JP2528443B2 - Low-dissolution drug solution, infusion, blood transfusion device - Google Patents

Description

TECHNICAL FIELD The present invention relates to a medical liquid agent / infusion / blood transfusion device having excellent dissolution properties, and in particular, improved balance of moldability, transparency, rigidity, and dissolution properties. It relates to the device.

[Prior Art] Propylene polymers have excellent mechanical properties as a material,
It is used in various applications by taking advantage of its features such as moldability.
However, depending on the application, transparency, elution, rigidity,
Further, performance such as moldability may be particularly required.
In particular, it is an indispensable requirement for medical fluids, infusions, and blood transfusion instruments to have these characteristics not only for confirming the contents but also for safety and strength.

Various techniques have been proposed in the past for improving the transparency and rigidity of propylene polymers. Among these, inorganic fillers such as talc, metal salts of carboxylic acids, aluminum salts of aromatic carboxylic acids, and sorbitol compounds. The method of adding a nucleating agent such as an aromatic metal phosphate is well known. In particular, the method of adding a sorbitol-based nucleating agent is widely used because of its excellent transparency improving effect.

JP-A-58-1736, JP-B-62-21377, JP-A-61-5
No. 3344 and JP-A No. 62-209151 disclose a composition in which an aromatic metal phosphate-based nucleating agent is added to a polyolefin.

[Problems to be Solved by the Invention] However, the method of adding a sorbitol-based nucleating agent has a problem that the sorbitol-based nucleating agent is extracted into hot water in addition to the problems such as odor and bleeding. There is.

[Means for Solving the Problems] As a result of studying various blends to solve the above problems, the present inventor has found that a propylene polymer composition obtained by blending a specific nucleating agent with a specific propylene polymer. It has been found that by molding, it is possible to obtain a medicinal liquid agent, an infusion solution, and a blood transfusion instrument having an excellent performance balance of rigidity, transparency, elution property, and moldability, and the object has been achieved.

That is, the present invention has a melt flow rate of 10 to 80 g /
10 minutes, 0.01 to 1 part by weight of a metal salt of aromatic phosphoric acid represented by the following general formula [I] is added to 100 parts by weight of a crystalline propylene random copolymer having an ethylene content of 0.5 to 7% by weight. A low-dissolution drug solution, infusion solution, blood transfusion instrument, characterized by being formed by molding the propylene polymer composition.

General formula (However, in the formula, R ¹ and R ² are each independently a hydrogen atom or an alkyl group, M is a metal of Group Ia or Group IIa, X is an alkylidene group, and a is a valence. [Detailed Description of the Invention] Propylene Random Copolymer The crystalline propylene random copolymer used in the present invention is a propylene / ethylene-random copolymer having a melt flow rate of 10 to 80 g. / 10 minutes, preferably 12 to 50 g / 10 minutes melt flow rate, particularly preferably 15 to 40 g / 10 minutes. If the melt flow rate is out of these ranges, moldability, rigidity, impact resistance, etc. will become problems.

This propylene random copolymer is 0.5 to 7% by weight, preferably 2 to 5% by weight, particularly preferably 2.5 to 4.5%.
It contains ethylene units by weight. If the ethylene content is less than the above lower limit, the transparency and impact strength will be unsatisfactory, and if it exceeds the upper limit, the decrease in rigidity will be a serious problem.

These propylene random copolymers include other α-
Olefins such as 1-butene, 1-pentene, 1-hexene, 4-methylpentene-1 and vinyl acetate may be contained in the copolymer as long as the effects of the present invention are not impaired.

These propylene-based random copolymers are generally produced by polymerizing propylene and the like with a Ziegler-Natta catalyst, and this catalyst has a catalyst component supported on a carrier such as magnesium chloride. So-called supported catalysts can also be used. As a polymerization method, in addition to the production in a slurry state in a solvent such as heptane, it is also possible to produce in a liquid phase state or a gas phase state without a solvent. Furthermore, due to recent advances in catalyst technology, polymer production processes that do not require a decatalysis step have been realized, and the propylene-based random copolymer produced by these processes is also the propylene-based random copolymer of the present invention. It can be applied to and is effective.

Aromatic phosphoric acid metal salt As a metal salt of aromatic phosphoric acid to be blended in the propylene-based random copolymer composition, which is a material of the device of the present invention, a metal salt of the general formula (However, in the formula, R ¹ and R ² are a hydrogen atom or an alkyl group, M
Represents a Group Ia or Group IIa metal, a represents the valence of M,
X represents an alkylidene group. ) Is added.

Among the metal salts of aromatic phosphoric acid represented by the above general formula, preferred is a = 1, that is, a Group Ia metal. Specific examples thereof include 2,2'-methylene-bis (4,6-
Sodium salt and lithium salt of di-t-butylphenyl) phosphoric acid, sodium salt and lithium salt of 2,2′-ethylidene-bis (4,6-di-t-butylphenyl) phosphoric acid,
Examples thereof include potassium salt of 2,2′-methylidene-bis (4,6-di-t-butylphenyl) phosphoric acid, but are not limited thereto. Among these, sodium 2,2'-methylene-bis (4,6-di-t-butylphenyl) phosphate, 2,2'-methylene-bis (4,6-di-t-butylphenyl) phosphorus Lithium acid is preferable, and particularly 2,2′-methylene-bis (4,6) in terms of elution, rigidity and transparency of the composition.
Most preferred is lithium di-t-butylphenyl) phosphate.

The amount of the metal salt of aromatic phosphoric acid added is 0.01 to 1 part by weight based on 100 parts by weight of the propylene random copolymer,
It is preferably 0.03 to 0.5 part by weight. If the amount is less than this range, the nucleation effect is small, and if the amount exceeds this range, it is uneconomical and the impact strength of the molded product may be affected.

Other compounding agents The propylene-based random copolymer composition used in the present invention may be compounded with other additional compounding agents as long as the effects of the present invention are not significantly impaired.

In other words, phenol-based, sulfur-based, phosphite-based and phosphonite-based antioxidants, benzoate-based, benzophenone-based, triazole-based, hindered amine-based, light stabilizers such as nickel-based, and other metal deactivation as necessary. Agents, antistatic agents, lubricants, organic and inorganic pigments, fillers, peroxides, blowing agents, flame retardants, other nucleating agents,
A rubber component such as a propylene / ethylene-based copolymer rubber or an ethylene / butene-based copolymer rubber can be added within a range that does not significantly impair the effects of the present invention.

Production of Propylene Random Copolymer Composition The propylene random copolymer composition used in the present invention can be produced by a usual method for producing a composition. For example, the metal salt of aromatic phosphoric acid represented by the above general formula is added to the powder of the propylene random copolymer, antioxidants and other components are added if necessary, and the mixture is stirred with a Henschel mixer. After mixing, they are melt-kneaded by an extruder and extruded to obtain pellets.

It is common to process these pellets by injection molding, extrusion molding, etc. to process them into the desired molded product, but by making a masterbatch in which the additive components are concentrated to a high concentration and adding this during molding processing It may be.

Molded Article The above-mentioned composition used in the present invention is a container for various foods; a test tube, a sample storage container (vial), a flask, a graduated cylinder, a physics and chemistry laboratory instrument such as a filter carrier; It can be suitably used by molding it into a medical device such as a set or a blood collecting device, but in particular, a medicinal solution, an infusion solution, or a blood transfusion device can remarkably enjoy the effects. Usually, it is heated and molded at a temperature of 180 to 300 ° C.

Sterilization Medical liquid, infusion and blood transfusion instruments are generally sterilized before use. As the sterilization method, high-pressure steam, ethylene oxide gas, radiation or the like is used. X-rays, gamma rays, electron beams, etc. are used as the radiation, and in any case, it is suitable for the present molded article.

[Examples] The following compounds were used as the additives used in the following Examples and Comparative Examples.

A: 2,2'-methylene-bis (4,6-di-t-butylphenyl) sodium phosphate B: 2,2'-methylene-bis (4,6-di-t-butylphenyl) lithium phosphate C: sodium bis (4-t-butylphenyl) phosphate D: 1,3,2,4-di-p-methylbenzylidene-sorbitol E: calcium stearate F: bis (2,4-di-t-butylphenyl) ) Pentaerythritol diphosphite G: dimethyl-1- (2-hydroxyethyl) -succinate
4-Hydroxy-2,2,6,6-tetramethylpiperidine polycondensate (molecular weight> 73000) H: 2,5-di-methyl-2,5-di- (t-butylperoxy) hexane Example 1 5 and Comparative Examples 1 to 6 The propylene random copolymers or the block copolymers shown in Table 1 were blended with the above additives A to H, and then at a temperature of 230 ° C. in a 30 mmφ extruder. The mixture was melt-kneaded and extruded to obtain pellets of the propylene polymer composition.

This pellet was manufactured into an injection-molded piece having a thickness of 1 mm by an injection molding machine. Olsen flexural rigidity (ASTM
D-747) and Haze (JIS K-6714) were measured to examine bending rigidity and transparency. Further, the moldability was judged by visually observing the impact strength with a DuPont impact tester and the smoothness of the surface of the injection molded product.

Further, a test piece irradiated with radiation (2.5 megarad with gamma ray) was finely cut into a small piece, and a dissolution test of the plastics test piece was carried out by a plastics container test method for infusion. That is, 200 ml of distilled water was added to 40 g of strips,
The mixture was heated in a high-pressure sterilizer at ℃ for 1 hour. Then, measure the hydrogen ion concentration of the extracted solution, compare it with the blank, and measure the difference in pH (ΔpH), the difference in potassium permanganate consumption (ΔKMnO ₄ ) and the ultraviolet absorption spectrum (UV). The elution property was examined.

As shown by the results of the examples in Table 1, the molded articles of the propylene random copolymer composition of the present invention have a good balance of rigidity, transparency and elution property.

In addition, in the comparative examples shown in Table 1, those with excellent transparency have significantly poor elution (particularly ΔKMnO ₄ ), and those with high rigidity have poor transparency (Haze). The dissolution balance is insufficient.

[Effects of the Invention] The medicinal solution / infusion / blood transfusion device of the present invention is formed by molding a propylene-based random copolymer composition obtained by mixing a specific compounding agent with a specific propylene-based random copolymer. Which has moldability, rigidity,
It has an excellent performance balance of transparency and elution and is extremely useful as the device.

Claims (1)

(57) [Claims] 1. A fragrance represented by the following general formula [I] based on 100 parts by weight of a crystalline propylene random copolymer having a melt flow rate of 10 to 80 g / 10 minutes and an ethylene content of 0.5 to 7% by weight. A low-dissolution drug liquid / infusion / blood transfusion device, characterized by being formed by molding a propylene-based polymer composition containing 0.01 to 1 part by weight of a metal salt of group A phosphoric acid. General formula (However, in the formula, R ¹ and R ² are each independently a hydrogen atom or an alkyl group, M is a metal of Group Ia or Group IIa, X is an alkylidene group, and a is a valence. It is.)