JP6653073B2 - Borosilicate glass for pharmaceutical containers - Google Patents

Description

  The present invention relates to borosilicate glass for pharmaceutical containers used for glass for tube bottles such as vials and ampoules and for syringes of syringes.

Borosilicate glass for pharmaceutical containers such as vials and ampoules is required to have the following properties.
(A) The components in the chemical solution to be filled do not react with the components in the glass. (B) The chemical solution to be filled has high chemical durability and hydrolysis resistance so as not to contaminate the chemical solution. (C) having a low coefficient of thermal expansion so as not to be easily damaged by a thermal shock during a glass tube manufacturing process or processing into a vial, an ampule, etc. (d) a vial, After processing into an ampoule etc., the amount of heat during processing can be reduced so that the inner surface of the container does not deteriorate due to evaporate from the glass, etc. (e) There are few bubbles and foreign substances, and the appearance quality is excellent. standard pharmaceutical container borosilicate glass is present as a _component, contains a _{SiO 2, B 2 O 3,} Al 2 O 3, Na 2 O, K 2 O, CaO, BaO and a small amount of fining agents

JP 2014-214084A JP 2001-89158 A

  In recent years, the development of a drug solution to be filled has progressed, and a drug solution having a higher medicinal effect is being used. Some of these chemicals are chemically unstable and easily denatured, and have high reactivity with glass. Along with this, borosilicate glass for pharmaceutical containers constituting vials and ampoules is required to have glass having higher chemical durability and hydrolysis resistance than ever before. Further, when the glass contains BaO, the barium feldspar crystal is easily precipitated by the reaction with the alumina-based refractory when the glass is melted, thereby lowering the productivity. In addition, Ba ions eluted from the glass are converted into sulfate ions in the chemical solution. And may form an insoluble precipitate.

  Also, if bubbles are present in the glass after being processed into a medical container, it does not affect the efficacy of the filled chemical solution, but optical defects due to the presence of bubbles are mistaken as floating foreign substances in the chemical solution, There is a risk of being discarded as defective.

  Under such circumstances, for example, Patent Document 1 proposes a glass that does not contain BaO and has high hydrolysis resistance. Patent Document 2 proposes a method for producing glass with less bubbles by melting the glass under conditions suitable for a fining agent.

By the way, pharmaceutical containers such as vials and ampoules are produced by locally heating and processing glass tubes with burners. During the heating of the burner, B ₂ O ₃ , Na ₂ O and the like in the glass evaporate and condense on the inner surface of the medicine container, and a foreign layer may be formed. When the foreign layer is formed, the chemical durability and hydrolysis resistance of the glass substantially decrease, and B ₂ O ₃ , Na ₂ O, and the like are removed from the foreign layer during storage of the chemical solution or during autoclave treatment after filling the chemical solution. It may be eluted and may cause deterioration of the chemical component or a change in the pH of the chemical. In particular, glass that does not contain BaO as in Patent Literature 1 has lower workability than glass that contains BaO, and therefore requires a larger amount of heat 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.

  In addition, bubbles observed in glass after being processed into a pharmaceutical container are roughly classified into bubbles generated during glass production and bubbles generated during heating of a burner for processing the container. Patent Literature 2 proposes that various fining agents be melted under appropriate conditions in order to reduce bubbles during glass production. However, bubbles generated during burner heating cannot be reduced.

  It is an object of the present invention to provide a borosilicate glass for a pharmaceutical container which has good processability despite being free of BaO, and hardly generates bubbles due to heating of a burner during container processing.

As a result of various experiments, the inventors have found that the generation of bubbles due to the heating of the burner at the time of processing the container is due to the fact that the moisture remaining in the glass is vaporized by heat, and the amount of moisture in the glass It has been found that by controlling the temperature in an appropriate range, the bubbles generated at the time of heating the burner can be reduced. In addition, by regulating the ratio of the content of Al ₂ O _{3 to} the total amount of the alkali metal oxide, alkaline earth metal oxide and B ₂ O ₃ , the workability can be improved without deteriorating properties such as hydrolyzability. I found that it can be improved.

Pharmaceutical container borosilicate glass of the present invention, _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 0~5%, _Al 2 _O mass ratio _{3 / (Na 2 O + K} 2 O + Li 2 O + MgO + CaO + SrO + B 2 O ₃ ) is 0.35 to 0.60, contains substantially no BaO, and has a water content of 0.2 to 0.7 / mm in terms of β-OH value. And In addition, “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 expressed as Na ₂ O, K ₂ O, Li ₂ O, MgO, CaO, SrO. And B ₂ O ₃ divided by the total amount. Further, “substantially free of BaO” means that BaO is not actively added, and is not intended to exclude even those that are mixed as impurities. More specifically, it means that the content of BaO is 0.05% by mass or less. Further, the β-OH value representing the water content in the glass can be obtained using the following equation, and the smaller the β-OH value, the smaller the water content in the glass.

β-OH = (1 / t) × log ₁₀ (T ₁ / T ₂ )
t: wall thickness of glass (mm)
T ₁ : transmittance (%) at reference wavelength 3846 cm ⁻¹ (2600 nm)
T ₂ : transmittance (%) at a hydroxyl absorption wavelength of 3600 cm ⁻¹ (2800 nm)

  According to the above configuration, since BaO is not contained, barium feldspar crystals do not precipitate due to the reaction between BaO and the alumina-based refractory during glass melting or molding. In addition, a glass is obtained in which Ba ions are less eluted from the glass and hardly forms insoluble precipitates with sulfate ions in the chemical solution.

Further, according to the above configuration, it is possible to lower the processing temperature when manufacturing a medical container such as an ampoule or a vial from a glass tube, and to significantly reduce the amount of evaporation of B ₂ O ₃ and alkali metal oxide components from the glass. Can be reduced. As a result, excellent chemical durability and hydrolysis resistance can be maintained even after various heat treatments during container processing.

  Furthermore, according to the above configuration, the moisture in the glass is less likely to evaporate when the burner is heated for processing the container, and the generation of bubbles can be suppressed. Can be obtained.

The borosilicate glass for a pharmaceutical container of the present invention preferably contains 6.3 to 11% of Al ₂ O _{3 and} 0 to less than 0 to 1% of MgO + CaO in mass% as a glass composition.

In the present invention, the value of (Na ₂ O + K ₂ O + Li ₂ O—Al ₂ O ₃ ) / B ₂ O _{3 in} a molar ratio is preferably from 0.33 to 0.39. In addition, “(Na ₂ O + K ₂ O + Li ₂ O—Al ₂ O ₃ ) / B ₂ O ₃ ” means a mole of Al ₂ O _{3 based on} the total amount of moles of Na ₂ O, K ₂ O, and Li ₂ O. % Is the value obtained by dividing the value obtained by subtracting% from the molar% of B ₂ O ₃ .

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

  Further, according to the above configuration, since the processing temperature can be lowered, it is possible to suppress the generation (reboil) of bubbles due to vaporization of moisture during heating of the burner during container processing, and the bubbles in the glass remain even after the container processing. A container having few optical defects can be obtained.

  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, it is preferable that the mass reduction per unit area is 1.0 mg / dm ² or less.

In the present invention, it is preferable to have a working temperature of 1150C to 1250C. The working temperature is a temperature at which the viscosity of the glass becomes 10 ⁴ dPa · s.

According to the above configuration, it is possible to lower the processing temperature when producing a glass container such as an ampoule or a vial from a glass tube, and to significantly reduce the evaporation amount of B ₂ O ₃ and alkali metal oxide components from the glass. it can. As a result, it is possible to avoid deterioration of the chemical component stored in the glass container, increase in pH of the chemical solution, and occurrence of flakes.

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

  According to the above configuration, even when the Danner method is used for molding the glass tube, the glass tube is not easily devitrified during molding, which is preferable.

  The glass tube for a medical container of the present invention is characterized by being made of the above-mentioned borosilicate glass for a medical container.

  The pharmaceutical container of the present invention is made of the above-mentioned borosilicate glass for a pharmaceutical container.

  The borosilicate glass for a medical container of the present invention is substantially free of BaO. When BaO is contained in the glass composition, a crystal is precipitated or a precipitate is generated by a reaction with an alumina-based refractory or a reaction between Ba ions eluted from the glass and sulfate ions in a chemical solution. There is fear.

In the borosilicate glass for a pharmaceutical container of the present invention, the hydrolysis resistance is improved, but Al ₂ O ₃ , a component that increases the viscosity of the glass, and the viscosity of the glass are reduced, but the hydrolysis resistance is reduced. Balancing the contents of Na ₂ O, K ₂ O, Li ₂ O, MgO, CaO, SrO, and B ₂ O _{3, which} are components to be made, makes it possible to achieve both improvement in hydrolysis resistance and reduction in processing temperature. Desirable above. 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, and more preferably 0. 0.36 to 0.50, more preferably 0.37 to 0.50. 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 small, the hydrolysis resistance of the glass decreases. In addition, 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 a glass container such as an ampule or a vial from a glass tube becomes high. Thus, the amount of evaporation of B ₂ O ₃ , Na ₂ O, and the like in the glass at the time of heating the burner increases. In addition, bubbles are likely to be generated due to vaporization of moisture during heating of the burner.

In the borosilicate glass for a pharmaceutical container of the present invention, the water content in the glass is represented by a β-OH value of 0.2 to 0.7 / mm, 0.2 to 0.6 / mm, 0.2 to 0. It is preferably 5 / mm, particularly preferably 0.2 to 0.45 / mm. If the β-OH value is too low, it becomes difficult to absorb infrared rays, and the heating efficiency of the glass by the infrared rays radiated at the time of heating the burner decreases, so that it is necessary to heat the glass strongly, and B ₂ O ₃ or Na ₂ O Etc., the amount of evaporation increases. On the other hand, if the β-OH value is too high, bubbles are likely to be generated due to vaporization of water during heating of the burner. The adjustment of the water content in the glass can be performed by using a water-containing raw material, adjusting the melting temperature, and adjusting the flow rate of the glass.

In addition, the composition of the borosilicate glass for a medical container of the present invention is 65 to 80% by mass of SiO ₂ , 5 to 15% of Al ₂ O ₃ , _{2 to} 12% of B ₂ O ₃ , 3 to 10% of Na ₂ O by mass%, K ₂ O 0 to 5%, Li ₂ O 0 to 5%, MgO 0 to 5%, CaO 0 to 5%, SrO 0 to 5%, particularly 70 to 75.5% of SiO _{2 by} mass%, Al 6.3 to 11% ₂ O _{3, 3 to} 11.5% B ₂ O _3, 4.0 to 8.5% Na ₂ O, 0 to 5% K ₂ O, 0 to 0.2% Li ₂ O , MgO 0 to less than 1%, CaO 0 to less than 1%, SrO 0 to less than 4%, and MgO + CaO is preferably 0 to less than 1%.

  Hereinafter, the reasons for limiting the composition range of each component as described above will be described. In the following description,% means mass% unless otherwise specified.

SiO ₂ is one of the components constituting the glass network. The content of SiO ₂ is 65 to 80%, 62 to 75.5%, preferably 65 to 75.5%, 67 to 75%, especially 70 to 74.7%. preferable. If the content of SiO ₂ is too small, the chemical durability decreases, and the acid resistance required for the borosilicate glass for medical containers decreases. On the other hand, if the content of SiO ₂ is too large, the liquidus viscosity decreases, and the liquidus tends to be devitrified in the production process, lowering productivity.

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%, 6.3 to 11%, more than 6.3%, 10% or less, 6.4 to 8.5%, especially 6.4 to 8.3 %. If the content of Al ₂ O ₃ is too small, the above effects cannot be obtained. On the other hand, if 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 , Na ₂ O, and the like increases when processing into a pharmaceutical container. .

B ₂ O ₃ not only lowers the melting point of the glass, but also increases the liquidus viscosity and has the effect of suppressing 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%. % Is preferred. If the content of B ₂ O ₃ is too small, the working temperature will increase, and the amount of evaporation of B ₂ O ₃ , Na ₂ O, etc. will increase when processing into a pharmaceutical container. On the other hand, when the content of B ₂ O ₃ is too large, hydrolysis resistance and chemical durability are reduced.

Na ₂ O has an effect of reducing the viscosity of the glass and increasing the linear thermal expansion coefficient. The Na ₂ O content is 3-10%, 3.2 to 8.5%, from 3.5 to 8.3%, 4% to 8%, in particular 4% to 7%. If the content of Na ₂ O is too small, the working temperature will increase, and the amount of evaporation of B ₂ O ₃ , Na ₂ O, etc. will increase when processing into a pharmaceutical container. On the other hand, when the content of Na ₂ O is too large, the hydrolysis resistance decreases.

K 2 _O also reduces the viscosity of the glass as with Na 2 _O, an effect of increasing the coefficient of linear thermal expansion. The K ₂ O content is 0-5% 0.1% to 5%, 0.5 to 4.5%, from 1.0 to 3%, to be particularly from 1.5 to 3.0% preferable. If the content of K ₂ O is too large, the hydrolysis resistance decreases.

It is preferable to use both components of K ₂ O and Na ₂ O, since 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 by mass ratio. .7. If this ratio is small, the hydrolysis resistance decreases. On the other hand, if this ratio is large, the working temperature will be high, and the amount of evaporation of B ₂ O ₃ , Na ₂ O, etc., when processing into a pharmaceutical container will increase.

Li ₂ O has an effect of lowering the viscosity of 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%, and particularly preferably 0 to 0.01%. Unless otherwise specified, 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%, particularly 6 to 9%. When the total amount of these components is small, the working temperature increases. When the total amount of these components is large, chemical durability and hydrolysis resistance are reduced.

  MgO has the effect of lowering the high temperature viscosity of the glass. Further, 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%. If the content of MgO is too large, the hydrolysis resistance decreases.

  CaO has the effect of lowering 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%. If the CaO content is too large, the hydrolysis resistance decreases.

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 the glass to a preferable range. MgO + CaO is preferably 0 to 5%, 0 to less than 1%, particularly preferably 0 to 0.5%. If the content of MgO + CaO is too large, the high-temperature viscosity of the glass can be lowered, but the hydrolysis resistance of the glass is reduced. SrO has the effect of improving the chemical durability. The SrO content is 0 to 5%, preferably less than 0 to 4%, 0 to 2%, particularly preferably 0 to 1%. If the content of SrO is too large, the hydrolysis resistance decreases.

  In the present invention, it is possible to add various components other than the above.

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

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

Since Fe ₂ O ₃ may color the glass and lower 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, particularly preferably 0.5% or less. Among these fining agents, it is preferable to use Cl or SnO ₂ because 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, 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, the molar ratio of (Na ₂ O + K ₂ O + Li ₂ O—Al ₂ O ₃ ) / B ₂ O ₃ is 0.33 to 0.39, 0.33 to 0.37, 0.33. Preferably, it is less than 0.36, especially 0.33 to 0.35. If this value is too large, various heat treatments during processing increase the content of alkali metal oxides such as Na ₂ O, K ₂ O, and Li ₂ O, thereby increasing the amount of evaporation of these components, and increasing the chemical durability and water content. The working temperature rises due to a decrease in decomposition resistance or a low B ₂ O ₃ content, and alkali metal oxides such as Na ₂ O, K ₂ O and Li ₂ O are evaporated by various heat treatments during processing. And the chemical durability and hydrolysis resistance are reduced. In addition, bubbles accompanying moisture vaporization are likely to be generated. On the other hand, if this value is too small, the working temperature becomes high because the content of alkali metal oxides such as Na ₂ O, K ₂ O and Li ₂ O is small, and Na ₂ O, K ₂ O, Li ₂ O and B ₂ O ₃ are liable to evaporate, and the chemical durability and hydrolysis resistance are reduced and bubbles are easily generated due to the vaporization of water, or the B ₂ O ₃ content is reduced. Due to the large amount, chemical durability and hydrolysis resistance are reduced before processing the container.

  Further, the borosilicate glass for a medical container of the present invention preferably 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. , Especially 0.025 mL or less. If the consumption of hydrochloric acid is too large, when a pharmaceutical container such as an ampoule or a vial is prepared, filled with a chemical solution, and stored, the elution of a glass component, particularly an alkali metal component, may be significantly increased, and the chemical component may be deteriorated. .

In the acid resistance test according to DIN 12116, the mass loss per unit area is preferably at most 1.0 mg / dm ² , especially at most 0.8 mg / dm ² . When the mass loss increases, when a medical container such as an ampoule or a vial is prepared, and a chemical solution is filled and stored, the elution amount of the glass component is significantly increased, and the chemical component may be deteriorated.

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

Liquidus 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. When the liquidus viscosity is low, devitrification tends to occur at the time of glass tube molding 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, and particularly preferably 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 mixing glass raw materials so as to have the above-mentioned glass composition. Next, after continuously feeding the glass batch into a melting furnace at 1550 to 1700 ° C. to melt and clarify, while wrapping the obtained molten glass on a rotating refractory, while blowing air from a refractory tip, The glass is drawn out from the tip portion into a tube. Adjustment of the water content (β-OH value) in the glass is performed by adjusting the combustion method, use of water-containing raw materials, melting temperature, glass flow rate, and the like.

  The drawn tubular glass is cut into a predetermined length to obtain a glass tube for a medicine container. The glass tube thus obtained is used for the production of vials and ampules.

  In addition, the glass tube for medical containers of the present invention is not limited to the Danner method, and may be manufactured using any conventionally known method. 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 (Samples Nos. 1 to 6) of the present invention and Comparative Examples (Samples Nos. 7 and 8). Note that “ΣR ₂ O” in the table 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 batch is prepared by mixing glass raw materials so as to have the composition shown in the table. Next, after continuously feeding the glass batch into a melting furnace at 1550 to 1700 ° C. to melt and clarify, while wrapping the obtained molten glass on a rotating refractory, while blowing air from a refractory tip, The bubble-free glass is drawn out of the tip portion into a tube. The drawn tubular glass was cut into a predetermined length to obtain a glass tube. The thus obtained glass tube was subjected to various evaluations. The β-OH value of the glass was adjusted by restricting the use of a water-containing raw material or changing melting conditions.

  As is clear from Table 1, the sample No. 1 to 6 showed good hydrolysis resistance and chemical durability. In addition, No. 3 containing Sn in the glass composition. When the elution of Sn by hydrolysis resistance test was evaluated for 1, 3, and 4, the Sn elution amount was less than the lower limit of quantification in all samples. Further, the sample No. In Nos. 1 to 6, the β-OH value was within a predetermined range, and no generation of bubbles was observed when the tube end was sealed by the burner. On the other hand, the sample No. In Nos. 7 and 8, bubbles were recognized when the tube ends were sealed.

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

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

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

  For the measurement of the liquidus temperature, a platinum boat having a size of about 120 × 20 × 10 mm was filled with the crushed glass sample, and was placed in an electric furnace having a linear temperature gradient for 24 hours. Thereafter, the crystal deposition location was specified by microscopic observation, the temperature corresponding to the crystal deposition location was calculated from the temperature gradient graph of the electric furnace, and this temperature was taken as the liquidus temperature.

  The liquidus viscosity is calculated by calculating the viscosity curve of the glass from the strain point, the annealing point, the softening point, the working temperature and the Fulcher viscosity calculation formula, and calculating the viscosity of the glass at the liquidus temperature from the viscosity curve. Was taken as the liquidus viscosity.

  The hydrolysis resistance test was performed by pulverizing a sample using a mortar and pestle made of alumina and according to a method according to the powder test method of EP 8.0. 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 stainless steel sieves having openings of 710 μm, 425 μm, and 300 μm. What was left on the sieve was pulverized again and the same sieving operation was performed. The sample powder remaining on the 300 μm sieve was washed with ethanol and put into a glass container such as a beaker. Thereafter, the operation of adding ethanol, stirring, washing with an ultrasonic washing machine for 1 minute, and flowing out only the supernatant was performed six times. Then, 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 to an accuracy of ± 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 increased at a rate of 1 ° C./min from 100 ° C. to 121 ° C., and decreased at a rate of 2 ° C./min from 121 ° C. to 100 ° C. After cooling to 95 ° C., the sample was taken out into a conical beaker. The operation of washing the inside of the flask with 30 mL of ultrapure water and pouring it into a conical beaker was performed three times. After about 0.05 mL of methyl red was dropped into the liquid after the test, neutralization titration was performed with 0.02 mol / L hydrochloric acid, the consumption of hydrochloric acid was recorded, and the consumption of hydrochloric acid per 1 g of sample glass was calculated.

The acid resistance test was carried out in accordance with DIN12116 by setting the sample surface area to 50 cm ² and the amount of 6 mol / L hydrochloric acid as an eluate 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 all surfaces mirror-polished was prepared. As a pretreatment, the sample was treated with hydrofluoric acid (40% by mass) and hydrochloric acid (2 mol / L) at a volume ratio of 1: 9. The resulting mixture was immersed in a mixed solution and stirred with a magnetic stirrer for 10 minutes. Next, the sample piece was taken out, subjected to ultrasonic cleaning three times in ultrapure water for 2 minutes, and then subjected to ultrasonic cleaning twice in ethanol for 1 minute. Next, the sample pieces were dried in an oven at 110 ° C. for 1 hour and cooled in a desiccator for 30 minutes. In this way the mass m ₁ of the obtained sample pieces were measured to an accuracy ± 0.1 mg, it was recorded. Subsequently, 800 mL of 6 mol / L hydrochloric acid was placed in a quartz glass beaker, heated to boiling using an electric heater, and a sample piece suspended with a platinum wire was charged and held for 6 hours. The opening of the lid of the container was plugged with a gasket and cooling tube to prevent the liquid volume from decreasing during the test. Thereafter, the sample piece was taken out, subjected to ultrasonic cleaning for three minutes in ultrapure water for two minutes, and then subjected to ultrasonic cleaning for one minute in ethanol twice. Further, the washed sample was dried in an oven at 110 ° C. for 1 hour and cooled in a desiccator for 30 minutes. In this way the mass pieces m ₂ of sample treated was measured to an accuracy ± 0.1 mg, were recorded. Finally, the mass reduction per unit area was calculated from the masses m ₁ and m ₂ of the sample before and after being introduced into boiling hydrochloric acid and the total surface area Acm ^{2 of the} sample by the following formula 1, and the measured value was used as a measured value in the acid resistance test. .

[Equation 1] Mass loss per unit area = 100 × (m ₁ −m ₂ ) / 2 × A
The elution amount of Sn was analyzed using a test solution after the hydrolysis resistance test using an ICP emission spectrometer (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. A standard solution was prepared by diluting a Sn standard solution (manufactured by Wako Pure Chemical Industries, Ltd.) so that the Sn content became 0 mg / L, 0.05 mg / L, 0.5 mg / L, and 1.0 mg / L. . A calibration curve was prepared from these standard solutions, and the amount of Sn eluted in the test solution was calculated. The measurement wavelength of Sn was 189.925 nm.

  The water content in the glass was measured by the following procedure. A plate glass of 20 mm × 30 mm × 1 mm was processed from the produced glass, and both surfaces were mirror-polished. The transmittance of the glass was measured for the water content in the plate glass using FT-IR, and the β-OH value was calculated from the following equation.

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

  The evaluation of the reboilability of the foam during processing was performed according to the following procedure. While rotating the produced glass tube, the tube end was heated with an oxygen burner for a certain period of time, and the tube was sealed. The sealed portion was visually observed, and was evaluated as x when there was a bubble, and as o when there was no bubble.

  The borosilicate glass for a medical container of the present invention can be suitably used as a material for various medical containers such as ampules, vials, prefilled syringes, and cartridges.

Claims (9)

_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 %, MgO 0-5%, CaO 0-5%, SrO 0-5%, and 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 A borosilicate glass for a pharmaceutical container, wherein the borosilicate glass is 0.60, contains substantially no BaO, and has a water content of 0.2 to 0.5 / mm in terms of β-OH value. Mass% in _Al 2 _{O 3} content is from 6.3 to 11%, pharmaceutical container borosilicate glass according to claim 1, MgO + CaO is equal to or less than 0 to 1%. The pharmaceutical container according to claim 1, wherein the value of (Na ₂ O + K ₂ O + Li ₂ O—Al ₂ O ₃ ) / B ₂ O ₃ is 0.33 to 0.39 in a molar ratio. For borosilicate glass.   4. A powder test method for a hydrolysis resistance test according to EP 8.0, wherein a consumption of 0.02 mol / L hydrochloric acid per unit glass mass is 0.030 mL or less. The borosilicate glass for a pharmaceutical container according to any one of the above. In the acid resistance test according to DIN12116, pharmaceutical container borosilicate glass according to claim 1, weight loss per unit area, characterized in that a 1.0 mg / dm ² or less.   The borosilicate glass for a medical container according to any one of claims 1 to 5, wherein the borosilicate glass has a working temperature of 1150 ° C to 1250 ° C. 10 4.5 Pharmaceutical container borosilicate glass according to claim 1, characterized in that it comprises a ^{dPa · s} or more in the liquid phase viscosity.   A glass tube for a medical container, comprising the borosilicate glass for a medical container according to claim 1.   A pharmaceutical container comprising the borosilicate glass for a pharmaceutical container according to claim 1.