

〔effect〕

The soft vinyl chloride resin molded article of the present invention has the characteristic that it can maintain its function well when preserving blood. The properties of blood have not yet been completely elucidated, and it can be said that the functional relationship between blood and the storage container remains largely unknown. However, it is said that the plasticizer and the surface of the container act and change its function, and the crosslinked layer of the soft vinyl chloride resin molded product of the present invention prevents the elution of the plasticizer, and the crosslinked layer Since a copolymer layer is formed on top, it is thought that some kind of positive effect is produced synergistically.

The soft vinyl chloride resin molded body of the present invention can be used as a blood storage container,
It is especially excellent as a storage container for platelets and plasma, especially platelets. However, the uses of the soft vinyl chloride resin molded article of the present invention are not limited to these.

〔Evaluation methods〕

1) Blood sampling and preservation method Blood was removed from the right carotid artery of a rabbit under rabonal anesthesia. Using sodium citrate (1/9 of the entire surface) as an anticoagulant, concentrated platelet plasma was prepared by sedimentation by centrifugation immediately after blood collection, and was dispensed into a small test bag with an inner surface area of 70. In order to eliminate individual differences in blood in the experiment, a method was used in which pooled platelet concentrate plasma was dispensed into each bag. All operations were performed aseptically.

Each bag containing platelet plasma concentrate was stored at 22°C for 3 days with gentle horizontal shaking.

2> Functional evaluation of stored plasma plates The concentrated platelet plasma in the composite bag stored for 3 days was diluted with fresh plasma to give a platelet count of approximately 800,000/lTl1T13, and was used as a functional evaluation sample.

<1) ADP and collagen aggregation ability ADP and collagen were added to each sample at 10 μm and 10 μg/ml, respectively, and the aggregation ability was measured using an alibometer. The measured value is 100% of the platelet aggregation ability after 0 hours of storage.
and expressed in %.

(2) Osmotic shock recovery rate (%H3R>610 when 2 volumes of sample and 1 volume of distilled water were mixed using a spectrophotometer)
It was determined from the change in light transmittance over 2 minutes at 1 m. Values are stored as % H3R of platelets at 0 hours is taken as 100%.
It was expressed as

(3) Plasticizer elution amount By the method described above.

(Example〕 EXAMPLES The present invention will be explained in detail in the following examples.

Examples 1 to 2 and Comparative Examples 1 to 5 For 100 parts by weight of polyvinyl chloride resin, 55 parts by weight of di(2-ethylhexyl) phthalate, 5 parts by weight of epoxidized soybean oil, 1 part by weight of lubricant, 0 parts by weight of stabilizer. .6 rod-shaped high voltage application electrodes made of a vinyl chloride resin sheet (thickness 350 μm) made of a double matrix and covered with glass, and one drum-shaped member placed opposite the group of high voltage application electrodes. The treatment was carried out using a plasma processing apparatus having an internal electrode consisting of a ground electrode and a ground electrode. First, after exhausting the inside of the device to below 4x 10-3 Torr,
Replace the residual gas in the device twice with gas, and then 4X10T again.
After evacuation to below 0.000 mΩ, the device was maintained at 0.1 Torr without introducing H2 gas, and using a high voltage power supply of 1QKHz, the negative side output voltage was set to 5.0 mΩ. The treatment was performed continuously at a treatment intensity of OKV and a sheet speed of 15 m/min.

Next, a copolymer with a water content of 30% (PVC-q-NVP>
It is called. ) and polyethylene glycol monomethacrylate having an ethylene oxide chain of 100 repeating units to polyvinyl chloride. Mixed solvent of alcohol (
The mixture was dissolved in a mixture ratio of 70:30 wt%), applied to the treated surfaces of plasma-treated sheets 1 to 1 using a metering bar so that the dried film thickness was about 1 μm, and dried at 70'C for 5 minutes. The soft vinyl chloride sheets of the present invention produced in this manner are referred to as Examples 1 and 2, respectively.

In addition, as comparative examples, PVC-Ω-NV was added to untreated vinyl chloride sheets 1~ (comparative example 1), plasma treated sheets 1~ (comparative example 2), and untreated vinyl chloride sheets 1~ (comparative example 2).
Sheets coated with P and PVC-CI-PEGMloo in a thickness of about 1 μm (Comparative Examples 3 and 4, respectively) and vinyl chloride sheets coated with PVC-C1-PEGMloo in a thickness of about 20 μm
To the coated sheet 1 (Comparative Example 5) was prepared.

Each sheet was made so that the processed surface became the inner surface, and a small bag with an inner surface area of 70 rJK was made.

The bag was tested as described above to evaluate the platelet storage performance of the bag. These results are shown in Table 1.

Table 1 As shown in Table 1, the sheet of the present invention) (Examples 1 and 2) synergistically preserves the function of stored platelets higher than the plasma-treated sheet (Comparative Example 2) and the copolymer laminated sheet (Comparative Example 5). It's dripping.

Claims (1)

[Claims] (1) A medical soft vinyl chloride resin molded article, characterized in that a crosslinked layer and a polymer layer made of a copolymer of a hydrophobic monomer and a hydrophilic monomer are laminated on the surface of a soft vinyl chloride resin.