JPS5825464B2 - plastic medical equipment - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION This invention relates to improved plastic medical devices.

Currently, in the medical field, medical aids such as artificial valves, artificial blood vessels, blood transfusion sets, infusion sets, and blood bags are made of various plastic materials.

Among these medical aids, blood transfusion sets, infusion sets, and blood bags are flexible, transparent, and heat resistant enough to withstand high-pressure steam sterilization, and are usually disposable at °C, so they are inexpensive. It also needs to be made of plastic that can be easily processed and assembled by means such as thermal bonding.

Soft polyvinyl chloride is known as a plastic material that satisfies the above conditions, and is used in various medical aids.

In this case, an additive called a plasticizer is added to increase flexibility.

There are many types of plasticizers, but based on the results of various toxicity tests, phthalate ester compounds, especially dioctyl phthalate (DOP), are currently the most suitable for use.
There is.

This phthalate ester is widely used in various countries as a harmless substance, but recently there was an accident in Vietnam in which an American soldier died of pulmonary shock after receiving a transfusion of blood contained in a polyvinyl chloride bag, and the cause of death was due to polychloride. There was a rumor that this was due to the nystal phthalate plasticizers in vinyl being extracted by blood, which led to suspicions about phthalate esters.

In Japan, when hormone analysis in blood plasma was performed using polyvinyl chloride test tubes, phthalate esters were extracted from the blood plasma, and this caused abnormal hormone analysis values, so this phenomenon has been reported. There has been concern that if this occurs in the human body, collagen disease may be induced.

However, the problem of phthalate esters remains unsolved because plastic materials with the properties mentioned at the beginning cannot be obtained in the current field of plastic chemistry to replace polyvinyl chloride. be.

Additionally, research on modifying polyvinyl chloride has been conducted for some time, unrelated to this problem.

That is, one of them is non-toxic polyvinyl chloride with a reduced amount of plasticizer and the like.

However, the inventors have developed various types of polyvinyl chloride sheets made by varying the amount of plasticizer blended into the polyvinyl chloride resin. As a result of testing the amount of plasticizer using gas chromatography, it was found that even when a very small amount of plasticizer was added to the polyvinyl chloride sheet to the extent that it lost its flexibility, the plasticizer was eluted into the bloodstream regardless of the type of plasticizer. I confirmed the fact that

Therefore, it is dangerous to use other plasticizers whose DOP has not been studied in depth.

Other research is attempting to use various rubbery polymers as plasticizers.

For example, attempts have been made to mix butadiene, acrylonitrile, rubber, etc. to soften polyvinyl chloride, but generally rubbery polymers themselves contain various stabilizers, emulsifiers, etc., which are extracted by the liquid inside. It is known to elute floating matter into the fluid or destroy blood cells.

Another fatal drawback is that polyvinyl chloride loses its transparency, so it cannot be used as medical aids such as blood sets.

This invention is based on the above-mentioned known technology of adding a rubbery polymer to polyvinyl chloride as a plasticizer, but we have developed a material that can withstand use as a medical aid, and with this we have developed a material that can be used as a medical aid. It is used to make medical equipment.

As a result of repeated research into molding sheets and tubes by blending various synthetic resins with polyvinyl chloride resin, the inventor found that
We determined that polyurethane was the best choice, but as a result of further detailed research, we learned that depending on the quality of polyurethane, it may be inappropriate as a medical device.

Therefore, the inventor devised a method to test what quality of polyurethane can be blended with polyvinyl chloride resin, but only polyurethane that meets this test method can be blended with polyvinyl chloride for use in medical devices. The feature of this invention lies in the selection of this compatible polyurethane.

The inventor mixed various quality polyurethane resins into a polyvinyl chloride resin tool that does not contain any plasticizer, molded it into a sheet shape at °C, examined its quality as a medical device, and investigated the quality results and the characteristics of the polyvinyl chloride resin. We investigated the correlation with the quality of the blended polyurethane resin alone.

At this time, 0.5 to 2.0 parts of a non-toxic zinc and calcium stabilizer was added to the polyvinyl chloride resin.

That is, the molded sheet and the raw polyurethane resin sheet were cut into pieces of appropriate size, 2 g of each was placed in a test tube, and 10 m/ml of human blood was added thereto for 3 hours under sterile conditions.
After leaving it at 7°C for 24 hours, remove the blood sample.
Add the same amount of chloroform/methanol (2:1) mixture to this and extract 3 times. Combine all extracts and dry under reduced pressure below 50°C. Dissolve the dried product in a small amount of methanol and test. Do impurity peaks appear on the chart when using gas chromatography as a liquid and using chloroform NGW as a support and heating at °C?
I looked into it.

In addition, regarding cut pieces, Japanese Pharmacopoeia 8th Revised General Test Method 3
Tested in accordance with the provisions of 61-Plastic Container Test Method for Infusion.

On the other hand, for polyurethane, put 5g of the pieces into a flask, add 100ml of chloroform, seal the flask, leave it at room temperature for 3 hours, filter it, and then dry the p solution under reduced pressure at 50°C or less. methanol 1. Om/ was added to prepare a test solution, and 10 μg of it was loaded onto a 0.25 mm thick silica gel to perform thin layer chromatography (solvent: n
-Hexane/ethyl acetate (9:1), room temperature increased by 10°C)
, spots appearing on the thin layer were detected using the iodine vapor method.

The results of the polyurethane resin sheet according to the above test,
The first example shows the results of a sheet molded by mixing 100 parts of polyvinyl chloride resin with 100 parts of polyurethane resin.
Shown in the table.

Here, two typical types of polyurethane resins, A and B, were used as raw material polyurethane resins.

The typical polyurethane resin A shown here was developed as a result of examining various urethane synthesis methods, and it was developed by purifying the urethane raw material itself and conducting the reaction in a temperature range that does not cause side reactions during the reaction. and so on.
As a result, it does not contain the additives conventionally used to stabilize urethane, and has improved blendability with polyvinyl chloride. , consisting of polyester made of dicarboxylic acid and diisocyanate.

On the other hand, the polyurethane resin B is a normal commercially available polyurethane resin that has been used in food packaging and is kept at a temperature of 0.degree.

From the above results, only when a sheet is formed by blending raw material polyurethane resin A with polyvinyl chloride resin, in which only a sample residue spot is observed at the origin where the sample is loaded by thin layer chromatography, impurities are observed from the sheet into the bloodstream. It can be seen that a high-quality sheet can be obtained that does not elute and also meets the Japanese Pharmacopoeia infusion plastic container test stipulated as a standard for medical containers.

Regarding the amount of polyurethane resin to polyvinyl chloride resin, the higher the amount of polyurethane resin, the more flexible the sheet or tube can be obtained. This is not desirable because it not only deviates from the purpose of water permeability, but also significantly increases moisture permeability, thereby violating laws and regulations regulating water permeability of blood transfusion sets and the like.

In other words, the revised Ministry of Health and Welfare Notification No. 271, [Standards for vinyl chloride resin blood sets], stipulates the quality of blood bags, and as part of the liquid evaporation test, one set has a humidity of 65 ± 2%, When left for 14 days at a temperature of 20+2°C, the weight loss of the liquid content is less than 4.0.

” is clearly stated. Furthermore, polyurethane resin that did not produce any spots other than the origin in thin layer chromatography was blended with polyvinyl chloride resin in various amounts to make a sheet, which was then thermally bonded to form a bag. The results of the liquid evaporation test are shown in Table 2.

Since the amount of transpiration of the liquid inside is inversely proportional to the thickness of the bag, increasing the thickness of the bag can reduce the amount of transpiration of the liquid, but if the thickness of the bag is 0.
In this test, the thickness of the bag was set to 0.45 mm because if it exceeds 6 mm, the flexibility decreases and it becomes economically disadvantageous.

Incidentally, the amount of evaporation of the contents of the bag made only from polyurethane resin is 5.8 times.

However, flexibility is shown by items that can be processed into bags (1) and items that cannot be processed into bags.

From the above test results, when the amount of polyurethane resin exceeds the amount of polyvinyl chloride resin, the amount of content liquid evaporates exceeds the amount stipulated by law, and if the amount of polyurethane resin is less than 50 parts, there is no flexibility and it is difficult to mold the bag. Therefore, the blending amount is 50 to 10
Preferably 0 copies.

Example 100 parts of polyvinyl chloride resin, 80 parts of polyurethane resin, 15 parts of zinc-calcium stabilizer, and 0.7 parts of calcium stearate were gelled using a hot kneading roll at about 150°C, thoroughly mixed, and pelletized using a cutting machine. After P
It was extruded into a tube at 140 to 190°C using a VC extruder (screw L/D 26: 1, compression ratio 3.5).

1. The blood collection bag was molded using a high-frequency welding machine.

A blood bag was made from the above materials and a blood preservation solution was stored in it for testing.The results showed that the humidity was 65±2 degrees and the temperature was 20±2 degrees Celsius.
The amount of transpiration over 14 days was 2.38, which is within the range stipulated by the vinyl chloride resin blood set standards, and it was confirmed that the blood bag could withstand ethylene oxide gas and high-pressure steam sterilization.

Claims (1)

[Claims] 1. A plastic medical device characterized by using a plastic made of a material in which 50 to 100 parts of a polyurethane resin that does not produce spots other than the origin by thin layer chromatography is blended with 100 parts of polyvinyl chloride resin. .