TW201520179A - Glass assembly, glass container, and manufacturing method thereof - Google Patents

Abstract

The present invention provides a glass assembly, glass container (especially medical glass container) having advantageous water resistance, powder resistance, thermal tolerance, water tolerance, and alkali resistance and manufacturing method thereof. The present invention relates to a manufacturing method for glass container (especially medical glass container), and a glass container manufactured by the method. The aforementioned manufacturing method for the glass container is characterized by comprising the steps of: (1) treating the inside surface of the glass container with silane coupling agent and/or its partial hydrolysate; and (2) treating the treated surface from step(1) with amorphous fluorine resin.

Description

Glass member, glass container and manufacturing method thereof

The present invention relates to a glass member and a glass container, and more particularly to a glass container for medical use, and more particularly to a glass container for containing a medicine such as a medicine or an examination medicine.

As a medical container for accommodating medicines such as pharmaceuticals and pharmaceuticals for examination, glass containers having excellent isolation from water vapor and oxygen are widely used. The material of the glass container is generally made of borosilicate glass or soda lime glass from the viewpoint of cost and workability, but the contents are easily attached to the inner surface of the glass container (the surface is low in water resistance and powder resistance). When the modified ion (sodium ion or the like) contained in the glass is eluted, and the pharmaceutical solution having a high pH is used, the inner surface of the glass container is corroded to cause glass fragments and the like. In order to solve this problem, many medical glass containers for surface treatment of the inner surface of a glass container (for example, Patent Documents 1 to 4, etc.) have been proposed.

Further, a medical glass container (for example, a glass bottle) is usually heated to 250 ° C after being washed with distilled water for injection, and the heating material is not activated (the exothermic substance: cell membrane of Gram-negative bacteria), so-called "dry" Heat sterilization." Therefore, it is also required to sufficiently withstand the surface treatment of this dry heat sterilization.

[Patent Literature]

[Patent Document 1] Japanese Patent Laid-Open No. 54-97617

[Patent Document 2] Japanese Patent Laid-Open Publication No. 2008-6587

[Patent Document 3] Japanese Patent Publication No. 2011-523866

[Patent Document 4] Japanese Patent No. 2815595

Summary of invention

The object of the present invention is to provide a glass member, a glass container (especially a medical glass container) which has excellent water resistance, powder resistance, heat resistance, water resistance, alkali resistance, etc., and the modified ions of the glass are not eluted. Its manufacturing method.

In order to solve the above problems, the inventors of the present invention have found that the fluorinated coupling agent and/or the partially hydrolyzed product can be coated on the surface of the glass member or the inner surface of the glass container, and the amorphous fluorine-based resin is coated thereon. A glass member or a glass container (especially a medical glass container) that solves the above problems is obtained. The present invention has been completed in view of the above findings.

That is, the present invention provides a glass member or a glass container (particularly a medical glass container) which is subjected to the following surface treatment and a method for producing the same.

Item 1 is a method for producing a glass member, comprising: (1) a step of treating a surface of a glass member with a decane coupling agent and/or a partial hydrolyzate thereof; and (2) obtaining the step (1) The treated surface is treated with an amorphous fluorine-based resin.

The method according to Item 1, wherein the glass member is a glass container, and comprises: (1) a step of treating the inner surface of the glass container with a decane coupling agent and/or a partial hydrolyzate thereof; And (2) a step of treating the treated surface obtained in the step (1) with an amorphous fluorine-based resin.

Item 3 is the production method according to Item 1, wherein the decane coupling agent is a general formula (A): (R ¹ O) _4-n SiR ² _n (A)

(wherein, n represents 1, 2 or 3, R ¹ represents a lower alkyl group, and R ² represents a compound represented by a lower alkyl group which may have an amino group or an amine lower alkylamino group as a substituent).

Item 4 is the production method according to Item 3, wherein the decane coupling agent is a compound of the following formula (A), wherein n represents 1, R ¹ represents a C 1-3 alkyl group, and R ² represents A C2-6 alkyl group having an amino group or an amine C2~4 alkylamino group as a substituent.

The production method according to any one of items 1 to 4, wherein the amorphous fluorine-based resin is a repeating unit having a fluorine-containing cyclic ether structure.

The production method according to Item 5, wherein the amorphous fluorine-based resin has the formula (B):

The repeating unit shown.

Item 7 is the production method according to Item 6, wherein the amorphous fluorine-based resin contains 60 to 99 mol% of a repeating unit represented by the formula (B), and 40 to 1 mol% of the formula (B1). ):

The repeating unit shown.

Item 8 is the production method according to Item 5, wherein the amorphous fluorine-based resin has the formula (C) and/or (D):

(wherein, p represents 1 or 2, and q represents 1 or 2).

Item 9 is the production method according to Item 8, wherein the amorphous fluorine-based resin having a repeating unit represented by the above formula (C) and/or (D) has a substituent containing a carboxyl group or contains Formula (E). ):-CONH-R ³ -Si(OR ⁴ ) ₃ (E)

(wherein, R ³ represents a link, and R ⁴ represents a substituent represented by a lower alkyl group).

The production method according to Item 9, wherein the end of the amorphous fluororesin having a repeating unit represented by the above formula (C) and/or (D) has a formula represented by Formula (E) a part of the substituent.

The production method according to any one of items 1 to 10, wherein the glass structure or the glass container member is made of borosilicate glass.

The production method according to any one of Items 1 to 11, wherein the film thickness of the coating film obtained by the above formulas (1) and (2) is about 0.1 to 200 μm.

Item 13 is a glass member obtained by the production method according to any one of Items 1 to 12.

Item 14 is the glass member according to Item 13, which is a medical glass container.

Item 15 is a medical glass container in which the medicine is contained in the medical glass container described in the above item 14, and the medicine or the inspection medicine is stored.

Item 16 is the glass member according to Item 13, which is selected from the group consisting of a glass container, a glass plate, a glass meter, a glass chemical analysis instrument, a glass chemical synthesis instrument, a glass medical device, and a glass optical member. At least one of the group consisting of.

The glass member or the glass container of the present invention has excellent water resistance, powder resistance, heat resistance, water resistance, alkali resistance, delamination resistance and the like. Furthermore, there is no possibility of glass-modified ion elution and glass shards, and almost no fluoride ions are generated.

Further, in recent years, pharmaceutical products containing proteins and nucleic acids have been gradually developed. However, since these pharmaceutical products have high affinity with glass, the problem that the drug is absorbed on the inner surface of the container and the efficacy is lowered is reviewed. The glass container of the present invention can exert the effect of reducing the absorption of such pharmaceuticals.

As described above, since the glass container of the present invention is excellent in handleability, durability, storage stability of contents, and the like, it is possible to stably store various types of pharmaceuticals and medicines for examination. Accordingly, the glass container of the present invention can be effectively used as a medical glass container.

Fig. 1 is a view showing (2) the water resistance of the inner surface of the glass bottle in the evaluation of the water resistance of the test example 1 (Fig. 1 (a)) and "x: the water resistance of the inner surface of the glass bottle is not Photograph of the "all" (Fig. 1(b)).

Fig. 2 is a view showing the (3) evaluation of the anti-powder property of the test example 1, "◎: almost no adhering powder on the inner surface of the glass bottle" (Fig. 2 (a)) and "×: the inner surface of the glass bottle is attached A photograph of the appearance of a large amount of powder (Fig. 2(b)).

Fig. 3-1 shows the "no film peeling" in (4) dry heat durability evaluation, (6) hot water resistance evaluation, and (7) alkali resistance evaluation in Test Example 1 (Fig. 3-1 (a) )) and the photo of "film peeling" (Fig. 3-1(b)).

Fig. 3-2 shows the aspect of "4) dry heat durability evaluation, (6) hot water resistance evaluation, and (7) alkali resistance evaluation in Test Example 1 (Fig. 3-2 (Fig. 3-2) c)) And a picture of "having a poor resistance to water" (Figure 3-2(d)).

Figure 4 is a photograph of a section of the body of the bottle coated with the glass bottle manufactured in Example 1.

Figure 5 is a graph showing the measurement results of the contact angle of water in the coated film of each of the coated glass bottles measured in Test Example 2; (a) showing the surface-treated glass bottle of Example 1 (coated glass bottle 1) And (b) showing the glass bottle after the peeling treatment of the coated glass bottle 1, (c) showing the glass bottle after the peeling treatment of the coated glass bottle 2, and (d) showing that the coated glass bottle 3 is subjected to the peeling treatment The measurement result of the contact angle of the glass bottle.

Fig. 6 is a graph showing the relationship between the concentration of the BSA solution and the absorbance in Test Example 4.

Fig. 7 is a graph showing the measurement results of the absorbance of each sample in Test Example 4.

Fig. 8 shows the BSA residual ratio in each of the samples in Test Example 4.

Form for implementing the invention

The glass member of the present invention is produced by a production method comprising the steps of (1) treating the surface of the glass member with a decane coupling agent and/or the partial hydrolyzate; and (2) The treated surface obtained in the step (1) is treated with an amorphous fluorine-based resin. When the glass member is a glass container (particularly a medical glass container), it is produced by a manufacturing method comprising the steps of (1) hydrolyzing a decane coupling agent to the inner surface of the glass member and/or partially hydrolyzing the glass member. a step of treating the material; and (2) a step of treating the treated surface obtained in the step (1) with an amorphous fluorine-based resin. The glass member or the glass container (especially the medical glass container) is excellent in characteristics. Water resistance, powder resistance, heat resistance, water resistance, alkali resistance, delamination resistance, etc., and no glass-modified ion elution and glass fragments.

Hereinafter, a method for producing the inner surface treated glass member or glass container (particularly, a medical glass container) according to the present invention will be described.

step 1)

Step (1) treats the surface of the glass member with a decane coupling agent and/or the partial hydrolyzate. When the glass member is a glass container, the step (1) treats the inner surface of the glass container with a decane coupling agent and/or the partial hydrolyzate.

The glass member of the present invention is not particularly limited as long as it is a glass structure, and the shape thereof is not particularly limited. For example, a glass container, a glass plate, a glass meter, a glass chemical analysis instrument, a glass chemical synthesis instrument, a glass medical device, a glass optical member, etc. are mentioned.

The glass container is not particularly limited, and examples thereof include a medical glass container. The medical glass container is a glass container for accommodating a pharmaceutical product, an examination drug, or the like, and examples thereof include an ampoule, a glass bottle, and a syringe (injector).

The glass meter can be exemplified by a measuring cylinder, a measuring cup, and the like.

The glass chemical analyzer is, for example, a protein crystallization apparatus (for example, a crystal plate used in a centrifuge) for protein structure analysis, a light chamber, or the like.

The glass chemical synthesis apparatus may, for example, be a flask, a separatory funnel, a test tube or the like.

Examples of the glass medical device include a glass machine for culturing cells (such as iPS cells), a hematocrit capillary tube, a straw, a stirring rod, and a beating. The emitter, the injector as a medical device, and the like.

The glass optical member is, for example, an optical lens or the like.

The glass material of the glass member or the glass container is not particularly limited as long as it can achieve the purpose of the invention, and many materials can be used. For example, quartz glass, borosilicate glass, soda lime glass, and the like. Among them, borosilicate glass is preferred from the viewpoint of chemical stability and the like.

The glass member or the glass container may be subjected to substrate treatment as needed before being supplied to the process of the present invention. The substrate treatment may be, for example, an alkali treatment (for example, treatment with an aqueous sodium hydroxide solution or the like) or an acid treatment (for example, treatment with hydrochloric acid or the like).

The decane coupling agent can be of the general formula (A): (R ¹ O) _4-n SiR ² _n (A)

(wherein, n represents 1, 2 or 3, R ¹ represents a lower alkyl group, and R ² represents a compound represented by a lower alkyl group which may have an amine group or an amine lower alkylamino group).

n represents 1, 2 or 3, and n is preferably 1.

The lower alkyl group represented by R ¹ may, for example, be a linear or branched C1-6 alkyl group, preferably a straight chain or a branch of a methyl group, an ethyl group, a n-propyl group, an isopropyl group or a n-butyl group. A C1-4 alkyl group of the chain, and a C1-3 alkyl group is preferred, and a methyl group or an ethyl group is particularly preferred.

In the general formula (A), when a majority group (R ¹ O) is present, (where n is 1 or 2), R ¹ may be the same or different.

The substituent represented by R ² may be a lower alkyl group which may have an amino group or an amine lower alkyl group, and the substituent may, for example, be an C 2-6 alkyl group having an amine group or an amine C 2 4 alkylamino group. Specifically, it can be exemplified by the general formula (A1): -R ²⁰ (A1)

(wherein R ²⁰ represents a C2-6 alkyl group of a straight or branched chain), and the general formula (A2): -R ²¹ -NH ₂ (A2)

Wherein R ²¹ represents a C2-6 alkyl group of a straight or branched chain, preferably a propyl group, or a general formula (A3): -R ²² -NH-R ²³ -NH ₂ ( A3)

(wherein R ²² represents a C2-6 alkyl group of a straight or branched chain, and R ²³ represents a C2~4 alkyl group of a straight or branched chain,).

R ^{2 is} preferably a group represented by the general formula (A1) or a group represented by the general formula (A2), and a group represented by the general formula (A2) is more preferable. When R ² is a compound of the formula (A2), the transparency of the surface of the glass member (especially the inner surface of the glass container) can be effectively maintained in the heat treatment of the step (2). (not whitening).

In the general formula (A), when a plurality of groups R ² are present (w when n is 2 or 3), R ² may be the same or different.

An ideal decane coupling agent may, for example, be a general formula (A'): (R ¹ O) ₃ SiR ² (A')

A compound represented by the formula (wherein R ¹ and R ^{2 are the} same as defined above).

Specific examples of the decane coupling agent include methyltrimethoxydecane, methyltriethoxydecane, ethyltrimethoxydecane, ethyltriethoxydecane, and 3-aminopropyltrimethoxy. Decane, 3-aminopropyltriethoxydecane, 3-aminopropylmethyldimethoxydecane, 3-aminopropylmethyldiethoxylate Baseline, 2-aminoethyl-3-aminopropyltrimethoxydecane, 2-aminoethyl-3-aminopropyltriethoxydecane, 2-aminoethyl-3-amine Propyl propyl dimethoxy decane, 2-aminoethyl-3-aminopropyl methyl diethoxy decane, 2-aminoethyl trimethoxy decane, 2-aminoethyl three Ethoxy decane, 4-aminobutyl trimethoxy decane, 4-aminobutyl triethoxy decane, etc., and the decane coupling agent may be used alone or in combination of two or more.

Among the above decane coupling agents, preferred examples thereof include methyltrimethoxydecane, methyltriethoxydecane, 3-aminopropyltrimethoxydecane, and 3-aminoethyltrimethoxydecane. 3-aminopropyltriethoxydecane. In particular, 3-aminopropyltriethoxydecane is preferred.

The partial hydrolyzate can be obtained by hydrolyzing the decane coupling agent in the presence of water. Generally, it is produced by reacting a decane coupling agent and a predetermined amount of water in the presence of an acid catalyst such as acetic acid.

The decane coupling agent and/or the partial hydrolyzate are generally used in the form of a solution. This solution can be prepared by diluting a decane coupling agent with water, a mixed solvent of water and an alcohol, and the like, and using an acid catalyst such as acetic acid as needed. The concentration of the decane coupling agent is generally 0.05 to 10% by mass, preferably 0.1 to 5% by mass, and more preferably 0.1 to 3% by mass. The alcohol system may, for example, be a C1 to 3 alcohol such as methanol, ethanol or propanol.

The solution containing the decane coupling agent and/or the partial hydrolyzate may also contain a metal alkoxide of ruthenium, titanium, zirconium or the like (such as a tetraalkanoxane, etc.) in a range which can exert the effect of the present invention. Further, a decane coupling agent other than the above, and/or a hydrolyzate thereof or the like may be contained.

a solution comprising a decane coupling agent and/or the partial hydrolyzate, The method for treating the surface of the glass member (especially the inner surface of the glass container) is not particularly limited, and a conventional coating method such as dipping, spraying, brushing, or spin coating in a container filled solution can be employed. After coating the surface of the glass member (especially the inner surface of the glass container), the excess solution is removed by centrifugation or the like as needed, and then dried. The drying step is carried out at a temperature of usually from room temperature to 150 ° C for about 1 minute to 60 minutes. After that, it should be further subjected to heat treatment (baking), usually at a temperature of 80 to 250 ° C (preferably 80 to 200 ° C, more preferably 90 to 150 ° C), 5 minutes to 100 minutes (preferably 10 minutes to 80 minutes) .

As described above, a glass member or a glass container which is treated with a decane coupling agent and/or the partial hydrolyzate is obtained. The film thickness of the film obtained in the step (1) is generally about 0.001 to 5 μm, preferably 0.01 to 0.5 μm.

Step (2)

In the step (2), the treated surface obtained in the step (1) is treated with an amorphous fluorine-based resin.

The amorphous fluorine-based resin may, for example, be a repeating unit having a fluorine-containing cyclic ether structure in the molecule. Specifically, it has the formula (B):

The amorphous fluorine-based resin of the repeating unit shown, or having the formula (C) and/or (D):

(In the formula, p represents an amorphous fluorine-based resin of a repeating unit represented by 1 or 2, and q represents 1 or 2).

An amorphous fluorine-based resin having a repeating unit represented by the formula (B), for example, selected from perfluoro-2,2-dimethyl-1,3-di Bismuth (2,2-bistrifluoromethyl-4,5-dichloro-1,3-di a comonomer and an amorphous copolymer of at least one of the group consisting of: (a) tetrafluoroethylene; (b) chlorotrifluoroethylene; (c) vinylidene fluoride; (d) hexafluoropropylene; (e) trifluoroethylene; (f) formula CF ₂ = CFOR _F [wherein, R _F is a normal peroxyalkyl group having 1 to 3 carbon atoms] perfluoro(alkylethylene (g) Formula CF ₂ = CFOQZ [wherein Q is a perfluorinated alkyl group containing an ether oxygen atom of 0 to 5; here, the atomic sum of C and O in Q is 2 to 10 ; Z is a group selected from the group consisting of -COOR, -SO ₂ F, -CN, -COF, and -OCH ₃ ; here, R is a C 1-4 alkyl fluoride fluoroether; (h) fluoroethylene ( CH ₂ =CHF); and (i) R _f CH=CH ₂ [wherein R _f is a positive peroxyalkyl group of C1-8] (perfluoroalkyl)ethylene.

Among the aforementioned a) to i), a) is preferably tetrafluoroethylene.

Among the monomers constituting the amorphous copolymer, 2,2-bistrifluoromethyl-4,5-dichloro-1,3-di 呃, generally 60~99% by mole, preferably 65~99% by mole, more preferably 65~90%. The comonomer (especially a) tetrafluoroethylene selected from at least one of the groups a) to i) is generally 40 to 1 mol%, preferably 35 to 1 mol%, more preferably 35. ~10%.

The glass transition temperature of the amorphous copolymer is at least 140 ° C, and is preferably 145 to 320 ° C, more preferably 150 to 280 ° C.

In particular, the amorphous copolymer preferably comprises 2,2-bistrifluoromethyl-4,5-dichloro-1,3-di Copolymer of hydrazine (PDD) and tetrafluoroethylene (TFE). The molar % of PDD and TFE is preferably the aforementioned. Specifically, the repeating unit represented by the formula (B) in the copolymer may be 60 to 99 mol%, preferably 65 to 99 mol%, more preferably 65 to 90 mol%, and the formula ( B1):

The repeating unit is shown to be 40 to 1 mol%, preferably 35 to 1 mol%, more preferably 35 to 10 mol% of the amorphous copolymer.

The amorphous fluororesin system can be used by those skilled in the art, such as Japanese Patent No. 2615176, Japanese Patent No. 2713867, and Japanese It is easy to carry out the preparation by the description of the Japanese Patent No. 3, 137, s, and the Japanese Patent No. 2003-514956 (WO 01/037044), or the like. In addition, the amorphous fluorine-based resin may be, for example, a commercially available product such as Teflon AF (manufactured by Du Pont-Mitsui Fluorochemicals Company, Ltd., Teflon is a registered trademark).

The amorphous fluorine-based resin having a repeating unit represented by the formula (C) and/or (D) is a group of repeating units represented by the formula (C) and/or (D) in nature (a) ) a compound consisting of.

The amorphous fluorine-based resin is a compound having an intrinsic viscosity of at least 0.1. The molecular weight system is generally exemplified by 50,000 to 500,000, preferably from 100,000 to 200,000.

The glass transition temperature of the amorphous fluorine-based resin may be, for example, at least 100 ° C, preferably from 100 to 200 ° C, more preferably from 100 to 150 ° C.

The amorphous fluorine-based resin can be exemplified by a group of repeating units (a) which are induced by perfluoropropenyl vinyl ether and/or perfluorobutenyl vinyl ether, and are particularly essentially a group of repeating units ( a) and general formula: -(CF ₂ -CFX)-

(wherein X is selected from the group consisting of F, Cl, -O-CF ₂ CF ₂ CF ₃ , -O-CF ₂ CF(CF ₃ )OCF ₂ CF ₂ SO ₂ F, -O-CF ₂ CF ₂ CF ₂ COOCH ₃ ) A compound consisting of the group (b) of repeating units. The compound-based repeating unit (a) is 80 mol% or more, preferably 85 mol% or more, and more preferably 90 mol% or more of all the monomers constituting the amorphous copolymer.

In particular, the repeating unit (a) is preferably one which is induced by perfluorobutenyl vinyl ether (especially perfluoro(4-vinyloxy-1-butene) (BVE)). specific In the compound represented by the general formula (D), q is a repeating unit of 2.

The amorphous fluorine-based resin is a compound which cyclically polymerizes a monomer consisting of perfluorobutenyl vinyl ether (particularly, perfluoro(4-vinyloxy-1-butene) (BVE)). More preferably, a compound in which perfluorobutenyl vinyl ether (especially BVE) is cyclically polymerized is preferred.

An amorphous fluorine-based resin having a repeating unit represented by the above formula (C) and/or (D), and further preferably having a substituent containing a carboxyl group (-COOH), or a formula (E): -CONH-R ³ -Si(OR ⁴ ) ₃ (E)

(wherein, R ³ represents a link, and R ⁴ represents a lower alkyl group) is a substituent represented by a moiety. The substituent containing the carboxyl group or the substituent containing the moiety represented by the formula (E) is preferably bonded to the terminal (especially both ends) of the lock-shaped amorphous fluorine-based resin.

The link represented by R ³ is not particularly limited as long as it is a bondable ruthenium and a divalent group of a nitrogen atom, such as ethylene (-CH ₂ CH ₂ -), propyl (-CH ₂ CH ₂ CH ₂ -), and a C2~6 alkylene group of a straight or branched chain of butyl (-CH ₂ CH ₂ CH ₂ CH ₂ -), pentyl (-CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ -), etc. Propyl.

The lower alkyl group represented by R ⁴ may, for example, be a C1 to 6 alkyl group of a straight or branched chain, and is preferably a linear or branched chain such as a methyl group, an ethyl group, a n-propyl group, an isopropyl group or a n-butyl group. C1~4 alkyl, more preferably methyl or ethyl.

The moiety represented by the formula (E) is preferably -CONH-(CH ₂ ) ₃ -Si(OMe) ₃ or -CONH-(CH ₂ ) ₃ -Si(OEt) ₃ .

Among the amorphous fluorine-based resins, an amorphous fluorine-based resin having a repeating unit represented by the formula (D) (wherein q is 2) is preferable, and more preferably, it may be exemplified. An amorphous fluorine-based resin having a substituent represented by a moiety represented by the formula (E) (wherein R ³ represents a propyl group and R ⁴ represents a methyl group or an ethyl group) is provided at both ends.

An amorphous fluorine-based resin having a repeating unit represented by the above formula (C) and/or (D), which can be easily obtained by the person skilled in the art, as described in Japanese Laid-Open Patent Publication No. Hei No. No. No. No. No. Hei. modulation. Further, the amorphous fluorine-based resin is commercially available, such as amorphous fluororesin (CYTOP A TYPE, CYTOP M TYPE, CYTOP S TYPE (made by ASAHI GLASS CO., LTD), preferably CYTOP A TYPE, CYTOP M TYPE, More desirable is CYTOP M.

The amorphous fluorine-based resin is used in the form of a solution. This solution can be prepared by diluting an amorphous fluorine-based resin with a solvent. The solvent is not particularly limited as long as it can dissolve the amorphous fluorine-based resin, and is preferably a fluorine-based inert liquid. The fluorine-based inert liquid system may be a known one, such as a perfluorocarbon (FC-87, FC-72, FC-84, FC-3283, FC-40, FC-43, FC-70, etc.) or a mixture thereof, specifically In the above, 3M electronic fluorine (Fluorinet) (manufactured by Sumitomo 3M Limited) can be exemplified. The concentration of the amorphous fluorine-based resin in the solution is generally 0.1 to 10% by mass, preferably 0.2 to 6% by mass, and more preferably 0.5 to 5% by mass.

A solution containing an amorphous fluorine-based resin is applied to the surface of the glass member pretreated by the above step (1) (particularly, the inner surface of the glass container). The coating method is not particularly limited, and conventional coating such as dipping, spraying, brushing, filling a solution, and spin coating into a container may be employed. method. After being applied to the surface of the glass member (especially the inner surface of the glass container), the excess solution is removed by centrifugation or the like as needed, and then dried. The drying step is generally carried out at a temperature of from room temperature to 150 ° C for about 1 minute to 60 minutes. After that, it is preferable to carry out heat treatment (baking), and it is generally carried out at a temperature of 150 to 270 ° C (preferably 200 to 250 ° C) for 5 minutes to 100 minutes (preferably 20 minutes to 60 minutes).

The film thickness of the amorphous fluorine-based resin film obtained in the step (2) is usually 0.1 to 200 μm, preferably 0.5 to 150 μm, more preferably 1 to 100 μm, and particularly preferably 2 to 50 μm.

The film thickness of the coating film obtained by the steps (1) and (2) is generally 0.1 to 200 μm, preferably 0.5 to 150 μm, more preferably 1 to 100 μm, and particularly preferably 2 to 50 μm.

The film thickness described above can be cut by a cutter to cut a glass member or a glass container, and the cut surface can be observed with a microscope.

The glass member or glass container of the present invention is produced as described above. In particular, when it is used as a medical glass container, since the inner surface is coated with an amorphous fluorine-based resin, it has excellent water resistance, powder resistance, chemical stability, and hot water resistance. Moreover, since the adhesion between the amorphous fluorine-based resin and the glass surface is remarkably improved by the decane coupling agent, it has excellent heat resistance, water resistance, alkali resistance, delamination resistance, and the like. This can be considered as a quenching effect of a decane coupling agent for strongly bonding (hydrogen bonding, covalent bonding) of an amorphous fluorine-based resin and a glass surface.

In particular, for the glass surface, treatment is carried out by a decane coupling agent having a group represented by the general formula (A2) or the general formula (A3) in terms of R ² , and secondly, by having a repeat represented by the formula (B) It is preferable that the film obtained by treating the amorphous fluorine-based resin of the unit is obtained. The reason for this is that an amine group having a positive charge (positive charge distribution) of a decane coupling agent and a cyclic ether portion having a negative charge (negative charge distribution) of an amorphous fluorine-based resin are electrostatic mutual Further, since the radicals R ²¹ , R ²² and/or R ²³ derived from the decane coupling agent and the hydrofluorocarbon compound of the amorphous fluorine-based resin have a hydrophobic interaction, a strong leveling effect can be exhibited.

Thus, the surface treated glass member or the glass container of the present invention can satisfy extremely high requirements (such as water resistance, powder resistance, heat resistance, water resistance, and the like when accommodating medicines for pharmaceuticals, inspection drugs, and the like. It is useful as a medical glass container because it is resistant to alkali or the like, and has low adsorption property of a pharmaceutical product such as a protein preparation. The container may be in the form of a container for injections such as a glass bottle, an ampoule, or a syringe.

The form of the preparation of the pharmaceutical product and the test drug to be contained is not particularly limited, and may be any of a liquid preparation, a suspension, an emulsion, a gel preparation, a powder preparation, and a freeze-dried preparation. Further, the types of the medicines to be contained and the medicines to be inspected are not particularly limited, and a wide variety of types can be used.

The present invention also provides a glass container in which a medicine containing a medicine or an inspection medicine is contained in the medical glass container. When a medicine is administered, a syringe (injector) or the like can be used, and a medicine contained in a medicine storage glass helium can be taken and administered. In addition, in the case of use, the sterilizing water for injection can be injected into the drug storage glass container to prepare a liquid preparation such as a solution or a suspension, and the solution can be administered by suction using a syringe (injector) or the like.

Example

Hereinafter, the present invention will be specifically described by way of Examples and Comparative Examples, but the present invention is not limited thereto.

The following examples of the decane coupling agent and the amorphous fluororesin used in the following experiments were used.

<decane coupling agent>

‧Trimethoxyphenyl decane (KBM-13, Shin-Etsu Chemical Co., Ltd.)

‧3-Aminopropyltrimethoxydecane (KBE-903, manufactured by Shin-Etsu Chemical Co., Ltd.)

<Amorphous fluorine-based resin>

‧"Teflon AF"...Teflon/Perfluoroethylene Rhodium copolymer (TFE/PDD; Teflon AF1600, Tg: 160 ° C). A solution of a 6 wt% fluorine-based solvent (HFE) of Teflon AF (Teflon AF 1601 SOL FC, manufactured by Du Pont-Mitsui Fluorochemicals Company, Ltd.).

‧ "CYTOP M"... a copolymer having a repeating unit containing a perfluorotetrahydrofuran ring in the main chain and having a substituent having a moiety represented by the formula: -CONH~Si(OEt) ₃ at the end (CYTOP M, ASAHI) GLASS CO., LTD)

Example 1

(1) Pretreatment of decane coupling agent

The decane coupling agent (KBE-903, 3-aminopropyltrimethoxydecane) was diluted with purified water to prepare a solution having a decane coupling agent concentration of 0.5% by weight. This solution was applied to the inner surface of a glass bottle (20 mL of content, made of borosilicate glass, the same below), centrifuged, and discharged, and then dried at 100 ° C. The glass bottle treated with the decane coupling agent was produced by a minute calcination treatment.

(2) Fluorocarbon resin coating

The amorphous fluorine-based resin (Teflon AF) was diluted with a fluorine-based inert liquid (electron fluorinated liquid FC-40, manufactured by Sumitomo 3M Limited) to prepare a solution having an amorphous fluorine-based resin concentration of 4%.

This solution was applied to the inner surface of a glass bottle treated with the decane coupling agent obtained in the above (1), centrifuged, and discharged, and then calcined at 150 ° C for 20 minutes and at 250 ° C for 30 minutes. Manufacture of internally treated glass bottles.

The surface of the bottle of the surface-treated glass bottle was cut with an electric cutter, and the cut surface was observed with a microscope, and the film thickness of the coating layer was measured. The film thickness was 27 μm (refer to Fig. 4).

Example 2

The amorphous fluorine-based resin (CYTOP M) was diluted with a fluorine-based inert liquid (electron fluorinated liquid FC-40, manufactured by Sumitomo 3M Limited) to prepare a solution having an amorphous fluorine-based resin concentration of 4%.

This solution was applied to the inner surface of a glass bottle treated with the decane coupling agent obtained in (1), centrifuged, and discharged, and then calcined at 100 ° C for 20 minutes and at 250 ° C for 30 minutes. Treatment, manufacture of inner surface treated glass bottles.

Example 3

(1) Pretreatment of decane coupling agent

The decane coupling agent (KBM-13, trimethoxyphenyl decane) was diluted with purified water, and acetic acid was added thereto to adjust to pH 4, and the concentration of the decane coupling agent was adjusted to 2.0. % by weight solution. This solution was applied to the inner surface of a glass bottle, centrifuged, and discharged, and then baked at 200 ° C for 30 minutes to produce a glass bottle treated with a decane coupling agent.

(2) Fluorocarbon resin coating

The amorphous fluorine-based resin (Teflon AF) was diluted with a fluorine-based inert liquid (electron fluorinated liquid FC-40, manufactured by Sumitomo 3M Limited) to prepare a solution having an amorphous fluorine-based resin concentration of 1%.

This solution was applied to the inner surface of a glass bottle treated with the decane coupling agent obtained in the above (1), centrifuged, and discharged, and then baked at 150 ° C for 20 minutes and at 250 ° C for 30 minutes to produce. Glass bottle treated internally.

Example 4

The amorphous fluorine-based resin (CYTOP M) was diluted with a fluorine-based inert liquid (electron fluorinated liquid FC-40, manufactured by Sumitomo 3M Limited) to prepare a solution having a concentration of the amorphous fluorine-based resin of 1%.

This solution was applied to the inner surface of a glass bottle treated with the decane coupling agent obtained in (1) of Example 3, centrifuged, and discharged, and then calcined at 100 ° C for 20 minutes and 180 ° C for 30 minutes. Treatment, manufacture of inner surface treated glass bottles.

Comparative Example 1 (direct coating of amorphous fluorine-based resin)

The glass bottle was not treated with a decane coupling agent (Example 1 (1)), and directly treated with an amorphous fluorine-based resin (Teflon AF) according to Example 1 (2) to produce an internally treated glass. bottle.

Comparative Example 2 (coating only 矽)

A solution of dimethyloxy acrylate (KM-740, dimethylpolysiloxane concentration of 35%, Shin-Etsu Chemical Co., Ltd.) was diluted with purified water to prepare a solution having a concentration of 1% dimethylpolysiloxane.

This solution was applied to the inner surface of an untreated glass bottle, centrifuged, and discharged, and then baked at 300 ° C for 30 minutes to produce an inner surface treated glass bottle.

Comparative Example 3 (raw glass bottle)

An untreated glass bottle (content amount 20 mL, borosilicate glass) was used.

Test example 1

A glass bottle (hereinafter referred to as a coated glass bottle) surface-treated with the examples and the comparative examples was supplied to the following test. The test results are shown in Tables 1-3.

(1) Visual inspection

The inner surface of the glass bottle was visually observed under an inspection lamp and evaluated.

◎: no coating unevenness and transparency

○: There is only a little uneven and opaque part, no problem

×: A considerable amount of uneven coating and opacity (whitening)

(2) Water resistance evaluation

Purified water was filled into a coated glass bottle to visually evaluate the water resistance of the inner surface of the glass bottle.

◎: the water resistance of the inner surface of the glass bottle is uniform

○: The inner surface of the glass bottle is substantially uniform in water resistance.

×: uneven water resistance on the inner surface of the glass bottle

(3) Evaluation of powder resistance

After the fine powder (mixed vitamin micropowder, particle size of about 1 to 30 μm) was slightly filled into the coated glass bottle, the adhesion of the fine powder on the inner surface of the glass bottle was visually evaluated.

◎: The powder is almost not attached to the inner surface of the glass bottle.

○: Only a few micro-body is attached to the inner surface of the glass bottle

×: A large amount of powder adheres to the inner surface of the glass bottle

(4) Dry heat durability evaluation

The coated glass bottle was subjected to a dry heat test at 250 ° C for 30 minutes. The film peeling and water resistance after the test were evaluated.

◎: no film peeling and water resistance

○: There is only some film peeling and/or poor water resistance, no problem

×: There is film peeling and water resistance

(5) Ultrasonic wash resistance (US resistance) evaluation

The coated glass bottle was ultrasonically treated in purified water under ultrasonic wave treatment (using a 28 KHz washing machine) at 25 ° C for 40 seconds. Evaluation of film peeling and water resistance after the test.

◎: No increase in insoluble particles

○: There is only a little increase in insoluble particles, no problem

×: Confirmation of an increase in insoluble particles

(6) Evaluation of hot water resistance

The purified water was filled in a coated glass bottle and heat-treated at 121 ° C for 60 minutes. Evaluation of film peeling and water resistance after the test.

◎: no film peeling and water resistance

○: There is only some film peeling and/or poor water resistance, no problem

×: There is film peeling and water resistance

(7) Evaluation of alkali resistance

A 0.05 mol/L sodium hydroxide aqueous solution was added to purified water to adjust to pH 9, and the mixture was filled in a coating glass bottle, and heat-treated at 121 ° C for 60 minutes. Evaluation of film peeling and water resistance after the test.

◎: no film peeling and water resistance

○: There is only some film peeling and/or poor water resistance, no problem

×: There is film peeling and water resistance

(8) Evaluation of dissolved metal concentration from glass

Purified water, a buffer (phthalic acid buffer, phosphate buffer, and borate buffer) were filled in a coated glass bottle, and heat-treated at 121 ° C for 60 minutes. The concentration of metal ions (Na, B, Al, Si, Ca, and Ba) eluted from the inner surface of the glass bottle into the test liquid was measured. The Na system uses an atomic absorption spectrometry (AAS) device, and the other metals are measured using an inductively coupled plasma atomic emission spectrometry (ICP-AES) device. The results are shown in Table 3. The unit is ppm.

(9) Evaluation of dissolved fluorine concentration from glass

The purified water was filled in a coated glass bottle and heat-treated at 120 ° C for 60 minutes. The concentration of fluoride ion (F ^- ) eluted into the water from the inner surface of the glass bottle was measured. Fluoride ions (F ^- ) were measured by ion chromatography. The results are shown in Table 4. The unit is ppm.

In Tables 1 to 3, the glass bottles of Examples 1 to 4 were coated with a predetermined decane coupling agent and an amorphous fluorine-based resin, thereby exhibiting excellent effects. (water resistance, powder resistance, heat resistance, water resistance, alkali resistance, etc.). In particular, it has been found that when Teflon AF is used as the amorphous fluorine-based resin, the aforementioned effects are remarkably excellent.

On the other hand, when the amorphous fluorine-based resin was directly applied to the surface of the glass without being treated with a decane coupling agent (Comparative Example 1), it was confirmed that the hot water resistance and the alkali resistance were inferior, and the concentration of various metals eluted from the glass was increased.

In addition, in the untreated raw material glass bottle (Comparative Example 3) and the conventionally treated glass bottle (Comparative Example 2), it was confirmed that the hot water resistance and the alkali resistance were largely deteriorated, and the metal concentration eluted from the glass became Extremely high.

From Table 4, the glass bottle of Example 1 was coated with a fluorine-based resin, and the eluted fluoride ion was below the detection limit.

Test example 2

The glass bottle (coated glass bottle 1) which was surface-treated in Example 1 and supplied to the "(4) dry heat durability evaluation" glass bottle (coated glass bottle 2) in Test Example 1 or For the same treatment as the glass bottle supplied to "(4) Dry heat durability evaluation", a glass bottle (coated glass bottle 3) which was sterilized by damp heat at 121 ° C for 20 minutes was applied, and the density of the coated film was evaluated. Strength.

Cut the lower part of the bottle body of the glass bottle 1~3, and take the slice of the bottom of the glass bottle. For the inner surface (coating surface) of the bottom of the sliced glass bottle, a cellophane tape ((Scotch tape CT-15S manufactured by Nichiban Co., Ltd., width 15 mm) was attached, and the end of the cellophane tape was held, relative to the bottom. The surface was strongly peeled off once in the vertical direction.

For each of the coated glass bottles 1 to 3 after the above treatment, the water droplets were dropped, and the contact angle measuring instrument was used (Kyowa Interface Science). The contact angle was measured by CAX-150 (FAMAS) manufactured by Co., Ltd.). The result is shown in Fig. 5. The contact angle of the coated glass bottle 1 immediately after manufacture was 114.6°, and the contact angles after peeling treatment of the cellophane tape for the coated glass bottles 1 to 3 were 116.2°, 118.8°, and 119.5°, respectively.

In this way, the glass bottle (coated glass bottle 2) supplied to the "(4) dry heat durability test" can be confirmed by almost no change in the contact angle, and the supply to "( 4) The glass bottle of the dry heat durability evaluation is treated in the same manner, and then a glass bottle (coated glass bottle 3) which is sterilized by damp heat at 121 ° C for 20 minutes is applied, and the adhesion strength of the film is applied to the coated glass bottle. 1 is almost unchanged.

Test Example 3

For the glass bottle (coated glass bottle 1) which was surface-treated in Example 1, the impact resistance of the coated film was evaluated.

After measuring the empty weight of the coated glass bottle 1, a 70% aqueous solution of granulated sugar was filled to about 15 ml, and the weight was measured. A whole aqueous solution of granulated sugar was taken using a syringe with a needle, and then the weight of the glass bottle was measured (n = 5). The aqueous sugar solution adhered to the glass bottle which can obtain the difference between the two was 0.015 g.

2.5 g of glass beads (Φ 1.5 to 2.5 mm) was filled into the coated glass bottle 1 and stoppered with a rubber stopper. Hold the thin neck of the glass bottle and shake the bottom of the bottle to the palm of your hand for 50 times. The glass beads were taken out, washed and dried. After measuring the empty weight of the glass bottle, a 70% aqueous solution of granulated sugar was filled to about 15 ml, and the weight was measured. Aspirate the entire sucrose solution using a needle-attached syringe, and then measure the weight of the glass bottle. The aqueous sugar solution adhered to the glass bottle which can obtain the difference between the two was 0.014 g.

Thereby, the adhesion amount of the aqueous solution of the granulated sugar does not change regardless of the impact of the glass beads, and therefore, it is confirmed that the film on the inner surface of the glass bottle is not damaged. Accordingly, it has been found that the coated glass bottle 1 is a medical glass container having an impact strength which is practically problem-free.

Test Example 4

With respect to the glass bottles of Example 1, Comparative Example 2, and Comparative Example 3, the protein adsorption property of the coated film was evaluated.

Preparation of protein, bovine serum, bovine serum globulin (BSA) (amino acid residue number: 607, molecular weight 69.293, average amino acid molecular weight M ≒ 114) and 0.1 M citrate buffer at pH 6.2 A sample of 5 × 10 ^-3 (amino acid) mol / 1 (≒ 0.56 mg / m 1 ).

15.6 ml of each sample was placed in a glass bottle and sealed with a rubber stopper (the wetted area of the sample with the inner surface of the glass bottle was 28.8 cm ² ), and allowed to stand at 5 ° C for 7 days. Thereafter, the absorbance (ABS ₂₈₀ ) of the sample at the beginning and after 7 days was measured using a spectrophotometer (V-560 manufactured by JASCO Corporation), and the residual ratio of BSA in the sample was calculated.

Before the above measurement, a) 5.253 × 10 ^-3 (amino acid) mol / 1, b) 2.122 × 10 ^-3 (amino acid) mol / 1, c) 1.599 × 10 ^-3 (amino acid) mol /1,d)1.052×10 ^-3 (amino acid) mol / 1, e) 0.839 × 10 -3 ( amino acid) mol / 1, and f) 0.526 × 10 ^-3 (amino acid) mol / The BSA solution of 1 was measured for absorbance in the same manner as described above to prepare a calibration curve. Thereby, the molar absorption coefficient of the MSA of the BSA solution was obtained (Fig. 6).

The absorbance measurement results of the respective samples in the glass bottles of Example 1, Comparative Example 2, and Comparative Example 3 are shown in Fig. 7 . Also, the BSA in each sample The residual ratios are shown in Table 5 and Figure 8.

BSA residual rate (%) = (concentration after 7 days) / (filling liquid (starting) concentration) × 100

As a result, in the glass bottles of Example 1, it was confirmed that the amount of absorption of the protein was lowered as compared with the glass bottles of Comparative Examples 2 and 3.

Claims (14)

A method for producing a glass member, characterized by comprising: (1) a step of treating a surface of a glass member with a decane coupling agent and/or a partial hydrolyzate thereof; and (2) treating the surface obtained by the step (1) with The step of treating the amorphous fluorine-based resin. The manufacturing method according to claim 1, wherein the glass member is a glass container, and comprises: (1) a step of treating the inner surface of the glass container with a decane coupling agent and/or a partial hydrolyzate thereof; and 2) a step of treating the treated surface obtained in the step (1) with an amorphous fluorine-based resin. The production method according to claim 1 or 2, wherein the decane coupling agent is of the general formula (A): (R ¹ O) _4-n SiR ² _n (A) (wherein n represents 1, 2 or 3 R ¹ represents a lower alkyl group, and R ² represents a compound represented by a lower alkyl group which may have an amino group or an amine lower alkylamino group as a substituent. The production method according to claim 3, wherein the decane coupling agent is a compound of the following formula (A), that is, n represents 1, R ¹ represents a C 1-3 alkyl group, and R ² represents an amine group. Or a C2-6 alkyl group having an amino group C2~4 alkylamine as a substituent. The manufacturing method according to claim 1 or 2, wherein the aforementioned amorphous fluorine system The resin is a repeating unit having a fluorine-containing cyclic ether structure. The production method according to claim 5, wherein the amorphous fluorine-based resin has the formula (B): The repeating unit shown. The production method according to claim 6, wherein the amorphous fluorine-based resin contains 60 to 99 mol% of a repeating unit represented by the formula (B), and 40 to 1 mol% of the formula (B1): The repeating unit shown. The production method according to claim 5, wherein the amorphous fluorine-based resin has the formula (C) and/or (D): (wherein, p represents 1 or 2, and q represents 1 or 2). The production method according to claim 8, wherein the amorphous fluorine-based resin having a repeating unit represented by the above formula (C) and/or (D) has a substituent containing a carboxyl group or contains the formula (E) :-CONH-R ³ -Si(OR ⁴ ) ₃ (E) (wherein R ³ represents a link, and R ⁴ represents a lower alkyl group). The production method according to claim 9, wherein the end of the amorphous fluorine-based resin having the repeating unit represented by the above formula (C) and/or (D) has a portion represented by the formula (E) Substituent. A glass member obtained by the production method according to any one of the above claims 1 to 10. The glass member described in claim 11 is a medical glass container. A medical glass container containing a drug is a medical glass container according to claim 12, and is configured to store a pharmaceutical product or an inspection drug. The glass member according to claim 11 is selected from the group consisting of a glass container, a glass plate, a glass meter, a glass chemical analysis instrument, a glass chemical synthesis device, a glass medical device, and a glass optical member. At least one of the groups.