WO2020137779A1 - Medical glass container - Google Patents

Medical glass container Download PDF

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Publication number
WO2020137779A1
WO2020137779A1 PCT/JP2019/049763 JP2019049763W WO2020137779A1 WO 2020137779 A1 WO2020137779 A1 WO 2020137779A1 JP 2019049763 W JP2019049763 W JP 2019049763W WO 2020137779 A1 WO2020137779 A1 WO 2020137779A1
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WO
WIPO (PCT)
Prior art keywords
glass
glass container
pharmaceutical
less
sio
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PCT/JP2019/049763
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French (fr)
Japanese (ja)
Inventor
美樹 木村
裕基 横田
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日本電気硝子株式会社
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Application filed by 日本電気硝子株式会社 filed Critical 日本電気硝子株式会社
Priority to JP2020563151A priority Critical patent/JPWO2020137779A1/en
Publication of WO2020137779A1 publication Critical patent/WO2020137779A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers

Definitions

  • the present invention relates to a glass container for medicine.
  • the following characteristics are required for pharmaceutical glass containers such as vials and ampoules.
  • -Standard pharmaceutical glass containers that satisfy these required characteristics are generally made of borosilicate glass.
  • Patent Document 1 proposes a glass in which the amount of K 2 O added is adjusted to improve the hydrolysis resistance, but there is a problem that the hydrolysis resistance is still insufficient.
  • An object of the present invention is to provide a pharmaceutical glass container having excellent hydrolysis resistance.
  • crystallized glass is superior in hydrolysis resistance to amorphous glass such as borosilicate glass.
  • the pharmaceutical glass container of the present invention is characterized by being made of crystallized glass.
  • the pharmaceutical glass container of the present invention has a consumption of 0.01 mol/L hydrochloric acid per 100 mL of eluate of 0.50 mL or less. preferable.
  • the crystallized glass is preferably Li 2 O—Al 2 O 3 —SiO 2 -based crystallized glass.
  • ⁇ -quartz solid solution is precipitated as a main crystal in the crystallized glass. By doing so, it becomes easy to obtain a pharmaceutical glass container having a low coefficient of thermal expansion and a high transmittance.
  • the crystallized glass preferably contains SiO 2 40 to 75%, Al 2 O 3 6 to 30%, and Li 2 O 0.1 to 10% by weight.
  • the Young's modulus of the pharmaceutical glass container of the present invention is preferably 60 GPa or more.
  • the pharmaceutical glass container of the present invention preferably has a thermal expansion coefficient of 20 ⁇ 10 ⁇ 7 /° C. or less at 30 to 380° C. By doing so, it becomes easy to obtain a pharmaceutical glass container having excellent thermal shock resistance.
  • the pharmaceutical glass container of the present invention has a thickness of 1 mm and an average transmittance of 65% or more at a wavelength of 400 to 800 nm.
  • the glass container for pharmaceutical use of the present invention preferably has a thickness of 1 mm and a transmittance of 60% or less at a wavelength of 350 nm. By doing so, it becomes easier to shield the ultraviolet rays that may cause the deterioration of the drug.
  • the pharmaceutical glass container of the present invention preferably has a weight reduction amount ⁇ per unit area of 75 mg/dm 2 or less in an alkali resistance test according to ISO 695 (1991).
  • the pharmaceutical glass container of the present invention has a weight ratio of SiO 2 /(Li 2 O+Na 2 O+K 2 O+MgO+CaO+SrO+BaO) of 3 or more, and shows a weight reduction amount per unit area in an acid resistance test according to YBB00342004-2015. It is characterized in that S+ ⁇ , which is the total amount of the half amount S and the weight reduction amount ⁇ per unit area in the alkali resistance test according to ISO 695 (1991), is 70 mg/dm 2 or less. Since the pharmaceutical glass container of the present invention has excellent acid resistance and alkali resistance, it can be used for liquid chemicals having a wide pH range.
  • Quartz glass is excellent in acid resistance and alkali resistance, but it is difficult to process it into a complicated medical container shape such as a vial, an ampoule, or a syringe.
  • 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 after processing a glass tube to obtain a glass container, the glass container is heat-treated and crystallized.
  • 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), the consumption of 0.01 mol/L hydrochloric acid per 100 mL of the eluate.
  • the amount is preferably 0.50 mL or less.
  • the crystallized glass is preferably Li 2 O—Al 2 O 3 —SiO 2 -based crystallized glass, and more preferably 40 to 75% SiO 2 and 6 to 30% Al 2 O 3 in weight %. It contains 0.1 to 10% of Li 2 O.
  • % means “% by weight” unless otherwise specified.
  • SiO 2 is a component that forms a skeleton of glass and also constitutes a Li 2 O—Al 2 O 3 —SiO 2 system crystal.
  • the content of SiO 2 is preferably 75% or less, 74% or less, 73% or less, 70% or less, 69% or less.
  • 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, 65% or more.
  • Al 2 O 3 is a component that forms a skeleton of glass and also constitutes a Li 2 O—Al 2 O 3 —SiO 2 based 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. Further, the degree of crystallinity becomes low and the glass tends to become cloudy, making it difficult to confirm insoluble foreign matters and the like inside the container. Furthermore, the hydrolysis resistance tends to decrease.
  • Li 2 O is a component that constitutes a Li 2 O—Al 2 O 3 —SiO 2 type crystal, and has a great influence on the crystallinity, and also reduces the viscosity of the glass to improve the meltability and formability of the glass. It is a component that causes.
  • the content of Li 2 O is preferably 0.1 to 10%, 0.5 to 8%, 1 to 7%, 1 to 6%, and particularly 1 to 5%. If the content of Li 2 O is too small, mullite crystals tend to precipitate and the glass tends to devitrify.
  • Li 2 O—Al 2 O 3 —SiO 2 -based crystals are less likely to precipitate, and it is difficult to obtain crystallized glass excellent in hydrolysis resistance, alkali resistance, and acid resistance. become. Further, the meltability of the glass decreases, the viscosity of the glass melt increases, and it becomes difficult to clarify the glass or the molding of the glass becomes difficult and the productivity tends to decrease. On the other hand, if the content of Li 2 O is too large, the crystallinity becomes too strong, the glass tends to devitrify, and the transmittance tends to decrease, making it difficult to confirm insoluble foreign matters 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, Li 2 O—Al 2 O 3 —SiO 2 -based crystals are hard to precipitate, and white turbidity tends to reduce the transmittance. On the other hand, when the Al 2 O 3 /Li 2 O molar ratio is too large, Li 2 O—Al 2 O 3 —SiO 2 -based crystals are less likely to precipitate, and white turbidity tends to reduce the transmittance. Further, the hydrolysis resistance, alkali resistance, and acid resistance of the crystallized glass tend to decrease. Note that “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, and particularly 10 to 18. If SiO 2 /Li 2 O is too small, Li 2 O—Al 2 O 3 —SiO 2 -based crystals are hard to precipitate, and white turbidity tends to reduce the transmittance. Moreover, since the glass matrix is increased, the hydrolysis resistance, alkali resistance, and acid resistance of the crystallized glass may decrease. On the other hand, if SiO 2 /Li 2 O is too large, Li 2 O—Al 2 O 3 —SiO 2 -based crystals are less likely to precipitate, and white turbidity tends to reduce the transmittance.
  • 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, and particularly preferably 2.5 to 3.5. If SiO 2 /Al 2 O 3 is too small or too large, it becomes difficult for Li 2 O—Al 2 O 3 —SiO 2 -based crystals to precipitate, resulting in hydrolysis resistance, alkali resistance, and acid resistance of the crystallized glass. Sex tends to decrease. “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 .
  • the crystallized glass used in the present invention may contain the following components in the glass composition.
  • Na 2 O is a component that reduces 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 preferably 0.1 to 0.5%.
  • Na 2 O is a component that is difficult to form a solid solution with Li 2 O—Al 2 O 3 —SiO 2 type crystals, and is likely to remain 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 a component that lowers the viscosity of glass and improves the meltability and moldability of glass.
  • the content of K 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 preferably 0.1 to 0.5%.
  • K 2 O is a component that is difficult to form a solid solution in Li 2 O—Al 2 O 3 —SiO 2 type 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. It is also a component that lowers the viscosity of glass and improves the meltability and moldability.
  • the content of MgO is 0 to 10%, 0 to 5%, 0 to 3%, and it is particularly preferable not to contain it. When the content of MgO is too large, it becomes difficult to form a solid solution in the Li 2 O—Al 2 O 3 —SiO 2 type crystal, and it tends to remain in the glass matrix after crystallization.
  • the hydrolysis resistance, acid resistance, and alkali resistance of the crystallized glass tend to decrease. Further, since the difference in thermal expansion coefficient between the glass matrix and the crystal is likely to be large, there is a risk of damage during the crystallization process. Furthermore, scattered light is likely to occur due to the difference in refractive index between the glass matrix and the crystal. As a result, the transmittance of the crystallized glass is lowered, and it becomes difficult to confirm insoluble foreign matters 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 content of CaO is 0 to 10%, 0 to 5%, 0 to 3%, 0 to 1%, and it is particularly preferable not to contain it.
  • CaO is a component that is difficult to form a solid solution in the Li 2 O—Al 2 O 3 —SiO 2 type crystal, and easily remains in the glass matrix after crystallization. Therefore, if the content of CaO is too large, the hydrolysis resistance, acid resistance, and alkali resistance of the crystallized glass tend to decrease.
  • SrO is a component that reduces 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%, 0 to 1%, and it is particularly preferable not to contain it.
  • SrO is a component that does not easily form a solid solution in the Li 2 O—Al 2 O 3 —SiO 2 type crystal, 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. 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 is lowered, and it becomes difficult to confirm insoluble foreign matters and the like inside the container.
  • BaO is a component that reduces 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 not to contain it.
  • BaO is a component that does not easily form a solid solution in the Li 2 O—Al 2 O 3 —SiO 2 type 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. Further, scattered light is likely to be generated due to the difference in refractive index between the glass matrix and the crystal.
  • the weight ratio of 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 12 or more. If SiO 2 /(Li 2 O+Na 2 O+K 2 O+MgO+CaO+SrO+BaO) is too small, the acid resistance and hydrolysis resistance are likely 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.
  • 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 forms a solid solution with Li 2 O—Al 2 O 3 —SiO 2 type crystals and has a great influence on the crystallinity.
  • the content of ZnO is 0 to 10%, 0 to 5%, 0 to 3%, and 0 to 1%, and it is particularly preferable not to contain it. If the content of ZnO is too large, the crystallinity becomes too strong and devitrification easily occurs, the transmittance of the crystallized glass decreases, and it becomes difficult to confirm insoluble foreign matters and the like inside the container.
  • P 2 O 5 is a component that suppresses precipitation of coarse ZrO 2 crystals. Note that when coarse crystals are deposited, scattered light is likely to be generated. As a result, the transmittance of the crystallized glass is lowered, and it becomes difficult to confirm insoluble foreign matters 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 not to contain it. When the content of P 2 O 5 is too large, the amount of precipitation of Li 2 O—Al 2 O 3 —SiO 2 based crystals tends to decrease, and the thermal expansion coefficient tends to increase. Further, the hydrolysis resistance, acid resistance and alkali resistance of the crystallized glass tend to be lowered.
  • TiO 2 is a component that serves as a nucleating agent for precipitating crystals in the crystallization process. On the other hand, when it is contained in a large amount, it is also a component that markedly enhances the coloring of glass.
  • 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 large, the coloring of the glass tends to increase.
  • ZrO 2 is a nucleation component for precipitating crystals in the crystallization process.
  • the ZrO 2 content is preferably 0 to 8%, 0 to 5%, 0.5 to 5%, and particularly preferably 1 to 5%.
  • the content of ZrO 2 is too large, coarse ZrO 2 crystals are precipitated and the glass is easily devitrified, and the glass is easily broken.
  • SnO 2 is a component that acts as a fining 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%. When the content of SnO 2 is too large, the coloring of the glass tends to be strong.
  • As a fining 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 fining agents is preferably 1.5% or less, 1% or less, 0.7% or less, and particularly preferably 0.5% or less. Further, these fining agents may be used alone or in combination.
  • B 2 O 3 is a component that promotes the crystal transition from the ⁇ -quartz solid solution to the ⁇ -spodumene solid solution.
  • B 2 O 3 is not substantially contained (specifically, less than 0.05%).
  • Fe 2 O 3 is a component that enhances coloring of glass.
  • the content of Fe 2 O 3 is preferably 0 to 0.15%, 0.003 to 0.04%, and more preferably 0.003 to 0.03%. If the content of Fe 2 O 3 is too large, the coloring of the glass tends to increase. The smaller the content of Fe 2 O 3, the more it is possible to suppress the coloring, but it is preferable to use an expensive high-purity raw material in order to achieve a range of less than 0.003%, for example, and the manufacturing cost increases. Will end up.
  • the ⁇ -quartz solid solution is likely to precipitate in the crystallized glass having the above composition. If ⁇ -quartz solid solution is deposited as the main crystal, the crystallized glass easily transmits visible light and the transparency is easily increased. Further, it becomes easy to reduce the coefficient of thermal expansion of the glass.
  • the consumption of 0.01 mol/L hydrochloric acid per 100 mL of the eluate is 0.50 mL or less, 0.45 mL. In particular, it is preferably 0.40 mL or less, and in a 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 0.08 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 a medicinal solution is filled and stored in a pharmaceutical glass container, elution of a glass component, particularly an alkaline component, may be significantly increased to cause deterioration of the medicinal solution component.
  • the Young's modulus of the pharmaceutical glass container of the present invention is preferably 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 shock resistance tends to decrease.
  • the upper limit of the Young's modulus is not particularly limited, but is actually 300 GPa or less.
  • the pharmaceutical 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 / °C ⁇ 5 ⁇ 10 -7 /°C,-2.5 ⁇ 10 -7 /°C ⁇ 2.5 ⁇ 10 -7 / C., particularly ⁇ 2 ⁇ 10 ⁇ 7 /° C. to 2 ⁇ 10 ⁇ 7 /° C. is preferable.
  • the pharmaceutical glass container of the present invention preferably has a transparent appearance because it is necessary to confirm insoluble foreign matters and the like inside the container.
  • the average transmittance is 1 mm at a wavelength of 400 to 800 nm and 65%. % Or more, 68% or more, and particularly preferably 70% or more. If the average transmittance in the wavelength range is too low, the color of the pharmaceutical glass container becomes too strong and the transparency tends to decrease.
  • the pharmaceutical glass container of the present invention preferably has a thickness of 1 mm and a transmittance at a wavelength of 350 nm of 60% or less, 50% or less, 45% or less, and particularly 40% or less. If the transmittance at the wavelength is too high, it becomes difficult to shield ultraviolet rays that may cause the deterioration of the drug.
  • the medicinal glass container of the present invention has a weight loss ⁇ 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 ⁇ is too large, the quality of the drug filled inside may deteriorate.
  • the medicinal glass container of the present invention has a half amount S of the 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 the half amount S of the weight reduction amount is too large, the quality of the medicine filled inside may deteriorate.
  • S+ ⁇ which is the sum of the half amount S of the weight reduction amount per unit area in the acid resistance test according to YBB00342004-2015 and the weight reduction amount ⁇ per unit area in the alkali resistance test according to ISO 695 (1991). Is 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 acid resistance and alkali resistance.
  • the shape of the pharmaceutical 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.
  • the manufacturing method is not limited to the Dunner method, and may be manufactured using any conventionally known method such as the bellow method or the downdraw method.
  • glass batches by mixing the glass raw materials so that the above glass composition is obtained.
  • this glass batch was continuously charged into a melting furnace at 1550 to 1700° C. to be melted and clarified. Then, while winding the obtained molten glass around a rotating refractory, while blowing air from the tip of the refractory, A glass tube is obtained by pulling the glass into a tubular form from the tip and cooling it.
  • a glass container is obtained by cutting and processing the obtained glass tube into a predetermined length.
  • nucleation is carried out at 700 to 950° C. (preferably 730 to 900° C.) for 6 to 300 minutes (preferably 10 to 180 minutes), and subsequently, crystal growth is carried out at 800 to 1050° C. (preferably 800). Perform at 6 to 600 minutes (preferably 10 to 300 minutes) at up to 1000°C.
  • nucleation temperature and the crystal growth temperature are too low, and/or the nucleation time and the crystal growth time are too short, it becomes difficult for crystals to precipitate.
  • the nucleation temperature and the crystal growth temperature are too high, and/or if the nucleation time and the crystal growth time are too long, the ⁇ -spodumene solid solution tends to precipitate, and the crystal becomes coarse, so 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 of the present invention and comparative examples.
  • the pharmaceutical glass container of the example was produced as follows. Raw materials were prepared and mixed so as to obtain glass having the composition shown in Tables 1 and 2, and a raw material batch was obtained. This raw material batch is continuously charged into a melting kiln at 1600 to 1680° C., melted and clarified, and then the obtained molten glass is wound around a rotating refractory material while blowing air from the tip portion of the refractory material, A glass tube having an outer diameter of 12 to 15 mm ⁇ was obtained by pulling the glass out of the section in a tubular shape and cooling it. The obtained glass tube was cut into a length of 160 to 300 mm, and one end of the glass tube was fused with a burner to obtain a glass container having a length of 80 to 150 mm (glass container before crystallization).
  • the glass container is heat-treated at 730 to 780° C. for 5 to 180 minutes for nucleation, and then further heat-treated at 870 to 920° C. for 5 to 60 minutes to grow crystals, thereby obtaining a glass container for medicine. It was Regarding the obtained pharmaceutical glass container (glass container after crystallization), precipitated crystals, hydrolysis resistance, alkali resistance, acid resistance, Young's modulus, coefficient of thermal expansion, average transmittance at wavelength 400 to 800 nm, wavelength 350 nm The transmittance was evaluated. The results are shown in Tables 1 and 2.
  • the precipitated crystals were evaluated using an X-ray diffractometer (manufactured by Rigaku, fully automatic multipurpose horizontal X-ray diffractometer, Smart Lab).
  • the hydrolysis resistance was evaluated by the hydrolysis resistance test method according to ISO 4802-1 (1988) and the hydrolysis resistance test method according to ISO 720 (1985).
  • the detailed test procedure is as follows.
  • the glass container was taken out from the autoclave, allowed to stand in a tray containing purified water, and cooled to room temperature. After cooling, the eluate (10 mL) in the glass container was transferred to a 200 mL conical beaker. The same operation was performed 5 times using 5 glass containers obtained in the same manner as in the example to obtain 50 mL of the eluate. 25 mL of the eluate was collected using a whole pipette and transferred to two 50 mL conical beakers. Similarly, for the blank, 25 mL each was collected from 50 mL of purified water using a whole pipette and transferred to two 50 mL conical beakers.
  • the inner and outer surfaces of the glass container obtained in Example were thoroughly wiped with ethanol, the sample was crushed with an alumina mortar and pestle, and then classified using three sieves of stainless steel openings 710 ⁇ m, 425 ⁇ m, and 300 ⁇ m. ..
  • the glass powder remaining on the 300 ⁇ m sieve was collected, and the glass remaining on the 700 ⁇ m and 425 ⁇ m sieve was ground again. The same operation was repeated until the amount of glass powder on the 300 ⁇ m sieve was 10 g or more.
  • the sample powder remaining on the 300 ⁇ m 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 the same operation was repeated 4 times thereafter. After that, 30 mL of acetone was poured into a beaker and gently shaken by hand to discard only the supernatant, which was repeated three times. After making a plurality of holes in the beaker with aluminum foil, the beaker was dried in an oven at 110° C. for 30 minutes. After that, 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, put 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 from 100° C. to 121° C. at 1° C./min, and cooled from 121° C. to 100° C. at 2° C./min. After cooling to 95° C., the flask was taken out and allowed to stand on a tray containing ultrapure water and cooled for 30 minutes. After cooling, the eluate in the flask was transferred to a conical beaker.
  • the alkali resistance was evaluated by the 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 in which all surfaces were mirror-polished was prepared. As a pretreatment, the sample was hydrofluoric acid (40 wt %) 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 subjected to ultrasonic cleaning for 2 minutes in ultrapure water three times, and then ultrasonic cleaning for 1 minute in ethanol 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 to an accuracy of ⁇ 0.1 mg and recorded.
  • 800 mL of a solution prepared by mixing a 1 mol/L sodium hydroxide aqueous solution and a 0.5 mol/L sodium carbonate aqueous solution at a volume ratio of 1:1 was placed in a stainless steel container and boiled using an electric heater. The sample was heated up to that temperature, a sample hung with a platinum wire was added, and the sample was held for 3 hours. The opening of the lid of the container was capped with a gasket and cooling tube to prevent loss of liquid volume during the test.
  • the acid resistance was evaluated by the method according to YBB00342004-2015.
  • the detailed test procedure is as follows. First, a glass sample having a total surface area of 50 cm 2 with all surfaces mirror-polished was prepared. As a pretreatment, the sample was hydrofluoric acid (40% by mass) and hydrochloric acid (2 mol/L) in a volume ratio of 1:9. The mixture was soaked in the mixed solution and stirred with a magnetic stirrer for 10 minutes. Then, the sample was taken out and subjected to ultrasonic cleaning for 1 minute three times in ultrapure water, and then ultrasonic cleaning for 1 minute twice in ethanol. 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 to an accuracy of ⁇ 0.1 mg.
  • 800 mL of 6 mol/L hydrochloric acid was placed in a beaker made of quartz glass, heated using an electric heater until it boiled, and a sample hung with a platinum wire was placed and held for 6 hours.
  • the opening of the lid of the container was capped with a gasket and cooling tube to prevent loss of liquid volume during the test.
  • the sample was taken out and subjected to ultrasonic cleaning for 1 minute three times in ultrapure water, and then ultrasonic cleaning for 1 minute twice in ethanol.
  • the washed sample was dried in an oven at 110° C. for 1 hour and cooled in a desiccator for 30 minutes.
  • the Young's modulus was measured by the resonance method (JE-RT3 manufactured by Nippon Techno Plus).
  • the thermal expansion coefficient was evaluated by the average linear thermal expansion coefficient measured in a temperature range of 30 to 380° C. using a sample processed to 20 mm ⁇ 5 mm ⁇ .
  • a dilatometer manufactured by NETZSCH 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 whose both sides were optically polished to a thickness of 1 mm.
  • a spectrophotometer V-670 manufactured by JASCO Corporation was used for the measurement.
  • Table 3 shows another glass composition example of the pharmaceutical container of the present invention.
  • the pharmaceutical 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 freeze-dried preparations, preparations that are easily deteriorated by ultraviolet rays, and the like.

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Abstract

Provided is a medical glass container that has an excellent hydrolysis resistance. The medical glass container is characterized by being made from crystallized glass.

Description

医薬用ガラス容器Pharmaceutical glass container
　本発明は、医薬用ガラス容器に関する。 The present invention relates to a glass container for medicine.
　バイアル、アンプル等の医薬用ガラス容器には、下記に示すような特性が要求される。
（ａ）充填される薬液中の成分とガラス中の成分が反応しないこと
（ｂ）充填される薬液を汚染しないように耐加水分解性が高いこと、また、容器加工時の種々の熱処理後も高い加水分解性が維持されること
（ｃ）ガラス管の製造工程や、バイアル、アンプル等への加工時に、サーマルショックによる破損が生じ難いように低熱膨張係数であること The following characteristics are required for pharmaceutical glass containers such as vials and ampoules.
(A) The components in the filled chemical liquid do not react with the components in the glass. (b) High hydrolysis resistance so as not to contaminate the filled chemical liquid, and even after various heat treatments during container processing. High hydrolyzability is maintained. (c) Low thermal expansion coefficient to prevent damage due to thermal shock during glass tube manufacturing process and processing into vials, ampoules, etc.
　これらの要求特性を満足する標準的な医薬用ガラス容器は、一般にホウケイ酸ガラスからなる。 -Standard pharmaceutical glass containers that satisfy these required characteristics are generally made of borosilicate glass.
特開２０１４－２１４０８４JP, 2014-214084, A
　近年、充填される薬液の開発が進み、より薬効の高い薬液が使用されつつある。これらの薬液の中には、化学的に不安定で変性しやすく、ガラスとの反応性が高いものもある。これに伴い、従来以上に耐加水分解性の高いガラスが要求されている。 In recent years, the development of filling chemicals has progressed, and chemicals with higher efficacy are being used. Some of these chemicals are chemically unstable and easily denatured, and have high reactivity with glass. Along with this, a glass having higher hydrolysis resistance than ever has been required.
　特許文献１では耐加水分解性を向上させるためにＫ２Ｏの添加量を調整したガラスを提案しているが、耐加水分解性が未だ不十分であるという問題がある。 Patent Document 1 proposes a glass in which the amount of K 2 O added is adjusted to improve the hydrolysis resistance, but there is a problem that the hydrolysis resistance is still insufficient.
　本発明の目的は、耐加水分解性に優れた医薬用ガラス容器を提供することである。 An object of the present invention is to provide a pharmaceutical glass container having excellent hydrolysis resistance.
　本発明者等が種々の実験を行った結果、結晶化ガラスがホウケイ酸ガラス等の非晶質ガラスより耐加水分解性に優れていることを見出した。 As a result of various experiments conducted by the present inventors, it was found that crystallized glass is superior in hydrolysis resistance to amorphous glass such as borosilicate glass.
　即ち、本発明の医薬用ガラス容器は、結晶化ガラスからなることを特徴とする。 That is, the pharmaceutical glass container of the present invention is characterized by being made of crystallized glass.
　本発明の医薬用ガラス容器は、ＩＳＯ　４８０２－１（１９８８）に準じた耐加水分解性試験において、溶出液１００ｍＬ当たりの０．０１ｍｏｌ／Ｌの塩酸の消費量が０．５０ｍＬ以下であることが好ましい。 In the hydrolysis resistance test according to ISO 4802-1 (1988), the pharmaceutical glass container of the present invention has a consumption of 0.01 mol/L hydrochloric acid per 100 mL of eluate of 0.50 mL or less. preferable.
　本発明の医薬用ガラス容器は、結晶化ガラスがＬｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶化ガラスであることが好ましい。 In the pharmaceutical glass container of the present invention, the crystallized glass is preferably Li 2 O—Al 2 O 3 —SiO 2 -based crystallized glass.
　本発明の医薬用ガラス容器は、結晶化ガラス中に、主結晶としてβ－石英固溶体が析出していることが好ましい。このようにすれば、熱膨張係数が低く、透過率が高い医薬用ガラス容器を得ることが容易になる。 In the pharmaceutical glass container of the present invention, it is preferable that β-quartz solid solution is precipitated as a main crystal in the crystallized glass. By doing so, it becomes easy to obtain a pharmaceutical glass container having a low coefficient of thermal expansion and a high transmittance.
　本発明の医薬用ガラス容器は、結晶化ガラスが、重量％で、ＳｉＯ２　４０～７５％、Ａｌ２Ｏ３　６～３０％、Ｌｉ２Ｏ　０．１～１０％を含有することが好ましい。 In the pharmaceutical glass container of the present invention, the crystallized glass preferably contains SiO 2 40 to 75%, Al 2 O 3 6 to 30%, and Li 2 O 0.1 to 10% by weight.
　本発明の医薬用ガラス容器は、ヤング率が６０ＧＰａ以上であることが好ましい。 The Young's modulus of the pharmaceutical glass container of the present invention is preferably 60 GPa or more.
　本発明の医薬用ガラス容器は、３０～３８０℃における熱膨張係数が２０×１０－７／℃以下であることが好ましい。このようにすれば、耐熱衝撃性に優れた医薬用ガラス容器を得ることが容易になる。 The pharmaceutical glass container of the present invention preferably has a thermal expansion coefficient of 20×10 −7 /° C. or less at 30 to 380° C. By doing so, it becomes easy to obtain a pharmaceutical glass container having excellent thermal shock resistance.
　本発明の医薬用ガラス容器は、厚み１ｍｍ、波長４００～８００ｎｍにおける平均透過率が６５％以上であることが好ましい。 It is preferable that the pharmaceutical glass container of the present invention has a thickness of 1 mm and an average transmittance of 65% or more at a wavelength of 400 to 800 nm.
　本発明の医薬用ガラス容器は、厚み１ｍｍ、波長３５０ｎｍにおける透過率が６０％以下であることが好ましい。このようにすれば、薬剤の変質を引き起す可能性がある紫外線を遮蔽しやすくなる。 The glass container for pharmaceutical use of the present invention preferably has a thickness of 1 mm and a transmittance of 60% or less at a wavelength of 350 nm. By doing so, it becomes easier to shield the ultraviolet rays that may cause the deterioration of the drug.
　本発明の医薬用ガラス容器は、ＩＳＯ　６９５（１９９１）に準じた耐アルカリ性試験において、単位面積当たりの重量減少量ρが７５ｍｇ／ｄｍ２以下であることが好ましい。 The pharmaceutical glass container of the present invention preferably has a weight reduction amount ρ per unit area of 75 mg/dm 2 or less in an alkali resistance test according to ISO 695 (1991).
　本発明の医薬用ガラス容器は、重量比で、ＳｉＯ２／（Ｌｉ２Ｏ＋Ｎａ２Ｏ＋Ｋ２Ｏ＋ＭｇＯ＋ＣａＯ＋ＳｒＯ＋ＢａＯ）が３以上であって、ＹＢＢ００３４２００４―２０１５に準じた耐酸性試験における単位面積当たりの重量減少量の半量ＳとＩＳＯ　６９５（１９９１）に準じた耐アルカリ性試験における単位面積当たりの重量減少量ρとの合量であるＳ＋ρが７０ｍｇ／ｄｍ２以下であることを特徴とする。本発明の医薬用ガラス容器は、耐酸性、耐アルカリ性に優れているため、幅広いｐＨの薬液に使用することができる。なお、石英ガラスは耐酸性、耐アルカリ性に優れるが、バイアル、アンプル、シリンジ等の複雑な医薬用容器の形状に加工することが困難である。ここで、ＳｉＯ２／（Ｌｉ２Ｏ＋Ｎａ２Ｏ＋Ｋ２Ｏ＋ＭｇＯ＋ＣａＯ＋ＳｒＯ＋ＢａＯ）は、ＳｉＯ２の含有量をＬｉ２Ｏ、Ｎａ２Ｏ、Ｋ２Ｏ、ＭｇＯ、ＣａＯ、ＳｒＯ、及びＢａＯの合量で除した値である。 The pharmaceutical glass container of the present invention has a weight ratio of SiO 2 /(Li 2 O+Na 2 O+K 2 O+MgO+CaO+SrO+BaO) of 3 or more, and shows a weight reduction amount per unit area in an acid resistance test according to YBB00342004-2015. It is characterized in that S+ρ, which is the total amount 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 pharmaceutical glass container of the present invention has excellent acid resistance and alkali resistance, it can be used for liquid chemicals having a wide pH range. Quartz glass is excellent in acid resistance and alkali resistance, but 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.
　本発明の医薬用ガラス容器の製造方法は、ガラス管を加工してガラス容器を得た後、ガラス容器を熱処理して結晶化させることを特徴とする。 The method for producing a pharmaceutical glass container of the present invention is characterized in that after processing a glass tube to obtain a glass container, the glass container is heat-treated and crystallized.
　本発明によれば、耐加水分解性に優れた医薬用ガラス容器を提供することができる。 According to the present invention, it is possible to provide a pharmaceutical glass container having excellent hydrolysis resistance.
　本発明の医薬用ガラス容器は、結晶化ガラスからなることを特徴とし、ＩＳＯ　４８０２－１（１９８８）に準じた耐加水分解性試験において、溶出液１００ｍＬ当たりの０．０１ｍｏｌ／Ｌの塩酸の消費量が０．５０ｍＬ以下であることが好ましい。 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), the consumption of 0.01 mol/L hydrochloric acid per 100 mL of the eluate. The amount is preferably 0.50 mL or less.
　まず、本発明に使用される結晶化ガラスについて説明する。 First, the crystallized glass used in the present invention will be described.
　結晶化ガラスは、Ｌｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶化ガラスであることが好ましく、さらに好ましくは、重量％で、ＳｉＯ２　４０～７５％、Ａｌ２Ｏ３　６～３０％、Ｌｉ２Ｏ　０．１～１０％を含有する。組成を上記のように限定した理由を以下に示す。なお、以下の各成分の含有量に関する説明において、特に断りのない限り、「％」は「重量％」を意味する。 The crystallized glass is preferably Li 2 O—Al 2 O 3 —SiO 2 -based crystallized glass, and more preferably 40 to 75% SiO 2 and 6 to 30% Al 2 O 3 in weight %. It contains 0.1 to 10% of Li 2 O. The reasons for limiting the composition as described above are shown below. In the following description regarding the content of each component, "%" means "% by weight" unless otherwise specified.
　ＳｉＯ２はガラスの骨格を形成するとともに、Ｌｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶を構成する成分である。ＳｉＯ２の含有量が多すぎると、ガラスの溶融性が低下したり、ガラス融液の粘度が高くなって、清澄しにくくなったりガラスの成形が難しくなって生産性が低下しやすくなる。そのため、ＳｉＯ２の含有量は７５％以下、７４％以下、７３％以下、７０％以下、６９％以下であることが好ましい。一方、ＳｉＯ２の含有量が少なすぎると、熱膨張係数が高くなる傾向があり、耐熱衝撃性に優れた結晶化ガラスが得られにくくなる。また、耐加水分解性、耐アルカリ性、耐酸性が低下する傾向がある。そのため、ＳｉＯ２の含有量は４０％以上、４５％以上、５０％以上、５５％以上、６０％以上、６４％以上、６５％以上であることが好ましい。 SiO 2 is a component that forms a skeleton of glass and also constitutes a Li 2 O—Al 2 O 3 —SiO 2 system crystal. When the content of SiO 2 is too large, the meltability of the glass is lowered, the viscosity of the glass melt is increased, refining is difficult, and the glass is difficult to mold, and the productivity is likely to be lowered. Therefore, the content of SiO 2 is preferably 75% or less, 74% or less, 73% or less, 70% or less, 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. Moreover, 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, 65% or more.
　Ａｌ２Ｏ３はガラスの骨格を形成するとともに、Ｌｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶を構成する成分である。Ａｌ２Ｏ３の含有量は６～３０％、１０～３０％、１２～２９％、１３～２８％、特に１５～２８％であることが好ましい。Ａｌ２Ｏ３の含有量が少なすぎると、熱膨張係数が高くなる傾向があり、耐熱衝撃性に優れた結晶化ガラスが得られにくくなる。また、結晶化度が低くなりガラスが白濁する傾向があり、容器内部の不溶性異物等を確認し難くなる。さらに、耐加水分解性が低下する傾向がある。一方、Ａｌ２Ｏ３の含有量が多すぎると、ガラスの溶融性が低下したり、ガラス融液の粘度が高くなって清澄しにくくなったり、ムライトの結晶が析出し易くなり、ガラスが失透ガラスの成形が難しくなって生産性が低下しやすくなる。 Al 2 O 3 is a component that forms a skeleton of glass and also constitutes a Li 2 O—Al 2 O 3 —SiO 2 based 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. Further, the degree of crystallinity becomes low and the glass tends to become cloudy, making it difficult to confirm insoluble foreign matters and the like inside the container. Furthermore, the hydrolysis resistance tends to decrease. On the other hand, when the content of Al 2 O 3 is too large, the meltability of the glass decreases, the viscosity of the glass melt increases, and it becomes difficult to clarify, and the crystals of mullite tend to precipitate, and the glass is lost. It becomes difficult to mold the transparent glass, and the productivity tends to decrease.
　Ｌｉ２ＯはＬｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶を構成する成分であり、結晶性に大きな影響を与えるとともに、ガラスの粘度を低下させて、ガラスの溶融性および成形性を向上させる成分である。Ｌｉ２Ｏの含有量は０．１～１０％、０．５～８％、１～７％、１～６％、特に１～５％であることが好ましい。Ｌｉ２Ｏの含有量が少なすぎると、ムライトの結晶が析出してガラスが失透する傾向がある。また、ガラスを結晶化させる際に、Ｌｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶が析出しにくくなり、耐加水分解性、耐アルカリ性、耐酸性に優れた結晶化ガラスを得ることが困難になる。さらに、ガラスの溶融性が低下したり、ガラス融液の粘度が高くなって、清澄しにくくなったりガラスの成形が難しくなって生産性が低下しやすくなる。一方、Ｌｉ２Ｏの含有量が多すぎると、結晶性が強くなりすぎて、ガラスが失透し透過率が低下する傾向があり、容器内部の不溶性異物等を確認し難くなる。 Li 2 O is a component that constitutes a Li 2 O—Al 2 O 3 —SiO 2 type crystal, and has a great influence on the crystallinity, and also reduces the viscosity of the glass to improve the meltability and formability of the glass. It is a component that causes. The content of Li 2 O is preferably 0.1 to 10%, 0.5 to 8%, 1 to 7%, 1 to 6%, and particularly 1 to 5%. If the content of Li 2 O is too small, mullite crystals tend to precipitate and the glass tends to devitrify. Further, when crystallizing glass, Li 2 O—Al 2 O 3 —SiO 2 -based crystals are less likely to precipitate, and it is difficult to obtain crystallized glass excellent in hydrolysis resistance, alkali resistance, and acid resistance. become. Further, the meltability of the glass decreases, the viscosity of the glass melt increases, and it becomes difficult to clarify the glass or the molding of the glass becomes difficult and the productivity tends to decrease. On the other hand, if the content of Li 2 O is too large, the crystallinity becomes too strong, the glass tends to devitrify, and the transmittance tends to decrease, making it difficult to confirm insoluble foreign matters and the like inside the container.
　Ａｌ２Ｏ３／Ｌｉ２Ｏは１～１０、１．５～９、２～８、２．５～７、３～６、特に４～６であることが好ましい。Ａｌ２Ｏ３／Ｌｉ２Ｏが小さすぎると、Ｌｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶が析出し難くなり、白濁して透過率が低くなる傾向がある。一方、Ａｌ２Ｏ３／Ｌｉ２Ｏのモル比率が大きすぎると、Ｌｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶が析出し難くなり、白濁して透過率が低くなる傾向がある。また、結晶化ガラスの耐加水分解性、耐アルカリ性、耐酸性が低下する傾向がある。なお、「Ａｌ２Ｏ３／Ｌｉ２Ｏ」は、Ａｌ２Ｏ３の含有量をＬｉ２Ｏの含有量で除した値である。 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, Li 2 O—Al 2 O 3 —SiO 2 -based crystals are hard to precipitate, and white turbidity tends to reduce the transmittance. On the other hand, when the Al 2 O 3 /Li 2 O molar ratio is too large, Li 2 O—Al 2 O 3 —SiO 2 -based crystals are less likely to precipitate, and white turbidity tends to reduce the transmittance. Further, the hydrolysis resistance, alkali resistance, and acid resistance of the crystallized glass tend to decrease. Note that “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.
　ＳｉＯ２／Ｌｉ２Ｏは５～２０、８～１９、特に１０～１８であることが好ましい。ＳｉＯ２／Ｌｉ２Ｏが小さすぎるとＬｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶が析出し難くなり、白濁して透過率が低くなる傾向がある。また、ガラスマトリクスが多くなるため、結晶化ガラスの耐加水分解性、耐アルカリ性、耐酸性が低下する可能性がある。一方、ＳｉＯ２／Ｌｉ２Ｏが大きすぎるとＬｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶が析出し難くなり、白濁して透過率が低くなる傾向がある。また、ガラス融液の粘度が高くなり溶融性や成形性が低下し、生産性が低下しやすくなる。なお、「ＳｉＯ２／Ｌｉ２Ｏ」は、ＳｉＯ２の含有量をＬｉ２Ｏの含有量で除した値である。 SiO 2 /Li 2 O is preferably 5 to 20, 8 to 19, and particularly 10 to 18. If SiO 2 /Li 2 O is too small, Li 2 O—Al 2 O 3 —SiO 2 -based crystals are hard to precipitate, and white turbidity tends to reduce the transmittance. Moreover, since the glass matrix is increased, the hydrolysis resistance, alkali resistance, and acid resistance of the crystallized glass may decrease. On the other hand, if SiO 2 /Li 2 O is too large, Li 2 O—Al 2 O 3 —SiO 2 -based crystals are less likely to precipitate, and white turbidity tends to reduce the transmittance. In addition, the viscosity of the glass melt becomes high, the meltability and moldability deteriorate, and the productivity tends to decrease. “SiO 2 /Li 2 O” is a value obtained by dividing the content of SiO 2 by the content of Li 2 O.
　ＳｉＯ２／Ａｌ２Ｏ３は１～７、１．５～６、２～５、２．２～４、特に２．５～３．５であることが好ましい。ＳｉＯ２／Ａｌ２Ｏ３が小さすぎても大きすぎても、Ｌｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶が析出し難くなり、結結晶化ガラスの耐加水分解性、耐アルカリ性、耐酸性が低下する傾向がある。なお、「ＳｉＯ２／Ａｌ２Ｏ３」は、ＳｉＯ２の含有量をＡｌ２Ｏ３の含有量で除した値である。 SiO 2 /Al 2 O 3 is preferably 1 to 7, 1.5 to 6, 2 to 5, 2.2 to 4, and particularly preferably 2.5 to 3.5. If SiO 2 /Al 2 O 3 is too small or too large, it becomes difficult for Li 2 O—Al 2 O 3 —SiO 2 -based crystals to precipitate, resulting in hydrolysis resistance, alkali resistance, and acid resistance of the crystallized glass. Sex tends to decrease. “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 .
　本発明に使用される結晶化ガラスは、上記成分以外にも、ガラス組成中に下記の成分を含有してもよい。 In addition to the above components, the crystallized glass used in the present invention may contain the following components in the glass composition.
　Ｎａ２Ｏはガラスの粘度を低下させて、ガラスの溶融性および成形性を向上させる成分である。Ｎａ２Ｏの含有量は０～１０％、０～５％、０～４％、０～３％、０～２％、０．１～１．５％、０．１～１％、０．１～０．８％、特に０．１～０．５％であることが好ましい。Ｎａ２ＯはＬｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶に固溶し難い成分であり、結晶化後にガラスマトリクス中に残存し易い。そのため、Ｎａ２Ｏの含有量が多すぎると、結晶化ガラスの耐加水分解性、耐酸性、耐アルカリ性が低下する傾向がある。 Na 2 O is a component that reduces 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 preferably 0.1 to 0.5%. Na 2 O is a component that is difficult to form a solid solution with Li 2 O—Al 2 O 3 —SiO 2 type crystals, and is likely to remain 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.
　Ｋ２Ｏはガラスの粘度を低下させて、ガラスの溶融性および成形性を向上させる成分である。Ｋ２Ｏの含有量は０～１０％、０～５％、０～４％、０～３％、０～２％、０．１～１．５％、０．１～１％、０．１～０．８％、特に０．１～０．５％であることが好ましい。Ｋ２ＯはＬｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶に固溶し難い成分であり、結晶化後にガラスマトリクス中に残存し易い。そのため、Ｋ２Ｏの含有量が多すぎると、結晶化ガラスの耐加水分解性、耐酸性、耐アルカリ性が低下する傾向がある。 K 2 O is a component that lowers the viscosity of glass and improves the meltability and moldability of glass. The content of K 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 preferably 0.1 to 0.5%. K 2 O is a component that is difficult to form a solid solution in Li 2 O—Al 2 O 3 —SiO 2 type 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はＬｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶に固溶し、Ｌｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶の熱膨張係数を調整する成分である。また、ガラスの粘度を低下させて溶融性及び成形性を向上させる成分である。ＭｇＯの含有量は０～１０％、０～５％、０～３％、特に含有しないことが好ましい。ＭｇＯの含有量が多すぎると、Ｌｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶に固溶し難くなり、結晶化後にガラスマトリクス中に残存し易くなる。そのため、結晶化ガラスの耐加水分解性、耐酸性、耐アルカリ性が低下する傾向がある。また、ガラスマトリクスと結晶との熱膨張係数差が大きくなり易いため、結晶化工程中に破損する虞れがある。さらに、ガラスマトリクスと結晶との屈折率差により散乱光が発生し易くなる。その結果、結晶化ガラスの透過率が低下し、容器内部の不溶性異物等を確認し難くなる。 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. It is also a component that lowers the viscosity of glass and improves the meltability and moldability. The content of MgO is 0 to 10%, 0 to 5%, 0 to 3%, and it is particularly preferable not to contain it. When the content of MgO is too large, it becomes difficult to form a solid solution in the Li 2 O—Al 2 O 3 —SiO 2 type crystal, 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 thermal expansion coefficient between the glass matrix and the crystal is likely to be large, there is a risk of damage during the crystallization process. Furthermore, scattered light is likely to occur due to the difference in refractive index between the glass matrix and the crystal. As a result, the transmittance of the crystallized glass is lowered, and it becomes difficult to confirm insoluble foreign matters and the like inside the container.
　ＣａＯはガラスの粘度を低下させて、ガラスの溶融性および成形性を向上させる成分である。ＣａＯの含有量は０～１０％、０～５％、０～３％、０～１％、特に含有しないことが好ましい。ＣａＯはＬｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶に固溶し難い成分であり、結晶化後にガラスマトリクス中に残存し易い。そのため、ＣａＯの含有量が多すぎると、結晶化ガラスの耐加水分解性、耐酸性、耐アルカリ性が低下する傾向がある。また、結晶化工程にて異種結晶を析出させる傾向があり、異種結晶とＬｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶との屈折率差により散乱光が発生し易くなる。その結果、結晶化ガラスの透過率が低下する傾向がある。 CaO is a component that lowers the viscosity of glass and improves the meltability and moldability of glass. The content of CaO is 0 to 10%, 0 to 5%, 0 to 3%, 0 to 1%, and it is particularly preferable not to contain it. CaO is a component that is difficult to form a solid solution in the Li 2 O—Al 2 O 3 —SiO 2 type crystal, and easily remains in the glass matrix after crystallization. Therefore, if the content of CaO is too large, the hydrolysis resistance, acid resistance, and alkali resistance of the crystallized glass tend to decrease. In addition, there is a tendency to deposit different crystals in the crystallization process, and scattered light is likely to be generated due to the difference in refractive index between the different crystals and the Li 2 O—Al 2 O 3 —SiO 2 -based crystals. As a result, the transmittance of the crystallized glass tends to decrease.
　ＳｒＯはガラスの粘度を低下させて、ガラスの溶融性および成形性を向上させる成分である。ＳｒＯの含有量は０～１０％、０～５％、０～３％、０～１％、特に含有しないことが好ましい。ＳｒＯの含有量が多すぎると、ガラスが失透しやすくなり、ガラスが破損しやすくなる。ＳｒＯはＬｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶に固溶し難い成分であり、結晶化後にガラスマトリクス中に残存し易い。そのため、ＳｒＯの含有量が多すぎると、結晶化ガラスの耐加水分解性、耐酸性、耐アルカリ性が低下する傾向がある。また、ガラスマトリクスと結晶との屈折率差により散乱光が発生し易くなる。その結果、結晶化ガラスの透過率が低下し、容器内部の不溶性異物等を確認し難くなる。 SrO is a component that reduces 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%, 0 to 1%, and it is particularly preferable not to contain it. When the content of SrO is too large, the glass is likely to be devitrified and the glass is easily broken. SrO is a component that does not easily form a solid solution in the Li 2 O—Al 2 O 3 —SiO 2 type crystal, 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. 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 is lowered, and it becomes difficult to confirm insoluble foreign matters and the like inside the container.
　ＢａＯはガラスの粘度を低下させて、ガラスの溶融性および成形性を向上させる成分である。ＢａＯの含有量は０～１０％、０～５％、０～４％、特に含有しないことが好ましい。ＢａＯはＬｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶に固溶し難い成分であり、結晶化後にガラスマトリクス中に残存し易い。そのため、ＢａＯの含有量が多すぎると、結晶化ガラスの耐加水分解性、耐酸性、耐アルカリ性が低下する傾向がある。また、ガラスマトリクスと結晶との屈折率差により散乱光が発生し易くなる。その結果、結晶化ガラスの透過率が低下し、容器内部の不溶性異物等を確認し難くなる。さらに、ガラス容器中にて硫酸塩を含む薬液を充填、保存した際に、ガラスマトリクス中のＢａＯが薬液中に溶出し硫酸バリウム結晶を生成し不溶性異物となる虞れがある。 BaO is a component that reduces 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 not to contain it. BaO is a component that does not easily form a solid solution in the Li 2 O—Al 2 O 3 —SiO 2 type 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. 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 is lowered, and it becomes difficult to confirm insoluble foreign matters and the like inside the container. Furthermore, when a chemical solution containing a sulfate is filled and stored in a glass container, BaO in the glass matrix may be eluted into the chemical solution to form barium sulfate crystals and become insoluble foreign matter.
　また、重量比で、ＳｉＯ２／（Ｌｉ２Ｏ＋Ｎａ２Ｏ＋Ｋ２Ｏ＋ＭｇＯ＋ＣａＯ＋ＳｒＯ＋ＢａＯ）が３以上、４以上、６以上、９以上、１０以上、１１以上、特に１２以上であることが好ましい。ＳｉＯ２／（Ｌｉ２Ｏ＋Ｎａ２Ｏ＋Ｋ２Ｏ＋ＭｇＯ＋ＣａＯ＋ＳｒＯ＋ＢａＯ）が小さすぎると、耐酸性や耐加水分解性が低下し易くなる。一方、ＳｉＯ２／（Ｌｉ２Ｏ＋Ｎａ２Ｏ＋Ｋ２Ｏ＋ＭｇＯ＋ＣａＯ＋ＳｒＯ＋ＢａＯ）が大きすぎると、溶解性が低下し易くなる。そのため、ＳｉＯ２／（Ｌｉ２Ｏ＋Ｎａ２Ｏ＋Ｋ２Ｏ＋ＭｇＯ＋ＣａＯ＋ＳｒＯ＋ＢａＯ）は３３以下、３０以下、２５以下、２０以下、特に１８以下であることが好ましい。 Further, the weight ratio of 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 12 or more. If SiO 2 /(Li 2 O+Na 2 O+K 2 O+MgO+CaO+SrO+BaO) is too small, the acid resistance and hydrolysis resistance are likely 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はＬｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶に固溶し、結晶性に大きな影響を与える成分である。ＺｎＯの含有量は０～１０％、０～５％、０～３％、０～１％、特に含有しないことが好ましい。ＺｎＯの含有量が多すぎると、結晶性が強くなりすぎて失透しやすくなり、結晶化ガラスの透過率が低下し、容器内部の不溶性異物等を確認し難くなる。 ZnO is a component that forms a solid solution with Li 2 O—Al 2 O 3 —SiO 2 type crystals and has a great influence on the crystallinity. The content of ZnO is 0 to 10%, 0 to 5%, 0 to 3%, and 0 to 1%, and it is particularly preferable not to contain it. If the content of ZnO is too large, the crystallinity becomes too strong and devitrification easily occurs, the transmittance of the crystallized glass decreases, and it becomes difficult to confirm insoluble foreign matters and the like inside the container.
　Ｐ２Ｏ５は粗大なＺｒＯ２結晶の析出を抑制する成分である。なお、粗大な結晶が析出すると、散乱光が発生し易くなる。その結果、結晶化ガラスの透過率が低下し、容器内部の不溶性異物等を確認し難くなる。Ｐ２Ｏ５の含有量は０～５％、０～４％、０～３％、特に含有しないことが好ましい。Ｐ２Ｏ５の含有量が多すぎると、Ｌｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶の析出量が少なくなり、熱膨張係数が高くなる傾向がある。また、結晶化ガラスの耐加水分解性、耐酸性、耐アルカリ性が低下する傾向がある。 P 2 O 5 is a component that suppresses precipitation of coarse ZrO 2 crystals. Note that when coarse crystals are deposited, scattered light is likely to be generated. As a result, the transmittance of the crystallized glass is lowered, and it becomes difficult to confirm insoluble foreign matters 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 not to contain it. When the content of P 2 O 5 is too large, the amount of precipitation of Li 2 O—Al 2 O 3 —SiO 2 based crystals tends to decrease, and the thermal expansion coefficient tends to increase. Further, the hydrolysis resistance, acid resistance and alkali resistance of the crystallized glass tend to be lowered.
　ＴｉＯ２は結晶化工程で結晶を析出させるための核形成剤となる成分である。一方で、多量に含有するとガラスの着色を著しく強める成分でもある。ＴｉＯ２の含有量は０～８％、０～７％、０．５～５％、特に１～５％であることが好ましい。ＴｉＯ２の含有量が多すぎると、ガラスの着色が強まりやすい。 TiO 2 is a component that serves as a nucleating agent for precipitating crystals in the crystallization process. On the other hand, when it is contained in a large amount, it is also a component that markedly enhances the coloring of glass. 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 large, the coloring of the glass tends to increase.
　ＺｒＯ２は結晶化工程で結晶を析出させるための核形成成分である。ＺｒＯ２の含有量は０～８％、０～５％、０．５～５％、特に１～５％であることが好ましい。ＺｒＯ２の含有量が多すぎると、粗大なＺｒＯ２結晶が析出してガラスが失透しやすくなり、ガラスが破損しやすくなる。 ZrO 2 is a nucleation component for precipitating crystals in the crystallization process. The ZrO 2 content is preferably 0 to 8%, 0 to 5%, 0.5 to 5%, and particularly preferably 1 to 5%. When the content of ZrO 2 is too large, coarse ZrO 2 crystals are precipitated and the glass is easily devitrified, and the glass is easily broken.
　ＳｎＯ２は清澄剤として作用する成分である。ＳｎＯ２の含有量は０～３％、０．００１～２％、０．００５～１％、０．００３～０．７％、特に０．０１～０．５％であることが好ましい。ＳｎＯ２の含有量が多すぎると、ガラスの着色が強まりやすい。 SnO 2 is a component that acts as a fining 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%. When the content of SnO 2 is too large, the coloring of the glass tends to be strong.
　また、ＳｎＯ２以外の清澄剤としてＡｓ２Ｏ３、Ｓｂ２Ｏ３、Ｃｌ、Ｆ、Ｎａ２ＳＯ４等を含有しても良い。これらの清澄剤の含有量の合計は１．５％以下、１％以下、０．７％以下、特に０．５％以下であることが好ましい。また、これらの清澄剤は単独で使用しても良いし、併せて使用することもできる。 As a fining 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 fining agents is preferably 1.5% or less, 1% or less, 0.7% or less, and particularly preferably 0.5% or less. Further, these fining agents may be used alone or in combination.
　Ｂ２Ｏ３はβ－石英固溶体からβ－スポジュメン固溶体への結晶転移を促進する成分である。なお、β－石英固溶体がβ－スポジュメンに転移すると、β－スポジュメンの析出に起因する局所的な熱膨張係数の増大によって、ガラスが破損しやすくなる。このため、Ｂ２Ｏ３は実質的に含有しない（具体的には０．０５％未満）ことが好ましい。 B 2 O 3 is a component that promotes the crystal transition from the β-quartz solid solution to the β-spodumene solid solution. When the β-quartz solid solution is transformed into β-spodumene, the glass tends to be broken due to the local increase in the coefficient of thermal expansion due to the precipitation of β-spodumene. Therefore, it is preferable that B 2 O 3 is not substantially contained (specifically, less than 0.05%).
　Ｆｅ２Ｏ３はガラスの着色を強める成分である。Ｆｅ２Ｏ３の含有量は０～０．１５％、０．００３～０．０４％、特に０．００３～０．０３％であることが好ましい。Ｆｅ２Ｏ３の含有量が多すぎると、ガラスの着色が強まりやすい。Ｆｅ２Ｏ３の含有量は少ない程、着色を抑制できるため好ましいが、例えば０．００３％を下回るような範囲にするには高価な高純度原料を使用する必要があり、製造コストが高くなってしまう。 Fe 2 O 3 is a component that enhances coloring of glass. The content of Fe 2 O 3 is preferably 0 to 0.15%, 0.003 to 0.04%, and more preferably 0.003 to 0.03%. If the content of Fe 2 O 3 is too large, the coloring of the glass tends to increase. The smaller the content of Fe 2 O 3, the more it is possible to suppress the coloring, but it is preferable to use an expensive high-purity raw material in order to achieve a range of less than 0.003%, for example, and the manufacturing cost increases. Will end up.
　上記の組成を有する結晶化ガラス中には、β－石英固溶体が析出しやすい。β─石英固溶体を主結晶として析出させれば、結晶化ガラスが可視光を透過しやすく、透明性が高まりやすい。またガラスの熱膨張係数を低下させることが容易になる。 The β-quartz solid solution is likely to precipitate in the crystallized glass having the above composition. If β-quartz solid solution is deposited as the main crystal, the crystallized glass easily transmits visible light and the transparency is easily increased. Further, it becomes easy to reduce the coefficient of thermal expansion of the glass.
　本発明の医薬用ガラス容器は、ＩＳＯ　４８０２－１（１９８８）に準じた耐加水分解性試験において、溶出液１００ｍＬ当たりの０．０１ｍｏｌ／Ｌの塩酸の消費量が０．５０ｍＬ以下、０．４５ｍＬ以下、特に０．４０ｍＬ以下であることが好ましく、ＩＳＯ　７２０（１９８５）に準じた耐加水分解性試験において、ガラス粉末１ｇ当たりの０．０２ｍｏｌ／Ｌの塩酸の消費量が０．１ｍＬ以下、０．０８ｍＬ以下、０．０６ｍＬ以下、０．０４ｍＬ以下、特に０．０３ｍＬ以下であることが好ましい。塩酸消費量が多すぎると、医薬用ガラス容器に薬液を充填、保存した際、ガラス成分、特にアルカリ成分の溶出が大幅に増加して薬液成分の変質を引き起こす恐れがある。 In the pharmaceutical glass container of the present invention, in a hydrolysis resistance test according to ISO 4802-1 (1988), the consumption of 0.01 mol/L hydrochloric acid per 100 mL of the eluate is 0.50 mL or less, 0.45 mL. In particular, it is preferably 0.40 mL or less, and in a 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 0.08 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 a medicinal solution is filled and stored in a pharmaceutical glass container, elution of a glass component, particularly an alkaline component, may be significantly increased to cause deterioration of the medicinal solution component.
　本発明の医薬用ガラス容器は、ヤング率が６０ＧＰａ以上、６５ＧＰａ以上、特に７０ＧＰａ以上であることが好ましい。ヤング率が小さすぎると、耐熱衝撃性が低下しやすくなる。なお、ヤング率の上限は特に限定されないが、現実的には３００ＧＰａ以下である。 The Young's modulus of the pharmaceutical glass container of the present invention is preferably 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 shock resistance tends to decrease. The upper limit of the Young's modulus is not particularly limited, but is actually 300 GPa or less.
　本発明の医薬用ガラス容器は、３０～３８０℃における熱膨張係数が、２０×１０－７／℃以下、１５×１０－７／℃以下、１０×１０－７／℃以下、７×１０－７／℃以下、５×１０－７／℃以下、特に２×１０－７／℃以下であることが好ましい。なお、耐熱衝撃性が特に必要とされる場合は、－５×１０－７／℃～５×１０－７／℃、－２．５×１０－７／℃～２．５×１０－７／℃、特に－２×１０－７／℃～２×１０－７／℃であることが好ましい。 The pharmaceutical 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 / C., particularly −2×10 −7 /° C. to 2×10 −7 /° C. is preferable.
　本発明の医薬用ガラス容器は、容器内部の不溶性異物等を確認する必要があるため、外観が透明であることが好ましく、具体的には、厚み１ｍｍ、波長４００～８００ｎｍにおける平均透過率が６５％以上、６８％以上、特に７０％以上であることが好ましい。当該波長域における平均透過率が低すぎると、医薬用ガラス容器の着色が強くなりすぎるとともに、透明性が低下しやすくなる。 The pharmaceutical glass container of the present invention preferably has a transparent appearance because it is necessary to confirm insoluble foreign matters and the like inside the container. Specifically, the average transmittance is 1 mm at a wavelength of 400 to 800 nm and 65%. % Or more, 68% or more, and particularly preferably 70% or more. If the average transmittance in the wavelength range is too low, the color of the pharmaceutical glass container becomes too strong and the transparency tends to decrease.
　本発明の医薬用ガラス容器は、厚み１ｍｍ、波長３５０ｎｍにおける透過率が６０％以下、５０％以下、４５％以下、特に４０％以下であることが好ましい。当該波長における透過率が高すぎると、薬剤の変質を引き起す可能性がある紫外線を遮蔽し難くなる。 The pharmaceutical glass container of the present invention preferably has a thickness of 1 mm and a transmittance at a wavelength of 350 nm of 60% or less, 50% or less, 45% or less, and particularly 40% or less. If the transmittance at the wavelength is too high, it becomes difficult to shield ultraviolet rays that may cause the deterioration of the drug.
　本発明の医薬用ガラス容器は、ＩＳＯ　６９５（１９９１）に準じた耐アルカリ性試験において、単位面積当たりの重量減少量ρが７５ｍｇ／ｄｍ２以下、７０ｍｇ／ｄｍ２以下、特に６５ｍｇ／ｄｍ２以下であることが好ましい。重量減少量ρが大きすぎると、内部に充填した薬剤の品質劣化を起こす虞がある 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.
　本発明の医薬用ガラス容器は、ＹＢＢ００３４２００４－２０１５に準じた耐酸性試験において、単位面積当たりの重量減少量の半量Ｓが１０ｍｇ／ｄｍ２以下、８ｍｇ／ｄｍ２以下、特に６ｍｇ／ｄｍ２以下であることが好ましい。重量減少量の半量Ｓが大きすぎると、内部に充填した薬剤の品質劣化を起こす虞がある In the acid resistance test according to YBB00342004-2015, the medicinal glass container of the present invention has a half amount S of the 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 the half amount S of the weight reduction amount is too large, the quality of the medicine filled inside may deteriorate.
　また、ＹＢＢ００３４２００４―２０１５に準じた耐酸性試験における単位面積当たりの重量減少量の半量ＳとＩＳＯ　６９５（１９９１）に準じた耐アルカリ性試験における単位面積当たりの重量減少量ρとの合量であるＳ＋ρが７０ｍｇ／ｄｍ２以下、６０ｍｇ／ｄｍ２以下、５０ｍｇ／ｄｍ２以下、４５ｍｇ／ｄｍ２以下、４０ｍｇ／ｄｍ２以下、３５ｍｇ／ｄｍ２以下、特に３０ｍｇ／ｄｍ２以下であることが好ましい。このようにすれば、更に耐酸性、耐アルカリ性を向上させることが可能である。 In addition, S+ρ, which is the sum of the half amount S of the weight reduction amount per unit area in the acid resistance test according to YBB00342004-2015 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, 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 acid resistance and alkali resistance.
　なお、本発明の医薬用ガラス容器の形状は特に限定されず、底面を有する容器形状でも、底面を有しない管形状であっても構わない。 The shape of the pharmaceutical 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.
　次に本発明の医薬用ガラス容器を製造する方法を説明する。以下の説明は、ダンナー法を用いた例である。なお、ダンナー法に限らず、ベロー法やダウンドロー法等の従来周知の任意の手法を用いて製造しても良い。 Next, a method for producing the pharmaceutical glass container of the present invention will be described. The following description is an example using the Dunner method. It should be noted that the manufacturing method is not limited to the Dunner method, and may be manufactured using any conventionally known method such as the bellow method or the downdraw method.
　まず、上記のガラス組成になるように、ガラス原料を調合してガラスバッチを作製する。次いで、このガラスバッチを１５５０～１７００℃の溶融窯に連続投入して溶融、清澄した後、得られた溶融ガラスを回転する耐火物上に巻きつけながら、耐火物先端部からエアを吹き出しつつ、当該先端部からガラスを管状に引き出し、冷却することによりガラス管を得る。得られたガラス管を所定の長さに切断、加工することにより、ガラス容器を得る。 First, prepare glass batches by mixing the glass raw materials so that the above glass composition is obtained. Next, this glass batch was continuously charged into a melting furnace at 1550 to 1700° C. to be melted and clarified. Then, while winding the obtained molten glass around a rotating refractory, while blowing air from the tip of the refractory, A glass tube is obtained by pulling the glass into a tubular form from the tip and cooling it. A glass container is obtained by cutting and processing the obtained glass tube into a predetermined length.
　次に得られたガラス容器を熱処理して結晶化させる。結晶化条件としては、まず核形成を７００～９５０℃（好ましくは７３０～９００℃）で６～３００分（好ましくは１０～１８０分）行い、続いて結晶成長を８００～１０５０℃（好ましくは８００～１０００℃）で６～６００分（好ましくは１０～３００分）行う。このようにしてβ－石英固溶体結晶が主結晶として析出した透明な医薬用ガラス容器を得ることができる。なお、核形成温度、結晶成長温度が低すぎる、及び／又は核形成時間、結晶成長時間が短すぎると、結晶が析出しにくくなる。また、核形成温度、結晶成長温度が高すぎる、及び／又は核形成時間、結晶成長時間が長すぎると、β─スポジュメン固溶体が析出する傾向があり、結晶が粗大化するため、透過率が低下する傾向がある。 Next, heat the resulting glass container to crystallize it. As crystallization conditions, first, nucleation is carried out at 700 to 950° C. (preferably 730 to 900° C.) for 6 to 300 minutes (preferably 10 to 180 minutes), and subsequently, crystal growth is carried out at 800 to 1050° C. (preferably 800). Perform at 6 to 600 minutes (preferably 10 to 300 minutes) at up to 1000°C. In this way, a transparent pharmaceutical glass container in which β-quartz solid solution crystals are deposited as main crystals can be obtained. Note that if the nucleation temperature and the crystal growth temperature are too low, and/or the nucleation time and the crystal growth time are too short, it becomes difficult for crystals to precipitate. Further, if the nucleation temperature and the crystal growth temperature are too high, and/or if the nucleation time and the crystal growth time are too long, the β-spodumene solid solution tends to precipitate, and the crystal becomes coarse, so the transmittance decreases. Tend to do.
　（実施例１）
　以下、本発明を実施例に基づいて説明するが、本発明はこれらの実施例に限定されるものではない。表１、２は本発明の実施例、及び比較例を示している。 (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 of the present invention and comparative examples.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
　実施例の医薬用ガラス容器は次のようにして作製した。表１、２に記載の組成を有するガラスとなるように原料を調合、混合し、原料バッチを得た。この原料バッチを１６００～１６８０℃の溶融窯に連続投入して溶融、清澄した後、得られた溶融ガラスを回転する耐火物上に巻きつけながら、耐火物先端部からエアを吹き出しつつ、当該先端部からガラスを管状に引き出し冷却することにより、外径１２～１５ｍｍφのガラス管を得た。得られたガラス管を長さ１６０～３００ｍｍに切断した後、ガラス管の片端をバーナーで融封することにより、長さ８０～１５０ｍｍのガラス容器（結晶化前のガラス容器）を得た。 The pharmaceutical glass container of the example was produced as follows. Raw materials were prepared and mixed so as to obtain glass having the composition shown in Tables 1 and 2, and a raw material batch was obtained. This raw material batch is continuously charged into a melting kiln at 1600 to 1680° C., melted and clarified, and then the obtained molten glass is wound around a rotating refractory material while blowing air from the tip portion of the refractory material, A glass tube having an outer diameter of 12 to 15 mmφ was obtained by pulling the glass out of the section in a tubular shape and cooling it. The obtained glass tube was cut into a length of 160 to 300 mm, and one end of the glass tube was fused with a burner to obtain a glass container having a length of 80 to 150 mm (glass container before crystallization).
　ガラス容器に対して、７３０～７８０℃で５～１８０分熱処理して核形成を行った後、さらに８７０～９２０℃で５～６０分の熱処理を行い結晶成長させることにより医薬用ガラス容器を得た。得られた医薬用ガラス容器（結晶化後のガラス容器）について、析出結晶、耐加水分解性、耐アルカリ性、耐酸性、ヤング率、熱膨張係数、波長４００～８００ｎｍにおける平均透過率、波長３５０ｎｍにおける透過率を評価した。結果を表１、２に示す。 The glass container is heat-treated at 730 to 780° C. for 5 to 180 minutes for nucleation, and then further heat-treated at 870 to 920° C. for 5 to 60 minutes to grow crystals, thereby obtaining a glass container for medicine. It was Regarding the obtained pharmaceutical glass container (glass container after crystallization), precipitated crystals, hydrolysis resistance, alkali resistance, acid resistance, Young's modulus, coefficient of thermal expansion, average transmittance at wavelength 400 to 800 nm, wavelength 350 nm The transmittance was evaluated. The results are shown in Tables 1 and 2.
　析出結晶はＸ線回折装置（リガク製 全自動多目的水平型Ｘ線回折装置　Ｓｍａｒｔ　Ｌａｂ）を用いて評価した。 The precipitated crystals were evaluated using an X-ray diffractometer (manufactured by Rigaku, fully automatic multipurpose horizontal X-ray diffractometer, Smart Lab).
　耐加水分解性は、ＩＳＯ　４８０２－１（１９８８）に準じた耐加水分解性試験方法、及びＩＳＯ　７２０（１９８５）に準じた耐加水分解試験方法により評価した。詳細な試験手順は以下の通りである。 The hydrolysis resistance was evaluated by the hydrolysis resistance test method according to ISO 4802-1 (1988) and the hydrolysis resistance test method according to ISO 720 (1985). The detailed test procedure is as follows.
　（ＩＳＯ　４８０２－１（１９８８））
　実施例で得られたガラス容器の内面と外面を精製水で洗浄した。ガラス容器の全容積の９０％に相当する精製水（１０.６ｍＬ）を、ガラス容器に充填した。ガラス容器の口部分はアルミホイルで蓋をし、輪ゴムで止めた。精製水を入れたガラス容器を、オートクレーブ内に設置し、室温から１００℃まで昇温後、１００℃から１２１℃までは１℃／分の昇温速度で加熱した。１２１℃に到達後６０分間保持し、さらに１００℃まで０．５℃／分で冷却した。その後、オートクレーブからガラス容器を取り出し、精製水を入れたトレイ内に静置させ常温まで冷却した。冷却後、ガラス容器内の溶出液（１０ｍＬ）を２００ｍＬのコニカルビーカーに移した。実施例の方法で同様にして得られた５個のガラス容器を用いて、同様の操作を５回行うことにより溶出液５０ｍＬを得た。ホールピペットを用いて溶出液２５ｍＬずつ分取し、２つの５０ｍＬのコニカルビーカーへ移した。ブランクも同様に精製水５０ｍＬからホールピペットを用いて２５ｍＬずつ分取し、２つの５０ｍＬのコニカルビーカーへ移した。溶出液とブランクにそれぞれメチルレッド指示薬を５０μＬずつ添加した。０．０１ｍｏｌ／Ｌの塩酸をビュレットに充填し、溶出液２５ｍＬに対して中和滴定を行った。溶出液の色がブランクの色と同じになったときの塩酸消費量を記録した。試験はｎ＝２で実施し、平均値を算出後、溶出液１００ｍＬに対する塩酸消費量を算出した。 (ISO 4802-1 (1988))
The inner surface and the outer surface of the glass container obtained in the example were washed with purified water. Purified water (10.6 mL) corresponding to 90% of the total volume of the glass container was filled in the glass container. The mouth of the glass container was covered with aluminum foil and secured with a rubber band. A glass container containing purified water was placed in an autoclave, heated from room temperature to 100°C, and then heated from 100°C to 121°C at a heating rate of 1°C/min. After reaching 121°C, the temperature was maintained for 60 minutes, and further cooled to 100°C at 0.5°C/minute. After that, the glass container was taken out from the autoclave, allowed to stand in a tray containing purified water, and cooled to room temperature. After cooling, the eluate (10 mL) in the glass container was transferred to a 200 mL conical beaker. The same operation was performed 5 times using 5 glass containers obtained in the same manner as in the example to obtain 50 mL of the eluate. 25 mL of the eluate was collected using a whole pipette and transferred to two 50 mL conical beakers. Similarly, for the blank, 25 mL each was collected from 50 mL of purified water using a whole pipette and transferred to two 50 mL conical beakers. 50 μL of methyl red indicator was added to each of the eluate and the blank. A bullet was filled with 0.01 mol/L hydrochloric acid, and 25 mL of the eluate was subjected to neutralization titration. The hydrochloric acid consumption was recorded when the color of the eluate was the same as the color of the blank. The test was performed at n=2, and after calculating the average value, the hydrochloric acid consumption amount with respect to 100 mL of the eluate was calculated.
　（ＩＳＯ　７２０（１９８５））
　実施例で得られたガラス容器の内面と外面をエタノールで良く拭き、アルミナ製の乳鉢と乳棒で試料を粉砕した後、ステンレス製の目開き７１０μｍ、４２５μｍ、３００μｍの３つの篩を用いて分級した。３００μｍの篩上に残ったガラス粉末は採取し、７００μｍ、４２５μｍの篩に残ったガラスは再度粉砕した。３００μｍの篩上のガラス粉末が１０ｇ以上になるまで同じ作業を繰り返した。３００μｍの篩上に残った試料粉末をビーカーへ移し、３０ｍＬのアセトンを注ぎ１分間超音波洗浄を行った。上澄み液を廃棄し、その後４回同じ作業を繰り返した。その後、３０ｍＬのアセトンをビーカーに注ぎ、手で軽くゆすり上澄み液だけを廃棄する作業を３回繰り返した。ビーカーの口をアルミホイルで多い、複数個所穴を空けた後、１１０℃のオーブンで３０分間乾燥させた。その後、取り出しデシケーター内で３０分間冷却した。得られた試料粉末を、電子天秤を用いて１０ｇ±０．０００１ｇで秤量し、２５０ｍＬのフラスコに入れ、超純水５０ｍＬを加えた。ブランクとして超純水５０ｍＬのみを充填したフラスコも準備した。フラスコの口を石英容器で塞ぎ、オートクレーブに入れて１２１℃、３０分間熱処理を行った。この時、１００℃から１２１℃までは１℃／分で昇温し、１２１℃から１００℃までは２℃／分で冷却した。９５℃まで冷却後、フラスコを取り出し超純水が入ったトレイに静置させ３０分間冷却した。冷却後、フラスコ内の溶出液をコニカルビーカーに移した。１５ｍＬの超純水をホールピペットで採取し、フラスコ内に注ぎいれ、軽くゆすり上澄み液だけをコニカルビーカーに流し入れた。同様の作業をあと２回行った。ブランクについても同様の操作を行い溶出液を得た。サンプルとブランクの溶出液にメチルレッドをそれぞれ０．０５ｍＬ滴下した。０．０２ｍｏｌ／Ｌの塩酸をサンプルの溶出液に滴下し、ブランクと同じ色になったときの塩酸消費量を記録し、ガラス１ｇ当たりの塩酸消費量を算出した。 (ISO 720 (1985))
The inner and outer surfaces of the glass container obtained in Example were thoroughly wiped with ethanol, the sample was crushed with an alumina mortar and pestle, and then classified using three sieves of stainless steel openings 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 ground again. The same operation was repeated until the amount of glass powder on the 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 the same operation was repeated 4 times thereafter. After that, 30 mL of acetone was poured into a beaker and gently shaken by hand to discard only the supernatant, which was repeated three times. After making a plurality of holes in the beaker with aluminum foil, the beaker was dried in an oven at 110° C. for 30 minutes. After that, 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, put 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 from 100° C. to 121° C. at 1° C./min, and cooled from 121° C. to 100° C. at 2° C./min. After cooling to 95° C., the flask was taken out and allowed to stand on a tray containing ultrapure water and cooled 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, gently 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 of methyl red was added dropwise to each of the sample and blank eluates. 0.02 mol/L hydrochloric acid was added dropwise to the eluate of the sample, the hydrochloric acid consumption when the same color as the blank was recorded, and the hydrochloric acid consumption per 1 g of glass was calculated.
　耐アルカリ性はＩＳＯ　６９５（１９９１）に準じた方法により評価した。詳細な試験手順は以下の通りである。まず、全ての面を鏡面研磨仕上げとした総表面積が１５ｃｍ２のガラスサンプルを準備し、前処理として試料をフッ酸（４０重量％）と塩酸（２ｍｏｌ／Ｌ）を体積比で１：９となるように混合した溶液に浸漬させ、１０分間マグネティックスターラーで攪拌した。次いでサンプルを取出し、超純水中で２分間の超音波洗浄を３回行った後、エタノール中で１分間の超音波洗浄を２回行った。次に、試料を１１０℃のオーブンの中で１時間乾燥させ、デシケーター内で３０分間冷却した。このようにして得られた試料の重量ｍ１を精度±０．１ｍｇまで測定し、記録した。続いてステンレス製の容器に１ｍｏｌ／Ｌの水酸化ナトリウム水溶液と０．５ｍｏｌ／Ｌの炭酸ナトリウム水溶液を体積比で１：１となるように混合した溶液を８００ｍＬ入れ、電熱器を用いて沸騰するまで加熱し、白金線で吊したサンプルを投入して３時間保持した。試験中の液量の減少を防ぐために、容器の蓋の開口部はガスケット及び冷却管で栓をした。その後、サンプルを取り出し、１ｍｏｌ／Ｌの塩酸５００ｍＬの入ったビーカーに３回浸漬した後、超純水中で１分間の超音波洗浄を３回行い、エタノール中で１分間の超音波洗浄を２回行った。さらに洗浄したサンプルを１１０℃のオーブンの中で１時間乾燥し、デシケーター内で３０分間冷却した。このようにして処理した試料の重量ｍ２を精度±０．１ｍｇまで測定し、記録した。最後に沸騰溶液に投入する前後の試料の重量ｍ１、ｍ２ｍｇと試料の総表面積Ａｃｍ２から式１によって単位面積当たりの重量減少量ρを算出した。
　［式１］　単位面積当たりの重量減少量ρ＝１００×（ｍ１－ｍ２）／Ａ The alkali resistance was evaluated by the 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 in which all surfaces were mirror-polished was prepared. As a pretreatment, the sample was hydrofluoric acid (40 wt %) 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 subjected to ultrasonic cleaning for 2 minutes in ultrapure water three times, and then ultrasonic cleaning for 1 minute in ethanol 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 to an accuracy of ±0.1 mg and recorded. Subsequently, 800 mL of a solution prepared by mixing a 1 mol/L sodium hydroxide aqueous solution and a 0.5 mol/L sodium carbonate aqueous solution at a volume ratio of 1:1 was placed in a stainless steel container and boiled using an electric heater. The sample was heated up to that temperature, a sample hung with a platinum wire was added, and the sample was held for 3 hours. The opening of the lid of the container was capped with a gasket and cooling tube to prevent loss of liquid volume during the test. Then, the sample was taken out, immersed in a beaker containing 500 mL of 1 mol/L hydrochloric acid three times, then ultrasonically cleaned in ultrapure water for 1 minute 3 times, and ultrasonically cleaned in ethanol for 1 minute 2 times. I went there. The washed sample was 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 to an accuracy of ±0.1 mg and recorded. Finally, the weight reduction amount ρ per unit area was calculated by Formula 1 from the weights m 1 and m 2 of the sample before and after the addition to the boiling solution and the total surface area Acm 2 of the sample.
[Formula 1] Weight reduction amount per unit area ρ=100×(m 1 −m 2 )/A
　耐酸性は、ＹＢＢ００３４２００４―２０１５に準じた方法により評価した。詳細な試験手順は以下の通りである。まず全ての表面を鏡面研磨仕上げとした総表面積が５０ｃｍ２のガラスサンプルを準備し、前処理として試料をフッ酸（４０質量％）と塩酸（２ｍｏｌ／Ｌ）を体積比で１：９となるように混合した溶液に浸漬し、１０分間マグネティックスターラーで攪拌した。次いでサンプルを取出し、超純水中で１分間の超音波洗浄を３回行った後、エタノール中で１分間の超音波洗浄を２回行った。次に、サンプルを１１０℃のオーブンの中で１時間乾燥させ、デシケーター内で３０分間冷却した。このようにして得られたサンプルの質量ｍ１を精度±０．１ｍｇまで測定し記録した。続いて石英ガラス製のビーカーに６ｍｏｌ／Ｌの塩酸８００ｍＬを入れ、電熱器を用いて沸騰するまで加熱し、白金線で吊したサンプルを投入して６時間保持した。試験中の液量の減少を防ぐために、容器の蓋の開口部はガスケット及び冷却管で栓をした。その後、サンプルを取り出し、超純水中で１分間の超音波洗浄を３回行った後、エタノール中で１分間の超音波洗浄を２回行った。さらに洗浄したサンプルを１１０℃のオーブンの中で1時間乾燥し、デシケーター内で３０分間冷却した。このようにして処理した試料の質量片ｍ２を精度±０．１ｍｇまで測定し、記録した。最後に沸騰塩酸に投入する前後の試料の質量ｍ１、ｍ２ｍｇと試料の総表面積Ａｃｍ２から以下の式２によって単位面積当たりの重量減少量の半量Ｓを算出した。
　［式２］　単位面積当たりの重量減少量の半量Ｓ＝１００×（ｍ１－ｍ２）／（２×Ａ） The acid resistance was evaluated by the method according to YBB00342004-2015. The detailed test procedure is as follows. First, a glass sample having a total surface area of 50 cm 2 with all surfaces mirror-polished was prepared. As a pretreatment, the sample was hydrofluoric acid (40% by mass) and hydrochloric acid (2 mol/L) in a volume ratio of 1:9. The mixture was soaked in the mixed solution and stirred with a magnetic stirrer for 10 minutes. Then, the sample was taken out and subjected to ultrasonic cleaning for 1 minute three times in ultrapure water, and then ultrasonic cleaning for 1 minute twice in ethanol. 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 to 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 using an electric heater until it boiled, and a sample hung with a platinum wire was placed and held for 6 hours. The opening of the lid of the container was capped with a gasket and cooling tube to prevent loss of liquid volume during the test. Then, the sample was taken out and subjected to ultrasonic cleaning for 1 minute three times in ultrapure water, and then ultrasonic cleaning for 1 minute twice in ethanol. The washed sample was 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 thus treated was measured to an accuracy of ±0.1 mg and recorded. Finally, 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, the half amount S of the weight reduction amount per unit area was calculated by the following formula 2.
[Formula 2] Half amount of weight reduction per unit area S=100×(m 1 −m 2 )/(2×A)
　ヤング率は、共振法（日本テクノプラス製ＪＥ－ＲＴ３）にて測定した。 The Young's modulus was measured by the resonance method (JE-RT3 manufactured by Nippon Techno Plus).
　熱膨張係数は、２０ｍｍ×５ｍｍφに加工した試料を用いて、３０～３８０℃の温度域で測定した平均線熱膨張係数により評価した。測定にはＮＥＴＺＳＣＨ製Ｄｉｌａｔｏｍｅｔｅｒを用いた。 The thermal expansion coefficient was evaluated by the average linear thermal expansion coefficient measured in a temperature range of 30 to 380° C. using a sample processed to 20 mm×5 mmφ. A dilatometer manufactured by NETZSCH was used for the measurement.
　波長４００～８００ｎｍにおける平均透過率、及び波長３５０ｎｍにおける透過率は、肉厚１ｍｍに両面光学研磨した試料について、分光光度計を用いて測定した波長３５０～８００ｎｍでの透過率により評価した。測定には日本分光製分光光度計 Ｖ－６７０を用いた。 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 whose both sides were optically polished to a thickness of 1 mm. For the measurement, a spectrophotometer V-670 manufactured by JASCO Corporation was used.
　表１、２から明らかなように、実施例１～１４は、β－石英固溶体が析出しており、耐加水分解性、透過特性に優れており、ヤング率が高く、熱膨張係数が０に近かった。一方、比較例１、２は、非晶質ガラスであり、塩酸消費量が多く耐加水分解性に劣っており、また熱膨張係数が４０×１０－７／℃以上と高かった。 As is clear from Tables 1 and 2, in Examples 1 to 14, β-quartz solid solution was precipitated, the hydrolysis resistance and the permeation characteristics were excellent, the Young's modulus was high, and the thermal expansion coefficient was 0. It was close. On the other hand, Comparative Examples 1 and 2 were amorphous glasses, consumed a large amount of hydrochloric acid, had poor hydrolysis resistance, and had a high coefficient of thermal expansion of 40×10 −7 /° C. or higher.
　（実施例２）
　本発明の別の医薬用容器のガラス組成例を表３に示す。 (Example 2)
Table 3 shows another glass composition example of the pharmaceutical container of the present invention.
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
　本発明の医薬用ガラス容器は、アンプル、バイアル、プレフィルドシリンジ、カートリッジ、凍結乾燥製剤用容器、紫外線により変質しやすい製剤等の、一次包装材料、保護用容器等として好適に使用できる。 The pharmaceutical 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 freeze-dried preparations, preparations that are easily deteriorated by ultraviolet rays, and the like.

Claims (12)

  1. 　結晶化ガラスからなることを特徴とする医薬用ガラス容器。 A glass container for medicine, which is made of crystallized glass.
  2. 　ＩＳＯ　４８０２－１（１９８８）に準じた耐加水分解性試験において、溶出液１００ｍＬ当たりの０．０１ｍｏｌ／Ｌの塩酸の消費量が０．５０ｍＬ以下であることを特徴とする請求項１に記載の医薬用ガラス容器。 In the hydrolysis resistance test according to ISO 4802-1 (1988), the consumption of 0.01 mol/L hydrochloric acid per 100 mL of the eluate is 0.50 mL or less, The method according to claim 1, Pharmaceutical glass container.
  3. 　結晶化ガラスがＬｉ２Ｏ－Ａｌ２Ｏ３－ＳｉＯ２系結晶化ガラスであることを特徴とする請求項１又は２に記載の医薬用ガラス容器。 The pharmaceutical glass container according to claim 1 or 2, wherein the crystallized glass is a Li 2 O-Al 2 O 3 -SiO 2 system crystallized glass.
  4. 　結晶化ガラス中に、主結晶としてβ－石英固溶体が析出していることを特徴とする請求項１～３のいずれかに記載の医薬用ガラス容器。 The pharmaceutical 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.
  5. 　結晶化ガラスが、重量％で、ＳｉＯ２　４０～７５％、Ａｌ２Ｏ３　６～３０％、Ｌｉ２Ｏ　０．１～１０％を含有することを特徴とする請求項１～４のいずれかに記載の医薬用ガラス容器。 The crystallized glass contains, by weight, 40 to 75% of SiO 2 , 6 to 30% of Al 2 O 3 and 0.1 to 10% of Li 2 O, according to any one of claims 1 to 4. The glass container for pharmaceuticals according to 1.
  6. 　ヤング率が６０ＧＰａ以上であることを特徴とする請求項１～５のいずれかに記載の医薬用ガラス容器。 The pharmaceutical glass container according to any one of claims 1 to 5, wherein the Young's modulus is 60 GPa or more.
  7. 　３０～３８０℃における熱膨張係数が２０×１０－７／℃以下であることを特徴とする請求項１～６のいずれかに記載の医薬用ガラス容器。 7. The pharmaceutical glass container according to claim 1, which has a thermal expansion coefficient of 20×10 −7 /° C. or less at 30 to 380° C.
  8. 　厚み１ｍｍ、波長４００～８００ｎｍにおける平均透過率が６５％以上であることを特徴とする請求項１～７のいずれかに記載の医薬用ガラス容器。 The pharmaceutical glass container according to any one of claims 1 to 7, which has a thickness of 1 mm and an average transmittance of 65% or more at a wavelength of 400 to 800 nm.
  9. 　厚み１ｍｍ、波長３５０ｎｍにおける透過率が６０％以下であることを特徴とする請求項１～８のいずれかに記載の医薬用ガラス容器。 The pharmaceutical glass container according to any one of claims 1 to 8, which has a thickness of 1 mm and a transmittance at a wavelength of 350 nm of 60% or less.
  10. 　ＩＳＯ　６９５（１９９１）に準じた耐アルカリ性試験において、単位面積当たりの重量減少量ρが７５ｍｇ／ｄｍ２以下であることを特徴とする請求項１～９のいずれかに記載の医薬用ガラス容器。 The glass container for pharmaceutical use according to any one of claims 1 to 9, wherein a weight loss amount ρ per unit area is 75 mg/dm 2 or less in an alkali resistance test according to ISO 695 (1991).
  11. 　重量比で、ＳｉＯ２／（Ｌｉ２Ｏ＋Ｎａ２Ｏ＋Ｋ２Ｏ＋ＭｇＯ＋ＣａＯ＋ＳｒＯ＋ＢａＯ）が３以上であって、ＹＢＢ００３４２００４―２０１５に準じた耐酸性試験における単位面積当たりの重量減少量の半量ＳとＩＳＯ　６９５（１９９１）に準じた耐アルカリ性試験における単位面積当たりの重量減少量ρとの合量であるＳ＋ρが７０ｍｇ／ｄｍ２以下であることを特徴とする医薬用ガラス容器。 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 is half the weight reduction amount per unit area S and ISO 695 (1991) in the acid resistance test according to YBB00342004-2015. A pharmaceutical glass container, wherein S+ρ, which is the total amount with the weight reduction amount ρ per unit area in a similar alkali resistance test, is 70 mg/dm 2 or less.
  12. 　ガラス管を加工してガラス容器を得た後、ガラス容器を熱処理して結晶化させることを特徴とする医薬用ガラス容器の製造方法。 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.
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JP2012533509A (en) * 2009-07-20 2012-12-27 ショット アクチエンゲゼルシャフト High performance glass ceramic and method for producing high performance glass ceramic
JP2015013793A (en) * 2013-06-06 2015-01-22 日本電気硝子株式会社 Glass for pharmaceutical containers
CN104495007A (en) * 2014-12-10 2015-04-08 甘肃惠森药业发展有限公司 Method for storing traditional Chinese medicinal materials by microcrystalline glass

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