JP2017048091A - Borosilicate glass for pharmaceutical container - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide borosilicate glass for pharmaceutical container, having good processability even when BaO is not contained.SOLUTION: Provided is borosilicate glass for pharmaceutical container comprising SiO, AlO, BO, and RO (R is one or more selected from Li, Na, and K) as essential components and substantially not containing BaO, where a water content in the glass, in terms of a β-OH value, is 0.3 to 0.8/mm, and the glass contains, in mass%, 70.0 to 75.5% of SiO, 6.3 to 11% of AlO, 3 to 11.5% of BO, 4.0 to 8.5% of NaO, 0 to 5% of KO, and 0 to 0.2% of LiO. Further provided is the borosilicate glass for pharmaceutical container, where a content of MgO, CaO, and SrO is 0 to 4 mass%, 0≤MgO+CaO+SrO≤4 mass%, preferably 0≤MgO+CaO<1 mass%, and preferably 5≤NaO+KO+LiO≤10 mass%.SELECTED DRAWING: None

Description

  The present invention relates to borosilicate glass for pharmaceutical containers 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) Production of glass tube Low coefficient of thermal expansion so that damage due to thermal shock is unlikely to occur during processing or processing into vials, ampoules, etc. (d) After processing into vials, ampoules, etc., the inner surface of the container deteriorates due to evaporation from the glass, etc. The amount of heat at the time of processing can be reduced so that the standard borosilicate glass for pharmaceutical containers satisfying these required characteristics is composed of SiO ₂ , B ₂ O ₃ , Al ₂ O ₃ , Na ₂ O, K _It contains ₂ O, CaO, BaO and a small amount of fining agent.

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.

By the way, pharmaceutical containers such as vials and ampoules are produced by locally heating and processing tube glass with a burner. 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.

  An object of the present invention is to provide a borosilicate glass for a pharmaceutical container having good processability even though it does not contain BaO.

  The inventors conducted various experiments and found that when the amount of moisture in the glass is large, absorption in the infrared region is strengthened, and the amount of heat during processing of the container can be reduced.

The borosilicate glass for pharmaceutical containers of the present invention contains SiO ₂ , Al ₂ O ₃ , B ₂ O ₃ , R ₂ O (R is one or more selected from Li, Na, K) as essential components, and contains BaO. It is not substantially contained, and the moisture content in the glass is 0.30 to 0.80 / mm in terms of β-OH value. “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%.

  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 amount 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.

Moreover, according to the said structure, absorption arises in infrared region (2800 nm vicinity) by the hydroxyl group which exists in glass. For this reason, the glass absorbs infrared light radiated when the container is processed by the burner, and the glass can be efficiently heated. As a result, the amount of heat required for processing the container can be reduced. This can reduce the amount of evaporation of such B ₂ O ₃ and Na 2 _O during container processing, it is possible to obtain a hard pharmaceutical container is formed heterogeneous layers on the inner surface. As a result, the chemical durability and hydrolysis resistance of the pharmaceutical container are increased, and it is difficult to cause alteration of chemical components and pH change of the chemical solution due to autoclaving during storage of the chemical solution or after filling with the chemical solution. The “heat amount” is the heat amount supplied from the flame of the burner, and corresponds to the sum of the heat amount contributing to the heating of the glass and the heat amount contributing to the heating of things other than the glass.

The borosilicate glass for a pharmaceutical container of the present invention is SiO ₂ 70.0-75.5% by mass%, Al ₂ O ₃ 6.3-11%, B ₂ O ₃ 3.0-11.5%, Na _{2 O 4.0~8.5%, K 2 O} 0~5.0%, preferably contains Li 2 O 0~0.2%.

  According to the said structure, it becomes easy to obtain the glass excellent in chemical durability or hydrolysis resistance.

  In the present invention, the contents of MgO, CaO and SrO are preferably 0 to 4% by mass, respectively.

  According to the said structure, it becomes easy to obtain glass with a low working temperature, suppressing the chemical durability and the fall of hydrolysis resistance.

  In the present invention, MgO + CaO + SrO is preferably 0 to 4% by mass. “MgO + CaO + SrO” means the total content of MgO, CaO and SrO.

  In the present invention, MgO + CaO is preferably 0 to less than 1% by mass.

In the present invention, preferably further _{Na 2 O + K 2 O +} Li 2 O is from 5 to 10 wt%. “Na ₂ O + K ₂ O + Li ₂ O” means the total amount of Na ₂ O, K ₂ O and Li ₂ O.

  According to the said structure, it becomes easy to obtain glass with a low working temperature, suppressing the chemical durability and the fall of hydrolysis resistance.

In the present invention, the content of Fe ₂ O ₃ is preferably 0 to less than 0.2% by mass.

  According to the said structure, it becomes possible to prevent the coloring of glass effectively.

In the present invention, it is preferable to adjust the value of (MgO + CaO + SrO) / (Na ₂ O + K ₂ O + Li ₂ O) to 0.10 or less by mass ratio. Note that “(MgO + CaO + SrO) / (Na ₂ O + K ₂ O + Li ₂ O)” means the total content of MgO, CaO and SrO is the total content of Na ₂ O, K ₂ O and Li ₂ O. It is the value divided.

  According to the said structure, it becomes easy to obtain glass with a low working temperature, suppressing the chemical durability and the fall of hydrolysis resistance.

In the present invention, the mass _{ratio, CaO / (Na 2 O +} K 2 O + Li 2 O) is preferably a 0 to 0.10. “CaO / (Na ₂ O + K ₂ O + Li ₂ O)” is a value obtained by dividing the content of CaO by the total content of Na ₂ O, K ₂ O and Li ₂ O.

  According to the said structure, glass with high hydrolysis resistance is obtained.

In the present invention, the mass _ratio, K ₂ O / Na 2 O is preferably a 0.2 to 1.0. K ₂ O / Na ₂ O is a value obtained by dividing the content of K ₂ O by the content of Na ₂ O.

  According to the said structure, it becomes easy to obtain glass with a low working temperature, suppressing the hydrolysis resistance fall.

In the present invention, a weight ratio _{Al 2 O 3 / (Na 2} O + K 2 O + Li 2 O) is preferably a 0.7 to 1.5. “Al ₂ O ₃ / (Na ₂ O + K ₂ O + Li ₂ O)” is a value obtained by dividing the content of Al ₂ O _{3 by} the total content of Na ₂ O, K ₂ O and Li ₂ O. It is.

  According to the above configuration, the hydrolysis performance can be further improved.

  In the present invention, 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.

In the present invention, in the acid resistance test according to DIN12116, the mass loss per area is preferably 1.0 mg / dm ² or less.

In the present invention, the working temperature is preferably 1150 ° C to 1250 ° C. 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 component stored in the glass container is altered or the pH of the chemical solution is increased.

In the present invention, it is preferable to have a liquid phase viscosity of 10 ^4.5 dPa · s or more.

  According to the said structure, even when a dunner method is employ | adopted for shaping | molding of a glass tube, devitrification at the time of shaping | molding does not arise easily, and it is preferable.

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

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

The borosilicate glass for pharmaceutical containers of the present invention contains SiO ₂ , Al ₂ O ₃ , B ₂ O ₃ , R ₂ O (R is one or more selected from Li, Na and K) as essential components.

  Moreover, the borosilicate glass for pharmaceutical containers of the present invention does not substantially contain BaO. When BaO is contained in the glass composition, as described above, crystals are precipitated by the reaction with the alumina-based refractory, the reaction between Ba ions eluted from the glass and sulfate ions in the chemical solution, There is a risk of generating.

  The glass for pharmaceutical containers of the present invention represents the water content in the glass as a β-OH value and is 0.3 to 0.8 / mm, 0.35 to 0.80 / mm, 0.4 to 0.75 / mm. mm, particularly 0.45 to 0.70 / mm is preferred. If the β-OH value is too low, the amount of absorbed infrared rays is small, so that the heat of the burner is difficult to be transmitted, and it is necessary to process with high heat during processing, which causes the inner surface of the container to be altered. On the other hand, if the β-OH value is too high, the glass absorbs infrared rays too much and is heated suddenly by the burner, so that it becomes easy to soften and deform, making it difficult to maintain the container shape during processing.

The β-OH value representing the amount of moisture in the glass can be obtained using the following formula.
β-OH = (1 / t) × log 10 (T ₁ / T ₂ )
t: Glass thickness (mm)
T ₁ : Transmittance (%) at a reference wavelength of 3846 cm ⁻¹ (2600 nm)
T ₂ : Transmittance (%) at a hydroxyl group absorption wavelength of 3600 cm ⁻¹ (2800 nm)

In the present invention, is not particularly limited on the composition of borosilicate glass, _SiO 2 70.0 to _75.5% by _{mass%, Al 2 O 3 6.3~11%} , B 2 O 3 3.0~11 0.5%, Na ₂ O 4.0-8.5%, K ₂ O 0-5.0%, Li ₂ O 0-0.2% and a borosilicate glass substantially free of BaO. 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 preferably 70.0 to 75.5%, less than 70.0 to 75.5%, 70.0 to 75.0%, particularly preferably 70.0 to 74.7%. 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, if the content of SiO ₂ is too large liquidus viscosity lowers productivity and is more prone to devitrification in the production 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 preferably 6.3 to 11%, 6.4 to 10%, 6.5 to 8.5%, particularly 6.7 to 8.0%. If the content of Al ₂ O ₃ is too small, the above effect cannot be obtained. On the other hand, Al ₂ O viscosity of the glass when the content is too large for ₃ rises, the working temperature increases, the amount of heat required to process the pharmaceutical container becomes large.

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 3.0 to 11.5%, 5.5 to 11.4%, 8.5 to 11.0%, particularly 9 to less than 11.0%. B ₂ O content of ₃ is too small working temperature increases, the amount of heat required to process the 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 4.0 to 8.5%, 4.2 to 8.4%, 4.5 to 8.0%, particularly preferably 5.0 to 7.0%. The working temperature is the Na 2 _O content is too small is increased, the amount of heat required to process the pharmaceutical container becomes large. 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 preferably 0 to 5%, 0.1 to 5%, 0.5 to 4.5%, 1.0 to 3%, particularly preferably 1.5 to 3.0%. 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 becomes high, and the amount of heat required for processing into a pharmaceutical container increases.

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 preferably 0 to 0.2%, 0 to 0.1%, 0 to 0.05%, particularly preferably 0 to 0.01%. If there is no special circumstance, Li ₂ It is desirable to use other alkali metal oxides other than 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.

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

  MgO has an effect of improving chemical durability. The content of MgO is preferably 0 to 4.0%, 0 to 2.0%, particularly 0 to 1.0%. 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 preferably 0 to 4.0%, 0 to 1.5%, 0 to 1.1%, 0 to 0.9%, particularly 0 to 0.5%. When there is too much CaO content, hydrolysis resistance will fall.

  SrO has an effect of improving chemical durability. The content of SrO is preferably 0 to 4.0%, 0 to 2.0%, particularly 0 to 1.0%. When there is too much content of SrO, hydrolysis resistance will fall.

  The total content of MgO, CaO and SrO is preferably 0 to 4.0%, 0 to 3.0%, 0 to 2.0%, 0 to less than 1.0%, especially 0 to 0.5%. % Is preferred. When there is too much total amount of these components, hydrolysis resistance will fall.

  The total content of MgO and CaO is preferably 0 to less than 1%, 0 to 0.8%, particularly 0 to 0.5%. When there is too much total amount of these components, hydrolyzability will fall.

TiO ₂ has the effect of improving hydrolysis resistance. The content of TiO ₂ is preferably 0 to less than 7.0%, more preferably 0 to 5.0%, 0 to 4.0%, and particularly preferably 0 to 1.5%. Working temperature and the content of TiO ₂ is too large increases, the amount of heat required to process the pharmaceutical container becomes large.

ZrO ₂ has an effect of improving hydrolysis resistance. The content of ZrO ₂ is preferably 0 to less than 7.0%, more preferably 0 to 5.0%, 0 to 4.0%, and particularly preferably 0 to 1.5%. Working temperature and the content of ZrO ₂ is too large increases, the amount of heat required to process the pharmaceutical container becomes large.

Since Fe ₂ O ₃ may color the glass and reduce the transmittance in the visible range, its content is limited to 0.2% or less, 0.1% or less, particularly 0.02% or less. It is desirable.

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 3% or less, preferably 1% or less, more preferably 0.5% or less. Among these fining agents, it is preferable to use Cl or SnO ₂ because it has little influence on the melting temperature and the environment. 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 preferably 2% or less, more preferably 0.5% or less.

In the present invention, in order to obtain a glass having a low viscosity and a high hydrolysis resistance, the value of (MgO + CaO + SrO) / (Na ₂ O + K ₂ O + Li ₂ O) is set to 0.10 or less, 0.0. It is preferable to adjust to 08 or less, 0.07 or less, and particularly less than 0.07. If this value is too large, the hydrolysis resistance decreases. For the same reason, the value of CaO / (Na ₂ O + K ₂ O + Li ₂ O) by mass ratio is 0.10 or less, more preferably 0.08 or less, particularly 0.07 or less, more preferably less than 0.07. It is preferable to adjust. If this value is too large, the hydrolysis resistance decreases.

In the present invention also improves the resistance to hydrolysis, and Al ₂ O ₃ is a component to increase the viscosity of the glass, but reduces the viscosity of the glass, Na ₂ is a component that lowers the resistance to hydrolysis It is desirable to balance the contents of O, K ₂ O, Li ₂ O, MgO, CaO, SrO, and B ₂ O ₃ in order to achieve both hydrolysis resistance and good workability. Specifically, the mass ratio of Al ₂ O ₃ / (Na ₂ O + K ₂ O + Li ₂ O + MgO + CaO + SrO + B ₂ O ₃ ) is preferably 0.32 or more, particularly preferably 0.34 or more, and this value is 0.60 or less, In particular, it is desirable that it is 0.50 or less. “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 It is the value divided by the total content of B ₂ O ₃ content.

Furthermore, it is desirable that Al ₂ O ₃ / (Na ₂ O + K ₂ O + Li ₂ O) is 0.7 to 1.5, 0.75 to 1.5, and particularly 0.75 to 1.2 in terms of mass ratio. If this ratio is too small, the hydrolysis resistance will decrease, and if it is too high, the working temperature will increase, and the amount of heat required for processing into a pharmaceutical container will increase.

In the present invention, the molar ratio of (Na ₂ O + K ₂ O + Li ₂ O—Al ₂ O ₃ ) / B ₂ O ₃ is 0.315 to 0.350, preferably 0.320 to 0.345, It is desirable that it is 0.320 to 0.340, especially less than 0.325 to 0.340. 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. “Na ₂ O + K ₂ O + Li ₂ O—Al ₂ O ₃ ” is a value obtained by subtracting the content of Al ₂ O ₃ from the total amount of Na ₂ O, K ₂ O and Li ₂ O. “(Na ₂ O + K ₂ O + Li ₂ O—Al ₂ O ₃ ) / B ₂ O ₃ ” means a value obtained by dividing the value of (Na ₂ O + K ₂ O + Li ₂ O—Al ₂ O ₃ ) by B ₂ O _3. means.

  Moreover, it is preferable that the borosilicate glass 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 1250 ° C. or lower, 1150 ° C. to 1250 ° C., more preferably 1150 ° C. to 1240 ° C., particularly 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 preferably 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. s or more. 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 an important parameter in the thermal shock resistance of glass. In order for the glass to obtain sufficient thermal shock resistance, the linear thermal expansion coefficient in the temperature range of 30 to 380 ° C. is preferably 58 × 10 ⁻⁷ / ° C. or less, particularly 48 to 55 × 10 ⁻⁷ / ° C. .

  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. The water content (β-OH value) in the glass is adjusted by using a water-containing raw material, adjusting the melting temperature, and the glass flow rate.
The drawn tubular glass is cut into a predetermined length to obtain a glass tube for a pharmaceutical container. 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.

Tables 1 and 2 show examples of the present invention (sample Nos. 1 to 15) and comparative examples (sample No. 16). In the table, “ΣR ₂ O” represents “K ₂ O + Na ₂ O + Li ₂ O”, and “ΣRO)” represents “MgO + CaO + SrO”.

  Each sample was prepared as follows.

  First, a glass-built 500 g batch was prepared so as to have the composition shown in the table, and melted at 1650 ° C. for 4 hours using a platinum crucible. In order to remove bubbles in the melt, stirring was performed twice during melting. After melting, an ingot was prepared, processed into a shape necessary for measurement, and subjected to various evaluations. The β-OH value of the glass was adjusted by controlling the blending of the water-containing raw material and the melting atmosphere.

As apparent from Tables 1 and 2, Sample No. 1-15 showed good hydrolysis resistance and chemical durability. Moreover, it turned out that each sample has the working temperature of 1220 degrees C or less. Moreover, No. containing Sn in the glass composition. When the elution of Sn by a hydrolysis resistance test was evaluated about 2 and 6-15, Sn elution amount was less than a detection minimum in any sample. Sample No. In Nos. 1 to 15, the β-OH value was within a predetermined range, and the glass could be heated efficiently during container processing with a burner. Therefore, it is considered that the evaporation amount of B ₂ O ₃ and Na ₂ O does not increase even though BaO is not contained. Sample No. which is a comparative example. No. 16 had a low β-OH value, and the glass could not be efficiently heated during container processing with a burner. Therefore, since the amount of heat more than necessary is required when processing the glass tube, there is a concern that the amount of evaporation of B ₂ O ₃ and Na ₂ O increases.

  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 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 2, and used as the measured value in the acid resistance test. .

[Formula 2] Mass reduction amount 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.

  The amount of water in the glass was measured by the following procedure. A 20 mm × 30 mm × 1 mm plate glass was processed from the produced glass, and both surfaces were mirror-polished. The transmittance | permeability of glass was measured for the moisture content in this plate glass using FT-IR, and (beta) -OH value was computed from the following formula | equation 1. FIG.

[Formula 1] β-OH = (1 / t) log 10 (T ₁ / T ₂ )
t: Glass thickness (mm)
T ₁ : Transmittance (%) at a reference wavelength of 3846 cm ⁻¹ (2600 nm)
T ₂ : Transmittance (%) at a hydroxyl group absorption wavelength of 3600 cm ⁻¹ (2800 nm)

  The workability of the glass was evaluated by the following procedure. While rotating the produced tube glass, the tube end was heated with an oxygen burner for a certain time and fused. After heating, the end of the sealed tube was visually observed. If the shape was good, it was marked as ◯, and if the shape could not be maintained, it was marked as x.

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

Claims (17)

SiO ₂ , Al ₂ O ₃ , B ₂ O, R ₂ O (R is any one or more of Li, Na, K) is contained as an essential component, BaO is not substantially contained, and the moisture content in the glass is Borosilicate glass for pharmaceutical containers, characterized in that it is 0.30 to 0.80 / mm in terms of β-OH value. _SiO 2 70.0 to _75.5% by _{mass%, Al 2 O 3 6.3~11%} , B 2 O 3 3~11.5%, Na 2 O 4.0~8.5%, K 2 O 0 to _5%, pharmaceutical container borosilicate glass according to claim 1, characterized by containing Li 2 O 0~0.2%.   Content of MgO, CaO, and SrO is 0-4 mass%, respectively, The borosilicate glass for pharmaceutical containers of Claim 1 or Claim 2 characterized by the above-mentioned.   MgO + CaO + SrO is 0-4 mass%, The borosilicate glass for pharmaceutical containers of Claims 1-3 characterized by the above-mentioned.   The borosilicate glass for pharmaceutical containers according to any one of claims 1 to 4, wherein MgO + CaO is 0 to less than 1% by mass. _{Na 2 O + K 2 O +} Li 2 O pharmaceutical container borosilicate glass according to claim 1, characterized in that 5 to 10 wt%. The borosilicate glass for a pharmaceutical container according to any one of claims 1 to 6, wherein the content of Fe ₂ O ₃ is 0 to less than 0.2% by mass. The value of the mass ratio _{(MgO + CaO + SrO) /} (Na 2 O + K 2 O + Li 2 O) The pharmaceutical container borosilicate glass according to any one of claims 1-7, characterized in that 0.10 or less. A mass _{ratio, CaO / (Na 2 O +} K 2 O + Li 2 O) The pharmaceutical container borosilicate glass according to claim 1, characterized in that the 0 to 0.10. The borosilicate glass for pharmaceutical containers according to claim 1, wherein K ₂ O / Na ₂ O is 0.2 to 1 in terms of mass ratio. The borosilicate glass for a pharmaceutical container according to claim 1, wherein Al ₂ O ₃ / (Na ₂ O + K ₂ O + Li ₂ O) is 0.7 to 1.5 by mass ratio. .   The powder test method of the hydrolysis resistance test according to EP 8.0, wherein the consumption of 0.02 mol / L hydrochloric acid per unit glass mass is 0.030 mL or less. The borosilicate glass for pharmaceutical containers according to any one of the above. In the acid resistance test according to DIN12116, pharmaceutical container borosilicate glass according to any one of claims 1 to 12, weight loss per unit area is characterized by comprising a 1.0 mg / dm ² or less.   The borosilicate glass for a pharmaceutical container according to any one of claims 1 to 13, which has an operating temperature of 1150C to 1250C. The borosilicate glass for a pharmaceutical container according to any one of claims 1 to 14, which has a liquid phase viscosity of 10 ^4.5 dPa · s or more.   A glass tube for a pharmaceutical container comprising the borosilicate glass for a pharmaceutical container according to any one of claims 1 to 15.   A pharmaceutical container comprising the borosilicate glass for a pharmaceutical container according to any one of claims 1 to 16.