Glass for pharmaceutical containers, glass tubes for pharmaceutical containers, and pharmaceutical containers

Abstract

A medicine container glass according to the present invention has a glass composition comprising, in terms of mol%, 70-85% of SiO2, 3-13% of Al2O3, 0-5% of B2O3, 0.1-18% of Li2O + Na2O + K2, and 0-10% of MgO + CaO + SrO + BaO, and is characterized in that the value of the molar ratio of (Li2O + Na2O + K2O) / Al2O3 is 1 or greater, and the value of the molar ratio of (Li2O + Na2O + K2O + MgO + CaO +SrO + BaO-Al2O3) / (SiO2 + Al2O3) is 0.2 or less.

Description

[Technical Field]

[0001] The present invention relates to a glass for pharmaceutical containers, a glass tube for pharmaceutical containers, and pharmaceutical containers, which have excellent processability and hydrolysis resistance. [Background technology]

[0002] Conventionally, various glass containers have been used as pharmaceutical containers.

[0003] Pharmaceuticals are broadly divided into two types: oral and parenteral. In particular, parenteral drugs are filled and stored in glass containers and administered directly into the patient's bloodstream. For this reason, extremely high quality is required of the glass containers used to fill parenteral drugs.

[0004] Pharmaceutical containers are also required to prevent the components of the drugs filled in them from changing in quality. If glass components leach into the drugs, they can change the properties of the drugs, potentially affecting the patient's health or even their life. For this reason, pharmacopoeias in various countries have set limits on the amount of glass components that can leach from glass containers. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2013 / 063275 Summary of the Invention [Problem to be solved by the invention]

[0006] In recent years, advances in medicine and pharmacology have led to the development of highly effective drugs. However, when such drugs are filled and stored in borosilicate glass containers, the inner surface of the glass container may erode and peel, resulting in flakes floating in the drug, a phenomenon known as delamination. If insoluble foreign matter resulting from delamination or the like is injected into a patient's body together with the drug, it may cause fatal problems such as the formation of blood clots in the blood vessels.

[0007] Furthermore, since glass for pharmaceutical containers is processed into complex shapes such as ampoules, vials, pre-filled syringes, and cartridges, it is also desirable that the working temperature during processing be low.

[0008] For example, Patent Document 1 describes that reducing the content of B2O3 in the glass composition can suppress delamination, but in that case, the viscosity of the glass increases, raising the working temperature during processing, which may cause glass components to evaporate during processing and contaminate the inner surface of the glass container or chemicals. On the other hand, the glass described in Patent Document 1 contains a large amount of Na2O in the glass composition to lower the working temperature during processing, but in this case, the problem of reduced hydrolysis resistance arises. In short, it was difficult for the glass described in Patent Document 1 to achieve both hydrolysis resistance and processability.

[0009] In view of the above circumstances, the technical object of the present invention is to provide a glass for pharmaceutical containers, a glass tube for pharmaceutical containers, and a pharmaceutical container that have a low B2O3 content in the glass composition and that are capable of achieving both hydrolysis resistance and processability. [Means for solving the problem]

[0010] After extensive research, the present inventors have found that the above-mentioned problems can be solved by strictly controlling the content of each glass component, and have proposed this finding as the present invention. Specifically, the glass for pharmaceutical containers of the present invention is characterized by having a glass composition, in mole percent, of SiO2 70-85%, Al2O3 3-13%, B2O3 0-5%, Li2O + Na2O + K2O 0.1-18%, and MgO + CaO + SrO + BaO 0-10%, with the molar ratio (Li2O + Na2O + K2O) / Al2O3 being 1 or greater and the molar ratio (Li2O + Na2O + K2O + MgO + CaO + SrO + BaO - Al2O3) / (SiO2 + Al2O3) being 0.2 or less. This makes it possible to achieve both hydrolysis resistance and processability while suppressing delamination.

[0011] Here, "Li2O + Na2O + K2O" refers to the total content of Li2O, Na2O, and K2O. "MgO + CaO + SrO + BaO" refers to the total content of MgO, CaO, SrO, and BaO. "(Li2O + Na2O + K2O) / Al2O3" refers to the value obtained by dividing the total content of Li2O, Na2O, and K2O by the content of Al2O3. "(Li2O + Na2O + K2O + MgO + CaO + SrO + BaO - Al2O3) / (SiO2 + Al2O3)" refers to the value obtained by subtracting the content of Al2O3 from the total content of Li2O, Na2O, K2O, MgO, CaO, SrO, and BaO, and dividing the result by the total content of SiO2 and Al2O3.

[0012] Furthermore, in the glass for pharmaceutical containers of the present invention, the content of Li2O is preferably 0 to 8.1 mol%, the content of Na2O is preferably 0.1 to 8 mol%, and the content of K2O is preferably 0.01 to 5 mol%, which can effectively improve hydrolysis resistance.

[0013] Furthermore, in the glass for pharmaceutical containers of the present invention, the content of MgO+CaO+SrO+BaO is preferably 0 to 5 mol %, which can effectively improve hydrolysis resistance.

[0014] Furthermore, in the glass for pharmaceutical containers of the present invention, the MgO content is preferably 0 to 1.5 mol%, the CaO content is preferably 0 to 4 mol%, the SrO content is preferably 0 to 0.3 mol%, and the BaO content is preferably 0 to 0.3 mol%, which can effectively improve hydrolysis resistance.

[0015] In addition, in the glass for pharmaceutical containers of the present invention, the molar ratio Li2O / (Li2O + Na2O + K2O) is preferably 0.6 or less, where "Li2O / (Li2O + Na2O + K2O)" refers to the value obtained by dividing the content of Li2O by the total content of Li2O, Na2O, and K2O.

[0016] Furthermore, in the glass for pharmaceutical containers of the present invention, the molar ratio (Li2O+Na2O+K2O) / Al2O3 is preferably at least 2. This can improve processability.

[0017] In the glass for pharmaceutical containers of the present invention, the molar ratio CaO / (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO) is preferably less than 0.018, where "CaO / (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO)" refers to the value obtained by dividing the CaO content by the total content of Li2O, Na2O, K2O, MgO, CaO, SrO, and BaO.

[0018] Furthermore, the glass for pharmaceutical containers of the present invention preferably contains CaO, with a molar ratio of Li2O / CaO of 3.1 or less. This makes it easier to achieve both hydrolysis resistance and processability. Here, "Li2O / CaO" refers to the value obtained by dividing the Li2O content by the CaO content.

[0019] Furthermore, in the glass for pharmaceutical containers of the present invention, the content of SiO2+Al2O3+Li2O+Na2O+K2O+MgO+CaO+SrO+BaO is preferably 90 mol% or more. This makes it easier to achieve both hydrolysis resistance and processability. Here, "SiO2+Al2O3+Li2O+Na2O+K2O+MgO+CaO+SrO+BaO" refers to the total content of Li2O, Na2O, K2O, MgO, CaO, SrO, and BaO.

[0020] Furthermore, in the glass for pharmaceutical containers of the present invention, the content of B2O3 is preferably 0.01 to 1 mol %, which can improve processability while suppressing the occurrence of delamination.

[0021] In addition, in the glass for pharmaceutical containers of the present invention, the content of ZrO2 is preferably 0 to 2 mol %.

[0022] The glass for pharmaceutical containers of the present invention has a glass composition containing, in mole percent, 70 to 85% SiO2, 3 to 10% Al2O3, 0 to 5% B2O3, 0.1 to less than 13.9% Li2O + Na2O + K2O, and 0 to 10% MgO + CaO + SrO + BaO, characterized in that the molar ratio Li2O / (Li2O + Na2O + K2O) is 0.5 or less, the molar ratio (Li2O + Na2O + K2O) / Al2O3 is 2.0 or more, the molar ratio (Li2O + Na2O + K2O + MgO + CaO + SrO + BaO - Al2O3) / (SiO2 + Al2O3) is 0.156 or less, and the molar ratio CaO / (Li2O + Na2O + K2O + MgO + CaO + SrO + BaO) is less than 0.018.

[0023] The glass for pharmaceutical containers of the present invention has a glass composition containing, in mole percent, 70 to 85% SiO2, 3 to 10% Al2O3, 0 to 5% B2O3, and 0.1 to less than 13.9% Li2O+Na2O+K2O; it also contains CaO; and is characterized by having a molar ratio of Li2O / (Li2O+Na2O+K2O) of 0.5 or less, a molar ratio of (Li2O+Na2O+K2O) / Al2O3 of 2.0 or more, a molar ratio of (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO-Al2O3) / (SiO2+Al2O3) of 0.156 or less, and a molar ratio of Li2O / CaO of 3.1 or less.

[0024] In addition, in the glass for pharmaceutical containers of the present invention, it is preferable that the molar ratio (MgO + CaO + SrO + BaO) / (Li2O + Na2O + KO2O + MgO + CaO + SrO + BaO) is 0.06 or less, which refers to the value obtained by dividing the total content of MgO, CaO, SrO, and BaO by the total content of Li2O, Na2O, KO, MgO, CaO, SrO, and BaO.

[0025] The glass for pharmaceutical containers of the present invention has a glass composition containing, in mole percent, 75 to 85% SiO2, 3 to 13% Al2O3, 0 to 4% B2O3, 0.11 to 16% Li2O + Na2O + K2O, 0.1 to 15% Na2O, and 0.01 to 5% K2O, characterized in that the molar ratio (Li2O + Na2O + K2O) / Al2O3 is 2 or more, the molar ratio (MgO + CaO + SrO + BaO) / (Li2O + Na2O + K2O + MgO + CaO + SrO + BaO) is 0.06 or less, and the molar ratio (Li2O + Na2O + K2O + MgO + CaO + SrO + BaO - Al2O3) / (SiO2 + Al2O3) is 0.2 or less.

[0026] Furthermore, in the glass for pharmaceutical containers of the present invention, the molar ratio CaO / (MgO+CaO+SrO+BaO) is preferably 0.5 or more, which can improve hydrolysis resistance.

[0027] The glass for pharmaceutical containers of the present invention has a glass composition containing, in mole percent, 70 to 85% SiO2, 3 to 13% Al2O3, 0 to 5% B2O3, 0.1 to 16% Li2O+Na2O+K2O, 0.1 to 15% Na2O, and 0.1 to 5% MgO+CaO+SrO+BaO, characterized in that the molar ratio (Li2O+Na2O+K2O) / Al2O3 is 2 or more, the molar ratio CaO / (MgO+CaO+SrO+BaO) is 0.5 or more, and the molar ratio (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO-Al2O3) / (SiO2+Al2O3) is 0.2 or less. Here, "CaO / (MgO+CaO+SrO+BaO)" refers to the value obtained by dividing the CaO content by the total content of MgO, CaO, SrO, and BaO.

[0028] Furthermore, in the glass for pharmaceutical containers of the present invention, the molar ratio SiO2 / Al2O3 is preferably at least 10. Here, "SiO2 / Al2O3" refers to the value obtained by dividing the SiO2 content by the Al2O3 content.

[0029] The glass for pharmaceutical containers of the present invention has a glass composition containing, in mole percent, 70-85% SiO2, 3-13% Al2O3, 0-5% B2O3, 0.21-16% Li2O + Na2O + K2O, 0.1-10% Li2O, 0.1-15% Na2O, 0.01-5% K2O, and 0-6% MgO + CaO + SrO + BaO, characterized in that the molar ratio (Li2O + Na2O + K2O) / Al2O3 is 1 or more, the molar ratio SiO2 / Al2O3 is greater than 13.2, and the molar ratio (Li2O + Na2O + K2O + MgO + CaO + SrO + BaO - Al2O3) / (SiO2 + Al2O3) is less than 0.155.

[0030] Furthermore, the glass for pharmaceutical containers of the present invention preferably has a class of at least HGA1 in a hydrolysis resistance test (acetone washing) in accordance with ISO 720. Here, "hydrolysis resistance test (acetone washing) in accordance with ISO 720" refers to the following test. (1) The glass sample is crushed in an alumina mortar and classified into particles of 300 to 425 μm using a sieve. (2) The obtained powder sample is washed with acetone and dried in an oven at 140°C. (3) After drying, 10 g of the powder sample was placed in a quartz flask, 50 mL of purified water was added, and the flask was then autoclaved under the following conditions: the temperature was raised from 100°C to 121°C at 1°C / min, then held at 121°C for 30 minutes, and then cooled to 100°C at 0.5°C / min. (4) After autoclaving, transfer the solution in the quartz flask to another beaker, and then wash the inside of the quartz flask three times with 15 mL of purified water, and add the washings to the beaker. (5) Add methyl red indicator to the beaker and titrate with 0.02 mol / L hydrochloric acid aqueous solution. (6) 1 mL of 0.02 mol / L hydrochloric acid solution is equivalent to 620 μg of Na2O, and converted into the amount of alkali elution per 1 g of glass.

[0031] Note that "class HGA1 in the hydrolysis resistance test (acetone washing) in accordance with ISO 720" means that the amount of alkali elution per gram of glass, calculated as Na2O, determined by the above test is 62 μg / g or less.

[0032] Furthermore, the glass for pharmaceutical containers of the present invention preferably has a working point of 1300°C or less. 4.0 This refers to the temperature at which the viscosity becomes dPa·s.

[0033] The glass tube for pharmaceutical containers of the present invention is preferably made of the glass for pharmaceutical containers described above.

[0034] The pharmaceutical container of the present invention is preferably made of the glass for pharmaceutical containers described above. [Brief explanation of the drawings]

[0035] [Figure 1] This is a graph in which the horizontal axis represents the molar ratio (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO-Al2O3) / (SiO2+Al2O3) of various glasses, and the vertical axis represents the data of hydrolysis resistance tests. In the table, R'O stands for MgO+CaO+SrO+BaO. [Figure 2] 2 is a graph showing the presence or absence of MgO+CaO+SrO+BaO in FIG. 1 with different plots. [Figure 3] 2 is a graph showing data extracted from the data shown in FIG. 1 for a glass that does not contain MgO+CaO+SrO+BaO. [Figure 4] 2 is a graph showing data for a glass containing MgO+CaO+SrO+BaO extracted from the data shown in FIG. 1. DETAILED DESCRIPTION OF THE INVENTION

[0036] The reasons for limiting the range of each component are as follows: In the following explanation, "%" means "mol %" unless otherwise specified.

[0037] SiO2 is one of the components that constitute the network structure of glass. The lower the SiO2 content, the better the processability. However, if the content is too low, hydrolysis resistance tends to deteriorate, vitrification becomes difficult, and the thermal expansion coefficient increases, leading to a decrease in thermal shock resistance. On the other hand, the higher the SiO2 content, the better the hydrolysis resistance. However, if the SiO2 content is too high, the viscosity of the glass increases, leading to a decrease in processability, a rise in the liquidus temperature, and a tendency toward devitrification. Therefore, the SiO2 content is 70 to 85%, preferably 71 to 84%, 72 to 83%, 73 to 82.5%, 74 to 82%, 75 to 81.5%, and particularly 76 to 81%.

[0038] Al2O3 is one of the components that constitute the network structure of glass and also has the effect of improving hydrolysis resistance. If the Al2O3 content is too low, hydrolysis resistance is likely to deteriorate. On the other hand, if the Al2O3 content is too high, the viscosity of the glass increases. Therefore, the Al2O3 content is 3 to 13%, preferably 3.5 to 12%, 3.6 to 11%, 3.7 to 10%, 3.8 to 9.5%, 3.9 to 9%, 4 to 8.5%, 4.1 to 8%, 4.2 to 7.8%, 4.3 to 7.5%, 4.4 to 7.3%, and particularly 4.5 to 7%.

[0039] B2O3 has the effect of lowering the viscosity of glass and improving its melting property and processability. However, B2O3 is considered to be one of the factors that cause delamination, and if its content is too high, delamination resistance deteriorates and flakes tend to form. Therefore, the B2O3 content is 0 to 5%, preferably 0.01 to 4%, 0.02 to 3%, 0.03 to 2%, 0.04 to 1%, 0.04 to 0.8%, and particularly 0.05 to 0.5%.

[0040] The alkali metal oxides (RO), Li2O, Na2O, and K2O, are components that break the network structure of glass, reducing the viscosity of glass and improving its workability and meltability. The lower limit of the content of Li2O + Na2O + K2O is 0.1% or more, preferably 0.11% or more, 0.21% or more, 0.5% or more, 1% or more, 2% or more, 3% or more, 4% or more, 4.5% or more, 5% or more, 5.5% or more, 6% or more, 6.5% or more, 7% or more, 7.5% or more, and particularly 8% or more. When workability is particularly important, the lower limit of the content of Li2O + Na2O + K2O is preferably 8.5% or more, 9% or more, 9.5% or more, 10% or more, 10.5% or more, or 11% or more. On the other hand, if the content of Li2O+Na2O+K2O is too high, hydrolysis resistance deteriorates and the thermal expansion coefficient increases, reducing thermal shock resistance. Therefore, the upper limit of the content of Li2O+Na2O+K2O is 18% or less, and preferably 17% or less, 16.1% or less, 16% or less, 15.9% or less, 15.5% or less, 15% or less, 14.5% or less, 14% or less, 14.0% or less, 13.9% or less, less than 13.9%, 13.8% or less, less than 13.8%, 13.7% or less, 13.5% or less, and particularly 13% or less.

[0041] As mentioned above, Li2O has the effect of reducing the viscosity of glass and improving its workability and meltability. Among alkali metal oxides, Li2O has the greatest effect of reducing the viscosity of glass, followed by Na2O and K2O. However, if the Li2O content is too high, hydrolysis resistance tends to deteriorate. Therefore, the Li2O content is preferably 0 to 9%, 0 to 8.1%, 0 to 8%, 0 to 7%, 0 to 6.8%, 0 to 6.5%, 0 to 6.3%, 0 to 6%, 0 to 5.9%, 0 to 5.8%, 0 to 5.7%, 0 to 5.5%, 0 to 5.0%, 0 to 4.9%, and particularly preferably 0 to 4.8%. Note that if the Li2O content is 6% or less, devitrification is less likely to occur.

[0042] When emphasis is placed on workability, the Li2O content is preferably 0.1 to 9%, 0.5 to 8%, 1 to 7.5%, 2 to 7.4%, 2.5 to 7.3%, 3 to 7.2%, 3.5 to 7.1%, particularly preferably 4 to 7%.

[0043] When emphasis is placed on achieving both hydrolysis resistance and processability, the Li2O content is preferably 2 to 8%, 2.5 to 7%, 3 to 6.5%, 3.1 to 6.3%, 3.3 to 6.2%, 3.5 to 6.1%, particularly preferably 4 to 6%.

[0044] Like Li2O, Na2O has the effect of reducing the viscosity of the glass and improving its workability and meltability. Furthermore, if the Na2O content is too low, devitrification resistance may decrease. On the other hand, if the Na2O content is too high, hydrolysis resistance tends to deteriorate. Therefore, the Na2O content is preferably 0 to 12%, 0 to 10%, 0 to 9%, 0 to 8.5%, 0 to 8.3%, 0 to 8%, 0 to 7.9%, 0 to 7.5%, 0 to 7%, 0 to 6.5%, 0 to 6%, 0 to 5.5%, and particularly preferably 0 to 5%.

[0045] When emphasis is placed on workability, the Na2O content is preferably 0.1 to 12%, 0.5 to 11%, 1 to 10%, 2 to 9%, 2.5 to 8.5%, 3 to 8%, 3.3 to 7.5%, 3.5 to 7%, 3.8 to 6.5%, particularly 4 to 6%.

[0046] K2O has the effect of reducing the viscosity of glass and improving processability and meltability, although not as effectively as Li2O and Na2O. However, if the K2O content is too high, hydrolysis resistance is likely to deteriorate. On the other hand, if the K2O content is too low, devitrification resistance may decrease. Therefore, the K2O content is preferably 0 to 5%, 0 to 4%, 0 to 3.8%, 0 to 3.7%, 0 to 3.6%, 0 to 3.5%, 0 to 3.3%, 0 to 3.1%, or 0 to 3%, and particularly preferably 0 to less than 3%.

[0047] When emphasis is placed on workability, the K2O content is preferably 0.01 to 11%, 0.05 to 10%, 0.1 to 8%, 0.5 to 6%, 0.8 to 5.5%, 1 to 5%, 1.2 to 4.5%, 1.4 to 4.3%, particularly 1.5 to 4%.

[0048] Among alkali metal oxides (RO), LiO has the greatest effect in reducing the viscosity of glass, followed by NaO and KO. Therefore, from the viewpoint of reducing the viscosity of glass, the relationship of the alkali metal oxide contents is preferably LiO≧NaO≧KO, LiO≧NaO>KO, or LiO>Na2O≧KO, and particularly LiO>Na2O>KO. Furthermore, if the proportion of KO among the alkali metal oxides is too high, it becomes difficult to achieve both hydrolysis resistance and processability. Therefore, from the viewpoint of achieving both hydrolysis resistance and processability, NaO>KO is preferred.

[0049] If the proportion of Li2O among the alkali metal oxides is too high, devitrification resistance is likely to decrease. Therefore, from the viewpoint of devitrification resistance, the content relationship of the alkali metal oxides is preferably Na2O>Li2O. Furthermore, the effect of improving devitrification resistance is greatest with K2O, followed by Na2O and Li2O in that order. From the viewpoint of achieving both hydrolysis resistance and devitrification resistance, the relationships Li2O≧Na2O≧K2O, Li2O≧K2O>Na2O, or Li2O>Na2O≧K2O, particularly Li2O>K2O>Na2O, are preferred.

[0050] As mentioned above, if the proportion of Li2O among the alkali metal oxides is too high, devitrification resistance is likely to decrease. Therefore, from the viewpoint of devitrification resistance, the upper limit range of the molar ratio Li2O / (Li2O + Na2O + K2O) is preferably 0.8 or less, 0.7 or less, 0.6 or less, 0.55 or less, 0.54 or less, 0.53 or less, 0.52 or less, 0.51 or less, 0.5 or less, less than 0.50, 0.49 or less, 0.48 or less, 0.47 or less, 0.46 or less, particularly preferably 0.45 or less.

[0051] Furthermore, if the proportion of K2O among the alkali metal oxides is too high, the effect of lowering the viscosity of the glass will be reduced. Therefore, the upper limit range of the molar ratio K2O / (Li2O + Na2O + K2O) is preferably 0.6 or less, 0.5 or less, 0.4 or less, 0.24 or less, 0.22 or less, 0.21 or less, and particularly 0.2 or less. On the other hand, if the molar ratio K2O / (Li2O + Na2O + K2O) is too small, there is a risk of devitrification resistance being reduced. Therefore, the lower limit range of the molar ratio K2O / (Li2O + Na2O + K2O) is preferably more than 0, 0.01 or more, particularly 0.03 or more, 0.05 or more, 0.8 or more, 0.1 or more, and particularly 0.13 or more.

[0052] Increasing the Al2O3 content improves hydrolysis resistance, but also increases the viscosity of the glass. Furthermore, increasing the Li2O + Na2O + K2O content decreases the viscosity of the glass, but also deteriorates the hydrolysis resistance. Therefore, the molar ratio Al2O3 / (Li2O + Na2O + K2O) is preferably 50 or less, 40 or less, 30 or less, 20 or less, 10 or less, 5 or less, 3 or less, 2 or less, 1.2 or less, 0 to 1, 0 to 0.85, 0 to 0.8, greater than 0 to 0.74, 0.01 to 0.7, 0.1 to 0.67, 0.2 to 0.65, 0.3 to 0.61, 0.35 to 0.60, 0.4 to 0.59, and particularly greater than 0.4 to 0.55. If the molar ratio Al2O3 / (Li2O+Na2O+K2O) is outside the above range, it becomes difficult to achieve both hydrolysis resistance and processability, whereas if the molar ratio Al2O3 / (Li2O+Na2O+K2O) is 0.67 or less, it becomes particularly easy to achieve both hydrolysis resistance and processability.

[0053] As mentioned above, alkali metal oxides reduce the viscosity of glass and also reduce its chemical durability. This is because they disrupt the glass network structure. However, Al2O3 forms the glass network structure in association with alkali metal oxides. Therefore, the incorporation of Al2O3 into the glass composition can change the role of some alkali metal oxides from disrupting the network structure to forming it. Therefore, from the perspective of prioritizing hydrolysis resistance, it is preferable for all Al2O3 to form bonds with alkali metal oxides in the stoichiometric ratio. This state occurs when the molar ratio (Li2O + Na2O + K2O) / Al2O3 is greater than or equal to 1. Therefore, the closer the molar ratio (Li2O + Na2O + K2O) / Al2O3 is to 1, the greater the network structure and the better the hydrolysis resistance. However, this state also reduces the amount of alkali metal oxide, resulting in poor workability. Therefore, from the viewpoint of achieving both hydrolysis resistance and processability, the lower limit of the molar ratio (Li2O + Na2O + K2O) / Al2O3 is 1 or more, preferably 1.5 or more, 1.6 or more, 1.7 or more, 1.8 or more, 1.9 or more, 2 or more, 2.0 or more, 2.1 or more, 2.2 or more, 2.3 or more, 2.4 or more, and particularly 2.5 or more. On the other hand, if the molar ratio (Li2O + Na2O + K2O) / Al2O3 is too large, the processability improves but the hydrolysis resistance tends to deteriorate. Therefore, the upper limit of the molar ratio (Li2O + Na2O + K2O) / Al2O3 is preferably 5 or less, 4 or less, 3.5 or less, 3.4 or less, 3.3 or less, 3.2 or less, 3.1 or less, and particularly 3 or less.

[0054] If the Al2O3 content relative to SiO2 is too low, hydrolysis resistance is likely to deteriorate and devitrification resistance is also likely to decrease. Therefore, the upper limit range of the molar ratio SiO2 / Al2O3 is preferably 30 or less, 25 or less, 20 or less, 18 or less, 17 or less, 16 or less, and particularly 15 or less. On the other hand, if the Al2O3 content relative to SiO2 is too high, it becomes difficult to achieve both hydrolysis resistance and processability. Therefore, the lower limit range of the molar ratio SiO2 / Al2O3 is preferably 10 or more, 11 or more, 12 or more, 12.5 or more, 12.8 or more, 12.9 or more, 13 or more, 13.0 or more, 13.1 or more, 13.2 or more, and particularly more than 13.2.

[0055] In order to achieve both hydrolysis resistance and processability, it is preferable to control the component balance between SiO2 and alkali metal oxides, and the molar ratio SiO2 / (Li2O+Na2O+K2O) is preferably 10 or less, 8 or less, 7.9 or less, 7 or less, 6.9 or less, 6.5 or less, 6.1 or less, 6.0 or less, 5.9 or less, and particularly 5.8 or less. In particular, when the molar ratio SiO2 / (Li2O+Na2O+K2O) is 6.9 or less, it becomes particularly easy to achieve both hydrolysis resistance and processability.

[0056] The lower limit of the molar ratio Li2O / (Na2O+K2O) is preferably 0.1 or more, 0.2 or more, 0.3 or more, 0.4 or more, 0.5 or more, 0.6 or more, and particularly 0.7 or more. This allows the effects of Li2O to be adequately enjoyed while suppressing the adverse effects of Na2O, which deteriorates hydrolysis resistance. On the other hand, if the molar ratio Li2O / (Na2O+K2O) is too high, raw material costs will rise. Therefore, the upper limit of the molar ratio Li2O / (Na2O+K2O) is preferably 2.0 or less, 1.5 or less, 1.2 or less, 1.1 or less, 1.0 or less, less than 1.0, 0.9 or less, 0.85 or less, 0.83 or less, and particularly 0.82 or less.

[0057] The alkaline earth metal oxides (R'O), MgO, CaO, SrO, and BaO, are components that, like alkali metal oxides, break the network structure of glass and also have the effect of reducing the viscosity of glass. They also affect hydrolysis resistance. If the content of MgO + CaO + SrO + BaO is too high, not only is hydrolysis resistance likely to deteriorate, but devitrification resistance is also likely to decrease. Furthermore, there is a risk that alkaline earth metal oxides dissolved in the agent will precipitate as carbonates or sulfates. Therefore, from the viewpoint of prioritizing hydrolysis resistance, the content of MgO+CaO+SrO+BaO is 0 to 10%, preferably 0 to 5%, 0 to 4%, 0 to 3.7%, 0 to 3%, 0 to 2%, 0 to 1%, 0 to 0.9%, 0 to 0.8%, 0 to 0.7%, 0 to 0.6%, 0 to 0.5%, 0 to 0.4%, 0 to 0.3%, 0 to 0.2%, 0 to 0.1%, 0 to 0.01%, less than 0.01%, and particularly less than 0.001%. From the viewpoint of prioritizing workability, the content of MgO+CaO+SrO+BaO is preferably 0.01 to 11%, 0.05 to 10%, 0.1 to 9%, 0.5 to 8%, 0.7 to 7%, 0.9 to 6%, 1.0 to 5%, more than 1% to 4.9%, 1.1 to 4.8%, 1.2 to 4.7%, 1.3 to 4.6%, 1.4 to 4.3%, particularly 1.5 to 4%, 1.8 to less than 4%, and particularly 1.9 to 3.8%.

[0058] The degree of precipitation of carbonates or sulfates of alkaline earth metal oxides depends on the solubility of each salt. Specifically, MgO has the highest solubility, followed by CaO, SrO, and BaO in decreasing order. That is, MgO is least likely to cause salt precipitation, and BaO is most likely to cause salt precipitation. Therefore, when focusing on solubility, the content relationships between alkaline earth metal oxides are preferably MgO≧CaO (particularly MgO>CaO), MgO≧SrO (particularly MgO>SrO), MgO≧BaO (particularly MgO>BaO), CaO≧SrO (particularly CaO>SrO), CaO≧BaO (particularly CaO>BaO), and SrO≧BaO (particularly SrO>BaO), more preferably MgO≧CaO≧SrO≧BaO, and even more preferably MgO>CaO>SrO>BaO.

[0059] On the one hand, the effect of reducing the viscosity of glass is highest for BaO, and then decreases in the order of SrO, CaO, and MgO. Therefore, when focusing on workability, the relationship between the contents of alkaline earth metal oxides is preferably MgO≦CaO (especially MgO<CaO), MgO≦SrO (especially MgO<SrO), MgO≦BaO (especially MgO<BaO), CaO≦SrO (especially CaO<SrO), CaO≦BaO (especially CaO<BaO), SrO≦BaO (especially SrO<BaO), more preferably MgO≦CaO≦SrO≦BaO, and even more preferably MgO<CaO<SrO<BaO.

[0060] As described above, MgO is a component with high solubility of carbonate or sulfate and difficult to cause precipitation of salts. However, since Mg ions easily react with hydrated silicic acid, when Mg ions in the glass elute, there is a risk that they react with the hydrated silicic acid formed on the glass surface to form an insoluble magnesium silicate hydrate film. This film may peel off due to vibration or the like and become flaky insoluble foreign matter. Also, when the content of MgO is too high, the hydrolysis resistance tends to deteriorate. Therefore, the content of MgO is preferably 0 to 10%, 0 to 8%, 0 to 5%, 0 to 3%, 0 to 1.5%, 0 to 1%, 0 to 0.9%, 0 to 0.8%, 0 to 0.7%, 0 to 0.6%, 0 to 0.5%, 0 to 0.4%, 0 to 0.3%, 0 to 0.2%, 0 to 0.1%, 0 to 0.05%, 0 to 0.03%, less than 0 to 0.03%, 0 to 0.01%, less than 0 to 0.01%, particularly less than 0 to 0.001%. When emphasizing workability, MgO may be introduced at 0.01% or more.

[0061] Among alkaline earth metal oxides, CaO is a component that can reduce the viscosity of the glass while preventing the precipitation of salts and insoluble foreign matter. However, if the CaO content is too high, there is a risk of reduced hydrolysis resistance. Therefore, the CaO content is preferably 0 to 10%, 0 to 8%, 0 to 5%, 0 to 3%, 0 to 1%, 0 to 0.9%, 0 to 0.8%, 0 to 0.7%, 0 to 0.6%, 0 to 0.5%, 0 to 0.4%, 0 to 0.3%, 0 to 0.2%, or 0 to 0.1%, and is preferably 0 to 0.05%, 0 to 0.03%, less than 0 to 0.03%, 0 to 0.01%, or less than 0 to 0.01%, particularly preferably 0 to less than 0.001%. Furthermore, from the viewpoint of prioritizing workability, it is preferable to add CaO, and the CaO content is preferably more than 0 to 10%, 1 to 10%, 1.2 to 9%, 1.4 to 8%, 1.6 to 7%, 1.8 to 6%, 2 to 5%, 2.2 to 4.8%, 2.4 to 4.6%, 2.6 to 4.4%, 2.8 to 4.2%, 3 to 4%, and particularly 3.2 to 3.8%.

[0062] When hydrolysis resistance is important, the molar ratio CaO / (LiO+NaO+KO+MgO+CaO+SrO+BaO) is preferably 0.5 or less, 0.4 or less, 0.3 or less, 0.25 or less, 0.24 or less, 0.23 or less, 0.2 or less, 0.1 or less, 0.05 or less, 0.04 or less, 0.03 or less, 0.025 or less, 0.02 or less, 0.019 or less, 0.018 or less, less than 0.018, 0.015 or less, 0.01 or less, particularly 0.001 or less.

[0063] To achieve both hydrolysis resistance and workability, it is preferable to preferentially incorporate MgO and CaO, which are less likely to precipitate carbonates or sulfates, among the alkaline earth metal oxides. Furthermore, it is preferable to adjust the amount of CaO, which has a high effect of lowering the viscosity of the glass, to be relatively high. When prioritizing both workability and resistance to the precipitation of salts and insoluble impurities, it is preferable to increase the molar ratio CaO / (MgO+CaO+SrO+BaO), and the lower limit of the molar ratio CaO / (MgO+CaO+SrO+BaO) is preferably 0.01 or more, 0.03 or more, 0.05 or more, 0.1 or more, 0.2 or more, 0.3 or more, 0.4 or more, 0.5 or more, 0.6 or more, 0.7 or more, 0.8 or more, and particularly 0.9 or more.

[0064] The SrO content is preferably 0 to 1%, 0 to 0.9%, 0 to 0.8%, 0 to 0.7%, 0 to 0.6%, 0 to 0.5%, 0 to 0.4%, 0 to 0.3%, 0 to 0.2%, 0 to 0.1%, 0 to 0.01%, or 0 to less than 0.01%, particularly 0 to 0.001%. If the SrO content is too high, carbonates or sulfates are likely to precipitate and hydrolysis resistance is likely to deteriorate.

[0065] The BaO content is preferably 0 to 1%, 0 to 0.9%, 0 to 0.8%, 0 to 0.7%, 0 to 0.6%, 0 to 0.5%, 0 to 0.4%, 0 to 0.3%, 0 to 0.2%, 0 to 0.1%, 0 to 0.01%, or 0 to less than 0.01%, particularly 0 to 0.001%. If the BaO content is too high, carbonates or sulfates are likely to precipitate and hydrolysis resistance is likely to deteriorate.

[0066] MgO is a component that has high solubility in carbonates or sulfates and is less likely to precipitate these salts. On the other hand, Mg ions are a component that easily reacts with hydrated silicic acid, which may result in the formation of an insoluble magnesium silicate hydrate coating. Therefore, the molar ratio MgO / (MgO + CaO + SrO + BaO) is preferably 1 or less, less than 1, 0.9 or less, 0.8 or less, 0.7 or less, 0.6 or less, 0.5 or less, less than 0.5, 0.4 or less, 0.3 or less, 0.2 or less, 0.1 or less, 0.01 or less, and particularly preferably 0.001 or less.

[0067] From the viewpoint of suppressing the formation of an insoluble magnesium silicate hydrate coating, the molar ratio MgO / (LiO+NaO+KO+MgO+CaO+SrO+BaO) is preferably 0.5 or less, 0.4 or less, 0.3 or less, 0.2 or less, 0.1 or less, 0.09 or less, 0.08 or less, 0.07 or less, 0.06 or less, less than 0.06, 0.05 or less, 0.04 or less, 0.03 or less, 0.02 or less, 0.01 or less, and particularly preferably 0.001 or less.

[0068] From the viewpoint of prioritizing hydrolysis resistance, the molar ratio (MgO+CaO+SrO+BaO) / (Li2O+Na2O+KO+MgO+CaO+SrO+BaO) is preferably 0.5 or less, 0.4 or less, 0.3 or less, 0.2 or less, 0.1 or less, 0.09 or less, 0.08 or less, 0.07 or less, 0.06 or less, less than 0.06, 0.05 or less, 0.04 or less, 0.03 or less, 0.02 or less, 0.01 or less, and particularly preferably 0.001 or less.

[0069] The content of MgO+CaO is preferably 0-10%, 0-5%, 0-4%, 0-3.7%, 0-3%, 0-2%, 0-1%, 0-0.9%, 0-0.8%, 0-0.7%, 0-0.6%, 0-0.5%, 0-0.4%, 0-0.3%, 0-0.2%, 0-0.1%, 0-0.01%, or 0-less than 0.01%, particularly 0-0.001%. If the content of MgO+CaO is too high, carbonates or sulfates are likely to precipitate. Note that "MgO+CaO" refers to the total content of MgO and CaO.

[0070] As mentioned above, MgO may form an insoluble magnesium silicate hydrate film, but CaO is a component that is less likely to react with SiO2 than MgO and is less likely to form an insoluble film. Therefore, from the viewpoint of improving the safety of pharmaceutical containers, the molar ratio MgO / CaO is preferably less than 9.0, 8.0 or less, 6.0 or less, 5.0 or less, 3.0 or less, 1.0 or less, 0.9 or less, 0.7 or less, 0.5 or less, 0.4 or less, 0.3 or less, 0.2 or less, and particularly less than 0.1. If the molar ratio MgO / CaO is too large, hydrolysis resistance is likely to deteriorate.

[0071] When balancing the LiO and CaO components to achieve both hydrolysis resistance and processability, and when the LiO content is important, it is preferable to regulate the molar ratio LiO / CaO. The molar ratio LiO / CaO is preferably 100 or less, 90 or less, 80 or less, 70 or less, 60 or less, 50 or less, 40 or less, 30 or less, 20 or less, 10 or less, 9 or less, 8 or less, 7 or less, 6 or less, 5 or less, 4 or less, 3.5 or less, 3.4 or less, 3.3 or less, 3.2 or less, 3.1 or less, 3 or less, 2 or less, 1.8 or less, 1.7 or less, 1.6 or less, and particularly preferably 1.5 or less.

[0072] When the CaO content is important in achieving a balance between LiO and CaO to achieve both hydrolysis resistance and processability, it is preferable to regulate the molar ratio CaO / LiO, which is preferably 2.0 or less, 1.5 or less, 1.2 or less, 1.1 or less, 1.0 or less, less than 1.0, 0.9 or less, 0.8 or less, 0.7 or less, 0.6 or less, 0.5 or less, 0.4 or less, 0.3 or less, 0.2 or less, 0.1 or less, and particularly preferably 0.001 or less.

[0073] The content of SiO2+Al2O3+Li2O+Na2O+K2O+MgO+CaO+SrO+BaO is preferably 90% or more, 93% or more, 95% or more, 96% or more, 97% or more, 98% or more, 98.5% or more, particularly 99% or more. If the content of SiO2+Al2O3+Li2O+Na2O+K2O+MgO+CaO+SrO+BaO is too low, it becomes difficult to achieve both hydrolysis resistance and processability.

[0074] The molar ratio (Li2O + Na2O + K2O + MgO + CaO + SrO + BaO - Al2O3) / (SiO2 + Al2O3) refers to the ratio of components that break the network structure in glass to components that form the network structure in glass. As mentioned above, alkali metal oxides and alkaline earth metal oxides have the effect of breaking the network structure in glass, but Al2O3 forms the network structure in glass together with alkali metal oxides, so an amount of alkali metal oxide equal to the amount of Al2O3 does not have the effect of breaking the network. Furthermore, SiO2 and Al2O3 are components that form the network structure in glass. In other words, the smaller the molar ratio (Li2O + Na2O + K2O + MgO + CaO + SrO + BaO - Al2O3) / (SiO2 + Al2O3), the fewer components that break the network structure compared to the components that form the network structure, resulting in improved chemical durability, especially hydrolysis resistance. Therefore, the upper limit of the molar ratio (Li2O + Na2O + K2O + MgO + CaO + SrO + BaO-Al2O3) / (SiO2 + Al2O3) is 0.2 or less, and preferably 0.19 or less, 0.018 or less, 0.17 or less, 0.16 or less, less than 0.159, 0.158 or less, 0.157 or less, 0.156 or less, less than 0.155, 0.15 or less, 0.14 or less, 0.13 or less, 0.12 or less, and particularly 0.11 or less. In particular, when the molar ratio (Li2O + Na2O + K2O + MgO + CaO + SrO + BaO-Al2O3) / (SiO2 + Al2O3) is 0.156 or less, it becomes particularly easy to achieve both hydrolysis resistance and processability. On the other hand, if the molar ratio (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO-Al2O3) / (SiO2+Al2O3) is too small, the viscosity of the glass tends to be high. Therefore, the lower limit of the molar ratio (Li2O+Na2O+K2O+MgO+CaO+SrO+BaO-Al2O3) / (SiO2+Al2O3) is preferably 0 or more, 0.01 or more, 0.02 or more, 0.03 or more, 0.04 or more, 0.05 or more, 0.06 or more, 0.07 or more, 0.08 or more, 0.09 or more, particularly 0.1 or more.

[0075] In addition to the above components, other components may be incorporated.

[0076] ZrO2 is a component that improves alkali resistance. However, if the ZrO2 content is too high, the viscosity of the glass increases and devitrification resistance tends to decrease. Therefore, the ZrO2 content is preferably 0 to 3%, 0 to 2.5%, 0 to 2%, 0 to 1.5%, 0.1 to 0.8%, and particularly preferably 0.2 to 0.6%.

[0077] ZnO has the effect of reducing the viscosity of the glass. However, if the ZnO content is too high, it will have a negative effect on hydrolysis resistance. Therefore, the ZnO content is preferably 0 to 4%, 0 to 1%, and particularly 0 to 0.01%.

[0078] To color the glass, TiO2 and Fe2O3 can be added to the batch raw materials, and the total and individual contents of TiO2 and Fe2O3 are preferably 7% or less, 6% or less, more than 0% to 5%, 0.001% to 1%, and particularly 0.1% to 0.5%.

[0079] TiO2 and Fe2O3 are also components contained as impurities in, for example, SiO2 raw materials. Therefore, TiO2 and Fe2O3 may be contained in glass even if the glass is not colored. When the glass is not colored, the TiO2 content is preferably 0.1% or less, 0.08% or less, 0.05% or less, 0.03% or less, 0.01% or less, and particularly 0.005% or less, and the Fe2O3 content is preferably 0.1% or less, 0.08% or less, 0.05% or less, 0.03% or less, 0.01% or less, and particularly 0.005% or less.

[0080] One or more fining agents, such as F, Cl, Sb2O3, SnO2, and SO3, may be incorporated. The total content and individual content of these fining agents are preferably 5% or less, 1% or less, 0.5% or less, and particularly 0.3% or less. Even if Cl is not added as a fining agent, it may be present in the glass as an impurity contained in the batch raw materials. If the Cl content is too high, white defects are likely to occur during heat processing of the glass. Therefore, the Cl content is preferably 0.1% or less, 0.05% or less, 0.01% or less, 0.005% or less, and particularly 0.04% or less.

[0081] To improve chemical durability, high-temperature viscosity, etc., P2O5, Cr2O3, PbO, La2O3, WO3, Nb2O3, Y2O3, etc. may be incorporated in amounts of 3% or less, 2% or less, 1% or less, less than 1%, and 0.5% or less, respectively.

[0082] Impurities such as H, CO, CO, H0, He, Ne, Ar, and N may be introduced up to 0.1% each. The amount of each of precious metal elements such as Pt, Rh, and Au is preferably 500 ppm or less, and more preferably 300 ppm or less.

[0083] The glass for pharmaceutical containers of the present invention preferably has a class of at least HGA2, and particularly preferably HGA1, in a hydrolysis resistance test (acetone washing) in accordance with ISO720.

[0084] Furthermore, the amount of alkali elution, calculated as Na2O, in a hydrolysis resistance test (acetone washing) according to ISO 720 is preferably less than 527 μg / g, 200 μg / g or less, 100 μg / g or less, 90 μg / g or less, 80 μg / g or less, 70 μg / g or less, less than 62 μg / g, 60 μg / g or less, 57 μg / g or less, 55 μg / g or less, 53 μg / g or less, and particularly 50 μg / g or less. If the amount of alkali elution is too high, when the glass is processed into an ampule or vial, filled with a drug, and stored, there is a risk that the drug component will be altered by the alkaline component eluted from the glass.

[0085] Furthermore, the alkali resistance according to a test in accordance with ISO 695 is preferably at least Class 2. Here, the "alkali resistance test in accordance with ISO 695" refers to the following test. (1) Surface area of ​​all mirror-finished surfaces: Acm 2 (However, A is 10 to 15 cm 2A sample of (specimen number 1) is prepared. First, as a pretreatment, a solution is prepared by mixing hydrofluoric acid (40% by mass) and hydrochloric acid (2 mol / L) in a volume ratio of 1:9. The sample is immersed in this solution and stirred with a magnetic stirrer for 10 minutes. The sample is then removed and subjected to ultrasonic cleaning with purified water for 2 minutes three times, and ultrasonic cleaning with ethanol for 1 minute twice. (2) Then, dry the sample in an oven at 110°C for 1 hour and allow it to cool in a desiccator for 30 minutes. (3) Measure and record the mass m1 of the sample to an accuracy of ±0.1 mg. (4) Prepare 800 mL of a solution by mixing a sodium hydroxide solution (1 mol / L) and a sodium carbonate solution (0.5 mol / L) in a volume ratio of 1:1. Place this solution in a stainless steel container and boil it using a mantle heater. Next, add the sample suspended by a platinum wire and hold for 3 hours. Then, remove the sample and ultrasonically clean it with purified water for 2 minutes three times, then ultrasonically clean it with ethanol for 1 minute twice. Then, dry the sample in an oven at 110°C for 1 hour and allow it to cool in a desiccator for 30 minutes. (5) Measure and record the mass m2 of the sample to an accuracy of ±0.1 mg. (6) The mass m1 and m2 (mg) and the surface area A (cm2) of the sample before and after immersion in the boiling alkaline solution 2 ) and calculate the mass loss per unit area using the following formula, which is the measurement value for the alkali resistance test. (Mass loss per unit area) = 100 × (m1-m2) / A

[0086] "Class 2 alkali resistance in a test conforming to ISO 695" means that the mass loss per unit area calculated as above is 175 mg / dm 2 This means that the mass loss per unit area calculated above is 75 mg / dm 2 If the glass for pharmaceutical containers of the present invention has a mass loss per unit area of ​​130 mg / dm or less, it is classified as "Class 1 in alkali resistance in a test according to ISO 695." 2 Below 75 mg / dm 2 The following is the result.

[0087] Delamination often occurs when a drug containing a solution (such as citric acid or phosphate buffer) that behaves like a strong alkaline solution even when the pH is near neutral is filled into a glass container and stored. The mass loss per unit area determined by a test in accordance with ISO 695 is 175 mg / dm 2 Therefore, in the glass for pharmaceutical containers of the present invention, the mass loss per unit area is preferably 130 mg / dm 2 Below 75 mg / dm 2 The following is the result.

[0088] In an acid resistance test in accordance with YBB·BR>O0342004, the mass loss per unit area is preferably 1.5 mg / dm 2 Below 0.7 mg / dm 2 If this mass loss is large, when pharmaceutical containers such as ampoules and vials are manufactured, filled with a drug solution, and then stored, the amount of glass components eluted increases significantly, which may cause deterioration of the drug solution components.

[0089] "Acid resistance test in accordance with YBB00342004" refers to the following test. (1) Surface area of ​​all mirror-finished surfaces: Acm 2 (However, A is 100±5cm 2 A sample of (specimen number 1) is prepared. First, as a pretreatment, a solution is prepared by mixing hydrofluoric acid (40% by mass) and hydrochloric acid (2 mol / L) in a volume ratio of 1:9. The sample is immersed in this solution and stirred with a magnetic stirrer for 10 minutes. The sample is then removed and subjected to ultrasonic cleaning with purified water for 2 minutes three times, and ultrasonic cleaning with ethanol for 1 minute twice. (2) Then, dry the sample in an oven at 110°C for 1 hour and allow it to cool in a desiccator for 30 minutes. (3) Measure and record the mass m1 of the sample to an accuracy of ±0.1 mg. (4) Prepare 800 mL of hydrochloric acid solution (6 mol / L). Place this hydrochloric acid solution in a silica glass container and boil it using an electric heater. Add the sample suspended from a platinum wire and hold for 6 hours. Remove the sample and ultrasonically clean it with purified water for 2 minutes three times, then ultrasonically clean it with ethanol for 1 minute twice. Then, dry the sample in an oven at 110°C for 1 hour and allow it to cool in a desiccator for 30 minutes. (5) Measure and record the mass m2 of the sample to an accuracy of ±0.1 mg. (6) The mass m1 and m2 (mg) and the surface area A (cm2) of the sample before and after immersion in the boiling acid solution 2 ) and calculate half of the mass loss per unit area using the following formula, which is the measurement value for the acid resistance test. (Mass loss per unit area) = 1 / 2 x 100 x (m1 - m2) / A

[0090] In the glass for pharmaceutical containers of the present invention, the working point is preferably 1350°C or lower, 1300°C or lower, 1260°C or lower, and particularly 1250°C or lower. As the working point increases, the processing temperature when processing the glass tube into an ampoule or vial becomes higher, resulting in a significant increase in the volatilization of alkali components contained in the glass. The volatilized alkali components adhere to the inner wall of the glass tube, and the glass tube in this state is processed into a glass container. Such glass containers can cause the deterioration of medicines when filled and stored. Furthermore, in the case of glass containing a large amount of boron, a high working point increases the amount of boron volatilized, which can cause delamination.

[0091] The glass for pharmaceutical containers of the present invention can be subjected to a chemical strengthening treatment (ion exchange treatment) to form a compressive stress layer on its surface. When the glass for pharmaceutical containers of the present invention is subjected to a chemical strengthening treatment by immersion in a KNO3 molten salt at 475°C for 7 hours, the compressive stress value of the compressive stress layer formed is preferably 100 MPa or more, more preferably 200 MPa or more, and particularly preferably 300 MPa or more. Furthermore, when the glass for pharmaceutical containers of the present invention is subjected to a chemical strengthening treatment by immersion in a KNO3 molten salt at 475°C for 7 hours, the stress depth of the compressive stress layer formed is preferably 10 μm or more, more preferably 20 μm or more, and particularly preferably 30 μm or more.

[0092] The compressive stress value and stress depth of the compressive stress layer can be measured as follows. First, both surfaces of the sample are mirror-polished, and then the sample is chemically strengthened by immersing it in molten KNO3 at 475°C for 7 hours. Next, the sample surface is cleaned, and the compressive stress value and stress depth are calculated from the number and spacing of interference fringes observed using a surface stress meter (FSM-6000, manufactured by Orihara Seisakusho Co., Ltd.). For the calculations, the refractive index of the sample is set to 1.50 and the photoelastic constant to 29.5 [(nm / cm) / MPa]. Note that although the glass composition in the glass surface layer differs microscopically before and after chemical strengthening, the glass composition does not substantially change when viewed as a whole.

[0093] Next, a method for producing a glass tube for a pharmaceutical container according to the present invention will be explained using the Danner method.

[0094] First, glass raw materials are mixed to form a batch to obtain a predetermined glass composition. Next, this batch is continuously fed into a melting furnace at 1550 to 1700°C for melting and fining. The resulting molten glass is then wound around a rotating refractory while air is blown out from the tip of the refractory, and the glass is drawn out in a tubular shape from the tip of the refractory.

[0095] The drawn tubular glass is then cut to a predetermined length to obtain a glass tube, which is used to manufacture pharmaceutical containers such as vials and ampoules.

[0096] The glass tube for pharmaceutical containers of the present invention may be produced by other methods (for example, the Vello method or the down-draw method) in addition to the Danna method.

[0097] Next, a method for manufacturing the pharmaceutical container of the present invention will be described. Hereinafter, a method for manufacturing the pharmaceutical container by processing a glass tube using a vertical processing method will be described, but this method is only an example.

[0098] First, a glass tube is prepared and placed vertically. One end of the glass tube is heated with a burner, and a forming tool is used to form a shoulder and a mouth. Next, the portion of the glass tube above the shoulder is heated with the burner to fuse and cut it. The fused portion is then heated and shaped with the burner to form the bottom, thereby obtaining a pharmaceutical container.

[0099] The fused portion of the glass tube is opened by heating with a burner and used to manufacture the next pharmaceutical container. By repeating this process, multiple pharmaceutical containers can be obtained from the glass tube.

[0100] If necessary, pharmaceutical containers such as ampoules and vials can be immersed in KNO3 molten salt for ion exchange to obtain chemically strengthened pharmaceutical containers.

[0101] The glass tube for pharmaceutical containers and the pharmaceutical containers may have a coating on their inner and / or outer surfaces, such as inorganic coatings containing fluorine, silicone, surfactants, etc., or organic coatings. [Example]

[0102] The present invention will be described below based on examples. Note that the following examples are merely illustrative and do not limit the present invention in any way.

[0103] Tables 1 to 6 show examples of the present invention (samples Nos. 1 to 69). In the tables, "R2O" means Li2O + Na2O + K2O, "R'O" means MgO + CaO + SrO + BaO, and "NA" means not measured.

[0104] [Table 1]

[0105] [Table 2]

[0106] [Table 3]

[0107] [Table 4]

[0108] [Table 5]

[0109] [Table 6]

[0110] Each sample was prepared as follows. First, a 550 g batch was prepared to obtain the glass composition shown in the table, and then melted in a platinum crucible at 1550°C for 2.5 hours. To improve the homogeneity of the sample, the mixture was stirred twice during the melting process. To further improve the homogeneity of the molten glass, the molten glass was water-crushed and dried, and then melted again in a platinum crucible at 1550°C for 1 hour. After stirring once, the mixture was melted again at 1600°C for 2 hours to reduce bubbles in the glass. The molten glass was then poured out to produce an ingot, which was then processed into the shape required for measurement and subjected to various evaluations. The results are shown in the table.

[0111] The strain point Ps was determined by a fiber drawing method in accordance with ASTM C336. The annealing point Ta and softening point Ts were determined by a fiber drawing method in accordance with ASTM C388.

[0112] Working point (glass viscosity is 10 4.0 dPa·s) and the temperature at which the glass viscosity is 10 3.0 The temperature at which the viscosity reaches dPa·s was determined by the platinum sphere pulling method.

[0113] The hydrolysis resistance test was conducted using a hydrolysis resistance test (acetone washing) in accordance with ISO 720. The detailed test procedure is as described above.

[0114] Acid resistance was evaluated by an acid resistance test in accordance with YBB00342004, and alkali resistance was evaluated by a test in accordance with ISO695.

[0115] The linear thermal expansion coefficient was measured in a temperature range of 20 to 300°C using a dilatometer, using a glass molded into a rod shape of approximately 5 mmφ×20 mm as a measurement sample.

[0116] The liquidus temperature was determined by filling a platinum boat of approximately 120 x 20 x 10 mm with crushed glass, placing it in an electric furnace with a linear temperature gradient for 24 hours, identifying the location of crystal precipitation through microscopic observation, and determining the temperature corresponding to the location of crystal precipitation from a temperature gradient graph of the electric furnace.

[0117] The liquidus viscosity logη at TL is calculated by finding a viscosity curve of the glass from the strain point, annealing point, softening point, working temperature and Fulcher's viscosity formula, and then calculating the viscosity of the glass at the liquidus temperature from this viscosity curve.

[0118] As is clear from the table, Samples Nos. 1 to 69 had a low content of B2O3 in the glass composition, a working temperature of 1321°C or less, and an alkali elution amount of 102.9µg / g or less in the hydrolysis resistance test.

[0119] Figure 1 is a graph plotting the molar ratio (Li2O + Na2O + K2O + MgO + CaO + SrO + BaO - Al2O3) / (SiO2 + Al2O3) of various glasses on the horizontal axis and the data of hydrolysis resistance tests on the vertical axis. As can be seen from Figure 1, there is a correlation between the molar ratio (Li2O + Na2O + K2O + MgO + CaO + SrO + BaO - Al2O3) / (SiO2 + Al2O3) and hydrolysis resistance, and it can be seen that the smaller the molar ratio (Li2O + Na2O + K2O + MgO + CaO + SrO + BaO - Al2O3) / (SiO2 + Al2O3), the better the hydrolysis resistance. Figure 2 is a graph showing the same results as in Figure 1, with different plots depending on whether or not the glass contains MgO + CaO + SrO + BaO. Fig. 3 is a graph showing data for a glass that does not contain MgO+CaO+SrO+BaO extracted from the data shown in Fig. 1. Fig. 4 is a graph showing data for a glass that contains MgO+CaO+SrO+BaO extracted from the data shown in Fig. 1. [Industrial Applicability]

[0120] The glass for pharmaceutical containers of the present invention is suitable as a pharmaceutical glass for producing pharmaceutical containers such as ampoules, vials, prefilled syringes, and cartridges, and can also be applied to pharmaceutical containers for oral pharmaceuticals and beverage bottles.

Claims

1. The glass composition is, in mol%, SiO ２ 70-85%, Al ２ O ３ 3-13%, B ２ O ３ 0-2%, MgO 0-0.8%, CaO 0-4%, SrO 0-1%, BaO 0-1%, Li ２ O + Na ２ O+K ２ O 0.1 to 18%, MgO + CaO + SrO + BaO 0 to 10%, and the molar ratio (Li ２ O + Na ２ O+K ２ O) / Al ２ O ３ The value of is 1 or more, and the molar ratio (Li ２ O + Na ２ O+K ２ O+MgO+CaO+SrO+BaO-Al ２ O ３ ) / (SiO ２ +Al ２ O ３ ) is 0.2 or less.

2. Li ２ The content of O is 0 to 8.1 mol %, Na ２ The content of O is 0.1 to 8 mol %, ２ 2. The glass for pharmaceutical containers according to claim 1, wherein the O content is 0.01 to 5 mol %.

3. 3. The glass for pharmaceutical containers according to claim 1, wherein the content of MgO+CaO+SrO+BaO is 0 to 5 mol %.

4. 4. The glass for pharmaceutical containers according to claim 1, wherein the MgO content is 0 to 0.8 mol %, the SrO content is 0 to 0.3 mol %, and the BaO content is 0 to 0.3 mol %.

5. Molar ratio Li ２ O / (Li ２ O + Na ２ O+K ２ 5. The glass for pharmaceutical containers according to claim 1, wherein the glass has a refractive index of 0.0 or less.

6. Molar ratio (Li ２ O + Na ２ O+K ２ O) / Al ２ O ３ 6. The glass for pharmaceutical containers according to claim 1, wherein the ratio of the number of molten metals to the number of molten metals is 2 or more.

7. Molar ratio CaO / (Li ２ O + Na ２ O+K ２ 7. The glass for pharmaceutical containers according to claim 1, wherein the total mass of the glass is 0.018 or less.

8. Contains CaO, and the molar ratio Li ２ 8. The glass for pharmaceutical containers according to claim 1, wherein O / CaO is 3.1 or less.

9. SiO ２ +Al ２ O ３ +Li ２ O + Na ２ O+K ２ 9. The glass for pharmaceutical containers according to claim 1, wherein the content of O+MgO+CaO+SrO+BaO is 90 mol % or more.

10. B ２ O ３ 10. The glass for pharmaceutical containers according to claim 1, wherein the content of

11. ZrO ２ 11. The glass for pharmaceutical containers according to claim 1, wherein the content of

12. The glass composition is, in mol%, SiO ２ 70-85%, Al ２ O ３ 3-10%, B ２ O ３ 0-2%, Li ２ O + Na ２ O+K ２ O 0.1 to less than 13.9%, MgO + CaO + SrO + BaO 0 to 10%, and a molar ratio of Li ２ O / (Li ２ O + Na ２ O+K ２ O) is 0.5 or less, and the molar ratio (Li ２ O + Na ２ O+K ２ O) / Al ２ O ３ is 2.0 or more, and the molar ratio (Li ２ O + Na ２ O+K ２ O+MgO+CaO+SrO+BaO-Al ２ O ３ ) / (SiO ２ +Al ２ O ３ ) is 0.156 or less, and the molar ratio CaO / (Li ２ O + Na ２ O+K ２ 1. A glass for pharmaceutical containers, characterized in that the total mass of glass (MgO+MgO+CaO+SrO+BaO) is less than 0.

018.

13. The glass composition is, in mol%, SiO ２ 70-85%, Al ２ O ３ 3-10%, B ２ O ３ 0-5%, Li ２ O + Na ２ O+K ２ O 0.1 to less than 13.9%, CaO, and a molar ratio of Li ２ O / (Li ２ O + Na ２ O+K ２ O) is 0.5 or less, and the molar ratio (Li ２ O + Na ２ O+K ２ O) / Al ２ O ３ is 2.0 or more, and the molar ratio (Li ２ O + Na ２ O+K ２ O+MgO+CaO+SrO+BaO-Al ２ O ３ ) / (SiO ２ +Al ２ O ３ ) is 0.156 or less, and the molar ratio Li ２ A glass for pharmaceutical containers, characterized in that O / CaO is 3.1 or less.

14. Molar ratio (MgO + CaO + SrO + BaO) / (Li ２ O + Na ２ O+K ２ 14. The glass for pharmaceutical containers according to claim 1, wherein the total mass of the glass is 0.06 or less.

15. The glass composition is, in mol%, SiO ２ 75-85%, Al ２ O ３ 3-13%, B ２ O ３ 0-2%, Li ２ O + Na ２ O+K ２ O 0.11-16%, Na ２ O 0.1-15%, K ２ O 0.01 to 5%, and the molar ratio (Li ２ O + Na ２ O+K ２ O) / Al ２ O ３ is 2 or more, the molar ratio (MgO + CaO + SrO + BaO) / (Li ２ O + Na ２ O+K ２ O + MgO + CaO + SrO + BaO) is 0.06 or less, and the molar ratio (Li ２ O + Na ２ O+K ２ O+MgO+CaO+SrO+BaO-Al ２ O ３ ) / (SiO ２ +Al ２ O ３ ) is 0.2 or less.

16. 16. The glass for pharmaceutical containers according to claim 1, wherein the molar ratio CaO / (MgO+CaO+SrO+BaO) is 0.5 or more.

17. The glass composition is, in mol%, SiO ２ 70-85%, Al ２ O ３ 3-13%, B ２ O ３ 0-5%, Li ２ O + Na ２ O+K ２ O 0.1-16%, Na ２ O 0.1 to 15%, MgO + CaO + SrO + BaO 0.1 to 4%, and the molar ratio (Li ２ O + Na ２ O+K ２ O) / Al ２ O ３ is 2 or more, the molar ratio CaO / (MgO+CaO+SrO+BaO) is 0.5 or more, the molar ratio (Li ２ O + Na ２ O+K ２ O+MgO+CaO+SrO+BaO-Al ２ O ３ ) / (SiO ２ +Al ２ O ３ ) is 0.2 or less.

18. Molar ratio SiO ２ / Al ２ O ３ 18. The glass for pharmaceutical containers according to claim 1, wherein the glass has a viscosity of 10 or more.

19. The glass composition is, in mol%, SiO ２ 70-85%, Al ２ O ３ 3-13%, B ２ O ３ 0-2%, Li ２ O + Na ２ O+K ２ O 0.21-16%, Li ２ O 0.1-10%, Na ２ O 0.1-15%, K ２ O 0.01 to 5%, MgO + CaO + SrO + BaO 0 to 6%, and the molar ratio (Li ２ O + Na ２ O+K ２ O) / Al ２ O ３ is 1 or more, the molar ratio SiO ２ / Al ２ O ３ is greater than 13.2, and the molar ratio (Li ２ O + Na ２ O+K ２ O+MgO+CaO+SrO+BaO-Al ２ O ３ ) / (SiO ２ +Al ２ O ３ ) is less than 0.

155.

20. 20. The glass for pharmaceutical containers according to claim 1, characterized in that its class in a hydrolysis resistance test (acetone washing) in accordance with ISO 720 is at least HGA1.

21. 21. The glass for pharmaceutical containers according to claim 1, wherein the working point is 1300° C. or lower.

22. A glass tube for pharmaceutical containers, comprising the glass for pharmaceutical containers according to any one of claims 1 to 21.

23. A pharmaceutical container comprising the glass for pharmaceutical containers according to any one of claims 1 to 21.

Images