JPWO2017115728A1 - Method for producing aluminoborosilicate glass for pharmaceutical containers - Google Patents

Abstract

Provided is a method for producing an aluminoborosilicate glass for a pharmaceutical container that can suppress the evaporation of B ₂ O ₃ and Na ₂ O by reducing the amount of heat required in the thermal processing step for forming the pharmaceutical container.
After melting the glass batch containing the Al-introduced raw material, the resulting molten glass is molded to obtain an aluminoborosilicate glass for a pharmaceutical container. It includes natural minerals and Al-containing chemicals, and Al / (Al in Al-containing natural minerals + Al in Al-containing chemicals) in the mass ratio is 0 to 0.9. Features.

Description

  The present invention relates to a method for producing aluminoborosilicate glass for pharmaceutical containers.

Pharmaceutical containers include vials and ampoules, and the glass used for these is required to have the following characteristics.
(A) The components in the chemical solution to be filled do not react with the components in the glass.
(B) The chemical durability and the hydrolysis resistance are high so as not to contaminate the chemicals to be filled, and they are maintained even after various heat treatments such as processing the container.
(C) The coefficient of thermal expansion is low so that damage due to thermal shock is unlikely to occur during the manufacturing process of the glass tube, which is an intermediate product, and the thermal processing process for pharmaceutical containers.
(D) The amount of heat in the thermal processing step can be reduced in order to suppress the formation of a heterogeneous layer on the inner surface of the container.

Conventionally, soda lime glass, borosilicate glass, and alumino borosilicate glass have been used as glass for pharmaceutical containers. Then, standard pharmaceutical container alumino borosilicate glass, as a _component, contains _{SiO 2, B 2 O 3,} Al 2 O 3, Na 2 O, K 2 O, CaO, BaO and a small amount of fining agents There are many.

JP 2014-214084 A

  In recent years, development of chemicals to be filled has progressed, and chemicals with higher medicinal effects are being used. Some of these chemical solutions are chemically unstable, easily denatured, and have high reactivity with glass. Accordingly, aluminoborosilicate glass for pharmaceutical containers is required to have higher chemical durability and hydrolysis resistance than ever before.

  Further, when the aluminoborosilicate glass contains BaO, barium feldspar crystals are likely to precipitate due to reaction with the alumina-based refractory when the glass is melted, and the productivity is lowered. There is a possibility that the barium ions eluted from the water react with sulfate ions in the chemical solution to generate insoluble precipitates.

By the way, pharmaceutical containers such as vials and ampoules can be obtained by locally heating a glass tube made of aluminoborosilicate glass with a burner, followed by molding. During this thermal processing, B ₂ O ₃ , Na ₂ O, etc. contained in the aluminoborosilicate glass may evaporate and condense on the inner surface of the pharmaceutical container, thereby forming a heterogeneous layer.

The formation of the heterogeneous layer substantially reduces the chemical durability and hydrolysis resistance of the pharmaceutical container. That is, B ₂ O ₃ , Na ₂ O and the like are eluted from the heterogeneous layer during storage of the chemical solution or during autoclaving after filling with the chemical solution, causing alteration of the chemical component or pH change of the chemical solution.

  This heterogeneous layer also causes the inner surface of the pharmaceutical container to peel off and cause insoluble foreign substances called flakes to be generated in the chemical solution.

Therefore, Patent Document 1 proposes a glass in which BaO is not contained and the amount of K ₂ O added is adjusted in order to improve hydrolysis resistance. However, K ₂ O itself is not only easily evaporated, but also has an insufficient effect of suppressing the evaporation of B ₂ O ₃ and Na ₂ O. For this reason, the heterogeneous layer formed on the inner surface of the pharmaceutical container at the time of heat processing cannot be sufficiently suppressed.

An object of the present invention is to provide a method for producing an aluminoborosilicate glass for a pharmaceutical container that can suppress the evaporation of B ₂ O ₃ and Na ₂ O by reducing the amount of heat required in the thermal processing step for molding the pharmaceutical container. Is to provide.

The inventors have conducted various experiments, and the evaporation amount of B ₂ O ₃ or Na ₂ O that evaporates when the aluminoborosilicate glass for pharmaceutical containers is heat-processed is not only the composition of the glass but also the local composition. It was found to be related to homogeneity. That is, when striae showing local inhomogeneity of the glass composition was remarkable, it was found that a large amount of B ₂ O ₃ and Na ₂ O were evaporated when thermally processed into a pharmaceutical container.

  Furthermore, the present inventors have found that this striae is largely related to the composition of the Al-introducing raw material contained in the glass batch.

  That is, the method for producing an aluminoborosilicate glass for a pharmaceutical container according to the present invention is a pharmaceutical container for obtaining an aluminoborosilicate glass for a pharmaceutical container by melting a glass batch containing an Al-introducing raw material and then molding the obtained molten glass. In the method for producing aluminoborosilicate glass for use, Al-containing natural mineral and Al-containing chemical product are included as Al-introducing raw materials, and Al / (Al + Al content in Al-containing natural mineral is included by mass ratio) It is characterized in that Al) in the chemical product is more than 0 to 0.9.

Here, the aluminoborosilicate glass is glass containing SiO ₂ , B ₂ O ₃ and Al ₂ O ₃ as essential components. Further, the glass batch of the present invention contains an Al-containing natural mineral and an Al-containing chemical product as an Al-introducing raw material. The Al content in each raw material can be determined by XRF or chemical analysis.

A method of manufacturing a medicament container aluminoborosilicate glass of the present invention, it is preferable to use Al-containing natural minerals containing 1 wt% or more of Al in terms of Al ₂ O _3.

  Moreover, it is preferable that the manufacturing method of the aluminoborosilicate glass for pharmaceutical containers of this invention uses a feldspar group mineral as said Al containing natural mineral.

  Moreover, it is preferable that the manufacturing method of the alumino borosilicate glass for pharmaceutical containers of this invention uses aluminum oxide and / or aluminum hydroxide as said Al containing chemical product.

  Moreover, it is preferable that the manufacturing method of the alumino borosilicate glass for pharmaceutical containers of this invention introduce | transduces an alkali carbonate raw material and / or an alkali nitrate raw material further into the said glass batch.

A method of manufacturing a medicament container aluminoborosilicate glass of the present invention has a glass composition, in _{mass%, SiO 2 70.0~77.0%, Al} 2 O 3 4.5~11%, B 2 O ₃ 3.0 to 11.5%, Na ₂ O 3.0 to 8.5%, K ₂ O 0 to 5.5%, Li ₂ O 0 to 3.5%, MgO + CaO 0 to less than 4.0% It is preferable to prepare the glass batch so that an aluminoborosilicate glass for pharmaceutical containers containing 0 to less than 4.0% of SrO is obtained.

  Moreover, it is preferable that the manufacturing method of the alumino borosilicate glass for pharmaceutical containers of this invention prepares a glass batch so that the alumino borosilicate glass for pharmaceutical containers which does not contain BaO substantially as a glass composition may be obtained.

Moreover, the manufacturing method of the aluminoborosilicate glass for pharmaceutical containers of the present invention has a value of Al ₂ O ₃ / (B ₂ O ₃ + Li ₂ O + Na ₂ O + K ₂ O + MgO + CaO + SrO) in a mass ratio in the glass composition of 0.20 to 0.20. It is preferable to prepare the glass batch so as to obtain an aluminoborosilicate glass for a pharmaceutical container that is 0.70.

  Moreover, it is preferable that the manufacturing method of the alumino borosilicate glass for pharmaceutical containers of this invention shape | molds the obtained molten glass in a tubular shape.

  If the method for producing an aluminoborosilicate glass for pharmaceutical containers according to the present invention is used, the resulting glass has good compositional homogeneity, and local differences in properties such as glass viscosity, heat capacity, thermal conductivity, specific heat, etc. are reduced. Can do. For example, when it shape | molds to a glass tube, the bending and uneven thickness of a glass tube can also be reduced. Therefore, in the subsequent heat processing step, the local difference in heat history can be reduced, and the amount of heat necessary for molding can be suppressed.

  As a result, the aluminoborosilicate glass for pharmaceutical containers obtained in the present invention can suppress the formation of a heterogeneous layer on the inner surface of the pharmaceutical container in the heat processing step, and thus has excellent chemical durability and after various heat treatments. Hydrolysis resistance can be maintained, and when this glass is used in a pharmaceutical container, it is possible to suppress alteration of chemical components, increase in pH of chemical solutions, and generation of flakes.

  In the production method of the present invention, an Al-containing natural mineral and an Al-containing chemical product are contained as an Al-introducing raw material in the glass batch, and Al / (Al + Al-containing chemical product in the Al-containing natural mineral) In which the mass ratio of Al) exceeds 0, 0.01 or more, 0.05 or more, 0.1 or more, 0.15 or more, 0.20 or more, 0.25 or more, 0.30 or more, 0. It is preferably set to 32 or more, and more preferably 0.90 or less, 0.85 or less, 0.80 or less, 0.75 or less, 0.70 or less, 0.60 or less, or 0.57 or less.

When this mass ratio is too small, the usage rate of the Al-containing natural mineral increases as the Al-introducing raw material in the glass batch. Natural minerals generally have a broader particle size distribution compared to chemical products, and in glass batches, segregation and melting separation with differences in melting rates are likely to occur, making it difficult to melt glass homogeneously. The compositional homogeneity of the glass decreases. As a result, an excessive amount of heat is applied during heat processing, and a heterogeneous layer is formed on the inner surface of the pharmaceutical container, which decreases the chemical durability and hydrolysis resistance of the pharmaceutical container. Increases pH and causes flakes.
Furthermore, when the Al-containing natural minerals form a solid solution with each other, the composition of the Al-containing natural mineral is not constant, and the resulting glass composition may vary. Furthermore, when the Al-containing natural mineral is a mixture of natural minerals, there is a concern not only of inhomogeneous mixing and segregation, but also the composition of the glass batch and the resulting glass composition may vary.

  If the mass ratio is too large, the use ratio of Al-containing chemical products such as aluminum oxide and aluminum hydroxide, which are hardly soluble raw materials, increases in the glass batch, making it difficult to melt the glass homogeneously. Homogeneity decreases. As a result, an excessive amount of heat is applied during heat processing, and a heterogeneous layer is formed on the inner surface of the drug container, resulting in a decrease in chemical durability and hydrolysis resistance of the drug container. Triggers the occurrence of flakes.

Further, the Al-containing natural mineral used in the present invention preferably contains Al in an amount of Al ₂ O ₃ of 1% or more, 2% or more, 5% or more, 10% or more, 15% or more, and 90% Hereinafter, it is preferable to contain 50% or less, 40% or less, or 30% or less.

  When this ratio is too small, the use ratio of the hardly soluble Al-containing chemical product increases, it becomes difficult to melt uniformly, and the compositional homogeneity of the glass decreases. As a result, an excessive amount of heat is applied during heat processing, and a heterogeneous layer is formed on the inner surface of the drug container, resulting in a decrease in chemical durability and hydrolysis resistance of the drug container. Triggers the occurrence of flakes. In addition, the amount of Al-containing natural mineral used may be unduly increased. In that case, there is a possibility that a glass batch having the target composition cannot be produced, and that there is a possibility that segregation or melting separation that causes a difference in melting speed occurs. is there.

  On the other hand, if this ratio is too large, the solubility of the Al-containing natural mineral itself is lowered, so that it is difficult to melt uniformly, and the compositional homogeneity of the glass is lowered. As a result, an excessive amount of heat is applied during heat processing, and a heterogeneous layer is formed on the inner surface of the drug container, resulting in a decrease in chemical durability and hydrolysis resistance of the drug container. Triggers the occurrence of flakes.

  Examples of Al-containing natural minerals include, but are not limited to, feldspar group minerals, kaolin, clay, and silica sand.

Moreover, it is preferable to use a feldspar group mineral as the Al-containing natural mineral. Here, the feldspar group mineral is a raw material containing at least 5% by mass of feldspar such as soda feldspar (NaAlSi ₃ O ₈ ), potash feldspar (KAlSi ₃ O ₈ ), anorthite (CaAl ₂ Si ₂ O ₈ ). It exists in various forms on the earth. For example, alkali feldspar is a feldspar in which soda feldspar and potash feldspar are dissolved, and plagioclase is a feldspar in which soda feldspar and anorthite are dissolved. It is also possible to use weathered granite called common mackerel composed of potash feldspar, soda feldspar, quartz, a small amount of mica, and the like.
Further, the Al-containing natural mineral preferably contains feldspar in 5% by mass, 20% or more, 30% or more, 50% or more, 70% or more, 90% or more. The feldspar exists abundantly on the earth, and since it is mined in large quantities, it is easy to obtain and contains a large amount of Al, which is suitable as an Al introducing raw material.

  Moreover, although aluminum oxide, aluminum hydroxide, aluminum metaphosphate etc. are preferable as an Al containing chemical product, it is not restricted to these.

Aluminum oxide and aluminum hydroxide are suitable because they are inexpensive as Al-containing chemical products and are easy to obtain. In addition, aluminum metaphosphate is suitable because it is difficult to deliquesce and easy to handle when it is desired to introduce the P ₂ O ₅ component into a glass batch.

  Moreover, in this invention, it is preferable to introduce | transduce an alkali carbonate raw material and / or an alkali nitrate raw material into a glass batch. Alkali is lithium, sodium, potassium, rubidium, or cesium.

By introducing an alkali carbonate raw material or an alkali nitrate raw material, the glass batch is melted at a lower temperature, and the energy required for melting can be reduced. When the amount of alkali metal to be introduced is large, an alkali carbonate or alkali nitrate having a higher alkali content than natural minerals may be added. In the case of using a polyvalent oxides such as SnO ₂ or Sb ₂ O ₃ as a fining agent, by adding an alkali nitrate as oxidizing agent, it is possible to promote the fining action.

It is preferable to use the glass batch adjusted so that it may become the following aluminoborosilicate (or aluminosilicate) glass for the manufacturing method of this invention.
SiO ₂ from 70.0 to 77.0% (preferably 70.0 to 75.5%),
Al ₂ O ₃ 4.5-11% (preferably 6.3-11%)
B ₂ O _{3 0 to} 11.5% (preferably 3.0 to 11.5%)
Li ₂ O 0-3.5% (preferably 0-0.2%)
Na ₂ O 3.0-8.5% (preferably 4.0-8.5%)
K ₂ O 0~5.5% (preferably 0-5%)
MgO + CaO 0 to less than 4.0% (preferably less than 0 to 1.0%)
SrO 0 to less than 4.0%

  Hereinafter, the reason why the composition range of each component is limited as described above will be described. In the following description, unless otherwise specified,% display means mass%.

SiO ₂ is one of the components constituting the glass network. The content of SiO ₂ is 70.0-77.0%, preferably 70.0-76.0%, 70.5-75.5%, 71.0-75.0%, In particular, it is 72.0-74.7%. When the content of SiO ₂ is too small decreases chemical durability, acid resistance required for the pharmaceutical container is lowered. On the other hand, if the content of SiO ₂ is too large liquidus viscosity lowers, the productivity decreases easily devitrified in the manufacturing process of the glass tube.

Al ₂ O ₃ is a component that suppresses the devitrification of glass and improves chemical durability and hydrolysis resistance. The content of Al ₂ O ₃ is 4.5 to 11%, preferably less than 5.1 to 11%, 5.5 to 10%, 6.3 to 9%, more than 6.3% to 10%, More preferably, it is 6.4 to 8.5%, further preferably 6.4 to 8.3%, particularly 6.4 to 8.0%. If the content of Al ₂ O ₃ is too small, the above effect cannot be obtained. On the other hand, if the content of Al ₂ O ₃ is too large, the viscosity of the glass increases, the heat processing temperature increases, and the amount of evaporation of B ₂ O ₃ and Na ₂ O increases when processed into a pharmaceutical container. End up.

B ₂ O ₃ not only lowers the melting point of the glass but also increases the liquid phase viscosity and suppresses devitrification. Therefore, the content of B ₂ O ₃ is 0 to 11.5%, more than 0 to 11.5%, 1 to 11.5%, 3 to 11.5%, preferably less than 5.5 to 11.5% More preferably, it is less than 8.5-11.5%, More preferably, it is less than 9-11.5%. If the content of B ₂ O ₃ is too small, the heat processing temperature becomes high, and the amount of evaporation of B ₂ O ₃ or Na ₂ O increases when processing into a pharmaceutical container. On the other hand, B ₂ when the content of O ₃ is too much resistance to hydrolysis and chemical durability is lowered.

Li ₂ O has an effect of decreasing the viscosity of the glass and increasing the linear thermal expansion coefficient. However, when Li ₂ O is added, the refractory is easily eroded when the glass is melted. It also leads to an increase in production costs. Therefore, the content of Li ₂ O is 0 to 3.5%, preferably 0 to 3.0%, 0 to 2.0%, 0 to 0.1%, 0 to 0.5%, 0 to 0 0.2%, preferably 0-0.1%, more preferably 0-0.05%, still more preferably 0-0.01%, but there are other alkalis other than Li ₂ O unless there are special circumstances. It is desirable to use a metal oxide.

Na ₂ O has the effect of lowering the viscosity of the glass and increasing the linear thermal expansion coefficient in the same manner as Li ₂ O. The content of Na ₂ O is 3.0 to 8.5%, preferably 3.5 to less than 8.5%, more preferably 4.0 to 8.0%, and even more preferably 4.0 to 7%. 0.0%. When the content of Na ₂ O is too small, the heat processing temperature becomes high, and the amount of evaporation of B ₂ O ₃ and Na ₂ O increases when processing into a pharmaceutical container. On the other hand, hydrolysis resistance is deteriorated when the content of Na 2 _O is too large.

K ₂ O has the effect of reducing the viscosity of the glass and increasing the linear thermal expansion coefficient, like Li ₂ O and Na ₂ O. The content of K ₂ O is 0 to 5.5%, preferably more than 0 to 5.0%, less than 0.1 to 5.0%, more preferably 0.5 to 4.5%, still more preferably. Is 1.0 to 3.0%, particularly 1.5 to 3.0%. K 2 When the content of _O is too large resistance to hydrolysis is reduced.

Note that it is desirable to use both components of K ₂ O and Na ₂ O because the hydrolysis resistance is improved by the mixed alkali effect. In order to improve the hydrolysis resistance, the value of _{K 2} O / Na 2 O in weight ratio, 0～1,0 super ～0.99,0.05～0.95,0.1～0. 9, 0.2 to 0.85, more preferably 0.20 to 0.80, still more preferably 0.2 to 0.75, and particularly preferably 0.2 to 0.7. If this ratio is small, the hydrolysis resistance decreases. On the other hand, when this ratio is large, the heat processing temperature becomes high, and the amount of evaporation of B ₂ O ₃ , Na ₂ O and the like increases when processing into a pharmaceutical container.

The total content of Li ₂ O, Na ₂ O and K ₂ O is 5 to 13%, preferably 5 to 12.5%, 5.5 to 10%, and particularly 6 to 9%. When the total amount of these components is small, the heat processing temperature becomes high. Moreover, when there are many total amounts of these components, chemical durability and hydrolysis resistance will fall.

  MgO has the effect of reducing the high temperature viscosity of the glass. In addition, there is an effect of improving chemical durability. The content of MgO is 0 to 3.0%, preferably 0 to 2.0%, 0 to 1.0%, 0 to less than 1.0%, particularly 0 to 0.5%. When there is too much content of MgO, hydrolysis resistance will fall.

  CaO has the effect of reducing the high temperature viscosity of the glass. The content of CaO is 0 to 4.0%, preferably 0 to 2.0%, 0 to 1.5%, 0 to 1.0%, 0 to less than 1.0%, particularly 0 to 0.0. 5%. When there is too much CaO content, hydrolysis resistance will fall.

  MgO + CaO is the total content of MgO and CaO, and is an important index for adjusting the high-temperature viscosity and hydrolysis resistance of glass to a preferred range. MgO + CaO is 0 to 4.0%, preferably 0 to 3.0%, 0 to 2.0%, 0 to 1.0%, 0 to less than 1.0%, especially 0 to 0.5%. is there. When there is too much MgO + CaO, the high temperature viscosity of glass can be reduced, but the hydrolysis resistance of glass will fall.

  In the present invention, various components other than the above can be added.

  SrO has an effect of improving chemical durability. The SrO content is 0 to less than 4.0%, preferably 0 to 2.0%, more preferably 0 to 1.0%. When there is too much content of SrO, hydrolysis resistance will fall.

TiO ₂ has the effect of improving hydrolysis resistance. The content of TiO ₂ is 0 to less than 7.0%, preferably 0 to 5.0%, more preferably 0 to 4.0%, and still more preferably 0 to 1.5%. When the content of TiO ₂ is too large, the heat processing temperature becomes high, and the amount of evaporation of B ₂ O ₃ , Na ₂ O and the like increases when processed into a pharmaceutical container.

ZrO ₂ has an effect of improving hydrolysis resistance. The content of ZrO ₂ is 0 to less than 7.0%, preferably 0 to 5.0%, more preferably 0 to 4.0%, still more preferably 0 to 1.5%, 0 to 1.0%, 0 to less than 1.0%, especially 0 to 0.5%. When the content of ZrO ₂ is too large, the heat processing temperature becomes high, and the amount of evaporation of B ₂ O ₃ , Na ₂ O and the like increases when processed into a pharmaceutical container.

Since Fe ₂ O ₃ may color the glass and reduce the transmittance in the visible range, its content is 0.2% or less, preferably 0.1% or less, more preferably 0.02% or less. It is.

The _F as a fining _{agent, Cl, Sb 2 O 3,} SnO 2, SO 3 may contain one or more kinds of such. The total content of these fining agents is 3% or less, preferably 1% or less, more preferably 0.5% or less. Among these fining agents, Cl and SnO ₂ are used because of environmental aspects, melting of the aluminoborosilicate glass for pharmaceutical containers of the present invention, compatibility with the fining temperature, and less harm to the human body. It is preferable to do. When Cl is used, its content is preferably 3% or less, more preferably 1% or less, and particularly preferably 0.2% or less. When SnO ₂ is used, its content is 2% or less, preferably 0.5% or less.

  The content of BaO is preferably 0 to 2.0%, 0 to 1.5%, 0 to 1.0%, and less than 0 to 1.0%, but the method for producing an aluminoborosilicate glass for pharmaceutical containers of the present invention It is more preferable that the glass batch does not substantially contain BaO as a glass composition.

  Here, “substantially free of BaO” means that BaO is not actively added, and is not intended to exclude substances that are mixed as impurities. More specifically, it means that the content of BaO is 0.05% or less by mass%. When BaO is contained in the glass, when it reacts with an alumina refractory during glass production or when used as a pharmaceutical container, crystals are formed by the reaction of Ba ions eluted from the glass with sulfate ions in the chemical solution. There is a risk of precipitation or generation of precipitates.

Furthermore, the values of Al ₂ O ₃ / (B ₂ O ₃ + Li ₂ O + Na ₂ O + K ₂ O + MgO + CaO + SrO) by mass ratio are 0.20 to 0.70, 0.25 to 0.68, 0.30 to 0.66, It is preferable to prepare a glass batch so that it may become 0.32-0.60 and 0.35-0.60.

If the value of Al ₂ O ₃ / (B ₂ O ₃ + Li ₂ O + Na ₂ O + K ₂ O + MgO + CaO + SrO) is too small, the hydrolysis resistance of the glass will be lowered, and B ₂ O ₃ or Na when heated into a pharmaceutical container _The amount of evaporation of alkali metal oxides such as ₂ O increases.
In addition, if the value of Al ₂ O ₃ / (B ₂ O ₃ + Li ₂ O + Na ₂ O + K ₂ O + MgO + CaO + SrO) is too large, the viscosity of the glass becomes high, and the processing temperature when heat-processing into a pharmaceutical container increases. As a result, the amount of evaporation of alkali metal oxides such as B ₂ O ₃ and Na ₂ O in the glass increases.

  In the production method of the present invention, the obtained molten glass is preferably formed into a tubular shape.

  First, each raw material is prepared so that it may become a target composition, and a glass batch is obtained.

  Next, the glass batch is continuously put into a melting furnace at 1550 to 1700 ° C., melted and clarified, and then the obtained glass melt is wound around a rotating refractory while air is blown out from the tip of the refractory. Then, the glass is drawn out from the tip portion into a tubular shape by the so-called Danner method. The drawn tubular glass is cut into a predetermined length to obtain a glass tube.

  In addition, when shape | molding the molten glass obtained by this invention to the glass tube, you may use not only the Danner method but a well-known method. For example, the bellows method and the downdraw method are effective methods.

  Moreover, when shape | molding the glass tube obtained by this invention in the container for pharmaceuticals, a well-known method can be used. For example, a method of cutting a glass tube to a predetermined length, melting the end with a flame such as a burner, and simultaneously heat-molding and sealing the bottom and mouth, and a method of molding the mouth after molding the bottom is there. The portion to be heated by a burner or the like may be any portion such as the outside, inside, and end of the glass tube as necessary, and the heating temperature varies depending on the melting temperature of the glass tube, but is generally about 1000 to 1300 ° C.

  Hereinafter, the present invention will be described based on examples.

  Tables 1 and 2 show examples of the present invention (sample Nos. 1 to 6, 9 to 16, A to J) and comparative examples (samples No. 7, 8, F, and G).

  Each sample was prepared as follows.

  First, glass raw materials were prepared so as to have the composition shown in the table, and a glass batch was produced. Only aluminum oxide, aluminum hydroxide, and feldspar were used as the Al introduction raw material in the glass batch. In addition, as for the kind and the usage-amount of Al containing natural mineral and Al containing chemical product, Al in the Al containing chemical product by mass ratio / (Al in Al containing natural mineral + Al in Al containing chemical product) is a predetermined ratio in the table. It selected so that it might become.

  Next, these glass batches are continuously charged into a melting furnace at 1550 to 1700 ° C., melted and clarified, and then the obtained molten glass is wound around a rotating refractory while air is blown out from the tip of the refractory. Then, the glass is pulled out from the tip portion into a tubular shape. The drawn tubular glass was cut into a predetermined length to obtain a glass tube. The glass tube thus obtained was subjected to various evaluations.

As is clear from Table 1, sample No. Nos. 1 to 6 use an Al-containing chemical product and an Al-containing natural mineral in combination as an Al-introducing raw material, and further Al / (Al in the Al-containing natural mineral + Al in the Al-containing chemical product). Therefore, the chemical durability and the hydrolysis resistance were good. Moreover, No. containing Sn in the glass composition. When the elution of Sn by the hydrolysis resistance test was evaluated for 1, 3, and 4, the Sn elution amount was less than the lower limit of quantification in any sample. Therefore, it is considered that even when these aluminoborosilicate glasses are used in a pharmaceutical container, alteration of chemical component, increase in pH of chemical solution, and generation of flakes are suppressed.
Moreover, the obtained glass tube had reduced dimensional accuracy of the glass tube, that is, bending and uneven thickness of the glass tube. From this, sample no. 1-6 can suppress the calorie | heat amount required for shaping | molding of a pharmaceutical container, and can improve the chemical durability and hydrolysis resistance of a pharmaceutical container.

  On the other hand, sample No. which is a comparative example. 7 and 8 were poor in hydrolysis resistance because the mass ratio of Al in the Al-containing chemical product / (Al in the Al-containing natural mineral + Al in the Al-containing chemical product) was outside the scope of the present invention. Furthermore, the dimensional accuracy of the glass tube was also outside the predetermined range.

  Sample No. Nos. 9 to 16 use an Al-containing chemical product and an Al-containing natural mineral as an Al-introducing raw material. Further, Al in the Al-containing chemical product / (Al in the Al-containing natural mineral + Al in the Al-containing chemical product) Thus, the obtained glass tube had reduced dimensional accuracy of the glass tube, that is, bending or uneven thickness of the glass tube. From this, sample no. 9-16 can suppress the calorie | heat amount required for shaping | molding of a pharmaceutical container, and can improve the chemical durability and hydrolysis resistance of a pharmaceutical container.

Next, sample Nos. Samples A to J in Table 2 show the same batch composition other than the Al-introduced raw material 1 but the Al-introduced raw material was changed to produce a glass batch of 100 g glass. G / glass 100g in the table | surface has shown the mass of the raw material required in order to obtain 100g of glass. As Al introduction raw materials, soda feldspar (NaAlSi ₃ O ₈ ), potash feldspar (KAlSi ₃ O ₈ ), anorthite (CaAl ₂ SiO ₈ ), plagioclase (soda feldspar: anorthite = 3: 1, free quartz 20% contained ) And aluminum oxide were used.

  Next, these glass batches are continuously charged into a melting furnace at 1550 to 1700 ° C., melted and clarified, and the resulting molten glass is formed into a ribbon shape, cut into a length of 1 mm, and immersed in benzyl alcohol. The striae was observed from the direction.

  Regarding the homogeneity of the composition of the glass, “X” indicates that striae are strongly recognized, and “◯” indicates that the striae level has no practical problem.

  Also, regarding the composition stability of the glass batch, ○ when there was no problem in composition variation of the glass batch, △ when there was compositional variation but there was no practical problem, and composition variation was practically problematic Was marked with x.

Samples A to E and H to J use both an Al-containing chemical and an Al-containing natural mineral as an Al introduction raw material, and Al / (Al + Al in the Al-containing natural mineral in the Al-containing natural mineral) Since the mass ratio of Al) was within a predetermined range, the striae were practically free from problems. Therefore, it is considered that the compositional homogeneity of the glass is excellent, and local differences are small with respect to glass viscosity, heat capacity, thermal conductivity, and specific heat.
Therefore, when these samples are molded into a glass tube, the dimensional accuracy of the glass tube becomes good, and the amount of heat necessary for molding a pharmaceutical container can be suppressed.
Therefore, it is considered that the obtained pharmaceutical container can maintain excellent chemical durability and hydrolysis resistance even after various heat treatments, and can suppress alteration of chemical component, pH increase of chemical solution, and generation of flakes.

  On the other hand, sample F used only aluminum oxide, which is an Al-containing chemical product, as an Al introduction raw material. Therefore, the hardly soluble aluminum oxide is difficult to dissolve, the glass composition is inhomogeneous, and strong striae are recognized. In Sample G, only soda feldspar, which is an Al-containing natural mineral, was used as an Al introduction raw material. Therefore, the glass composition homogeneity and the glass batch composition stability were unstable.

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

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

The working temperature was determined by obtaining a viscosity curve of the glass from the high temperature viscosity obtained by the platinum ball pulling method and the Fulcher viscosity calculation formula, and obtaining a temperature corresponding to 10 ⁴ dPa · s from this viscosity curve. The working temperature corresponds to the thermal processing temperature of the glass tube.

  The liquid phase temperature was measured by filling a crushed glass sample in a platinum boat of about 120 × 20 × 10 mm and placing it in an electric furnace having a linear temperature gradient for 24 hours. Then, the crystal precipitation location was identified by microscopic observation, the temperature corresponding to the crystal precipitation location was calculated from the temperature gradient graph of the electric furnace, and this temperature was defined as the liquidus temperature.

  The liquid phase viscosity is calculated by calculating the glass viscosity curve from the strain point, annealing point, softening point, working temperature and Fulcher's viscosity formula, and calculating the viscosity of the glass at the liquid phase temperature from this viscosity curve. Was the liquid phase viscosity.

  In the hydrolysis resistance test, the sample was pulverized using an alumina mortar and pestle, and a method according to the powder test method of EP 8.0 was used. The detailed test procedure is as follows. The surface of the sample was thoroughly wiped with ethanol, and the sample was pulverized with an alumina mortar and pestle, and then classified using three sieves made of stainless steel, 710 μm, 425 μm, and 300 μm. The material remaining on the sieve was pulverized again and subjected to the same sieve operation. The sample powder remaining on the 300 μm sieve was washed with ethanol and placed in a glass container such as a beaker. Then, ethanol was added and stirred, and after washing with an ultrasonic washing machine for 1 minute, the operation of pouring out only the supernatant was performed 6 times. Thereafter, it was dried in an oven at 110 ° C. for 30 minutes and cooled in a desiccator for 30 minutes. The obtained sample powder was weighed with an accuracy of 10 g ± 0.0001 g using an electronic balance, placed in a 250 mL quartz flask, and 50 mL of ultrapure water was added. After sealing, the flask was placed in an autoclave and kept at 121 ° C. for 30 minutes. The temperature was raised at 1 ° C./min from 100 ° C. to 121 ° C., and the temperature was lowered at 2 ° C./min from 121 ° C. to 100 ° C. Then, it cooled to 95 degreeC and took out the sample to the conical beaker. The inside of the flask was washed with 30 mL of ultrapure water and poured into a conical beaker three times. About 0.05 mL of methyl red was dropped into the liquid after the test, and neutralization titration was performed with 0.02 mol / L hydrochloric acid. The amount of hydrochloric acid consumed was recorded, and the amount of hydrochloric acid consumed per gram of sample glass was calculated.

As a method for evaluating chemical durability, an acid resistance test was performed in accordance with DIN12116 with a sample surface area of 50 cm ² and a 6 mol / L hydrochloric acid solution as an eluent in an amount of 800 mL. The detailed test procedure is as follows. First, a glass sample piece having a total surface area of 50 cm ² with a mirror polished finish on all surfaces was prepared. It was immersed in the solution so mixed and stirred with a magnetic stirrer for 10 minutes. Next, the sample piece was taken out and subjected to ultrasonic cleaning for 2 minutes in ultrapure water three times, and then ultrasonic cleaning for 2 minutes in ethanol was performed twice. Next, the sample piece was dried in an oven at 110 ° C. for 1 hour and cooled in a desiccator for 30 minutes. The mass m ₁ of the sample piece thus obtained was measured to an accuracy of ± 0.1 mg and recorded. Subsequently, 800 mL of 6 mol / L hydrochloric acid was placed in a beaker made of quartz glass, heated using an electric heater until boiling, and a sample piece suspended with a platinum wire was added and held for 6 hours. In order to prevent a decrease in the liquid volume during the test, the opening of the lid of the container was plugged with a gasket and a cooling pipe. Thereafter, the sample piece was taken out and subjected to ultrasonic cleaning for 3 minutes in ultrapure water three times, and then ultrasonic cleaning for 2 minutes in ethanol was performed twice. Further, the washed sample piece was dried in an oven at 110 ° C. for 1 hour and cooled in a desiccator for 30 minutes. The mass m ₂ of the sample piece treated in this way was measured to an accuracy of ± 0.1 mg and recorded. Finally, the amount of mass reduction per unit area was calculated from the masses m ₁ and m ₂ mg of the sample before and after being added to boiling hydrochloric acid and the total surface area Acm ^{2 of the} sample by the following formula 1, and used as the measured value in the acid resistance test. .
[Formula 1] Mass reduction per unit area = 100 × (m ₁ −m ₂ ) / 2 × A

  The elution amount of Sn was analyzed for the test solution after the hydrolysis resistance test using an ICP emission analyzer (manufactured by Varian). The detailed test procedure is as follows. The test solution after the hydrolysis resistance test was filtered through a membrane filter and collected in a centrifuge tube. The standard solution was prepared by diluting the Sn standard solution (manufactured by Wako Pure Chemical Industries) so that the Sn content was 0 mg / L, 0.05 mg / L, 0.5 mg / L, and 1.0 mg / L. . Calibration curves were prepared from these standard solutions, and the Sn elution amount in the test solution was calculated. The measurement wavelength of Sn was 189.925 nm.

  If the manufacturing method of the aluminoborosilicate glass for pharmaceutical containers of the present invention is used, for example, when it is formed into a glass tube, bending and uneven thickness of the glass tube can be reduced, so that the amount of heat necessary for forming can be suppressed. As a result, a pharmaceutical container excellent in chemical durability and hydrolysis resistance can be obtained even after various heat treatments, and can be applied to various glass compositions. In addition, the aluminoborosilicate glass for pharmaceutical containers according to the present invention can be suitably used as various pharmaceutical container materials such as ampoules, vials, prefilled syringes, cartridges and the like.

Claims (9)

In the method for producing an aluminoborosilicate glass for a pharmaceutical container, after melting a glass batch containing an Al-introduced raw material, molding the obtained molten glass to obtain an aluminoborosilicate glass for a pharmaceutical container,
As an Al introduction raw material, an Al-containing natural mineral and an Al-containing chemical product are included, and Al / (Al in the Al-containing natural mineral + Al in the Al-containing natural mineral product) is greater than 0 to 0 by mass ratio. A method for producing an aluminoborosilicate glass for a pharmaceutical container, characterized by being .9. The method for producing an aluminoborosilicate glass for a pharmaceutical container according to claim 1, wherein an Al-containing natural mineral containing 1% by mass or more of Al in terms of Al ₂ O ₃ is used.   The method for producing an aluminoborosilicate glass for a pharmaceutical container according to claim 1 or 2, wherein a feldspar group mineral is used as the Al-containing natural mineral.   The method for producing an aluminoborosilicate glass for a pharmaceutical container according to any one of claims 1 to 3, wherein aluminum oxide and / or aluminum hydroxide is used as the Al-containing chemical product.   The method for producing an aluminoborosilicate glass for a pharmaceutical container according to any one of claims 1 to 4, wherein an alkali carbonate raw material and / or an alkali nitrate raw material is introduced into the glass batch. As a glass composition, in _{mass%, SiO 2 70.0~77.0%, Al} 2 O 3 4.5~11%, B 2 O 3 3.0~11.5%, Li 2 O 0~3. Aluminoborosilicate for pharmaceutical containers containing 5%, Na ₂ O 3.0 to 8.5%, K ₂ O 0 to 5.5%, MgO + CaO 0 to less than 4.0%, SrO 0 to less than 4.0% A glass batch is prepared so that acid glass may be obtained, The manufacturing method of the alumino borosilicate glass for pharmaceutical containers in any one of Claims 1-6 characterized by the above-mentioned.   The method for producing an aluminoborosilicate glass for a pharmaceutical container according to claim 6, wherein a glass batch is prepared so that an aluminoborosilicate glass for a pharmaceutical container substantially free of BaO is obtained as a glass composition. Glass so that an aluminoborosilicate glass for a pharmaceutical container having a mass ratio of Al ₂ O ₃ / (B ₂ O ₃ + Li ₂ O + Na ₂ O + K ₂ O + MgO + CaO + SrO) in the glass composition of 0.20 to 0.70 is obtained. The method for producing an aluminoborosilicate glass for a pharmaceutical container according to claim 6 or 7, wherein a batch is prepared. The method for producing an aluminoborosilicate glass for a pharmaceutical container according to any one of claims 1 to 8, wherein the obtained molten glass is formed into a tubular shape.