JP2017057096A - Glass tube for medical container - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a glass tube for a medical container which is a borosilicate glass containing no BaO and can maintain excellent chemical durability or hydrolysis resistance even after various heat treatment in a processing process.SOLUTION: A glass tube for a medical container is formed of borosilicate glass containing, by mass%, SiOof 65 to 80%, AlOof 5 to 15%, BOof 2 to 12%, NaO of 3 to 10%, KO of 0 to 5%, LiO of 0 to 5%, MgO of 0 to 5%, CaO of 0 to 5%, SrO of 0 to 5% with a value of AlO/(NaO+KO+LiO+MgO+CaO+SrO+BO) of 0.35 to 0.60 by mass ratio, practically has no BaO, and has a value of (atomic concentration of Na)/(atomic concentration of Na+atomic concentration of Si) in a region by 200 nm depth from an inner surface of the glass tube of 0.01 to less than 0.5.SELECTED DRAWING: Figure 2

Description

  The present invention relates to a glass tube for a pharmaceutical container used for glass for tubes such as vials and ampoules and syringes for syringes.

Borosilicate glass for pharmaceutical containers such as vials and ampoules is required to have the following characteristics.
(A) Components in the chemical solution to be filled do not react with components in the glass (b) Chemical durability and hydrolysis resistance are high so as not to contaminate the chemical solution to be filled. (C) Low coefficient of thermal expansion so that damage due to thermal shock is unlikely to occur during the manufacturing process of glass tubes and processing into vials, ampoules, etc. (d) vials, After processing into ampoules, the amount of heat during processing can be reduced so that the inner surface of the container does not deteriorate due to evaporants from the glass, etc.Standard borosilicate glass for pharmaceutical containers that satisfies these required characteristics _{SiO 2, B 2 O 3,} Al 2 O 3, Na 2 O, K 2 O, CaO, contains a BaO and a small amount of fining agents.

JP2014-214084

  In recent years, development of chemicals to be filled has progressed, and chemicals with higher medicinal effects are being used. Some of these chemical solutions are chemically unstable, easily denatured, and have high reactivity with glass. Accordingly, borosilicate glass for pharmaceutical containers constituting vials and ampoules is required to have higher chemical durability and hydrolysis resistance than ever before. Further, when the glass contains BaO, barium feldspar crystals are likely to precipitate due to the reaction with the alumina refractory when the glass is melted, and the productivity is lowered, and Ba ions eluted from the glass are sulfate ions in the chemical solution. May generate insoluble precipitates.

  Under such circumstances, for example, Patent Document 1 proposes a glass that does not contain BaO and has high hydrolysis resistance. Moreover, in patent document 2, when manufacturing glass, the manufacturing method of glass with few bubbles is proposed by fuse | melting on the conditions suitable for a clarifying agent.

By the way, pharmaceutical containers such as vials and ampoules are produced by locally heating a glass tube with a burner and processing it. When this burner is heated, B ₂ O ₃ or Na ₂ O in the glass evaporates and condenses on the inner surface of the medicine container, and a heterogeneous layer may be formed. When the heterogeneous layer is formed, the chemical durability and hydrolysis resistance of the glass are substantially reduced, and B ₂ O ₃ and Na ₂ O are removed from the heterogeneous layer during storage of the chemical solution or during autoclaving after filling the chemical solution. Elution may cause changes in chemical solution components and changes in the pH of the chemical solution. In particular, a glass that does not contain BaO as in Patent Document 1 has a lower workability than a glass that contains BaO, and thus requires a larger amount of heat than before when processing containers. As a result, the amount of evaporation of B ₂ O ₃ and Na ₂ O from the glass tends to increase.

The formation of the heterogeneous layer also causes the inner surface of the container to peel off and insoluble foreign matter called flakes to be generated in the chemical solution. Patent Document 1 proposes a glass in which the addition amount of K ₂ O is adjusted in order to improve hydrolysis resistance. However, K ₂ O is easy to evaporate and at the same time, evaporates B ₂ O ₃ and Na ₂ O. The effect of suppressing cannot be expected. Therefore, like B ₂ O ₃ and Na 2 _O when burner heating for processing into a pharmaceutical container evaporates, is formed heterogeneous layers in a pharmaceutical container inner surface, B ₂ O ₃ and Na 2 _O, etc. are eluted from the heterogeneous layer However, there is a concern that the chemical solution may be deteriorated, the pH of the chemical solution may be increased, or flakes may be generated.

  An object of the present invention is to provide a glass tube for a pharmaceutical container that is a borosilicate glass that does not contain BaO and can maintain excellent chemical durability and hydrolysis resistance even after various heat treatments in the processing step. is there.

As a result of various experiments conducted by the inventors, the conventional glass tube has a high Na ₂ O content near the surface, which is related to the formation of the heterogeneous layer, and the Na ₂ O content. The increase in the temperature was caused by elution of the Na ₂ O component from the refractories used at the time of forming the glass tube, and the present invention was proposed.

The glass tube for pharmaceutical containers of the present invention is SiO ₂ 65-80%, Al ₂ O ₃ 5-15%, B ₂ O ₃ 2-12%, Na ₂ O 3-10%, K ₂ O 0 by mass%. _{~5%, Li 2 O 0~5%} , 0~5% MgO, CaO 0~5%, containing SrO 0 to 5%, by weight ratio _{Al 2 O 3 / (Na 2} O + K 2 O + Li 2 O + MgO + CaO + SrO + B 2 O ₃ ) The value of 0.35 to 0.60 is made of borosilicate glass substantially free of BaO, and in the region from the inner surface of the glass tube to a depth of 200 nm (atomic concentration of Na) / The value of (Na atomic concentration + Si atomic concentration) is 0.01 to less than 0.5. “Al ₂ O ₃ / (Na ₂ O + K ₂ O + Li ₂ O + MgO + CaO + SrO + B ₂ O ₃ )” means that the content of Al ₂ O ₃ is Na ₂ O, K ₂ O, Li ₂ O, MgO, CaO, SrO. And the value divided by the total content of B ₂ O ₃ content. Further, “substantially free of BaO” means that BaO is not actively added, and is not intended to exclude substances that are mixed as impurities. More specifically, it means that the content of BaO is 0.05% or less by mass%. Further, “(Na atomic concentration) / (Na atomic concentration + Si atomic concentration)” is a value obtained by dividing the atomic concentration of Na by the sum of the atomic concentration of Na and the atomic concentration of Si, and is 200 nm from the glass surface. It means the maximum value in the region up to the depth of.

  According to the above configuration, since it does not contain BaO, barium feldspar crystals do not precipitate due to the reaction between BaO and alumina refractory during glass melting or molding. Moreover, the elution of Ba ions from the glass is small, and a glass that hardly forms an insoluble precipitate with sulfate ions in the chemical solution can be obtained.

According to the above arrangement, since the optimizing the concentration of Na 2 _O near the surface, it is possible to suppress evaporation of like B ₂ O ₃ and Na 2 _O in the glass during the burner heating, formation of heterogeneous layer Can also be suppressed. At the same time, excellent chemical durability and hydrolysis resistance can be maintained even after various heat treatments during processing of the container, and alteration of chemical components, pH increase, and occurrence of flakes can be suppressed.

In the present invention, it is preferable that the content of Al ₂ O ₃ is 6.3 to 11% and MgO + CaO is 0 to less than 1%.

  According to the said structure, it becomes easy to obtain the glass excellent in hydrolyzability.

In the present invention, the value of a molar ratio _{(Na 2 O + K 2 O} + Li 2 O-Al 2 O 3) / B 2 O 3 is preferably made of borosilicate glass is 0.33 to 0.39. Note that “(Na ₂ O + K ₂ O + Li ₂ O—Al ₂ O ₃ ) / B ₂ O ₃ ” means the molar amount of Al ₂ O ₃ from the total amount of Na ₂ O, K ₂ O, and Li ₂ O. The value obtained by subtracting% is divided by the mol% of B ₂ O ₃ .

According to the above configuration, it becomes possible to lower the processing temperature when producing glass containers such as ampoules and vials from glass tubes, and the amount of evaporation of B ₂ O ₃ and alkali metal oxide components from the glass is significantly reduced. it can. As a result, excellent chemical durability and hydrolysis resistance can be maintained even after various heat treatments during container processing.

  In the present invention, in the powder test method of the hydrolysis resistance test according to EP 8.0, it consists of a borosilicate glass in which the consumption of 0.02 mol / L hydrochloric acid per unit glass mass is 0.030 mL or less. Is preferred.

In the present invention, in an acid resistance test according to DIN12116, it is preferably made of a borosilicate glass whose mass reduction amount per unit area is 1.0 mg / dm ² or less.

  According to the said structure, since elution of various components from glass and reaction with glass and a chemical | medical solution are suppressed, alteration of a chemical | medical solution component, pH rise of a chemical | medical solution, and generation | occurrence | production of flakes can be suppressed.

In this invention, it is preferable to consist of borosilicate glass which has a working temperature of 1150 degreeC-1250 degreeC. The working temperature is a temperature at which the viscosity of the glass is 10 ⁴ dPa · s.

According to the above configuration, it becomes possible to lower the processing temperature when producing glass containers such as ampoules and vials from glass tubes, and the amount of evaporation of B ₂ O ₃ and alkali metal oxide components from the glass is significantly reduced. it can. As a result, it is possible to avoid a situation in which the chemical solution components stored in the glass container are altered, the pH of the chemical solution is increased, and further, flakes are generated.

In the present invention, it is preferably made of borosilicate glass having a liquid phase viscosity of 10 ^4.5 dPa · s or more.

  According to the above configuration, even when the Danner method is adopted for forming the glass tube, it is difficult to devitrify during forming, which is preferable.

  The pharmaceutical container of the present invention is characterized by comprising the above borosilicate glass for a pharmaceutical container.

Sample No. 8 is a graph showing an analysis result of a concentration distribution of Na ₂ O near the surface of FIG. Sample No. ₂ is a graph showing an analysis result of Na ₂ O concentration distribution near the surface of 1. It is a graph which shows the result of the hydrolysis resistance test before and behind heat processing.

  The glass tube for pharmaceutical containers of the present invention is made of borosilicate glass substantially free of BaO. When BaO is contained in the glass composition, crystals are precipitated or precipitates are generated by reaction with the alumina-based refractory or by reaction of Ba ions eluted from the glass with sulfate ions in the chemical solution. There is a fear.

In the borosilicate glass constituting the glass tube for a pharmaceutical container of the present invention, although the hydrolysis resistance is improved, Al ₂ O ₃ which is a component for increasing the viscosity of the glass and the viscosity of the glass are decreased. Balancing the content of Na ₂ O, K ₂ O, Li ₂ O, MgO, CaO, SrO, and B ₂ O ₃ which are components that lower decomposition resistance improves hydrolysis resistance and processing temperature. It is desirable to achieve both reductions. Specifically, the value of Al ₂ O ₃ / (Na ₂ O + K ₂ O + Li ₂ O + MgO + CaO + SrO + B ₂ O ₃ ) by mass ratio is 0.35 to 0.60, preferably 0.35 to 0.50, more preferably 0. .36 to 0.50, and more preferably 0.37 to 0.50. When the value of Al ₂ O ₃ / (Na ₂ O + K ₂ O + Li ₂ O + MgO + CaO + SrO + B ₂ O ₃ ) is too small, the hydrolysis resistance of the glass decreases. Moreover, the amount of evaporation of B ₂ O ₃ and alkali metal oxide components from the glass during burner processing increases. If the value of Al ₂ O ₃ / (Na ₂ O + K ₂ O + Li ₂ O + MgO + CaO + SrO + B ₂ O ₃ ) is too large, the viscosity of the glass becomes high, and the processing temperature when producing glass containers such as ampoules and vials from the glass tube is high Thus, the amount of evaporation of B ₂ O ₃ and Na ₂ O in the glass during the heating of the burner increases.

In the glass tube for a pharmaceutical container of the present invention, the value of (Na atomic concentration) / (Na atomic concentration + Si atomic concentration) in a region from the inner surface of the glass tube to a depth of 200 nm is 0.01 to 0.00. It is less than 5, preferably 0.01 to less than 0.4, more preferably 0.01 to less than 0.3. If the value of (Na atomic concentration) / (Na atomic concentration + Si atomic concentration) in the region from the glass surface to a depth of 200 nm is too large, B ₂ O ₃ and alkali metal oxides from the glass during burner heating Increases evaporation of components. On the other hand, if the value of (Na atomic concentration) / (Na atomic concentration + Si atomic concentration) in the region from the glass surface to a depth of 200 nm is too small, flakes are likely to occur. In addition, the value of (Na atomic concentration) / (Na atomic concentration + Si atomic concentration) in the region from the glass surface to a depth of 200 nm is appropriate for the molding conditions of the glass tube and the type of refractory in contact with the glass. It can be adjusted by selecting. The atomic concentration of Na and the atomic concentration of Si can be quantified by, for example, X-ray photoelectron spectroscopy (ESCA).

  Further, the value of (Na atomic concentration) / (Na atomic concentration + Si atomic concentration) on the inner surface of the glass tube is X1, and (Na atomic concentration) / (Na atomic concentration + Si at a depth of 200 nm from the inner surface of the glass tube). When the value of (atomic concentration) is X2, the absolute value of (X1-X2) is preferably 0.1 to 0.3. If this value is not within the above range, flakes are likely to occur.

The composition of the borosilicate glass constituting the glass tube for a pharmaceutical container of the present invention is SiO ₂ 65-80%, Al ₂ O ₃ 5-15%, B ₂ O ₃ 2-12%, Na ₂ O 3 by mass%. _{~10%, K 2 O 0~5%} , Li 2 O 0~5%, 0~5% MgO, CaO 0~5%, a 0 to 5% SrO, containing _Al 2 _{O 3,} especially in mass% Preferably, the amount is 6.3-11% and MgO + CaO is less than 0-1%. Further, more specifically, _SiO 2 _70-75.5% by _{mass%, Al 2 O 3 6.3~11%} , B 2 O 3 3~11.5%, Na 2 O 4~8.5 _{%, K 2 O 0~5%,} Li 2 O 0~0.2%, less than 0 to 1% MgO, CaO less than 0 to 1%, SrO less than 0~4%, MgO + CaO is less than 0 to 1% It is preferable.

  Hereinafter, the reason why the composition range of each component is limited as described above will be described. In the following description, unless otherwise specified,% display means mass%.

SiO ₂ is one of the components constituting the glass network. The content of SiO ₂ is 65-80%, 62-75.5%, preferably 65-75.5%, 67-75%, especially 70-74.7%. preferable. When the content of SiO ₂ is too small decreases chemical durability, acid resistance required for the borosilicate glass for pharmaceutical containers is lowered. On the other hand, the liquidus viscosity is lowered when the content of SiO ₂ is too large, the productivity is easily devitrified in the manufacturing process is reduced.

Al ₂ O ₃ is a component that suppresses devitrification of glass and improves chemical durability and hydrolysis resistance. The content of Al ₂ O ₃ is 5-15%, exceeds 6.3-11%, 6.3%, 10% or less, 6.4-8.5%, particularly 6.4-8.3. % Is preferred. If the content of Al ₂ O ₃ is too small, the above effect cannot be obtained. On the other hand, when the content of Al ₂ O ₃ is too large, the viscosity of the glass increases, the working temperature increases, and the amount of evaporation of B ₂ O ₃ and Na ₂ O increases when processed into a pharmaceutical container. .

B ₂ O ₃ not only lowers the melting point of the glass but also increases the liquid phase viscosity and suppresses devitrification. Therefore, the content of B ₂ O ₃ is 2 to 12%, ₃ to 11.5%, 5.5 to less than 11.5%, 8.5 to less than 11.5%, particularly 9 to 11.5%. It is preferable that it is less than%. B and working temperature content is too low the ₂ O ₃ is increased, the evaporation amount of such B ₂ O ₃ and Na 2 _O in processing into pharmaceutical container becomes large. On the other hand, B ₂ when the content of O ₃ is too much resistance to hydrolysis and chemical durability is lowered.

Na ₂ O has the effect of reducing the viscosity of the glass and increasing the linear thermal expansion coefficient. The content of Na ₂ O is 3 to 10%, 3.2 to 8.5%, 3.5 to 8.3%, 4 to 8%, particularly 4 to 7%. If the content of Na ₂ O is too small, the working temperature increases, and the amount of evaporation of B ₂ O ₃ or Na ₂ O increases when processed into a pharmaceutical container. On the other hand, hydrolysis resistance is deteriorated when the content of Na 2 _O is too large.

K ₂ O, like Na ₂ O, has the effect of reducing the viscosity of the glass and increasing the linear thermal expansion coefficient. The content of K ₂ O is 0 to 5%, and is 0.1 to 5%, 0.5 to 4.5%, 1.0 to 3%, particularly 1.5 to 3.0%. preferable. K 2 When the content of _O is too large resistance to hydrolysis is reduced.

Note that it is desirable to use both components of K ₂ O and Na ₂ O because the hydrolysis resistance is improved by the mixed alkali effect. In order to improve the hydrolysis resistance, K ₂ O / Na ₂ O is 0.2 to 1, 0.20 to 0.95, 0.2 to 0.8, particularly 0.2 to 0 in terms of mass ratio. .7 is preferable. If this ratio is small, the hydrolysis resistance decreases. On the other hand, if this ratio is large, the working temperature increases, and the amount of evaporation of B ₂ O ₃ , Na ₂ O and the like increases when processed into a pharmaceutical container.

Li ₂ O has the effects of lowering the viscosity of the glass and increasing the linear thermal expansion coefficient, like Na ₂ O and K ₂ O. However, when Li ₂ O is added, the refractory is easily eroded when the glass is melted. It also leads to an increase in production costs. Therefore, the content of Li ₂ O is 0 to 5%, preferably 0 to 0.2%, 0 to 0.1%, 0 to 0.05%, particularly preferably 0 to 0.01%. If there are no special circumstances, it is desirable to use an alkali metal oxide other than Li ₂ O.

The total content of Li ₂ O, Na ₂ O and K ₂ O is preferably 5 to 10%, in particular 6 to 9%. When the total amount of these components is small, the working temperature becomes high. Moreover, when there are many total amounts of these components, chemical durability and hydrolysis resistance will fall.

  MgO has the effect of reducing the high temperature viscosity of the glass. In addition, there is an effect of improving chemical durability. The content of MgO is 0 to 5%, preferably 0 to less than 1%, particularly preferably 0 to 0.5%. When there is too much content of MgO, hydrolysis resistance will fall.

  CaO has the effect of reducing the high temperature viscosity of the glass. The content of CaO is 0 to 5%, preferably 0 to less than 1%, particularly preferably 0 to 0.5%. When there is too much CaO content, hydrolysis resistance will fall.

MgO + CaO is the total content of MgO and CaO, and is an important index for adjusting the high-temperature viscosity and hydrolysis resistance of glass to a preferred range. MgO + CaO is preferably 0 to 5%, 0 to less than 1%, particularly preferably 0 to 0.5%. If there is too much MgO + CaO, the high-temperature viscosity of the glass can be lowered, but the hydrolysis resistance of the glass decreases. SrO has the effect of improving chemical durability. The SrO content is 0 to 5%, preferably 0 to less than 4%, 0 to 2%, particularly preferably 0 to 1%. When there is too much content of SrO, hydrolysis resistance will fall.

  In the present invention, various components other than the above can be added.

TiO ₂ has the effect of improving hydrolysis resistance. The content of TiO ₂ is preferably 0 to less than 7%, 0 to 5%, 0 to 4%, particularly preferably 0 to 1.5%. If the content of TiO ₂ is too large, the working temperature increases, and the amount of evaporation of B ₂ O ₃ , Na ₂ O, etc. increases when processed into a pharmaceutical container.

ZrO ₂ has an effect of improving hydrolysis resistance. The content of ZrO ₂ is preferably 0 to less than 7%, 0 to 5%, 0 to 4%, particularly preferably 0 to 1.5%. Working temperature and the content of ZrO ₂ is too large increases, the amount of evaporation of such B ₂ O ₃ and Na 2 _O in processing into pharmaceutical container becomes large.

Since Fe ₂ O ₃ may color the glass and reduce the transmittance in the visible region, its content may be 0.2% or less, 0.1% or less, particularly 0.02% or less. preferable.

The _F as a fining _{agent, Cl, Sb 2 O 3,} SnO 2, may contain any one or more of such _Na 2 SO _4. The total content of these fining agents is preferably 3% or less, 1% or less, and particularly preferably 0.5% or less. Among these fining agents, it is preferable to use Cl or SnO ₂ for the reason that the melting temperature and the harm to the human body are small. When Cl is used, its content is preferably 3% or less, more preferably 1% or less, and particularly preferably 0.2% or less. When SnO ₂ is used, its content is 2% or less, preferably 0.5% or less.

In the present invention, a molar ratio _{(Na 2 O + K 2 O} + Li 2 O-Al 2 O 3) / the value of B 2 _{O 3} is, 0.33～0.39,0.33～0.37,0.33 It is preferable that it is -less than 0.36, especially 0.33-0.35. If this value is too large, the amount of evaporation of these substances increases due to the high content of alkali metal oxides such as Na ₂ O, K ₂ O, and Li ₂ O due to various heat treatments during processing. The decomposition temperature decreases or the B ₂ O ₃ content is low, so the working temperature becomes high, and alkali metal oxides such as Na ₂ O, K ₂ O, and Li ₂ O evaporate due to various heat treatments during processing. And the chemical durability and hydrolysis resistance are reduced. In addition, bubbles accompanying the vaporization of moisture are likely to occur. On the other hand, if this value is too small, the content of alkali metal oxides such as Na ₂ O, K ₂ O and Li ₂ O is low, so that the working temperature becomes high, and various heat treatments during processing cause Na ₂ O, K ₂ O, Li ₂ O, and B ₂ O ₃ are likely to evaporate, and chemical durability and hydrolysis resistance are reduced, and bubbles accompanying vaporization of water are easily generated, or the content of B ₂ O _{3 is} low. Therefore, chemical durability and hydrolysis resistance are reduced before processing the container.

  Moreover, it is preferable that the borosilicate glass which comprises the glass tube for pharmaceutical containers of this invention has the following characteristics.

  In the powder test method of the hydrolysis resistance test according to EP 8.0, the consumption of 0.02 mol / L hydrochloric acid per unit glass mass is preferably 0.030 mL or less, 0.028 mL or less, 0.026 mL or less. In particular, it is 0.025 mL or less. If the amount of hydrochloric acid consumed is too large, when a pharmaceutical container such as an ampoule or vial is prepared, filled with chemicals, and stored, the elution of glass components, especially alkali metal components, may increase significantly, causing chemical component alteration. .

In the acid resistance test according to DIN12116, the amount of mass reduction per unit area is preferably 1.0 mg / dm ² or less, particularly 0.8 mg / dm ² or less. When the amount of mass decrease increases, when a medical container such as an ampoule or vial is prepared, and a chemical solution is filled and stored, the elution amount of the glass component may greatly increase and the chemical solution component may be altered.

The working temperature is preferably 1150 ° C to 1250 ° C, 1150 ° C to 1240 ° C, and particularly preferably 1160 ° C to 1230 ° C. If the working temperature is too high, the processing temperature for producing a glass container such as an ampoule or a vial from the glass tube increases, and the amount of evaporation of B ₂ O ₃ and alkali metal oxide in the glass increases remarkably.

The liquid phase viscosity is 10 ^4.5 dPa · s or more, 10 ^5.0 dPa · s or more, 10 ^5.2 dPa · s or more, 10 ^5.4 dPa · s or more, particularly 10 ^5.6 dPa · s or more. It is preferable that When the liquid phase viscosity is low, devitrification is likely to occur during glass tube forming by the Danner method, and productivity is reduced.

The linear thermal expansion coefficient is preferably 45 to 58 × 10 ⁻⁷ / ° C., more preferably 48 to 55 × 10 ⁻⁷ / ° C. The coefficient of linear thermal expansion is an important characteristic regarding the thermal shock resistance of glass, and in order for the glass to obtain sufficient thermal shock resistance, this value needs to be within the above range. In addition, the linear thermal expansion coefficient in this invention means the linear thermal expansion coefficient in the temperature range of 30-380 degreeC.

  Next, a method for producing the glass tube for a pharmaceutical container of the present invention will be described. The following description is an example using the Danner method.

First, a glass batch is prepared by blending glass raw materials so as to have the above glass composition. Next, the glass batch was continuously charged into a melting furnace at 1550 to 1700 ° C., melted and clarified, and then the obtained molten glass was wound around a rotating refractory while blowing air from the tip of the refractory, Glass is pulled out from the tip portion into a tubular shape. Here, if a material having a low Na ₂ O content or a material in which the Na ₂ O component hardly elutes from the surface is selected as the refractory to be used, Na near the surface of the inner surface of the obtained glass tube (and glass container) is obtained. The content of ₂ O can be reduced.

  Subsequently, the drawn tubular glass is cut into a predetermined length to obtain the glass tube for a pharmaceutical container of the present invention. The glass tube thus obtained is used for manufacturing vials and ampoules.

  In addition, you may manufacture the glass tube for pharmaceutical containers of this invention not only with the Danner method but using the conventionally well-known arbitrary methods. For example, the bellows method and the downdraw method are also effective methods for producing the glass tube for a pharmaceutical container of the present invention.

  Hereinafter, the present invention will be described based on examples.

Table 1 shows Examples of the present invention (Sample Nos. 1 to 6) and Comparative Examples (Sample Nos. 7 and 8). In the table, “ΣR ₂ O” represents “K ₂ O + Na ₂ O + Li ₂ O”, and “ΣRO)” represents “MgO + CaO + SrO”.

  1 and 2 show analysis results of (Na atomic concentration) / (Na atomic concentration + Si atomic concentration) in a region from the glass surface to a depth of 200 nm. 8 and FIG. It is the analysis result of 1.

  Each sample was prepared as follows.

  First, glass raw materials were prepared so as to have the composition shown in the table, and a glass batch was produced. Next, the glass batch was continuously charged into a melting furnace at 1550 to 1700 ° C., melted and clarified, and then the obtained molten glass was wound around a rotating refractory while blowing air from the tip of the refractory, Glass was pulled out from the tip portion in a tubular shape. Further, the drawn tubular glass was cut into a predetermined length to obtain a glass tube. The glass tube thus obtained was subjected to various evaluations. The results are shown in Table 1. Sample No. 1 and no. FIG. 1 and FIG. 2 show the amount of change of (Na atomic concentration) / (Na atomic concentration + Si atomic concentration) on the inner surface of No. 8 glass tube. The value of (Na atomic concentration) / (Na atomic concentration + Si atomic concentration) on the inner surface of the glass tube was adjusted by changing the type of refractory used at the time of pipe drawing.

As is clear from Table 1, sample No. 1 to 6 showed good hydrolysis resistance and chemical durability. Moreover, No. containing Sn in the glass composition. When the elution of Sn by the hydrolysis resistance test was evaluated for 1, 3, and 4, the Sn elution amount was less than the lower limit of quantification in any sample. On the other hand, sample No. No. 7 had excellent hydrolysis resistance, but the amount of Na ion elution from the inner surface of the glass tube was large and pH change was likely to occur. Sample No. No. 8 had low hydrolysis resistance, and there was a concern that the amount of evaporation of B ₂ O ₃ , Na ₂ O and the like could not be reduced during container processing with a burner.

  The linear thermal expansion coefficient was measured in a temperature range of 30 to 380 ° C. with a dilatometer using a glass sample molded into a rod shape of about 5 mmφ × 50 mm.

  The strain point, annealing point, and softening point were measured by the fiber elongation method.

The working temperature was determined by obtaining a viscosity curve of the glass from the high temperature viscosity obtained by the platinum ball pulling method and the Fulcher viscosity calculation formula, and obtaining a temperature corresponding to 10 ⁴ dPa · s from this viscosity curve.

  The liquid phase temperature was measured by filling a crushed glass sample in a platinum boat of about 120 × 20 × 10 mm and placing it in an electric furnace having a linear temperature gradient for 24 hours. Then, the crystal precipitation location was identified by microscopic observation, the temperature corresponding to the crystal precipitation location was calculated from the temperature gradient graph of the electric furnace, and this temperature was defined as the liquidus temperature.

  The liquid phase viscosity is calculated by calculating the glass viscosity curve from the strain point, annealing point, softening point, working temperature and Fulcher's viscosity formula, and calculating the viscosity of the glass at the liquid phase temperature from this viscosity curve. Was the liquid phase viscosity.

  In the hydrolysis resistance test, the sample was pulverized using an alumina mortar and pestle, and a method according to the powder test method of EP 8.0 was used. The detailed test procedure is as follows. The surface of the sample was thoroughly wiped with ethanol, and the sample was pulverized with an alumina mortar and pestle, and then classified using three sieves made of stainless steel, 710 μm, 425 μm, and 300 μm. The material remaining on the sieve was pulverized again and subjected to the same sieve operation. The sample powder remaining on the 300 μm sieve was washed with ethanol and placed in a glass container such as a beaker. Then, ethanol was added and stirred, and after washing with an ultrasonic washing machine for 1 minute, the operation of pouring out only the supernatant was performed 6 times. Thereafter, it was dried in an oven at 110 ° C. for 30 minutes and cooled in a desiccator for 30 minutes. The obtained sample powder was weighed with an accuracy of 10 g ± 0.0001 g using an electronic balance, placed in a 250 mL quartz flask, and 50 mL of ultrapure water was added. After sealing, the flask was placed in an autoclave and kept at 121 ° C. for 30 minutes. The temperature was raised at 1 ° C./min from 100 ° C. to 121 ° C., and the temperature was lowered at 2 ° C./min from 121 ° C. to 100 ° C. After cooling to 95 ° C., the sample was removed into a conical beaker. The inside of the flask was washed with 30 mL of ultrapure water and poured into a conical beaker three times. About 0.05 mL of methyl red was dropped into the liquid after the test, and neutralization titration was performed with 0.02 mol / L hydrochloric acid. The amount of hydrochloric acid consumed was recorded, and the amount of hydrochloric acid consumed per gram of sample glass was calculated. The smaller this value, the higher the hydrolysis resistance.

The acid resistance test was performed according to DIN12116, with the sample surface area set to 50 cm ² and the amount of 6 mol / L hydrochloric acid as the eluent to 800 mL. The detailed test procedure is as follows. First, a glass sample piece having a total surface area of 50 cm ² with a mirror polished finish on all surfaces was prepared. It was immersed in the solution so mixed and stirred with a magnetic stirrer for 10 minutes. Next, the sample piece was taken out and subjected to ultrasonic cleaning for 2 minutes in ultrapure water three times, and then ultrasonic cleaning for 2 minutes in ethanol was performed twice. Next, the sample piece was dried in an oven at 110 ° C. for 1 hour and cooled in a desiccator for 30 minutes. The mass m ₁ of the sample piece thus obtained was measured to an accuracy of ± 0.1 mg and recorded. Subsequently, 800 mL of 6 mol / L hydrochloric acid was placed in a beaker made of quartz glass, heated using an electric heater until boiling, and a sample piece suspended with a platinum wire was added and held for 6 hours. In order to prevent a decrease in the liquid volume during the test, the opening of the lid of the container was plugged with a gasket and a cooling pipe. Thereafter, the sample piece was taken out and subjected to ultrasonic cleaning for 3 minutes in ultrapure water three times, and then ultrasonic cleaning for 2 minutes in ethanol was performed twice. Further, the washed sample piece was dried in an oven at 110 ° C. for 1 hour and cooled in a desiccator for 30 minutes. The mass m ₂ of the sample thus treated was measured to an accuracy of ± 0.1 mg and recorded. Finally, the amount of mass reduction per unit area was calculated from the masses m ₁ and m ₂ mg of the sample before and after being added to boiling hydrochloric acid and the total surface area Acm ^{2 of the} sample by the following formula 1, and used as the measured value in the acid resistance test. .

[Formula 1] Mass reduction per unit area = 100 × (m ₁ −m ₂ ) / 2 × A
The elution amount of Sn was analyzed for the test solution after the hydrolysis resistance test using an ICP emission analyzer (manufactured by Varian). The detailed test procedure is as follows. The test solution after the hydrolysis resistance test was filtered through a membrane filter and collected in a centrifuge tube. The standard solution was prepared by diluting the Sn standard solution (manufactured by Wako Pure Chemical Industries) so that the Sn content was 0 mg / L, 0.05 mg / L, 0.5 mg / L, and 1.0 mg / L. . Calibration curves were prepared from these standard solutions, and the Sn elution amount in the test solution was calculated. The measurement wavelength of Sn was 189.925 nm.

  “Na / Na + Si” indicating the maximum value of (Na atomic concentration) / (Na atomic concentration + Si atomic concentration) in the region from the glass surface to a depth of 200 nm, the inner surface of the glass tube, and the inner surface of the glass tube “| X1-X2 |”, which indicates the absolute value of the difference of (Na atomic concentration) / (Na atomic concentration + Si atomic concentration) at a depth of 200 nm to 200 nm, is cut into a semicircular glass tube. After that, a depth profile from the glass tube surface to a depth of 200 nm was prepared using X-ray photoelectron spectroscopy, and this was analyzed. Analytical elements were Si and Na.

  Evaluation of Na ion elution from the inner surface of the glass tube was performed according to the following procedure.

  The glass tube was cut to a length of 5 to 10 mm, sealed on one side with a rubber stopper, filled in a simple container prepared with water, and covered with aluminum foil. Then, the elution test was performed according to EP8.0, methyl red was dripped at the eluate and water, and the color was compared. When the color of the methyl red in the eluate changed, it was judged that there was elution of Na ions, and when it did not change, it was judged that there was no elution, and “◯” was given.

  Next, the hydrolysis resistance after various heat processing in a container processing process is demonstrated.

Sample No. produced as described above. Using the glass tubes 1 and 8, each sample was heat-treated at 600 ° C. and 900 ° C. for 5 hours in an electric furnace. In addition, 600 degreeC and 900 degreeC assume the heat processing after a process. About the sample before and behind heat processing, the hydrolysis resistance test was implemented and the elution amount of Na ion, K ion, and Ca ion in the obtained eluate was measured. It means that hydrolysis resistance is so high that the elution amount of Na ion, K ion, and Ca ion is small. Table 2 shows the total elution amount of each ion, and FIG. 3 shows the evaluation results for each heat treatment. Sample No. 1 is a value of Al ₂ O ₃ / (Na ₂ O + K ₂ O + Li ₂ O + MgO + CaO + SrO + B ₂ O ₃ ) and (Na atomic concentration) / (Na atomic concentration + Si atomic concentration) in a region from the glass surface to a depth of 200 nm. Since the value of is within the predetermined range in the present invention, the change in the elution amount of Na ions, K ions, and Ca ions accompanying the heat treatment was small, and excellent hydrolysis resistance was maintained. On the other hand, sample No. 8 is the value of Al ₂ O ₃ / (Na ₂ O + K ₂ O + Li ₂ O + MgO + CaO + SrO + B ₂ O ₃ ) and (Na atomic concentration) / (Na atomic concentration + Si atomic concentration) in the region from the glass surface to a depth of 200 nm. Since the value of is outside the predetermined range in the present invention, the elution amount of Na ions, K ions, and Ca ions increased with the heat treatment, and the hydrolysis resistance decreased.

  The glass tube for pharmaceutical containers of the present invention can be suitably used as various materials for pharmaceutical containers such as ampoules, vials, prefilled syringes and cartridges.

Claims (8)

_SiO 2 _65-80% by _{mass%, Al 2 O 3 5~15%} , B 2 O 3 2~12%, Na 2 O 3~10%, K 2 O 0~5%, Li 2 O 0~5 %, 0~5% MgO, CaO 0~5 %, containing SrO 0 to 5%, the value of _{Al 2 O 3 / (Na 2} O + K 2 O + Li 2 O + MgO + CaO + SrO + B 2 O 3) at a mass ratio, 0.35 0.60, made of borosilicate glass substantially free of BaO, and in the region from the inner surface of the glass tube to a depth of 200 nm (atomic concentration of Na) / (atomic concentration of Na + atomic concentration of Si) The glass tube for pharmaceutical containers characterized by having a value of 0.01 to less than 0.5. _{2. The} borosilicate glass tube for a pharmaceutical container according to claim 1, wherein the borosilicate glass tube is made of borosilicate glass having a mass% of Al ₂ O ₃ content of 6.3 to 11% and MgO + CaO of 0 to less than 1%. . Claim the value of a molar ratio _{(Na 2 O + K 2 O} + Li 2 O-Al 2 O 3) / B 2 O 3 , characterized in that the borosilicate glass is 0.33 to 0.39 1 or 2 2. A glass tube for a pharmaceutical container according to 1.   In the powder test method of the hydrolysis resistance test according to EP 8.0, it comprises borosilicate glass in which the consumption of 0.02 mol / L hydrochloric acid per unit glass mass is 0.030 mL or less. Item 4. A glass tube for a pharmaceutical container according to any one of Items 1 to 3. It consists of borosilicate glass whose mass reduction | decrease amount per unit area becomes 1.0 mg / dm < ² > or less in the acid resistance test according to DIN12116, For pharmaceutical containers in any one of Claims 1-4 characterized by the above-mentioned. Glass tube.   It consists of borosilicate glass which has a working temperature of 1150 degreeC-1250 degreeC, The glass tube for pharmaceutical containers in any one of Claims 1-5 characterized by the above-mentioned. The glass tube for a pharmaceutical container according to any one of claims 1 to 6, comprising a borosilicate glass having a liquid phase viscosity of 10 ^4.5 dPa · s or more.   A pharmaceutical container comprising the glass tube for a pharmaceutical container according to any one of claims 1 to 7.