Glass tubes, primary packaging containers for pharmaceuticals, and alkali silicate glass.

Abstract

Tube glass according to the present invention comprises alkali silicate glass and is characterized in that: the glass composition is substantially free of B2O3 and Al2O3; and the mass reduction amount ρ (mg / dm2) in an alkali-resistance test in conformance with ISO 695(199105-15) is class A1.

Description

[Technical Field]

[0001] This invention relates to glass tubes, primary packaging containers for pharmaceuticals, and alkali silicate glass. [Background technology]

[0002] Traditionally, borosilicate glass, which has high chemical durability and excellent visibility, has been used for primary pharmaceutical packaging containers (glass containers) such as vials and ampoules.

[0003] Primary pharmaceutical packaging containers, such as vials and ampoules, are manufactured by processing them into the desired container shape and then slowly cooling them in an annealing furnace heated to near the annealing point to remove residual stress. [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] Japanese Patent Publication No. 2017-218353 [Patent Document 2] Patent No. 6400168 [Overview of the project] [Problems that the invention aims to solve]

[0005] One method for shaping glass tubes into containers involves locally heating the glass with a burner while forming the mouth, neck, and bottom. However, during burner heating, alkaline borate evaporates are generated from the glass surface and can condense and deposit on the inner surface of the container, forming a foreign layer. This formation of a foreign layer significantly reduces the chemical durability and hydrolysis resistance of the glass, potentially causing alkaline components to leach out of the glass during storage of the chemical solution, leading to changes in the pH and deterioration of the solution. Furthermore, the foreign layer can peel off from the inner surface of the container, causing a phenomenon called delamination, where insoluble foreign matter known as flakes is generated in the chemical solution.

[0006] Therefore, in Patent Document 1, it is proposed to suppress the evaporation of alkali borate during burner heating by removing B2O3 from the glass composition of the glass container. However, since glass without B2O3 has a high high-temperature viscosity, the content of Na2O that reduces the high-temperature viscosity increases. As a result, there is a risk of an increase in the amount of alkali eluted from the glass, inducing a pH change in the chemical solution. If the pH of the chemical solution changes, there is a risk that the original performance of the chemical solution cannot be exhibited.

[0007] In addition, delamination often occurs when a chemical solution using a citrate buffer solution, a phosphate buffer solution, etc., which exhibits behavior similar to strong alkalinity even near neutrality, is filled and stored in a glass container. Therefore, the alkali resistance of the glass container is important for suppressing delamination.

[0008] By the way, in recent years, the number of Alzheimer's disease patients has been increasing. One of the causes of Alzheimer's disease is the intake of aluminum ions. If aluminum ions eluted from a glass container are taken into the body and accumulated, the risk of developing Alzheimer's disease may increase.

[0009] In addition, when a phosphate buffer solution is stored in a glass container containing Al2O3, insoluble foreign matter may occur due to the reaction between aluminum ions eluted from the glass and the phosphate buffer solution.

[0010] In Patent Document 2, in order to suppress the elution of aluminum ions, borosilicate glass not containing Al2O3 in the glass composition has been proposed. However, since this glass contains B2O3 in the glass composition, it cannot sufficiently suppress the evaporation of alkali borate during container processing.

[0011] The object of the present invention is to provide glass tubes, primary pharmaceutical packaging containers, and alkali silicate glass that have high alkali resistance, reduce the amount of alkali borate evaporated during burner heating, reduce the risk of developing Alzheimer's disease, and furthermore, are less likely to cause pH changes in the drug solution and are free from the risk of generating insoluble foreign matter caused by aluminum ions leached from the glass. [Means for solving the problem]

[0012] The inventors of the present invention have conducted various experiments and found that the above problems can be solved by substantially removing B2O3 and Al2O3 from the glass composition and increasing alkali resistance to a predetermined level, and propose this as the present invention. That is, the glass tube of the present invention is a glass tube made of alkali silicate glass, which substantially does not contain B2O3 and Al2O3 in the glass composition, and the mass loss ρ (mg / dm) when an alkali resistance test is performed in accordance with ISO 695 (199105-15) is... 2 The glass is characterized by being of class A1. "Substantially free of B2O3 and Al2O3 in the glass composition" means that the B2O3 content in the glass composition is 0.5 mol% or less, and the Al2O3 content is 0.5 mol% or less. The "alkali resistance test in accordance with ISO 695 (199105-15)" can be performed using the method described in the Examples section.

[0013] Furthermore, in the glass tube of the present invention, the total cation mass QC (mg / dm³) of eluted components per unit surface area when an elution test is performed in an acidic solution is obtained. 2 The QC (mg / dm³) is preferably 1.6 or less. 2 The calculation of QO can be performed using the method described in the "Measurement of Acid Resistance" section. Furthermore, the QO value, which is calculated by assuming that each eluted component is an oxide of the respective eluted component, can also be calculated using the method described in the "Measurement of Acid Resistance" section, and a QO of 3.1 or less is preferable.

[0014] Furthermore, in the glass tubes of the present invention, it is preferable that the amount of hydrochloric acid consumed H (mL / g) until the eluate is neutralized when alkaline components are eluted according to ISO 720 (1985) is of class HGA1 or HGA2 according to ISO 720 (1985). The "amount of hydrochloric acid consumed until the eluate is neutralized when alkaline components are eluted according to ISO 720 (1985)" can be measured by the method described in the Examples section.

[0015] Furthermore, the glass tubes of the present invention preferably contain, in molar percentages, SiO2 50-88%, Li2O+Na2O+K2O 0.1-20%, TiO2 0-20%, and ZrO2 0.005-12%, and substantially contain B2O3 and Al2O3. Note that "Li2O+Na2O+K2O" refers to the combined amounts of Li2O, Na2O, and K2O.

[0016] Furthermore, it is preferable that the glass tube of the present invention has a Na2O content of 0 to 20 mol% in its glass composition.

[0017] Furthermore, it is preferable that the glass tube of the present invention has a K2O content of 0 to 20 mol% in its glass composition.

[0018] Furthermore, the glass tube of the present invention preferably has a MgO+CaO+SrO+BaO content of 0.1 to 10 mol% in its glass composition. Note that "MgO+CaO+SrO+BaO" refers to the total amount of MgO, CaO, SrO, and BaO.

[0019] Furthermore, the glass tube of the present invention preferably has an average transmittance of 60% or more at an optical path length of 1 mm and a wavelength of 400 to 800 nm. The "average transmittance at an optical path length of 1 mm and a wavelength of 400 to 800 nm" can be measured with a commercially available spectrophotometer.

[0020] Furthermore, it is preferable that the glass tube of the present invention has a chemical resistance factor value of 98.5 or less, which is expressed as the sum of 10 times H, 10 times QC, and ρ, i.e., {(amount of hydrochloric acid consumed when a water resistance test is conducted in accordance with ISO 720) × 10 + (total cation mass of eluted components per unit surface area when an elution test is conducted in an acidic solution) × 10 + (mass loss when an alkali resistance test is conducted in accordance with ISO 695)}.

[0021] Furthermore, the glass tubing of the present invention is preferably used in primary packaging containers for pharmaceuticals, scientific and chemical equipment, and corrosion-resistant piping for chemical plants.

[0022] The present invention relates to a primary pharmaceutical packaging container made by processing a glass tube, characterized in that the glass tube is the glass tube described above.

[0023] The alkali silicate glass of the present invention is characterized in that it substantially does not contain B2O3 and Al2O3 in its glass composition, and has a chemical resistance factor value of 98.5 or less, which is expressed as the sum of 10 times H, 10 times QC, and ρ, i.e., {(amount of hydrochloric acid consumed when a water resistance test is performed in accordance with ISO 720 H) × 10 + (total cation mass of eluted components per unit surface area when an elution test is performed in accordance with an acidic solution QC) × 10 + (mass loss when an alkali resistance test is performed in accordance with ISO 695 ρ)}.

[0024] Furthermore, the alkali silicate glass of the present invention is characterized by having a glass composition of SiO2 60-88%, K2O 0.1-20%, CaO 0-6.5%, TiO2 0.1-20%, and ZrO2 0.005-12% in molar percentages, with a molar ratio of TiO2 / (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO) of 0.3-3.5 and a molar ratio of K2O / ZrO2 of 0.9 or higher, and being substantially free of B2O3 and Al2O3. Note that "Li2O+Na2O+K2O+MgO+CaO+SrO+BaO" refers to the combined amounts of Li2O, Na2O, K2O, MgO, CaO, SrO, and BaO. "TiO2 / (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO)" means the value obtained by dividing the TiO2 content by the total amount of Li2O, Na2O, K2O, MgO, CaO, SrO, and BaO. "K2O / ZrO2" means the value obtained by dividing the K2O content by the ZrO2 content.

[0025] Furthermore, in the alkali silicate glass of the present invention, the mass loss ρ (mg / dm) when an alkali resistance test was conducted in accordance with ISO 695 (199105-15) was obtained. 2 It is preferable that ) is of class A1.

[0026] Furthermore, in the alkali silicate glass of the present invention, the total cation mass QC (mg / dm³) of eluted components per unit surface area when an elution test is performed in an acidic solution is obtained. 2 It is preferable that ) is 1.6 or less.

[0027] Furthermore, in the alkali silicate glass of the present invention, it is preferable that the amount of hydrochloric acid consumed H (mL / g) until the eluate is neutralized when an alkaline component is eluted according to ISO 720 (1985) is of class HGA1 or HGA2 according to ISO 720 (1985). The "amount of hydrochloric acid consumed until the eluate is neutralized when an alkaline component is eluted according to ISO 720 (1985)" can be measured by the method described in the Examples section.

[0028] The alkali silicate glass of the present invention is characterized in that it substantially does not contain B2O3 and Al2O3 in its glass composition, and has a chemical resistance factor value of 98.5 or less, which is expressed as the sum of 10 times H, 10 times QC, and ρ, i.e., {(amount of hydrochloric acid consumed when a water resistance test is performed in accordance with ISO 720 H) × 10 + (total cation mass of eluted components per unit surface area when an elution test is performed in accordance with an acidic solution QC) × 10 + (mass loss when an alkali resistance test is performed in accordance with ISO 695 ρ)}.

[0029] Furthermore, the alkali silicate glass of the present invention is characterized by being substantially free of B2O3 and Al2O3 in its glass composition, containing SiO2 66% or more and less than 84% in molar percentage, MgO+CaO+SrO+BaO 10% or less, and ZrO 28.5% or less, with a molar ratio of (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO) / SiO2 of 0.4 or less. Note that "Li2O+Na2O+K2O+MgO+CaO+SrO+BaO" refers to the total amount of Li2O, Na2O, K2O, MgO, CaO, SrO, and BaO. "(Li2O+Na2O+K2O+MgO+CaO+SrO+BaO) / SiO2" refers to the value obtained by dividing the total amount of Li2O, Na2O, K2O, MgO, CaO, SrO, and BaO by SiO2.

[0030] Furthermore, in the alkali silicate glass of the present invention, the mass loss ρ (mg / dm) when an alkali resistance test was conducted in accordance with ISO 695 (199105-15) was obtained. 2 It is preferable that ) is of class A1.

[0031] Furthermore, in the alkali silicate glass of the present invention, the total cation mass QC (mg / dm³) of eluted components per unit surface area when an elution test is performed in an acidic solution is obtained. 2 It is preferable that ) is 1.6 or less.

[0032] In addition, in the alkali silicate glass of the present invention, it is preferable that the hydrochloric acid consumption H (mL / g) until the eluate is neutralized when eluting the alkali component in accordance with ISO 720 (1985) is class HGA1 or HGA2 in ISO 720 (1985). The "hydrochloric acid consumption until the eluate is neutralized when eluting the alkali component in accordance with ISO 720 (1985)" can be measured by the method described in the column of the examples.

[0033] In addition, the alkali silicate glass of the present invention contains, as a glass composition, in mol%, 66% or more and less than 84% of SiO2, 1% or less of B2O3, 1% or less of Al2O3, 10% or less of MgO + CaO + SrO + BaO, and 8.5% or less of ZrO2, and is characterized in that the molar ratio (Li2O + Na2O + K2O + MgO + CaO + SrO + BaO) / SiO2 is 0.4 or less.

[0034] In addition, the alkali silicate glass of the present invention preferably has a mass reduction amount ρ (mg / dm 2 ) of class A1 when performing an alkali resistance test in accordance with ISO 695 (199105-15).

[0035] In addition, the alkali silicate glass of the present invention preferably has a total cation mass QC (mg / dm 2 ) of the eluted component per unit surface area of 1.6 or less when performing an elution test with respect to an acidic solution.

[0036] In addition, in the alkali silicate glass of the present invention, it is preferable that the hydrochloric acid consumption H (mL / g) until the eluate is neutralized when eluting the alkali component in accordance with ISO 720 (1985) is class HGA1 or HGA2 in ISO 720 (1985).

Advantages of the Invention

[0037] According to the present invention, it is possible to provide glass tubes, primary pharmaceutical packaging containers, and alkali silicate glass that have high alkali resistance, reduce the amount of alkali borate evaporated during burner heating, reduce the risk of developing Alzheimer's disease, and are free from the risk of generating insoluble foreign matter caused by aluminum ions leached from the glass. [Brief explanation of the drawing]

[0038] [Figure 1] This graph shows the mol% of SiO2 in various types of glass on the horizontal axis and the total cation mass QC (mg / dm2) of eluted components per unit area on the vertical axis. [Modes for carrying out the invention]

[0039] Preferred embodiments of the present invention will be described below. However, the following embodiments are merely illustrative, and the present invention is not limited to these embodiments.

[0040] The glass tube of the present invention is an alkali silicate glass, and its glass composition preferably contains, in molar percentages, SiO2 50-88%, Li2O+Na2O+K2O 0.1-20%, TiO2 0-20%, and ZrO2 0.005-12%, and is substantially free of B2O3 and Al2O3. The reasons for limiting the composition range of each component as described above will be explained below. In the description of the content of each component, unless otherwise specified, percentages refer to mole percentages.

[0041] SiO2 is a component that forms the framework of glass and enhances chemical resistance, especially acid resistance. The SiO2 content is preferably 50% or more, 55% or more, 60% or more, 65% or more, 66% or more, 70% or more, 72% or more, and particularly 74% or more, preferably 88% or less, 85% or less, less than 84%, 83% or less, 81% or less, 79% or less, and particularly 77% or less. If the SiO2 content is too low, the glass structure becomes fragile and its chemical resistance tends to decrease. On the other hand, if the SiO2 content is too high, the meltability tends to decrease. Also, the viscosity of the molten glass increases, making it difficult to process into glass tubes.

[0042] The content of Li2O+Na2O+K2O is preferably 0.1% or more, 0.5% or more, 1% or more, 3% or more, 5% or more, 6% or more, 7% or more, and particularly 8% or more, preferably 20% or less, 19.5% or less, 19% or less, 16% or less, 14% or less, 12% or less, 11% or less, 10.5% or less, and particularly 10% or less. If the content of Li2O+Na2O+K2O is too low, the viscosity of the glass will increase, which may reduce the productivity and processability of the glass tubes. On the other hand, if the content of Li2O+Na2O+K2O is too high, the amount of alkali leached from the glass will increase, making it easier for the pH of the chemical solution to change.

[0043] Li2O is a component that reduces the viscosity of glass, thereby improving its meltability and moldability. The Li2O content is preferably 0% or more, 0.1% or more, particularly 2% or more, and preferably 10% or less, 8% or less, 6% or less, less than 4%, 3.5% or less, 3% or less, and particularly 2.5% or less. If the Li2O content is too high, the amount of alkali leached from the glass increases, making it easier for the pH of the chemical solution to change.

[0044] Na2O is a component that reduces the viscosity of glass, thereby improving its meltability and moldability. The Na2O content is preferably 0% or more, 0.1% or more, 3% or more, and particularly 4% or more, and preferably 20% or less, 18% or less, 16% or less, and particularly 13% or less. If the Na2O content is too high, the amount of alkali leached from the glass will increase, making it easier for the pH of the chemical solution to change. In addition, devitrified crystals containing SiO2-Na2O-ZrO2 may precipitate, which may reduce the productivity of glass tubes.

[0045] K2O, like Li2O and Na2O, is a component that reduces the viscosity of glass, thereby improving its meltability and moldability. The K2O content is preferably 0% or more, 0.1% or more, 3% or more, 5% or more, 7% or more, and particularly 8% or more, and preferably 20% or less, 18% or less, 15% or less, 12% or less, 11.5% or less, and particularly 11% or less. If the K2O content is too high, the amount of alkali leached from the glass will increase, making it easier for the pH of the chemical solution to change.

[0046] TiO2 is a component that reduces the viscosity of glass and enhances its chemical resistance, particularly alkali resistance. The TiO2 content is preferably 0% or more, 0.1% or more, 1% or more, 2% or more, 2.5% or more, 3% or more, 4.4% or more, 5% or more, 6% or more, and especially 7% or more, and preferably 20% or less, 18% or less, 16% or less, 15% or less, 14% or less, 12% or less, 11% or less, 10% or less, 9.5% or less, 9% or less, and especially 8.5% or less. If the TiO2 content is too low, the viscosity of the glass will increase, which may reduce the productivity and processability of the glass tubes. On the other hand, if the TiO2 content is too high, the color of the glass tubes tends to intensify, and the glass may devitrify, which may reduce the productivity and processability of the glass tubes.

[0047] ZrO2 is a component that enhances chemical resistance, particularly alkali resistance. It is also one of the components that can leach into the glass component as an impurity from refractories used in melting equipment. Exceptionally, if the glass composition is substantially free of ZrO2, the health risks can be reduced. "Substantially free of ZrO2 in the glass composition" means that the ZrO2 content in the glass composition is 0.005 mol% or less. The ZrO2 content is preferably 0% or more, 0.001% or more, 0.005% or more, 0.01%, 0.05% or more, 0.1% or more, 1% or more, 2.0% or more, 2.5% or more, 3% or more, 3.5% or more, 4.4% or more, particularly 5% or more, and 6% or more, and preferably 13% or less, 10% or less, 9% or less, 8.5% or less, 7% or less, 6% or less, and particularly 5% or less. If the ZrO2 content is too low, sufficient chemical resistance cannot be obtained, and the amount of components leaching from the glass will increase, potentially altering the chemical solution. On the other hand, if the ZrO2 content is too high, the glass may devitrify, potentially reducing the productivity and processability of the glass tubes.

[0048] B2O3 is a component that reduces the viscosity of glass, thereby improving its meltability and moldability. However, B2O3 evaporates along with the alkaline components in the glass when heated by a burner during container processing, and there is a risk of contamination of the inner surface of the container. Therefore, the B2O3 content should be restricted to a level where it is substantially absent (0.5% or less), preferably 0.4% or less, and particularly 0.3% or less.

[0049] Furthermore, if you wish to reduce the viscosity of the glass, you may intentionally add B2O3 in a range of 1% or less.

[0050] Al2O3 is an ingredient that enhances chemical resistance and suppresses devitrification. However, if the Al2O3 content is too high, it may leach into the drug solution as aluminum ions and be taken into the body by injection or other means. Aluminum ions taken into the body may increase the risk of developing Alzheimer's disease. In addition, if phosphate buffer is stored in a glass container containing Al2O3, aluminum ions leached from the glass may react with the phosphate buffer, producing insoluble foreign matter. Therefore, the Al2O3 content should be regulated to be substantially absent, i.e., 0.5% or less, preferably 0.4% or less, and particularly 0.3% or less.

[0051] Furthermore, refractories used in melting equipment may contain Al2O3. In this case, Al2O3 derived from the refractory may be mixed into the glass unintentionally, and in such cases, it is permissible to include Al2O3 in a range of 1% or less. In other exceptional cases where it is desired to enhance water resistance, it is also permissible to include Al2O3 in a range of 1% or less.

[0052] In addition to the above ingredients, the following ingredients may also be introduced.

[0053] The content of MgO+CaO+SrO+BaO is preferably 12% or less, 10% or less, 8.5% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4.5% or less, 4% or less, 3.8% or less, 2% or less, 1.5% or less, and especially 1.3% or less. If the content of MgO+CaO+SrO+BaO is too low, the viscosity of the glass will increase, which may reduce the productivity and processability of the glass tubes. On the other hand, if the content of MgO+CaO+SrO+BaO is too high, the amount of alkali leached from the glass will increase, which may easily cause a change in the pH of the chemical solution.

[0054] MgO is a component that reduces the viscosity of glass, thereby improving its meltability and moldability. The MgO content is preferably 5% or less, 4.8% or less, 4% or less, 3.5% or less, 3% or less, 2% or less, 1.5% or less, and particularly 1% or less, and preferably 0% or more, 0.05% or more, 0.1% or more, and particularly 0.3% or more. If the MgO content is too low, the viscosity of the glass will increase, which may reduce the productivity and processability of the glass tubes. On the other hand, if the MgO content is too high, the amount of alkali leached from the glass will increase, making it easier for the pH of the chemical solution to change.

[0055] CaO is a component that reduces the viscosity of glass, thereby improving its meltability and moldability. The CaO content is preferably 7% or less, 6.5% or less, 5% or less, 4.5% or less, 3.8% or less, 3.5% or less, 3% or less, 2% or less, 1.8% or less, 1.5% or less, and especially 1% or less, and preferably 0% or more, 0.1%, 0.5% or more, 0.7% or more, and especially 1% or more. If the CaO content is too low, the viscosity of the glass will increase, which may reduce the productivity and processability of the glass tubes. On the other hand, if the CaO content is too high, the amount of alkali leached from the glass will increase, making it easier for the pH of the chemical solution to change.

[0056] SrO is a component that reduces the viscosity of glass, thereby improving its meltability and moldability. The SrO content is preferably 5% or less, 4.7% or less, 4% or less, 3.3% or less, 3% or less, 2% or less, 1.6% or less, and especially 1% or less. If the SrO content is too high, the amount of alkali leached from the glass increases, making it easier for the pH of the chemical solution to change.

[0057] BaO is a component that reduces the viscosity of glass, thereby improving its meltability and moldability. The BaO content is preferably 5% or less, 4.7% or less, 4% or less, 3.3% or less, 3% or less, 2% or less, 1.6% or less, and particularly 1% or less, and preferably 0% or more, 0.05% or more, 0.1% or more, and particularly 0.3% or more. If the BaO content is too low, the viscosity of the glass will increase, which may reduce the productivity and processability of the glass tubes. On the other hand, if the BaO content is too high, the amount of alkali leached from the glass will increase, making it easier for the pH of the chemical solution to change. In addition, in the case of chemical solutions containing sulfates, it may precipitate as barium sulfate, potentially generating insoluble foreign matter.

[0058] ZnO is a component that reduces the viscosity of glass and improves its meltability and moldability, but if too much is added, it may reduce its resistance to devitrification and chemical durability. Preferably, the amount is 10% or less, 8% or less, 6% or less, less than 4.9%, 4.5% or less, 4% or less, 3% or less, 2.5% or less, especially 2% or less, 0% or more, 0.5% or more, 1% or more, especially 1.5% or more.

[0059] Fe2O3 is an impurity component that intensifies the coloration of glass. The Fe2O3 content is preferably 0.1% or less, more preferably 0.09% or less, particularly preferably 0.08% or less, preferably 0% or more, more preferably 0.001% or more, and particularly preferably 0.003% or more. If the Fe2O3 content is too high, the coloration of the glass becomes too strong. A lower Fe2O3 content is preferable because it suppresses coloration, but to achieve a range such as below 0.003%, it is necessary to use expensive high-purity raw materials, which increases batch costs.

[0060] SnO2 is a component that acts as a clarifying agent. The SnO2 content is preferably 3% or less, 2% or less, more preferably 1% or less, particularly preferably 0.5% or less, preferably 0% or more, 0.001% or more, even more preferably 0.005% or more, and particularly preferably 0.01% or more. If the SnO2 content is too low, the amount of residual bubbles in the glass tube will increase, and the appearance quality will tend to deteriorate. On the other hand, if the SnO2 content is too high, the glass will become discolored and the permeability will tend to decrease.

[0061] In addition to SnO2, SO3, Cl2, F2, Sb2O3, etc., can be used as clarifying agents. These may be used individually or in combination. The content of each component is preferably 3% or less, 2% or less, 1.5% or less, 1% or less, 0.8% or less, 0.5% or less, 0.3% or less, and particularly 0.1% or less, and preferably 0.001% or more, and particularly 0.003% or more. If the content of each component is too high, the risk of equipment corrosion and environmental pollution increases. On the other hand, if the content of each component is too low, the amount of residual bubbles in the glass tube increases, and the appearance quality tends to deteriorate.

[0062] The molar ratio TiO2 / (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO) is preferably 0.3 or higher, 0.5 or higher, 0.7 or higher, 0.9 or higher, 1 or higher, and particularly 1.1 or higher, and preferably 5.5 or lower, 3.5 or lower, 3 or lower, 2.5 or lower, 2 or lower, 1.5 or lower, and particularly 1.3 or lower. In this way, the effect of improving water resistance can be obtained more efficiently.

[0063] The molar ratio K2O / ZrO2 is preferably 0.1 or higher, 0.3 or higher, 0.5 or higher, 0.7 or higher, 0.8 or higher, 0.85 or higher, or 0.9 to 100. This allows for a more efficient improvement in alkali resistance.

[0064] The molar ratio (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO) / SiO2 is preferably 0.4 or less, 0.35 or less, 0.30 or less, 0.28 or less, 0.26 or less, 0.25 or less, especially 0.23 or less, preferably 0 or more, greater than 0, 0.05 or more, 0.1 or more, 0.1 or more, especially 0.15 or more. If (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO) / SiO2 is high, the viscosity of the glass decreases and it becomes easier to process, but the amount of alkali elution increases and there is a risk of changing the pH of the chemical solution. If (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO) / SiO2 is low, the amount of alkali elution is suppressed, but the viscosity of the glass increases and the processability decreases.

[0065] Furthermore, HfO2, SO3, Y2O3, and P2O5 may be included as impurities up to 0.5% each, and it is particularly preferable to include them at 0.001 to 0.1%.

[0066] Other impurities such as Cr2O3, PbO, La2O3, Bi2O3, MoO3, WO3, Nb2O3, and PbO2 may also be added in amounts of 3% or less, 2% or less, 1% or less, less than 1%, and especially 0.5% or less, respectively.

[0067] Furthermore, impurities such as H2, CO2, CO, H2O, He, Ne, Ar, and N2 may be included in amounts up to 0.1% each. It is also preferable that the amount of noble metal elements such as Pt, Rh, Au, and Ir is 500 ppm or less, and more preferably 300 ppm or less.

[0068] The glass tube of the present invention preferably has the following characteristics.

[0069] In the glass tube of the present invention, the chemical resistance factor value is expressed as {(amount of hydrochloric acid consumed when a water resistance test is performed in accordance with ISO 720 H) × 10 + (total cation mass of eluted components QC when an elution test is performed in an acidic solution QC) × 10 + (mass loss ρ when an alkali resistance test is performed in accordance with ISO 695)}, that is, the sum of 10 times H, 10 times QC, and ρ, and is preferably 98.5 or less, 90 or less, 80 or less, 70 or less, 60 or less, 50 or less, 45 or less, and particularly 40 or less. If the chemical resistance factor value is too large, the chemical resistance tends to decrease.

[0070] Mass loss ρ (mg / dm³) when alkali resistance test was performed in accordance with ISO 695 (199105-15) 2 The mass loss ρ is preferably 140 or less, 100 or less, 75 or less, 60 or less, 45 or less, 35 or less, 30 or less, and particularly 27 or less. If the mass loss ρ is too large, alkali resistance will be low. Note that the mass loss ρ (mg / dm 2 If the score is 75 or less, it will be classified as Class A1.

[0071] The total cation mass QC (mg / dm³) of the eluted components when an elution test was performed in an acidic solution. 2 ) is preferably 3 or less, 2.5 or less, 2 or less, 1.7 or less, 1.5 or less, and especially 1.3 or less.

[0072] In accordance with ISO 720 (1985), the amount of hydrochloric acid H (mL / g) consumed until the eluate is neutralized when eluting alkaline components is preferably 0.5 or less, 0.4 or less, 0.3 or less, 0.2 or less, and particularly 0.1 or less. If the amount of hydrochloric acid H is too high, the water resistance will be low. If the amount of hydrochloric acid H is 0.1 or less, it will be classified as Class HGA1, and if it is 0.85 or less, it will be classified as Class HGA2.

[0073] The liquidus temperature is preferably 1300°C or lower, 1250°C or lower, 1200°C or lower, 1150°C or lower, and particularly 1100°C or lower. If the liquidus temperature is too high, the glass is more likely to devitrify during processing into glass tubes.

[0074] The coefficient of thermal expansion is an important parameter indicating thermal shock resistance. The coefficient of thermal expansion in the temperature range of 30 to 380°C is preferably 85 × 10⁻⁶. -7 / ℃ or lower, especially 45-80 × 10 -7 The temperature is / °C. If the coefficient of thermal expansion is too high, the thermal shock resistance tends to decrease.

[0075] 10 2.5 The temperature at dPa·s is preferably 1650°C or lower, 1600°C or lower, 1590°C or lower, 1580°C or lower, and particularly 1570°C or lower. 10 2.5 If the temperature at dPa·s is too high, it becomes difficult to melt the glass.

[0076] 10 4.0 The temperature at dPa·s is preferably 1350°C or lower, 1300°C or lower, 1290°C or lower, 1280°C or lower, 1270°C or lower, and especially 1265°C or lower. 10 4.0 If the temperature at dPa·s is too high, it becomes difficult to process the glass into tubes.

[0077] The average transmittance at a path length of 1 mm and a wavelength of 400-800 nm is preferably 60% or higher, 70% or higher, 75% or higher, and particularly 85% or higher. If the average transmittance at a path length of 1 mm and a wavelength of 400-800 nm is too low, it becomes difficult to visually detect the deterioration of the drug.

[0078] Next, a method for manufacturing the glass tube of the present invention will be described. The following description is an example using the Danner process.

[0079] First, glass raw materials are mixed to create a glass batch with the desired glass composition. Next, this glass batch is continuously fed into a melting furnace at 1550-1700°C to melt and clarify the molten glass. The resulting molten glass is then wrapped around a rotating refractory material, and air is blown from the tip of the refractory material to draw the glass into a tubular shape. The drawn tubular glass is then cut to a predetermined length to obtain glass tubes. The glass tubes obtained in this way are used to manufacture vials and ampoules.

[0080] The present invention relates to a primary pharmaceutical packaging container made by processing a glass tube, characterized in that the glass tube is the glass tube described above.

[0081] In another embodiment, the alkali silicate glass of the present invention is characterized in that it substantially does not contain B2O3 and Al2O3 in its glass composition, and has a chemical resistance factor value of 98.5 or less, expressed as {(amount of hydrochloric acid consumed when a water resistance test is performed in accordance with ISO 720 H) × 10 + (total cation mass of eluted components per unit surface area QC when an elution test is performed in an acidic solution) × 10 + (mass loss ρ when an alkali resistance test is performed in accordance with ISO 695)}. Furthermore, in another embodiment, the alkali silicate glass of the present invention contains, in molar percentages, SiO2 60-88%, K2O 0.1-20%, CaO 0-6.5%, TiO2 0.1-20%, and ZrO2 0.1-12%, with a molar ratio of TiO2 / (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO) of 0.3-3.5 and a molar ratio of K2O / ZrO2 of 0.9 or more, and is characterized by being substantially free of B2O3 and Al2O3. The technical features of the alkali silicate glass of the present invention are the same as those of the tubular glass of the present invention, and a detailed explanation is omitted here.

[0082] Furthermore, in another embodiment, the alkali silicate glass of the present invention is characterized in that the glass composition contains 1% or less of B2O3 and 1% or less of Al2O3, and the chemical resistance factor value expressed as {(amount of hydrochloric acid consumed H when a water resistance test is performed in accordance with ISO 720) × 10 + (total cation mass QC of eluted components per unit surface area when an elution test is performed in an acidic solution) × 10 + (mass loss ρ when an alkali resistance test is performed in accordance with ISO 695)} is 98.5 or less. Furthermore, in another embodiment, the alkali silicate glass of the present invention is characterized in that, as a glass composition, it contains, in mol%, SiO2 66% or more and less than 84%, B2O 31% or less, Al2O 31% or less, MgO+CaO+SrO+BaO 10% or less, and ZrO 28.5% or less, and the molar ratio (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO) / SiO2 is 0.4 or less. The technical features of the alkali silicate glass of the present invention are the same as those of the glass tube of the present invention, and therefore a detailed explanation is omitted here. [Examples]

[0083] The present invention will be described below based on examples. However, the present invention is not limited to the following examples, and the following examples are merely illustrative.

[0084] Tables 1-11 show examples of the present invention (samples No. 1-14, 16-28, 30-107) and comparative examples (samples No. 15, 29). The numbers in parentheses in the tables are predicted values ​​obtained by factor calculation for each component.

[0085] [Table 1]

[0086] [Table 2]

[0087] [Table 3]

[0088] Table 4

[0089] Table 5

[0090] Table 6

[0091] Table 7

[0092] Table 8

[0093] Table 9

[0094] Table 10

[0095] Table 11

[0096] <Produced by ガラスの> Various glass raw materials were prepared and mixed in 500g units of glass to obtain raw material batches, resulting in different glass compositions. These raw material batches were placed in a 300cc platinum crucible and melted in an electric furnace heated to 1600°C. The melting time was 20 hours, during which the molten glass was stirred 1 hour after all the raw material batches were placed in the crucible and again 4 hours before pouring. After the second stirring, the electric furnace was heated to 1650°C and the glass was clarified. The molten glass was then poured onto a carbon plate and rapidly cooled using a metal roller to form it into a plate with a thickness of 5mm (roll forming) or into an ingot with a thickness of 15mm, thereby obtaining each sample.

[0097] <Measurement of hydrochloric acid consumption H> The amount of hydrochloric acid consumed by each sample was measured as follows. The surface of the sample was carefully wiped with ethanol, and the sample was ground using an alumina mortar and pestle. Then, it was classified using three stainless steel sieves with mesh sizes 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 710 μm and 425 μm sieves was ground again. The same process was repeated until the amount of glass powder on the 300 μm sieve was 10 g or more. The glass powder remaining on the 300 μm sieve was transferred to a beaker, 30 mL of acetone was poured in, and ultrasonic cleaning was performed for 1 minute. The supernatant was discarded, and the same process was repeated 5 times. After that, 30 mL of acetone was poured into the beaker, and the process of gently shaking it by hand and discarding only the supernatant was repeated 3 times. The mouth of the beaker was covered with aluminum foil, with several holes punctured, and then dried in a 120°C oven for 20 minutes. After that, the glass powder was removed and cooled in a desiccator for 30 minutes. The obtained glass powder was weighed to 10 g ± 0.0005 g using an electronic balance, placed in a 250 mL quartz flask, and 50 mL of ultrapure water was added. A quartz flask filled only with 50 mL of ultrapure water was also prepared as a blank. The mouth of the quartz flask was sealed with a quartz container, placed in an autoclave, held at 100°C for 10 minutes, and then heat-treated at 121°C for 30 minutes. During this time, the temperature was increased from 100°C to 121°C at a rate of 1 °C / min, and cooled from 121°C to 100°C at a rate of 0.5 °C / min. After cooling to 95°C, the quartz flask was removed and placed on a tray containing ultrapure water to cool for 30 minutes. After cooling, the eluate in the quartz flask was transferred to a conical beaker. 15 mL of ultrapure water was collected using a volumetric pipette and poured into a flask. After gently shaking, only the supernatant was transferred to a conical beaker. The same procedure was repeated twice. The same procedure was performed for the blank to obtain the eluate. 0.05 mL of methyl red solution was added dropwise to each eluate. 0.02 mol / L hydrochloric acid was added dropwise to the sample eluate, and the amount of hydrochloric acid consumed when the solution became the same color as the blank was recorded. The hydrochloric acid consumption per gram of glass, H (mL / g), was then calculated.

[0098] <Measurement of acid resistance> The detailed experimental procedure for the acid resistance test is as follows: First, all glass surfaces are polished to a mirror finish, and the total surface area is 25-30 cm². 2The sample was prepared by immersing it in a solution of hydrofluoric acid (40% by mass) and hydrochloric acid (2 mol / L) mixed in a volume ratio of 1:9 as a pretreatment, and stirring with a magnetic stirrer for 10 minutes. The sample was then removed and its length was measured. After that, it was ultrasonically washed three times for 1 minute each in ultrapure water, followed by ultrasonic washing twice for 1 minute each in ethanol. Next, the sample was dried in an oven at 110°C for 1 hour and cooled in a desiccator for 30 minutes. Subsequently, 65 mL of 6 mol / L hydrochloric acid was placed in a 120 mL sealed PTFE container, the PTFE container was covered, and it was preheated in an oven set to 120°C for 90 minutes. After that, the Teflon container containing the hydrochloric acid was removed, the lid was opened, and the sample was immersed in the hot hydrochloric acid solution, the lid was closed, and it was returned to the oven. It was held at 120±2°C for 6 hours. After 6 hours, the PTFE container was removed from the oven, the lid was quickly opened, and the sample was removed using plastic tweezers. The lid was then closed and the mixture was cooled to room temperature. The mass B (g) of the obtained hydrochloric acid was measured, and the concentration values ​​C of each component in the eluate were analyzed. n (μg / mL) was determined by ICP emission spectrometry. Total surface area of ​​the sample Acm² 2 Therefore, according to the following formula 1, the total cation mass QC (mg / dm²) of the eluted components per unit area is calculated. 2 The total oxide mass QO (mg / dm³) per unit area of ​​the eluted components was calculated by assuming the eluted components are oxides using the following Equation 2. 2 ) was calculated.

[0099] [Equation 1] The total cation mass of eluted components per unit area QC = B / 10 / A / d × ΣCn, where A is the total surface area of ​​the sample (cm²). 2 ) means, B means the amount of hydrochloric acid (g) obtained after the test, C n This refers to the analytical values ​​(μg / mL) of the concentration of each component in the solution, ΣC n d represents the sum of the analytical values ​​of the concentrations of each component in the solution (μg / mL), and d is the hydrochloric acid density after the test (g / cm³). 3 ) means multiplication, × means multiplication, and / means division.

[0100] [Equation 2] Total oxide mass of eluted components per unit area QO = B / 10 / A / d × Σ{Cn × E n / F n / M n} and A is the total surface area of ​​the sample (cm² 2 ) means, B means the amount of hydrochloric acid (g) obtained after the test, C n d represents the analytical concentration value (μg / mL) of each component in the solution, and d represents the hydrochloric acid density (g / cm³) after the test. 3 ) means, E n This refers to the oxide formula weight of the cation atom of the eluted component (e.g., the formula weight of SiO2 for Si), and F n The eluting component is represented by an oxide, and the molar ratio of the content of eluting component cation atoms when the amount of oxide is considered to be 1 mol (e.g., 1 for Si is SiO2, 2 for K is K2O), M n This represents the atomic weight of the eluted component cation atom, Σ{Cn×E n / F n / M n} is Cn and E n Multiply by F n and M n This means the sum of the values ​​obtained by dividing by , where × means multiplication and / means division.

[0101] <Measurement of alkali resistance> Alkali resistance was evaluated according to the method compliant with ISO 695 (1991). The detailed test procedure is as follows: First, all glass surfaces were polished to a mirror finish, and the total surface area was 15 cm². 2The sample was prepared, and as a pretreatment, it was immersed in a solution of hydrofluoric acid (40% by mass) and hydrochloric acid (2 mol / L) mixed in a volume ratio of 1:9, and stirred with a magnetic stirrer for 10 minutes. Next, the sample was removed and its length was measured. Then, it was ultrasonically cleaned three times for 1 minute each in ultrapure water, followed by ultrasonic cleaning twice for 1 minute each in ethanol. Next, the sample was dried in an oven at 110°C for 1 hour and cooled in a desiccator for 30 minutes. The mass m1 of the sample obtained in this way was measured to an accuracy of ±0.1 mg and recorded. Subsequently, 800 mL of a solution of 1 mol / L sodium hydroxide aqueous solution and 0.5 mol / L sodium carbonate aqueous solution mixed in a volume ratio of 1:1 was placed in a stainless steel container, heated using an electric heater until boiling, and the sample suspended by platinum wire was placed in and held for 3 hours. To prevent the volume of liquid from decreasing during the test, the opening of the container lid was sealed with a gasket and a cooling tube. The sample was then removed and immersed three times in a beaker containing 500 mL of 1 mol / L hydrochloric acid. Following this, it was ultrasonically washed three times for 1 minute each in ultrapure water, and then ultrasonically washed twice for 1 minute each in ethanol. The washed sample was then dried in a 110°C oven for 1 hour and cooled in a desiccator for 30 minutes. The mass m2 of the sample treated in this manner was measured and recorded with an accuracy of ±0.1 mg. Finally, the masses m1 (mg) and m2 (mg) of the sample before and after immersion in the boiling solution, and the total surface area A (cm²) of the sample were recorded. 2 From ), according to Equation 3, the mass reduction per unit area ρ (mg / dm 2 ) was calculated.

[0102] [Equation 3] Mass reduction per unit area ρ = 100 × (m1 - m2) / A

[0103] <Method for calculating chemical resistance factor value> The chemical resistance factor value is determined by the amount of hydrochloric acid consumed for water resistance (H) and the total cation mass (QC) of eluted components per unit surface area when elution tests are conducted in accordance with ISO 720. 2The following formula 4 was used to calculate the QC (mg / dm²) value, using the mass loss per unit area ρ from alkali resistance tests conducted in accordance with ) and ISO 695. Furthermore, the acid resistance score used when calculating the chemical resistance factor value was QC (mg / dm²). 2 ) was used.

[0104] [Equation 4] Chemical resistance factor value = H × 10 + QC × 10 + ρ

[0105] <Measurement of liquidus temperature> The liquidus temperature was measured as follows: The pulverized sample was packed into a platinum boat measuring approximately 120 × 20 × 10 mm and placed in an electric furnace with a linear temperature gradient for 24 hours. Subsequently, the crystal precipitation sites were identified by microscopic observation, and the temperatures corresponding to the crystal precipitation sites were calculated from the electric furnace's temperature gradient graph. This temperature was defined as the liquidus temperature.

[0106] <Measurement of thermal expansion coefficient> The linear thermal expansion coefficient was evaluated using the average linear thermal expansion coefficient measured over the temperature range shown in the table, using a sample processed to 20 mm × 5 mmφ. A NETZSCH dilatometer was used for the measurements.

[0107] <Measurement of low-temperature viscosity> The strain point, slow cooling point, and softening point were measured using the fiber elongation method.

[0108] <Measurement of high-temperature viscosity> The high-temperature viscosity was measured by the platinum ball pulling method. The viscosity curve of the glass was obtained from the high-temperature viscosity and Fulcher's viscosity calculation formula, and from this viscosity curve, 10 2.5 dPa·s, 10 3.0 dPa·s, 10 4.0 The temperature corresponding to dPa·s was determined.

[0109] <Measurement of Transmittance> Transmittance was measured using a spectrophotometer to obtain transmittance between 400 and 800 nm from strips of glass tube with a wall thickness of 1 mm. A JASCO V-670 spectrophotometer (with an integrating sphere) was used for the measurement.

[0110] As can be seen from Tables 1-11, samples 1-14, 16-28, and 30-107 substantially did not contain B2O3 and Al2O3 in their glass composition, resulting in low chemical resistance factor values. On the other hand, samples No. 15 and 29 did not contain ZrO2 in their glass composition, resulting in low alkali resistance.

[0111] Figure 1 shows the mol% of SiO2 in various glasses on the horizontal axis and the total cation mass (QC) of eluted components per unit area (mg / dm³) on the vertical axis. 2 This is a graph showing the relationship between the molar percentage of SiO2 and QC. As can be seen from Figure 1, there is a correlation between the molar percentage of SiO2 and QC, and it can be seen that a higher molar percentage of SiO2 results in a lower QC and better acid resistance. [Industrial applicability]

[0112] The tubular glass and alkali silicate glass of the present invention can be suitably used as primary packaging containers for pharmaceuticals, such as ampoules, vials, pre-filled syringes, and cartridges. They can also be used as physicochemical instruments such as beakers and flasks. Furthermore, they can be used as inner wall materials for corrosion-resistant piping in chemical plants where corrosion resistance is required. In addition to the above applications, the alkali silicate glass of the present invention can be used in various other applications where alkali resistance is required.

Claims

1. A glass tube made of alkali silicate glass, wherein the glass composition contains B ２ O ３ and Al ２ O ３ It substantially does not contain [the specified substance], and the mass loss ρ (mg / dm) when an alkali resistance test was performed in accordance with ISO 695 (199105-15) is measured. ２ ) is Class A1, As a glass composition, in mol%, SiO ２ 50 to 88%, Li ２ O + Na ２ O + K ２ O 0.1 to 20%, TiO ２ 0.1 to 20%, ZrO ２ A tube glass containing 0.005 to 12%.

2. The total cation mass QC (mg / dm²) of eluted components per unit surface area when an elution test was performed in an acidic solution. ２ The glass tube according to claim 1, wherein the ratio is 1.6 or less.

3. The glass tube according to claim 1 or claim 2, wherein the amount of hydrochloric acid H (mL / g) consumed until the eluate is neutralized when an alkaline component is eluted in accordance with ISO 720 (1985) is of class HGA1 or HGA2 according to ISO 720 (1985).

4. Na in glass composition ２ A glass tube according to any one of claims 1 to 3, wherein the oxygen content is 0 to 20 mol%.

5. K in glass composition ２ A glass tube according to any one of claims 1 to 4, wherein the oxygen content is 0 to 20 mol%.

6. A glass tube according to any one of claims 1 to 5, wherein the content of MgO + CaO + SrO + BaO in the glass composition is 0.1 to 10 mol%.

7. A glass tube according to any one of claims 1 to 6, wherein the optical path length is 1 mm and the average transmittance at a wavelength of 400 to 800 nm is 60% or more.

8. The glass tube according to any one of claims 1 to 7, wherein the chemical resistance factor value expressed as {(amount of hydrochloric acid consumed when a water resistance test is performed in accordance with ISO 720 H) × 10 + (total cation mass of eluted components per unit surface area QC when an elution test is performed in an acidic solution Q) × 10 + (mass loss ρ when an alkali resistance test is performed in accordance with ISO 695)} is 98.5 or less.

9. A glass tube according to any one of claims 1 to 8, for use in primary packaging materials for pharmaceuticals, laboratory equipment, and corrosion-resistant piping for chemical plants.

10. A primary pharmaceutical packaging container made by processing a glass tube, wherein the glass tube is the glass tube described in any one of claims 1 to 9.

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