WO2005121390A1

WO2005121390A1 - Method for suppressing adsorption of organic compound on surface of synthetic resin molded article

Info

Publication number: WO2005121390A1
Application number: PCT/JP2005/010457
Authority: WO
Inventors: Eiji Kusano; Hui Zhang; Zhaopeng Hu; Kazufumi Shiotani; Akio Kimura
Original assignee: Santen Pharmaceutical Co., Ltd.
Priority date: 2004-06-08
Filing date: 2005-06-08
Publication date: 2005-12-22

Abstract

Disclosed is a method for suppressing adsorption of an organic compound on the surface of a synthetic resin molded article. A thin-film layer of a metal, silicon or an oxide of the metal or silicon is formed on the surface of a synthetic resin molded article by a thin-film forming technique using plasma. Consequently, there can be suppressed adsorption of an organic compound on the synthetic resin molded article.

Description

Specification

Method for suppressing adsorption of organic compounds on synthetic resin molded product surface

Technical field

[0001] The present invention provides a synthetic resin of an organic compound, characterized in that a thin film layer of metal, silicon or their oxides is formed on the surface of a synthetic resin molded product such as a container by a thin film forming technique using plasma. The present invention relates to a method for suppressing adsorption to a molded product.

Background art

[0002] Synthetic resins are easily used in molding, are excellent in impact resistance, are lightweight and safe, and are therefore widely used as materials for various molded articles such as containers. However, since the synthetic resin molded article has a property that an organic compound is adsorbed on its surface, there are various restrictions in using the organic compound in direct contact with the organic compound. Therefore, attempts have been made to suppress the adsorption of organic compounds by modifying the surface of the synthetic resin.

[0003] As one of them, a plasma etching technique is known. This technique is characterized by homogenizing the surface of the synthetic resin by plasma treatment.However, it is possible to modify the surface structure of the synthetic resin even at a low temperature. It has been described that plasma irradiation of a copolymer plate in an argon gas atmosphere improves the hydrophilicity of its surface and suppresses the adsorption of insulin. It is described that when the rate plate is subjected to plasma treatment in an argon gas atmosphere to make it hydrophilic, proteins such as lysozyme, anolebumin, and γ_ globulin in artificial tears can be suppressed from being adsorbed on the surface of the polymethacrylate plate. Have been.

[0004] On the other hand, methods for forming a thin film of metal or metal oxide on the surface of a synthetic resin molded article by a thin film forming technique using plasma include sputtering, ion plating, plasma-enhanced chemical vapor deposition, and the like. There are arc ion plating, hollow sword vapor deposition, etc.Resin containers using these technologies to form thin films of metals and metal oxides have excellent permeability to oxygen and other gases. Is known.

[0005] For example, Patent Document 1 discloses forming a Si 特殊 film on the surface of a synthetic resin container such as polyethylene terephthalate (PET) or polyethylene (ΡΕ) using a special ionization coating method. It describes that the gas permeability is reduced to prevent oxidation of the contents. Patent Document 2 discloses that a gas barrier property for oxygen and the like is improved by subjecting a ceramic thin film layer containing silicon oxide as a main component to plasma chemical vapor deposition on an inner surface or an outer surface of a plastic molded article made of an ethylene polypropylene random copolymer. It is described. All of the above-mentioned prior art documents aim at protecting the contents by blocking the intrusion of gas such as oxygen into the container. There is no description about the suppression of adsorption of organic compounds by forming a thin film layer by using it, and it goes without saying that it is also suggested.

Patent Document 1: JP-A-60-2443

Patent Document 2: JP 2001-261866 A

Non-patent Document 1: Pharmaceutical Journal 119 (12) 929-935, 1999

Non-Patent Document 2: Chem. Pharm. Bull. 42 (9) 1896-1901, 1994

Disclosure of the invention

Problems to be solved by the invention

[0006] If the adsorption of an organic compound to the surface of a synthetic resin molded product can be suppressed, the synthetic resin can be more effectively used. As one of the methods, there is a plasma etching technique described in the background art. Although the plasma etching technique is a simple and useful method, radicals generated at the cross-linking site and the graft site on the surface of the synthetic resin molded product may cause a secondary reaction with oxygen in the air, etc. Development of a method for suppressing adsorption of organic compounds has been desired.

[0007] Synthetic resins are used for various purposes, and are also used in aqueous liquid containers such as eye drops. In an ophthalmic container, when organic compounds such as drugs and preservatives in the ophthalmic solution stored in the container are adsorbed on the inner surface of the container, a change in the concentration of the organic compound in the ophthalmic solution occurs and quality assurance can be achieved. Therefore, it is important to suppress the decrease in the content of organic compounds in eye drops.

Means for solving the problem

[0008] The inventors of the present invention have made intensive studies to solve the above-mentioned problems, and found that a thin film layer of metal, silicon or their oxides was formed on a synthetic resin molded product by a thin film forming technique using plasma. Then, they found that adsorption of an organic compound to the resin could be effectively suppressed, and the present invention was reached.

That is, the present invention

(1) Forming a thin film layer of metal, silicon, or their oxides on the surface of a synthetic resin molded product by a thin film forming technology using plasma Adsorption suppression method,

(2) A method for suppressing adsorption of organic compounds to the inner surface of a container, characterized by forming a thin film layer of metal, silicon or their oxides on the inner surface of a synthetic resin container by a thin film forming technique using plasma,

(3) The method according to (1) or (2), wherein the synthetic resin is a polyolefin resin, a polystyrene resin, or a polyester resin.

(4) The method according to (3), wherein the polyolefin resin is S, polyethylene resin, polypropylene resin or polyethylene terephthalate resin.

(5) Thin film formation technology using plasma The method according to (1) to (2), which is an S sputtering technology,

(6) Metal, silicon or their oxide power Ti, Ag, TiO or SiO before (1)-(

twenty two

2) described method,

(7) The method according to (1) to (2), wherein the thickness of the thin film layer is 1 / m or less,

(8) The method according to the above (1) to (2), wherein the organic compound is a drug or an additive that is acceptable for a pharmaceutical, a food or a beverage.

(9) The method according to (2), wherein the container made of synthetic resin is an aqueous liquid container.

(10) The method according to (9), wherein the aqueous solution container is an eye drop container or a plastic bottle,

(11) A synthetic resin molded article in which the adsorption of an organic compound is suppressed by the method described in the above (1),

(12) The synthetic resin container in which the adsorption of the organic compound is suppressed by the method described in (2) above,

(13) An organic compound is formed into a synthetic resin molded product by forming a thin film layer of metal, silicon or their oxides on the surface of the synthetic resin molded product by a thin film forming technique using plasma. Synthetic resin molded products with excellent adsorption suppression,

(14) By the thin film forming technology using plasma, metal, silicon or their A synthetic resin container excellent in suppressing adsorption of organic compounds to the inner surface of the container, characterized by forming a thin film layer of oxide;

About.

[0010] In the present invention, the kind of the synthetic resin is not particularly limited, and examples thereof include a polyolefin resin, a polystyrene resin, and a polyester resin, and a polyolefin resin is preferable. Examples of the polyolefin resin include polyethylene resin (PE), polypropylene resin (PP), polyethylene terephthalate resin (PET), polyvinyl chloride resin (PVC), and more preferably polyethylene resin (PE) and polypropylene resin. (PP) and polyethylene terephthalate resin (PET). These resins may be a homopolymer or a copolymer.

[0011] The synthetic resin container of the present invention is not particularly limited as long as it is a container capable of storing an aqueous solution, and examples thereof include an eyedropper container and a pet bottle. In addition, the method for suppressing the adsorption of organic compounds to synthetic resin molded articles by the thin film forming technique using plasma of the present invention is suitable for suppressing the adsorption of trace amounts of organic compounds in aqueous liquid preparations, and is therefore useful in gene research and the like. It can also be used for biochips for analysis technology.

In the present invention, the thin film forming technology using plasma is a technology for forming a thin film layer of metal, silicon or their oxides on the surface of a synthetic resin molded product by plasma irradiation. Technologies for Films and Coatings, NOYES PUBLICATIONS, 1982, pp170-243, NOYES PUBLICATIONS, 1990, pp160-182, etc., ion plating (HANDBOOK OF PLASMA PROCESSI NG TECHNOLOGY, NOYES PUBLICATIONS, 1990, ρ 338_355), plasma chemical vapor deposition (Deposition Technologies for Films and Coatings, NOYES PUBLICATI 〇NS, 1982, pp365-384), arc ion plating (HANDBOOK OF PLASMA PROCESSING TECHNOLOGY, NOYES PUBLICATIONS, 1990, pp419-446) ), Hollow force sword deposition (HANDBOOK OF PLASMA PROCESSING TECHNOLOGY, N〇Y ES PUBLICATIONS, 1990, pp308-335), and more preferably sputtering.

[0012] Examples of the metal, silicon or their oxides include Ti, Si, Ta, Al, Ni, Cr, Ag, S Examples thereof include n, Hf, Nb, TiO, SiO, SiO, and Al 2 O, and more preferably Ti, Ag, Ti〇, and SiO.

The thickness (average thickness) of the thin film layer of metal, silicon or their oxide is preferably 1 μm or less, more preferably 0.1 to 500 nm, and most preferably:! To 100 nm. The thin film layer effectively suppresses the adsorption of the organic compound to the surface of the synthetic resin molded product even in such a thin layer.

[0014] Furthermore, by repeatedly forming a thin film using plasma, a multi-layered thin film layer of metal, silicon or their oxides can be formed, whereby the adsorption suppressing effect can be further improved. An example of the two-layer thin film layer is a layer in which an Ag layer is formed on a TiO layer by vapor deposition.

[0015] The synthetic resin container according to the present invention generally stores an organic compound in the form of a solution or suspension. Examples of the organic compound having a property of being adsorbed on the inner surface of the container include vitamins such as vitamin E, local anesthetics such as dibuforcein hydrochloride, steroids such as fluorometholone, betamethasone, and triamcinolone, and prostaglandin derivatives such as latanoprost. Drugs such as peptides and proteins such as cyclosporine, lysozyme, anolebumin, and γ-globulin, and various additives such as preservatives and surfactants that are acceptable for pharmaceuticals, foods, beverages, and the like. Examples of the preservative include a paraben preservative such as butyl paraoxybenzoate and a quaternary ammonium preservative such as benzanolone chloride.

When the synthetic resin container of the present invention is an ophthalmic container, for example, a thin film made of a desired metal such as Ti, Ag, TiO, SiO, silicon or an oxide thereof is formed on the inner surface of the ophthalmic container by using a sputtering technique. Preferably, a layer is formed. The thickness of the thin film layer on the inner surface of the ophthalmic container is not particularly limited, and may be determined in consideration of the characteristics of the organic compound contained in the ophthalmic solution, the type of the thin film, and the like.

The invention's effect

[0017] If a thin film layer of metal, silicon or their oxides is formed on the surface of a synthetic resin molded article or the inner surface of a synthetic resin container by a thin film forming technique using plasma, the surface of the synthetic resin molded article or the synthetic resin Adsorption of the organic compound on the inner surface of the container can be effectively suppressed. As a specific example, the force described in detail in the section on adsorption suppression test below When a thin film layer of Ti, Ag, TiO, and SiO was formed on the resin, the reduction of the organic compound content was significantly suppressed in all cases.

BEST MODE FOR CARRYING OUT THE INVENTION

[0018] The results of an adsorption suppression test using a resin piece on which Ti, TiO, Ag, and SiO are plasma-deposited are shown below, but this is for better understanding of the present invention, and the scope of the present invention is as follows. This is not a limitation.

[Adsorption suppression test]

Test Example l [Vitamin E adsorption suppression test using a resin piece with Ti plasma deposited]

(experimental method)

Using a sputtering device (L-332S-FH, manufactured by ANELVA), applying DC power (discharge current: 0.4 A) to the target in the presence of Ar gas (discharge current: 0.5 Pa), evaporated Ti is target material, it was both surfaces vapor deposition of Po Riechiren resin piece plate-shaped which is attached to a holder on the target (thickness l _mm, 30 mm X 15 mm, hereinafter referred to as "PE piece".) . By controlling the plasma irradiation time (5 to 250 seconds) during the plasma irradiation, each Ti-sputtered thin film-treated PE piece with an average film thickness of 2 nm, 20 nm and 100 nm was obtained.

[0020] Next, a plurality of glass bottles each containing 1 .4 mL of a test solution containing 0.0007% vitamin E (w / v) were prepared. Two pieces of the treated PE were immersed in the test solution in separate glass bottles, and the test solution was shaken at 40 ° C. Vitamin E content in each test solution was measured using a high performance liquid chromatograph (Waters Waters2695 or 2487, unless otherwise specified) after 1, 2 and 7 days after immersion in PE pieces. .

[0021] The residual ratio of vitamin E was calculated by the following formula.

[0022] Persistence = Vitamin E content at measurement / Vitamin E content before immersion X 100

(Result)

Figure 1 shows the change in the residual ratio of vitamin E (average value of three times) at each film thickness.

[0023] (Discussion)

As is evident from Figure 1, the PE piece treated with the Ti sputtering thin film has excellent vitamin E adsorption suppression. Indicates for production.

Test Example 2 [Adsorption suppression test of dib-hydrochloric acid force using a resin piece on which Ti was plasma-deposited]

(experimental method)

Prepare a plurality of glass bottles each containing 5 mL of test solution containing 0.005% dibu-hydrochloric acid hydrochloride (w / v). Each piece was immersed in the test solution in a separate glass bottle, and the test solution was shaken at 40 ° C. 0 (before immersion in the PE piece), and 2 and 7 days later, the content of dibu-hydrochlorin was measured using a high performance liquid chromatograph.

[0025] The residual ratio of dibu-hydrochloric acid hydrochloride was calculated by the following formula.

[0026] Residual rate = content of dibu-hydrochloric acid at measurement / content of dibu-hydrochloric acid before immersion X 100

(Result)

Table 1 shows the change in the residual ratio of dibu-hydrochloric acid hydrochloride (average value of three times).

[table 1]

[0027] (Discussion)

As can be clearly seen from Table 1, the PE piece treated with the Ti sputtering thin film has an excellent dib hydrochloride force-in adsorption suppressing action.

Test Example 3 [Vitamin E adsorption suppression test using resin pieces on which Ti〇 was plasma-deposited]

2

(experimental method)

Using a sputtering device, 〇 was introduced in the presence of Ar gas (discharge pressure: 0.5 Pa) (flow rate:

2

By applying high-frequency power (discharge power: 40 W) to the target while 5 sccm), Ti as a target material was evaporated and vapor-deposited on both sides of the PE piece attached to the holder on the target. For plasma irradiation, plasma irradiation time (1200-3000 seconds) Was controlled to obtain PE pieces treated with TiO sputtering thin films having a thickness of 20 nm and 50 nm.

2

[0029] Next, a plurality of glass bottles each containing 14.4 mL of the test solution containing 0.0007% vitamin E (w / v) were prepared.

2

Two pieces of PE were immersed in the test solution in separate glass bottles, and the test solution was shaken at 40 ° C. The vitamin E content was measured using a high performance liquid chromatograph at 0 (before immersion in the PE piece) and 2 days later.

[0030] The residual ratio of vitamin E was calculated by the formula shown in Test Example 1.

[0031] (Result)

Table 2 shows the residual ratio of vitamin E at each film thickness (average value of three times).

[Table 2]

[0032] (Discussion)

As is evident from Table 2, TiO sputtered thin film-treated PE pieces have excellent vitamin E adsorption.

2

Shows inhibitory action.

Test Example 4 [Vitamin E adsorption suppression test using a resin piece on which plasma deposition of Ag was performed]

(experimental method)

By applying a DC power (discharge current: 0.4 A) to the target in the presence of Ar gas (discharge pressure: 0.5 Pa) using a sputtering device, Ag as a target material is evaporated, and a holder on the target is applied. Was vapor-deposited on both sides of the PE piece attached to the. At the time of plasma irradiation, the plasma irradiation time (3-100 seconds) was controlled to obtain 4 and 20 nm-thick Ag-sputtered thin-film-treated PE pieces.

[0034] Next, a plurality of glass bottles containing 14.4 mL of a test solution containing 0.0007% vitamin E (w / v) were prepared, and a 4 nm-thick and 20 nm-thick Ag-sputtered thin-film-treated PE piece and an untreated PE Two pieces were immersed in the test solution in separate glass bottles, and the test solution was shaken at 40 ° C. 0 The residual ratio of vitamin E was measured using a high performance liquid chromatograph (before immersion in the PE piece) and two days later.

The residual ratio of vitamin E was calculated by the calculation formula shown in Test Example 1.

[0036] (Result)

Table 3 shows the residual ratio of vitamin E at each film thickness (average value of three times).

[Table 3]

[0037] (Discussion)

As can be clearly seen from Table 3, the PE piece treated with the Ag sputtering thin film shows an excellent vitamin E adsorption suppression effect.

Test Example 5 [Adsorption of butyl paraoxybenzoate using resin pieces on which SiO was plasma-deposited]

2

Suppression test]

(experimental method)

Using a sputtering device, introduce 〇 in the presence of Ar gas (discharge pressure: 0.5Pa)

2

By applying high-frequency power (discharge power: 40 W) to the target, Si, which is the target material, was vaporized and vapor-deposited on both sides of the PE piece (distance between target and PE piece: 100 mm) attached to the holder on the target . During plasma irradiation, the holder was rotated (30 rpm), the plasma irradiation time was set to 4800 seconds, and SiO sputtering with an average film thickness of 100 nm was performed.

2

A thin film treated PE piece was obtained.

[0039] A plurality of glass bottles each containing 120 mL of a test solution containing 0.002% butyl paraoxybenzoate (w / v) were prepared.

2

The E pieces were immersed in test solutions in separate glass bottles three by three, and stored under the conditions of 40 ° C and 75% RH. The content of butyl paraoxybenzoate was measured using a high performance liquid chromatograph at 0 (before immersion in the PE piece) and after 84 days. [0040] The residual ratio of butyl paraoxybenzoate was calculated by the following formula.

[0041] Residual rate = content of butyl paraoxybenzoate at the time of measurement / content of butyl paraoxybenzoate before immersion X I 00

(Result)

Table 4 shows the residual ratio of butyl para-oxybenzoate (average of three times).

[Table 4]

[0042] (Discussion)

As is evident from Table 4, the PE piece treated with SiO sputtering

2

It shows an effect of suppressing adsorption of butyl perfate.

Brief Description of Drawings

FIG. 1 is a graph showing the results of an adsorption suppression test (change in the residual ratio of vitamin E) using a PE piece treated with a Ti sputtering thin film.

Claims

The scope of the claims

[I] A method for suppressing adsorption of an organic compound to a synthetic resin molded product, comprising forming a thin film layer of metal, silicon or their oxides on the surface of the synthetic resin molded product by a thin film forming technique using plasma. .

[2] A method for suppressing adsorption of organic compounds onto the inner surface of a container, comprising forming a thin film layer of metal, silicon or their oxides on the inner surface of a synthetic resin container by a thin film forming technique using plasma. .

[3] The method according to claim 2, wherein the synthetic resin is a polyolefin resin, a polystyrene resin, or a polyester resin.

[4] The method according to claim 3, wherein the resin is a polyethylene resin, a polypropylene resin or a polyethylene terephthalate resin.

[5] The method according to claim 1 or 2, wherein the thin film forming technology using plasma is S sputtering technology.

[6] Metal, silicon or oxides thereof Ti, Ag, TiO or SiO claim:! ~ 2

twenty two

The described method.

[7] The method according to any one of [1] to [2], wherein the thickness of the thin film layer is 1 μm or less.

[8] The method according to claim 2, wherein the organic compound is a drug or an additive acceptable for a drug, a pharmaceutical, a food or a beverage.

[9] The method according to claim 2, wherein the synthetic resin container is an aqueous solution container.

10. The method according to claim 9, wherein the aqueous solution container is an eye drop container or a PET bottle.

[II] A synthetic resin molded article in which adsorption of an organic compound is suppressed by the method according to claim 1.

[12] A synthetic resin container in which adsorption of an organic compound is suppressed by the method according to claim 2.

[13] A technique for forming a thin film of metal, silicon or their oxides on the surface of a synthetic resin molded article by using a thin film forming technique using plasma to suppress the adsorption of organic compounds to the synthetic resin molded article. Excellent synthetic resin molded product.

[14] A synthetic resin material that excels in suppressing the adsorption of organic compounds onto the inner surface of the container, characterized in that a thin film layer of metal, silicon or their oxides is formed on the inner surface of the container by a thin film forming technique using plasma. container.