JPWO2020137779A1 - Pharmaceutical glass container - Google Patents

Abstract

Provided is a medicated glass container having excellent hydrolysis resistance. A medicated glass container characterized by being made of crystallized glass.

Description

The present invention relates to a medicinal glass container.

Pharmaceutical glass containers such as vials and ampoules are required to have the following characteristics.
(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 hydrolysis resistance so as not to contaminate it, and even after various heat treatments during container processing. Maintaining high hydrolyzability (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.

Standard medicated glass containers that meet these required properties are generally made of borosilicate glass.

JP 2014-214084

In recent years, the development of filled chemicals has progressed, and more highly effective chemicals are being used. Some of these chemicals are chemically unstable, easily denatured, and highly reactive with glass. Along with this, there is a demand for glass having higher hydrolysis resistance than before.

It proposes a glass having an adjusted amount of K _{2 O} in order to improve the hydrolysis resistance in Patent Document 1, there is a problem that hydrolysis resistance is still insufficient.

An object of the present invention is to provide a medicinal glass container having excellent hydrolysis resistance.

As a result of various experiments conducted by the present inventors, it has been found that crystallized glass is superior in hydrolysis resistance to amorphous glass such as borosilicate glass.

That is, the medicinal glass container of the present invention is characterized by being made of crystallized glass.

The pharmaceutical glass container of the present invention has a hydrolysis resistance test according to ISO 4802-1 (1988), and the consumption of 0.01 mol / L hydrochloric acid per 100 mL of eluate is 0.50 mL or less. preferable.

In the medicinal glass container of the present invention, it is preferable that the crystallized _{glass is Li 2} O-Al ₂ O _{3 -SiO 2 system crystallized glass.}

In the medicinal glass container of the present invention, it is preferable that a β-quartz solid solution is precipitated as a main crystal in the crystallized glass. By doing so, it becomes easy to obtain a medicinal glass container having a low coefficient of thermal expansion and a high transmittance.

Pharmaceutical glass container of the present invention, crystallized glass, in _{weight%, SiO 2 40~75%, Al} 2 O 3 6~30%, preferably contains Li 2 O 0.1~10%.

The medicinal glass container of the present invention preferably has a Young's modulus of 60 GPa or more.

The medicinal glass container of the present invention preferably has a coefficient of thermal expansion of 20 × 10 ^-7 / ° C. or less at 30 to 380 ° C. By doing so, it becomes easy to obtain a medicinal glass container having excellent heat resistance and impact resistance.

The medicinal glass container of the present invention preferably has a thickness of 1 mm and an average transmittance of 65% or more at a wavelength of 400 to 800 nm.

The medicinal glass container of the present invention preferably has a thickness of 1 mm and a transmittance of 60% or less at a wavelength of 350 nm. In this way, it becomes easier to block ultraviolet rays that may cause alteration of the drug.

In the alkali resistance test according to ISO 695 (1991), the medicinal glass container of the present invention ^{preferably has a weight loss amount ρ per unit area of 75 mg / dm 2} or less.

The medicinal glass container of the present invention has SiO ₂ / (Li ₂ O + Na ₂ O + K ₂ O + MgO + CaO + SrO + BaO) of 3 or more in terms of weight ratio, and the amount of weight loss per unit area in the acid resistance test according to YBB00342004-2015. It is characterized in that S + ρ, which is the sum of the half amount S and the weight reduction amount ρ per unit area in the alkali resistance test according to ISO 695 (1991), is 70 mg / dm ^{2 or less.} Since the medicinal glass container of the present invention has excellent acid resistance and alkali resistance, it can be used for a wide range of pH chemicals. Although quartz glass is excellent in acid resistance and alkali resistance, it is difficult to process it into a complicated medical container shape such as a vial, an ampoule, or a syringe. Here, SiO ₂ / (Li ₂ O + Na ₂ O + K ₂ O + MgO + CaO + SrO + BaO) is _{a value obtained by dividing the content of SiO 2 by} the total amount of Li ₂ O, Na ₂ O, K ₂ O, MgO, CaO, SrO, and BaO. Is.

The method for producing a pharmaceutical glass container of the present invention is characterized in that a glass tube is processed to obtain a glass container, and then the glass container is heat-treated to be crystallized.

According to the present invention, it is possible to provide a pharmaceutical glass container having excellent hydrolysis resistance.

The pharmaceutical glass container of the present invention is characterized by being made of crystallized glass, and in a hydrolysis resistance test according to ISO 4802-1 (1988), consumption of 0.01 mol / L hydrochloric acid per 100 mL of eluent is consumed. The amount is preferably 0.50 mL or less.

First, the crystallized glass used in the present invention will be described.

Crystallized glass _is preferably _{Li 2 O-Al 2 O 3} -SiO 2 based crystallized glass, more preferably, in _{weight%, SiO 2 40~75%, Al} 2 O 3 6~30%, It _{contains Li 2} O 0.1 to 10%. The reasons for limiting the composition as described above are shown below. In the following description of the content of each component, "%" means "% by weight" unless otherwise specified.

SiO ₂ is a component that forms a glass skeleton and constitutes a _{Li 2} O—Al ₂ O ₃ −SiO _{2 system crystal.} If _{the content of SiO 2} is too large, the meltability of the glass is lowered, the viscosity of the glass melt becomes high, the clarification becomes difficult, the molding of the glass becomes difficult, and the productivity tends to be lowered. Therefore, _{the content of SiO 2} is preferably 75% or less, 74% or less, 73% or less, 70% or less, and 69% or less. On the other hand, _{if the content of SiO 2} is too small, the coefficient of thermal expansion tends to be high, and it becomes difficult to obtain crystallized glass having excellent thermal shock resistance. In addition, hydrolysis resistance, alkali resistance, and acid resistance tend to decrease. Therefore, _{the content of SiO 2} is preferably 40% or more, 45% or more, 50% or more, 55% or more, 60% or more, 64% or more, and 65% or more.

Al ₂ O ₃ is a component that forms a glass skeleton and constitutes a _{Li 2} O-Al ₂ O _{3 -SiO 2 system crystal.} The content of Al ₂ O ₃ is preferably 6 to 30%, 10 to 30%, 12 to 29%, 13 to 28%, and particularly preferably 15 to 28%. If _{the content of Al 2} O ₃ is too small, the coefficient of thermal expansion tends to be high, and it becomes difficult to obtain crystallized glass having excellent thermal shock resistance. In addition, the crystallinity is low and the glass tends to become cloudy, making it difficult to check insoluble foreign substances inside the container. In addition, hydrolysis resistance tends to decrease. On the other hand, _{if the content of Al 2} O ₃ is too large, the meltability of the glass is lowered, the viscosity of the glass melt becomes high and it becomes difficult to clarify, and the crystals of murite are easily precipitated, and the glass is lost. Molding of transparent glass becomes difficult and productivity tends to decrease.

Li ₂ O is _{a component constituting Li 2} O-Al ₂ O _{3 -SiO 2} system crystals, which has a great influence on crystallinity and lowers the viscosity of glass to improve the meltability and moldability of glass. It is an ingredient that makes you. The content of Li ₂ O is preferably 0.1 to 10%, 0.5 to 8%, 1 to 7%, 1 to 6%, and particularly preferably 1 to 5%. If the Li ₂ O content is too low, mullite crystals tend to precipitate and the glass tends to devitrify. Further, when the glass is crystallized, Li ₂ O-Al ₂ O _{3 -SiO 2} system crystals are less likely to precipitate, and it is difficult to obtain crystallized glass having excellent hydrolysis resistance, alkali resistance and acid resistance. become. Further, the meltability of the glass is lowered, the viscosity of the glass melt becomes high, the clarification becomes difficult, the molding of the glass becomes difficult, and the productivity tends to be lowered. On the other hand, _{if the content of Li 2} O is too large, the crystallinity becomes too strong, the glass tends to be devitrified and the transmittance tends to decrease, and it becomes difficult to confirm insoluble foreign substances and the like inside the container.

Al ₂ O 3 / Li ₂ O is preferably 1 to 10, 1.5 to 9, _{2 to 8, 2.5 to 7, 3 to 6, and particularly preferably 4 to 6.} If Al ₂ O ₃ / Li ₂ O is too small, _{it becomes difficult for Li 2} O-Al ₂ O _{3 -SiO 2} system crystals to precipitate, and the crystals tend to become cloudy and the transmittance tends to be low. On the other hand, if the molar ratio of _{Al 2} O ₃ / Li _{2 O is too large, it becomes difficult for Li 2} O-Al ₂ O _{3 -SiO 2} system crystals to precipitate, and the crystals tend to become cloudy and the transmittance tends to be low. In addition, the hydrolysis resistance, alkali resistance, and acid resistance of the crystallized glass tend to decrease. In addition, "Al ₂ O ₃ / Li ₂ O" is a value obtained by dividing the content of _{Al 2} O _{3 by} the content of Li _{2 O.}

SiO ₂ / Li ₂ O is preferably 5 to 20, 8 to 19, particularly preferably 10 to 18. When SiO ₂ / Li ₂ O is too small _{Li 2 O-Al 2 O 3} -SiO 2 based crystal is not easily precipitated, clouded by the transmittance tends to be low. Further, since the number of glass matrices increases, the hydrolysis resistance, alkali resistance, and acid resistance of the crystallized glass may decrease. On the other hand, when the _{SiO 2} / Li 2 O is too large _{Li 2 O-Al 2 O 3} -SiO 2 based crystal is not easily precipitated, clouded by the transmittance tends to be low. In addition, the viscosity of the glass melt becomes high, the meltability and moldability decrease, and the productivity tends to decrease. In addition, "SiO ₂ / Li ₂ O" is a value obtained by dividing the content of _{SiO 2 by} the content of Li _{2 O.}

SiO ₂ / Al ₂ O ₃ is preferably 1 to 7, 1.5 to 6, 2 to 5, 2.2 to 4, particularly 2.5 to 3.5. Too large or too small, _{SiO 2 / Al 2 O 3,} Li 2 O-Al 2 O 3 -SiO 2 based crystal is not easily precipitated, hydrolysis resistance forming crystallized glass, alkali resistance, acid resistance The sex tends to decrease. In addition, "SiO ₂ / Al ₂ O ₃ " is a value obtained by dividing the content of _{SiO 2 by} the content of Al ₂ O _3.

In addition to the above components, the crystallized glass used in the present invention may contain the following components in the glass composition.

Na ₂ O is a component that lowers the viscosity of glass and improves the meltability and moldability of glass. The content of Na ₂ O is 0 to 10%, 0 to 5%, 0 to 4%, 0 to 3%, 0 to 2%, 0.1 to 1.5%, 0.1 to 1%, 0. It is preferably 1 to 0.8%, particularly 0.1 to 0.5%. Na ₂ O is a _{component that is difficult to dissolve in Li 2} O-Al ₂ O _{3 -SiO 2} system crystals and easily remains in the glass matrix after crystallization. Therefore, _{if the content of Na 2} O is too large, the hydrolysis resistance, acid resistance, and alkali resistance of the crystallized glass tend to decrease.

K 2 _O is to lower the viscosity of the glass is a component that improves the meltability and formability of the glass. The content of K ₂ O 0-10%, 0-5%, 0-4%, 0-3%, 0-2% 0.1 to 1.5% 0.1% to 1%, 0. It is preferably 1 to 0.8%, particularly 0.1 to 0.5%. K ₂ O is a _{component that is difficult to dissolve in Li 2} O-Al ₂ O _{3 -SiO 2} system crystals and easily remains in the glass matrix after crystallization. Therefore, _{if the content of K 2} O is too large, the hydrolysis resistance, acid resistance, and alkali resistance of the crystallized glass tend to decrease.

MgO is a component dissolved in the _{Li 2 O-Al 2 O 3} -SiO 2 based _crystal, adjusting the thermal expansion coefficient of the _{Li 2 O-Al 2 O 3} -SiO 2 based crystal. Further, it is a component that lowers the viscosity of glass and improves meltability and moldability. The content of MgO is 0 to 10%, 0 to 5%, 0 to 3%, and it is particularly preferable that the content is not contained. If the content of MgO is too large, _{it becomes difficult to dissolve in Li 2} O-Al ₂ O _{3 -SiO 2} system crystals, and it tends to remain in the glass matrix after crystallization. Therefore, the hydrolysis resistance, acid resistance, and alkali resistance of the crystallized glass tend to decrease. Further, since the difference in the coefficient of thermal expansion between the glass matrix and the crystal tends to be large, there is a risk of damage during the crystallization process. Further, scattered light is likely to be generated due to the difference in refractive index between the glass matrix and the crystal. As a result, the transmittance of the crystallized glass decreases, and it becomes difficult to confirm insoluble foreign substances and the like inside the container.

CaO is a component that lowers the viscosity of glass and improves the meltability and moldability of glass. The CaO content is 0 to 10%, 0 to 5%, 0 to 3%, 0 to 1%, and it is particularly preferable that the CaO content is not contained. CaO is a _{component that is difficult to dissolve in Li 2} O-Al ₂ O _{3 -SiO 2} system crystals and easily remains in the glass matrix after crystallization. Therefore, if the CaO content is too high, the hydrolysis resistance, acid resistance, and alkali resistance of the crystallized glass tend to decrease. In addition, there is a tendency to precipitate dissimilar crystals in the crystallization step, and scattered light is likely to be generated due to the difference in refractive index between _{the dissimilar crystals and the Li 2} O-Al ₂ O _{3 -SiO 2 system crystals.} As a result, the transmittance of the crystallized glass tends to decrease.

SrO is a component that lowers the viscosity of glass and improves the meltability and moldability of glass. The content of SrO is 0 to 10%, 0 to 5%, 0 to 3%, and 0 to 1%, and it is particularly preferable that the SrO content is not contained. If the content of SrO is too high, the glass tends to be devitrified and the glass is easily broken. SrO is a _{component that is difficult to dissolve in Li 2} O-Al ₂ O _{3 -SiO 2} system crystals and easily remains in the glass matrix after crystallization. Therefore, if the content of SrO is too large, the hydrolysis resistance, acid resistance, and alkali resistance of the crystallized glass tend to decrease. In addition, scattered light is likely to be generated due to the difference in refractive index between the glass matrix and the crystal. As a result, the transmittance of the crystallized glass decreases, and it becomes difficult to confirm insoluble foreign substances and the like inside the container.

BaO is a component that lowers the viscosity of glass and improves the meltability and moldability of glass. The content of BaO is 0 to 10%, 0 to 5%, 0 to 4%, and it is particularly preferable that the content is not contained. BaO is a _{component that is difficult to dissolve in Li 2} O-Al ₂ O _{3 -SiO 2} system crystals and easily remains in the glass matrix after crystallization. Therefore, if the content of BaO is too large, the hydrolysis resistance, acid resistance, and alkali resistance of the crystallized glass tend to decrease. In addition, scattered light is likely to be generated due to the difference in refractive index between the glass matrix and the crystal. As a result, the transmittance of the crystallized glass decreases, and it becomes difficult to confirm insoluble foreign substances and the like inside the container. Further, when a chemical solution containing sulfate is filled and stored in a glass container, BaO in the glass matrix may elute into the chemical solution to form barium sulfate crystals and become an insoluble foreign substance.

Further, in terms of weight ratio, SiO ₂ / (Li ₂ O + Na ₂ O + K ₂ O + MgO + CaO + SrO + BaO) is preferably 3 or more, 4 or more, 6 or more, 9 or more, 10 or more, 11 or more, and particularly preferably 12 or more. If SiO ₂ / (Li ₂ O + Na ₂ O + K ₂ O + MgO + CaO + SrO + BaO) is too small, acid resistance and hydrolysis resistance tend to decrease. On the other hand, if SiO ₂ / (Li ₂ O + Na ₂ O + K ₂ O + MgO + CaO + SrO + BaO) is too large, the solubility tends to decrease. Therefore, SiO ₂ / (Li ₂ O + Na ₂ O + K ₂ O + MgO + CaO + SrO + BaO) is preferably 33 or less, 30 or less, 25 or less, 20 or less, and particularly preferably 18 or less.

ZnO is _{a component that dissolves in Li 2} O-Al ₂ O _{3 -SiO 2} system crystals and has a great influence on crystallinity. The content of ZnO is 0 to 10%, 0 to 5%, 0 to 3%, and 0 to 1%, and it is particularly preferable that the ZnO content is not contained. If the content of ZnO is too large, the crystallinity becomes too strong and devitrification is likely to occur, the transmittance of the crystallized glass decreases, and it becomes difficult to confirm insoluble foreign substances and the like inside the container.

P ₂ O ₅ is a component that suppresses the precipitation of coarse ZrO _{2 crystals.} When coarse crystals are deposited, scattered light is likely to be generated. As a result, the transmittance of the crystallized glass decreases, and it becomes difficult to confirm insoluble foreign substances and the like inside the container. The content of P ₂ O ₅ is 0 to 5%, 0 to 4%, 0 to 3%, and it is particularly preferable that the content is not contained. If _{the content of P 2} O ₅ is too large, the _{amount of precipitation of Li 2} O-Al ₂ O _{3 -SiO 2} system crystals tends to be small, and the coefficient of thermal expansion tends to be high. In addition, the hydrolysis resistance, acid resistance, and alkali resistance of the crystallized glass tend to decrease.

TiO ₂ is a component that serves as a nucleating agent for precipitating crystals in the crystallization step. On the other hand, it is also a component that remarkably enhances the coloring of glass when contained in a large amount. The content of TiO ₂ is preferably 0 to 8%, 0 to 7%, 0.5 to 5%, and particularly preferably 1 to 5%. If _{the content of TiO 2} is too high, the coloring of the glass tends to be strengthened.

ZrO ₂ is a nucleation component for precipitating crystals in the crystallization step. The content of ZrO ₂ is preferably 0 to 8%, 0 to 5%, 0.5 to 5%, and particularly preferably 1 to 5%. If _{the content of ZrO 2} is too large, coarse ZrO ₂ crystals are precipitated and the glass is liable to be devitrified, and the glass is liable to be broken.

SnO ₂ is a component that acts as a clarifying agent. The SnO ₂ content is preferably 0 to 3%, 0.001 to 2%, 0.005 to 1%, 0.003 to 0.7%, and particularly preferably 0.01 to 0.5%. If _{the content of SnO 2} is too large, the coloring of the glass tends to be strengthened.

Further, as a clarifying agent other than _{SnO 2 , As 2} O ₃ , Sb ₂ O ₃ , Cl, F, Na ₂ SO _{4 and the} like may be contained. The total content of these clarifying agents is preferably 1.5% or less, 1% or less, 0.7% or less, and particularly preferably 0.5% or less. In addition, these clarifying agents may be used alone or in combination.

B ₂ O ₃ is a component that promotes crystal transition from a β-quartz solid solution to a β-spodium solid solution. When the β-quartz solid solution is transferred to β-spojumen, the glass is liable to break due to the increase in the local coefficient of thermal expansion caused by the precipitation of β-spojumen. Therefore, _{it is preferable that B 2} O ₃ is substantially not contained (specifically, less than 0.05%).

Fe ₂ O ₃ is a component that enhances the coloring of glass. The content of Fe ₂ O ₃ is preferably 0 to 0.15%, 0.003 to 0.04%, and particularly preferably 0.003 to 0.03%. If _{the content of Fe 2} O ₃ is too large, the coloring of the glass tends to be strengthened. The _{smaller the content of Fe 2} O ₃ is, the more the coloring can be suppressed, which is preferable. Will end up.

A β-quartz solid solution is likely to precipitate in the crystallized glass having the above composition. If the β-quartz solid solution is precipitated as the main crystal, the crystallized glass easily transmits visible light and the transparency tends to increase. In addition, it becomes easy to reduce the coefficient of thermal expansion of the glass.

In the hydrolysis resistance test according to ISO 4802-1 (1988), the pharmaceutical glass container of the present invention consumes 0.01 mol / L of hydrochloric acid per 100 mL of eluent in an amount of 0.50 mL or less, 0.45 mL. Hereinafter, it is particularly preferable that the amount is 0.40 mL or less, and in the hydrolysis resistance test according to ISO 720 (1985), the consumption of 0.02 mol / L hydrochloric acid per 1 g of glass powder is 0.1 mL or less, 0. It is preferably 0.8 mL or less, 0.06 mL or less, 0.04 mL or less, and particularly preferably 0.03 mL or less. If the amount of hydrochloric acid consumed is too large, when the medicinal glass container is filled with the chemical solution and stored, the elution of the glass component, especially the alkaline component, may be significantly increased, which may cause deterioration of the chemical solution component.

The medicinal glass container of the present invention preferably has a Young's modulus of 60 GPa or more, 65 GPa or more, and particularly preferably 70 GPa or more. If the Young's modulus is too small, the thermal impact resistance tends to decrease. The upper limit of Young's modulus is not particularly limited, but is actually 300 GPa or less.

The medicinal glass container of the present invention has a coefficient of thermal expansion at 30 to 380 ° C. of 20 × ^10-7 / ° C or less, 15 × ^10-7 / ° C or less, 10 × ^10-7 / ° C or less, 7 × 10 ^{−. It is preferably 7} / ° C. or lower, 5 × 10 ^-7 / ° C. or lower, and particularly preferably 2 × 10 ^-7 / ° C. or lower. In the case where thermal shock resistance is particularly ^{required, -5 × 10 -7 / ℃ ~5} × 10 -7 /℃,-2.5×10 -7 /℃~2.5×10 -7 / ℃, particularly preferably -2 × 10 ^-7 / ° C to 2 × 10 ^-7 / ° C.

Since it is necessary to confirm insoluble foreign substances and the like inside the pharmaceutical glass container of the present invention, it is preferable that the appearance is transparent. Specifically, the average transmittance at a thickness of 1 mm and a wavelength of 400 to 800 nm is 65. % Or more, 68% or more, particularly preferably 70% or more. If the average transmittance in the wavelength range is too low, the coloring of the medicinal glass container becomes too strong and the transparency tends to decrease.

The medicinal glass container of the present invention preferably has a transmittance of 60% or less, 50% or less, 45% or less, and particularly preferably 40% or less at a thickness of 1 mm and a wavelength of 350 nm. If the transmittance at the wavelength is too high, it becomes difficult to block ultraviolet rays that may cause deterioration of the drug.

In the alkali resistance test according to ISO 695 (1991), the medicinal glass container of the present invention has a weight loss ρ per unit area of 75 mg / dm ² or less, 70 mg / dm ² or less, and particularly 65 mg / dm ² or less. It is preferable to have. If the weight loss amount ρ is too large, the quality of the drug filled inside may deteriorate.

In the acid resistance test according to YBB00342004-2015, the medicinal glass container of the present invention has a half amount S of weight loss per unit area of 10 mg / dm ² or less, 8 mg / dm ² or less, and particularly 6 mg / dm ² or less. It is preferable to have. If half the weight loss S is too large, the quality of the drug filled inside may deteriorate.

Further, S + ρ, which is the sum of half the weight loss amount S per unit area in the acid resistance test according to YBB00342004-2015 and the weight loss amount ρ per unit area in the alkali resistance test according to ISO 695 (1991). Is preferably 70 mg / dm ² or less, 60 mg / dm ² or less, 50 mg / dm ² or less, 45 mg / dm ² or less, 40 mg / dm ² or less, 35 mg / dm ² or less, and particularly preferably 30 mg / dm ² or less. By doing so, it is possible to further improve the acid resistance and alkali resistance.

The shape of the medicinal glass container of the present invention is not particularly limited, and may be a container shape having a bottom surface or a tube shape having no bottom surface.

Next, a method for manufacturing the pharmaceutical glass container of the present invention will be described. The following description is an example using the Dunner method. Not limited to the Dunner method, it may be manufactured by any conventionally known method such as a bellows method or a downdraw method.

First, a glass batch is prepared by blending glass raw materials so as to have the above glass composition. Next, this glass batch was continuously put into a melting kiln at 1550 to 1700 ° C. to melt and clarify it, and then the obtained molten glass was wound around a rotating refractory while blowing air from the tip of the refractory. A glass tube is obtained by pulling out the glass in a tubular shape from the tip and cooling it. A glass container is obtained by cutting and processing the obtained glass tube to a predetermined length.

Next, the obtained glass container is heat-treated and crystallized. As crystallization conditions, first nucleation is performed at 700 to 950 ° C. (preferably 730 to 900 ° C.) for 6 to 300 minutes (preferably 10 to 180 minutes), and then crystal growth is carried out at 800 to 950 ° C. (preferably 800). ~ 1000 ° C.) for 6 to 600 minutes (preferably 10 to 300 minutes). In this way, a transparent medicinal glass container in which β-quartz solid solution crystals are precipitated as main crystals can be obtained. If the nucleation temperature and crystal growth temperature are too low, and / or the nucleation time and crystal growth time are too short, crystals are less likely to precipitate. In addition, if the nucleation temperature and crystal growth temperature are too high, and / or the nucleation time and crystal growth time are too long, β-spojumen solid solution tends to precipitate and the crystals become coarse, so that the transmittance decreases. Tend to do.

(Example 1)
Hereinafter, the present invention will be described based on examples, but the present invention is not limited to these examples. Tables 1 and 2 show examples and comparative examples of the present invention.

The medicated glass container of the example was prepared as follows. The raw materials were prepared and mixed so as to obtain a glass having the composition shown in Tables 1 and 2, and a raw material batch was obtained. This raw material batch is continuously put into a melting kiln at 1600 to 1680 ° C. to be melted and clarified, and then the obtained molten glass is wound around a rotating refractory while blowing air from the tip of the refractory. By pulling out the glass from the portion into a tubular shape and cooling it, a glass tube having an outer diameter of 12 to 15 mmφ was obtained. After cutting the obtained glass tube to a length of 160 to 300 mm, one end of the glass tube was melted with a burner to obtain a glass container (glass container before crystallization) having a length of 80 to 150 mm.

A glass container is heat-treated at 730 to 780 ° C. for 5 to 180 minutes to form nuclei, and then further heat-treated at 870 to 920 ° C. for 5 to 60 minutes to grow crystals to obtain a medicinal glass container. rice field. The obtained medicinal glass container (glass container after crystallization) has precipitation crystals, hydrolysis resistance, alkali resistance, acid resistance, Young rate, thermal expansion coefficient, average transmittance at a wavelength of 400 to 800 nm, and a wavelength of 350 nm. The transmittance was evaluated. The results are shown in Tables 1 and 2.

Precipitated crystals were evaluated using an X-ray diffractometer (Rigaku's fully automatic multipurpose horizontal X-ray diffractometer Smart Lab).

The hydrolysis resistance was evaluated by a hydrolysis resistance test method according to ISO 4802-1 (1988) and a hydrolysis resistance test method according to ISO 720 (1985). The detailed test procedure is as follows.

(ISO 4802-1 (1988))
The inner and outer surfaces of the glass container obtained in the examples were washed with purified water. The glass container was filled with purified water (10.6 mL) corresponding to 90% of the total volume of the glass container. The mouth of the glass container was covered with aluminum foil and fastened with a rubber band. A glass container containing purified water was placed in an autoclave, and after heating from room temperature to 100 ° C., heating was performed from 100 ° C. to 121 ° C. at a heating rate of 1 ° C./min. After reaching 121 ° C., the mixture was held for 60 minutes and further cooled to 100 ° C. at 0.5 ° C./min. Then, the glass container was taken out from the autoclave and allowed to stand in a tray containing purified water to cool to room temperature. After cooling, the eluate (10 mL) in the glass container was transferred to a 200 mL conical beaker. Using the five glass containers obtained in the same manner by the method of the example, 50 mL of the eluate was obtained by performing the same operation 5 times. 25 mL each of the eluate was dispensed using a whole pipette and transferred to two 50 mL conical beakers. Similarly, the blank was separated from 50 mL of purified water by 25 mL using a whole pipette and transferred to two 50 mL conical beakers. 50 μL of each of the methyl red indicator was added to the eluate and the blank. The burette was filled with 0.01 mol / L hydrochloric acid, and neutralization titration was performed on 25 mL of the eluate. The hydrochloric acid consumption when the color of the eluate became the same as the color of the blank was recorded. The test was carried out at n = 2, and after calculating the average value, the amount of hydrochloric acid consumed with respect to 100 mL of the eluate was calculated.

(ISO 720 (1985))
The inner and outer surfaces of the glass container obtained in the examples were thoroughly wiped with ethanol, the sample was crushed with an alumina mortar and pestle, and then classified using three sieves with stainless steel openings of 710 μm, 425 μm, and 300 μm. .. The glass powder remaining on the 300 μm sieve was collected, and the glass remaining on the 700 μm and 425 μm sieve was pulverized again. The same operation was repeated until the amount of glass powder on a 300 μm sieve was 10 g or more. The sample powder remaining on the 300 μm sieve was transferred to a beaker, 30 mL of acetone was poured, and ultrasonic cleaning was performed for 1 minute. The supernatant was discarded, and then the same work was repeated 4 times. Then, 30 mL of acetone was poured into a beaker, and the work of lightly shaking by hand and discarding only the supernatant liquid was repeated three times. After making multiple holes in the mouth of the beaker with aluminum foil, the beaker was dried in an oven at 110 ° C. for 30 minutes. Then, it was cooled in a take-out desiccator for 30 minutes. The obtained sample powder was weighed at 10 g ± 0.0001 g using an electronic balance, placed in a 250 mL flask, and 50 mL of ultrapure water was added. A flask filled with only 50 mL of ultrapure water was also prepared as a blank. The mouth of the flask was closed with a quartz container, placed in an autoclave, and heat-treated at 121 ° C. for 30 minutes. At this time, the temperature was raised at 1 ° C./min from 100 ° C. to 121 ° C., and cooled at 2 ° C./min from 121 ° C. to 100 ° C. After cooling to 95 ° C., the flask was taken out and allowed to stand in a tray containing ultrapure water to cool for 30 minutes. After cooling, the eluate in the flask was transferred to a conical beaker. 15 mL of ultrapure water was collected with a whole pipette, poured into a flask, lightly shaken, and only the supernatant was poured into a conical beaker. The same work was done two more times. The same operation was performed on the blank to obtain an eluate. 0.05 mL each of methyl red was added dropwise to the eluate of the sample and the blank. 0.02 mol / L hydrochloric acid was added dropwise to the eluate of the sample, the amount of hydrochloric acid consumed when the color became the same as that of the blank was recorded, and the amount of hydrochloric acid consumed per 1 g of glass was calculated.

Alkali resistance was evaluated by a method according to ISO 695 (1991). The detailed test procedure is as follows. First, a glass sample having a total surface area of 15 cm ² with all surfaces mirror-polished was prepared, and as a pretreatment, the sample was mixed with hydrofluoric acid (40% by weight) and hydrochloric acid (2 mol / L) in a volume ratio of 1: 9. It was immersed in the mixed solution so that it was stirred with a magnetic stirrer for 10 minutes. Then, the sample was taken out and ultrasonically cleaned in ultrapure water for 2 minutes three times, and then ultrasonically cleaned in ethanol for 1 minute twice. The sample was then dried in an oven at 110 ° C. for 1 hour and cooled in a desiccator for 30 minutes. _{The weight m 1 of} the sample thus obtained was measured and recorded with an accuracy of ± 0.1 mg. Next, put 800 mL of a solution of 1 mol / L sodium hydroxide aqueous solution and 0.5 mol / L sodium carbonate aqueous solution in a volume ratio of 1: 1 in a stainless steel container, and boil using an electric heater. The sample was heated to the above, and the sample suspended by a platinum wire was put in and held for 3 hours. To prevent a decrease in liquid volume during the test, the opening of the container lid was plugged with a gasket and a condenser. Then, the sample was taken out and immersed in a beaker containing 500 mL of 1 mol / L hydrochloric acid three times, then ultrasonically cleaned in ultrapure water for one minute three times, and ultrasonically cleaned in ethanol for one minute. I went there times. Further washed samples were dried in an oven at 110 ° C. for 1 hour and cooled in a desiccator for 30 minutes. _{The weight m 2 of} the sample thus treated was measured and recorded to an accuracy of ± 0.1 mg. Was calculated weight loss ρ per unit area by the last weights before and after the sample to be introduced into the boiling solution m _1, m 2 _mg and Formula 1 from the total surface area Acm ² samples.
[Equation 1] Weight loss per unit area ρ = 100 × (m _{1 −} m ₂ ) / A

Acid resistance was evaluated by a method according to YBB00342004-2015. The detailed test procedure is as follows. ^{First, prepare a glass sample with a total surface area of 50 cm 2} with all surfaces mirror-polished, and use hydrofluoric acid (40% by mass) and hydrochloric acid (2 mol / L) as a pretreatment at a volume ratio of 1: 9. The mixture was immersed in the mixed solution and stirred with a magnetic stirrer for 10 minutes. Then, the sample was taken out and ultrasonically cleaned in ultrapure water for 1 minute three times, and then ultrasonically cleaned in ethanol for 1 minute twice. The sample was then 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 thus obtained was measured and recorded with an accuracy of ± 0.1 mg. Subsequently, 800 mL of 6 mol / L hydrochloric acid was placed in a beaker made of quartz glass, heated to a boil using an electric heater, and a sample suspended by a platinum wire was added and held for 6 hours. To prevent a decrease in liquid volume during the test, the opening of the container lid was plugged with a gasket and a condenser. Then, the sample was taken out and ultrasonically cleaned in ultrapure water for 1 minute three times, and then ultrasonically cleaned in ethanol for 1 minute twice. Further washed samples were dried in an oven at 110 ° C. for 1 hour and cooled in a desiccator for 30 minutes. _{The mass piece m 2} of the sample treated in this manner was measured and recorded with an accuracy of ± 0.1 mg. Was calculated half S of the weight loss per unit area by the mass m _1, m 2 _mg and Formula 2 below from the total surface area Acm ² samples before and after the sample finally put into boiling hydrochloric acid.
[Equation 2] Half the amount of weight loss per unit area S = 100 × (m _{1 −} m ₂ ) / (2 × A)

Young's modulus was measured by the resonance method (JE-RT3 manufactured by Nippon Techno Plus).

The coefficient of thermal expansion was evaluated by the average coefficient of linear thermal expansion measured in a temperature range of 30 to 380 ° C. using a sample processed to 20 mm × 5 mmφ. A NETZSCH Diratometer was used for the measurement.

The average transmittance at a wavelength of 400 to 800 nm and the transmittance at a wavelength of 350 nm were evaluated by the transmittance at a wavelength of 350 to 800 nm measured with a spectrophotometer for a sample that had been optically polished on both sides to a wall thickness of 1 mm. A spectrophotometer V-670 manufactured by JASCO Corporation was used for the measurement.

As is clear from Tables 1 and 2, in Examples 1 to 14, β-quartz solid solution is precipitated, excellent in hydrolysis resistance and permeation characteristics, high Young's modulus, and coefficient of thermal expansion of 0. It was close. On the other hand, Comparative Examples 1 and 2 were amorphous glasses, which consumed a large amount of hydrochloric acid and were inferior in hydrolysis resistance, ^{and had a high coefficient of thermal expansion of 40 × 10 -7} / ° C. or higher.

(Example 2)
Table 3 shows an example of the glass composition of another pharmaceutical container of the present invention.

The medicinal glass container of the present invention can be suitably used as a primary packaging material, a protective container, etc. for ampoules, vials, prefilled syringes, cartridges, containers for lyophilized preparations, preparations that are easily deteriorated by ultraviolet rays, and the like.

Claims (12)

A medicated glass container characterized by being made of crystallized glass. The first aspect of claim 1, wherein in a hydrolysis resistance test according to ISO 4802-1 (1988), the consumption of 0.01 mol / L hydrochloric acid per 100 mL of eluate is 0.50 mL or less. Medicinal glass container. The medicated glass container according to claim 1 or 2, wherein the crystallized glass is Li ₂ O-Al ₂ O _{3 -SiO 2 system crystallized glass.} The medicinal glass container according to any one of claims 1 to 3, wherein a β-quartz solid solution is precipitated as a main crystal in the crystallized glass. Crystallized glass, in _{weight%, SiO 2 40~75%, Al} 2 O 3 6~30%, any one of the preceding claims, characterized in that it contains Li 2 O 0.1 to 10% The medicated glass container described in. The medicinal glass container according to any one of claims 1 to 5, wherein the Young's modulus is 60 GPa or more. The medicinal glass container according to any one of claims 1 to 6, wherein the coefficient of thermal expansion at 30 to 380 ° C. is 20 × 10 ^{-7 / ° C. or less.} The medicinal glass container according to any one of claims 1 to 7, wherein the average transmittance at a thickness of 1 mm and a wavelength of 400 to 800 nm is 65% or more. The medicinal glass container according to any one of claims 1 to 8, wherein the transmittance is 60% or less at a thickness of 1 mm and a wavelength of 350 nm. The medicinal glass container according to any one of claims 1 to 9, wherein the weight loss amount ρ per unit area is 75 mg / dm ^{2 or less in the alkali resistance test according to ISO 695 (1991).} In terms of weight ratio, SiO ₂ / (Li ₂ O + Na ₂ O + K ₂ O + MgO + CaO + SrO + BaO) is 3 or more, and half the weight loss per unit area in the acid resistance test according to YBB00342004-2015 is S and ISO 695 (1991). A medicated glass container characterized in that S + ρ, which is the sum of the weight loss amount ρ per unit area in the same alkali resistance test, is 70 mg / dm ^{2 or less.} A method for manufacturing a medicinal glass container, which comprises processing a glass tube to obtain a glass container and then heat-treating the glass container to crystallize it.