JP4360230B2 - Pharmaceutical manufacturing plant components - Google Patents

Description

SUMMARY OF THE INVENTION The present invention relates to pharmaceutical production plants member made of a Ni-based alloy metal ion elution amount is excellent in significantly less corrosion resistance in an environment exposed to high and relatively weak acids and strong alkaline environment to a high temperature processability is there.

In recent years, in pharmaceutical manufacturing plants, GMP validation (establishment of preventive measures to eliminate defects in all processes from upstream to product shipping related to pharmaceutical manufacturing stipulated by the Pharmaceutical Affairs Law) to ensure the safety of pharmaceuticals There is a mandatory manufacturing method.
On the other hand, in the bulk drug production process, with the acceleration of drug discovery technology, the demand for high-mix low-volume production has been increasing year by year, and it is in a situation that cannot be handled unless different processes are performed on the same device. Therefore, there is an increasing need for multipurpose equipment materials for batch processing without causing contamination over a wide range of operating conditions (corrosive environment).

  On the other hand, the pharmaceutical manufacturing plant currently used is a pharmaceutical manufacturing plant having a structure in which contamination of the process liquid is minimized by applying glass lining to carbon steel. However, pharmaceutical manufacturing plants with this glass lining have the potential to break glass lining and cause glass fragments to enter the product, to generate static electricity and to explode during organic solvent handling, Disadvantages such as difficult conductivity control due to poor conductivity, and glass lining is vulnerable to hydrogen fluoride and alkali, causing contamination of pharmaceutical products obtained by operating in such an environment. was there.

  In order to overcome these drawbacks, as a material of a pharmaceutical manufacturing plant, for example, stainless steel excellent in high-temperature processability and corrosion resistance, and Hastelloy C-22 (trade name) (which has far superior corrosion resistance than stainless steel) ( Corrosion-resistant nickel-based alloys such as UNS No. 06022 are standardized and are being adopted.

  Since both stainless steel and Hastelloy C-22 have a corrosion rate (mm / year) before and after the corrosion test of less than 0.1 mm / year, they are judged to be excellent as structural members of a general pharmaceutical manufacturing plant. However, in order to satisfy the GMP validation to ensure the safety of pharmaceuticals as described above, and to carry out batch processes without contamination even if different processes are performed on the same device to produce a variety of products in small quantities In conventional stainless steel and Hastelloy C-22, a large amount of metal ions are eluted, and the eluted metal ions cause contamination, and are not sufficiently satisfactory materials.

Therefore, as a material with less metal ion elution and excellent corrosion resistance, it is expressed in mass% (hereinafter,% indicates mass%) Cr: 38 to 50%, one or two of Mo and W: 0.0. 1 to 2%, and if necessary, (i) Cu: 0.1 to 2%, (ii) Ca: 0.001 to 0.01%, (iii) Zr, Nb, Ta and Hf One or more of: 0.1 to 3%, (iv) One or more of Y and rare earth elements: 0.001 to 0.01%, (i) to (iv) above 1 or 2 or more, and the remainder is composed of Ni and inevitable impurities, and the contents of C and N components as inevitable impurities are C: 0.05% or less, N: 0.00. 04% or less, and other inevitable impurities Fe: 0.3% or less, Mn: 0.3% or less, Ti: 0.3% or less Corrosion-resistant Ni—Cr alloys having excellent bending workability containing Al: 0.3% or less and Mg: 0.05% or less are known (see Patent Document 1). It has begun to attract attention as a material for pharmaceutical manufacturing plants.
Japanese Patent Publication No. 6-94579

  However, although the Ni-Cr-based alloy has excellent corrosion resistance and bending workability, it is inferior in hot workability, for example, because its deformability at high temperatures that is an index of hot extrudability is low, It is difficult to produce seamless pipes and other complex shaped machine parts. One of the causes of the deterioration of the deformability at high temperature is that the phase stability is not good, but if the phase stability is not good, the elution of metal ions increases, especially from the weld and its heat-affected zone. There were problems such as significant elution of ions.

Accordingly, the present inventors have intensively studied to obtain a metal material that is excellent in high-temperature workability and has very little metal ion elution, particularly metal ion elution from a weld.
As a result, the Ni-based alloy containing Cr: 29-42% in mass% (hereinafter,% indicates mass%), Ta: more than 1 to 3%, Mg: 0.001 to 0.05%, N: 0.001 to 0.04%, Mn: 0.05 to 0.5%, B: 0.0005 to 0.01%, and Mo: 0.1 to 2 as necessary %, Fe: 0.05 to 1.0% and Si: 0.01 to 0.1% are contained in one kind or two or more kinds, and the rest is made of Ni and inevitable impurities, and C as an inevitable impurity is 0 The Ni-based alloy having a composition adjusted to 0.05% or less is excellent in high-temperature workability and has a corrosion rate (mm / year) of less than 0.1 mm / year in a relatively weak acid or strong alkaline environment. Of Ni-C having this component composition System alloy has a more excellent effect as a material such as a relatively weak acid and strong pharmaceutical production plant in an alkaline environment, it was obtained a finding that.

This invention has been made based on such knowledge,
(1) By mass%, Cr: 29 to less than 42%, Ta: more than 1 to 3%, Mg: 0.001 to 0.05%, N: 0.001 to 0.04%, Mn: 0.05 0.5%, B: 0.0005% to 0.01%, with the balance being Ni and inevitable impurities, Ni group having a composition in which the amount of C contained as inevitable impurities is adjusted to 0.05% or less Pharmaceutical manufacturing plant parts made of alloys ,
(2) By mass%, Cr: 29 to less than 42%, Ta: more than 1 to 3%, Mg: 0.001 to 0.05%, N: 0.001 to 0.04%, Mn: 0.05 -0.5%, B: 0.0005-0.01%, Mo: 0.1-2% further, the balance consisting of Ni and inevitable impurities, the amount of C contained as inevitable impurities A pharmaceutical production plant member comprising a Ni-based alloy having a composition adjusted to 0.05% or less,
(3) By mass%, Cr: 29 to less than 42%, Ta: more than 1 to 3%, Mg: 0.001 to 0.05%, N: 0.001 to 0.04%, Mn: 0.05 -0.5%, B: 0.0005-0.01%, and Fe: 0.05-1.0% and Si: 0.01-0.1% A pharmaceutical production plant member comprising a Ni-based alloy having a composition in which the balance is made of Ni and inevitable impurities, and the amount of C contained as inevitable impurities is adjusted to 0.05% or less,
(4) By mass%, Cr: 29 to less than 42%, Ta: more than 1 to 3%, Mg: 0.001 to 0.05%, N: 0.001 to 0.04%, Mn: 0.05 -0.5%, B: 0.0005-0.01%, Mo: 0.1-2%, Fe: 0.05-1.0% and Si: 0.01 Production of a pharmaceutical comprising a Ni-based alloy having a composition containing one or two of ~ 0.1%, the balance being Ni and inevitable impurities, and the amount of C contained as inevitable impurities being adjusted to 0.05% or less The plant member has a feature.

Next, the reason for limitation of each element in a pharmaceutical production plant member made of a Ni-based alloy with a remarkably small amount of metal ion elution of the present invention will be described in detail.

Cr, Ta:
In a relatively weak acid or strong alkali environment such as a pharmaceutical manufacturing plant, the corrosion resistance is remarkably improved by simultaneously containing Cr and Ta. In that case, it is necessary to contain 29% or more of Cr, but if it contains 42% or more, it becomes difficult to form a single phase in combination with Ta, and the amount of elution of metal ions increases, which is not preferable. Therefore, the Cr content is set to 29 to less than 42%. More preferably, it is 35 to 41%.
Similarly, it is necessary to contain Ta in excess of 1%. However, inclusion in excess of 3% is not preferable because phase stability deteriorates in combination with Cr, and the elution amount of metal ions increases. Therefore, the Ta content is determined to be more than 1 to 3% (more preferably less than 1.1 to 2.5%).

N, Mn and Mg:
By making N, Mn, and Mg coexist, phase stability can be improved. That is, N, Mn, and Mg have the effect of stabilizing the Ni-fcc phase that is the parent phase, promoting the solid solution of Cr, and making the second phase difficult to precipitate. As a result, high-temperature workability, especially high temperature deformability, corrosion resistance at welds and their heat-affected zones, especially deterioration of their corrosion resistance in relatively weak acid or strong alkali environments such as pharmaceutical manufacturing plants effective. However, if the content of N is less than 0.001%, there is no effect of phase stabilization, and therefore there is no effect on improvement of high temperature workability and suppression of deterioration of corrosion resistance of welds, while on the other hand, if it exceeds 0.04% Nitride is formed, high temperature workability deteriorates, and at the same time, the elution amount of metal ions in the welded part and its heat-affected zone increases, so the N content is 0.001 to 0.04% (more preferably 0 0.005 to 0.03%).
Similarly, when the content of Mn is less than 0.05%, there is no effect of phase stabilization, and therefore, it is not preferable because there is no effect on improvement of high-temperature workability and deterioration of corrosion resistance of welds, whereas 0.5% If it exceeds V, the phase stability is impaired, the high temperature workability deteriorates, and at the same time the elution amount of metal ions in the welded part and its heat-affected zone increases, so the Mn content is 0.05 to 0.5% ( More preferably, it was 0.1% to 0.4%.
Similarly, if the Mg content is less than 0.001%, there is no effect of phase stabilization, and therefore, there is no effect on improvement of high-temperature workability and suppression of deterioration of corrosion resistance of welds. If the content exceeds 05%, the phase stability is impaired, the high temperature workability deteriorates, and at the same time, the elution amount of metal ions in the welded part and its heat-affected zone increases, so the content of Mg is 0.001 to 0.05. % (More preferably 0.002% to 0.04%).
The effects of these three elements are not equal to each other, and it has been found that there is no effect unless the three elements are simultaneously contained in a predetermined range.

B:
B has an effect of improving hot deformability and at the same time has an effect of suppressing deterioration of corrosion resistance of the welded portion by suppressing Cr segregation in the weld solidified portion. However, if the content is less than 0.0005%, the desired effect cannot be obtained, which is not preferable. On the other hand, if the content exceeds 0.01%, the hot deformability is reduced at the same time. Therefore, the B content is determined to be 0.0005 to 0.01% because the corrosion resistance in the weld solidified portion tends to be deteriorated. A more preferable range is 0.001 to 0.01%.

Mo:
Mo has an effect of suppressing an increase in the elution amount of metal ions when the sulfuric acid concentration is increased in a relatively weak acid or strong alkaline environment such as a pharmaceutical manufacturing plant that contains a particularly small amount of sulfuric acid. Although it is added as necessary, in that case, the effect is shown by containing 0.1% or more, but if it exceeds 2%, the phase stability deteriorates, making it difficult to solidify the Cr-bcc phase. Therefore, it is not preferable because a micro battery is formed between the Ni-fcc phase and the Cr-bcc phase, which are the parent phases, and as a result, the elution amount of metal ions is increased. Therefore, Mo contained in the Ni-based alloy of the present invention is set to 0.1 to 2%. A more preferred range is from more than 0.1 to less than 0.5%.

Fe and Si:
Fe and Si have the effect of improving strength, so they are added as necessary. However, Fe is effective when contained in an amount of 0.05% or more. Since the elution amount of metal ions in a weak acid or strong alkali environment increases, the Fe content is set to 0.05% to 1% (more preferably, less than 0.1 to 0.5%).
Similarly, if Si is contained in an amount of 0.01% or more, the effect is exhibited, but if it exceeds 0.1%, the phase stability is deteriorated, and therefore, high-temperature workability is deteriorated and corrosion resistance of welds is deteriorated. The Si content is set to 0.01% to 0.1% (more preferably 0.02 to 0.05%).

C:
Although C is included as an inevitable impurity, C forms a carbide with Cr in the vicinity of the grain boundary and increases the elution amount of metal ions. Therefore, the lower the content of C, the better the content of C contained in the inevitable impurities. The upper limit of the amount was set to 0.05%.

The member of the present invention is excellent in high-temperature workability, so that it is possible to produce a seamless pipe by hot extrusion, which is the most difficult to process, and it is also possible to produce a member having a complicated shape. Since the elution of metal ions is extremely small, quality control is particularly severe and it is exposed to relatively weak acid and strong alkali environments, and when used as a pharmaceutical production plant member that dislikes contamination due to elution of metal ions, an excellent effect is brought about.

All prepared raw materials with low C content, melted and cast using a normal high-frequency melting furnace, and made of a Ni-based alloy having the composition shown in Tables 1 to 3; thickness: 40 mm, weight An ingot having about 5 kg was prepared. This ingot is subjected to a homogenization heat treatment at 1230 ° C. for 10 hours and maintained within a range of 1000 to 1230 ° C., and the thickness of the pharmaceutical product of the present invention having a thickness of 30 mm is reduced by 1 hot rolling. Manufacturing plant members 1 to 23, comparative pharmaceutical manufacturing plant members 1 to 12 and conventional pharmaceutical manufacturing plant members 1 to 2 were produced. These pharmaceutical manufacturing plant members 1 to 23, comparative pharmaceutical manufacturing plant members 1 to 12 and conventional pharmaceutical manufacturing plant members 1 to 2 are partially cut to produce a 30 mm thick plate. The solution was solidified by holding at 30 ° C. for 30 minutes and quenching with water.
On the other hand, the remaining part that has been partially cut is further rolled to a final thickness of 3 mm, held at 1200 ° C. for 30 minutes and subjected to solid solution treatment by water quenching, and the surface is buffed to form a thin plate Was made. Using the thick plate and the thin plate thus produced, hot deformability was evaluated by performing a hot twist test under the following conditions, and corrosion resistance was evaluated by further performing a corrosion test.

(A) Machining a 30 mm thick plate made of the present invention pharmaceutical production plant members 1 to 23, comparative pharmaceutical production plant members 1 to 12 and conventional pharmaceutical production plant members 1 and 2 produced in the hot twist test destination As a result, a hot twist test piece having a chuck portion on both sides and a twist portion having a diameter of 8 mm and a length of 30 mm was produced. After holding the hot twist test piece at a temperature of 950 ° C. for 15 minutes, the test was carried out by adjusting the twist rotational speed so that the strain rate was 2.0 / second. The deformability at high temperature was evaluated by measuring and showing the results in Tables 4-6.

(B) Corrosion test The present invention pharmaceutical production plant members 1 to 23, the comparative pharmaceutical production plant members 1 to 12 and the conventional pharmaceutical production plant members 1 to 2 and the conventional pharmaceutical production plant members 1 to 2 were each made of a thin plate of 3 mm in length: 30 mm, Horizontal: Cut to 20 mm size to produce a corrosion test piece without welding.
Subsequently, the present invention pharmaceutical manufacturing plant members 1 to 23, comparative pharmaceutical manufacturing plant members 1 to 12 and conventional pharmaceutical manufacturing plant members 1 to 2 are made of the same material type using an argon arc welder. Butt welding was performed, and the weld bead was cut from the plate including the butt welded portion into a dimension of 30 mm in length and 20 mm in width so that the weld bead was located in the center, thereby producing a corrosion test piece with welding. The surfaces of these test pieces were polished and finally polished with a water-resistant emery paper # 400 finish, and then these were degreased by being kept in an ultrasonic vibration state in acetone for 5 minutes.

Furthermore, it simulates an environment containing relatively weak acids (hydrochloric acid, sulfuric acid, hydrofluoric acid, organic acids, etc.) and strong alkali used in pharmaceutical production, pH: 0.5 hydrochloric acid aqueous solution, pH: 0.5 sulfuric acid aqueous solution It was prepared by preparing a sodium hydroxide aqueous solution of pH: 12 at room temperature. Further, prepare a Teflon container, fill the Teflon container with a hydrochloric acid aqueous solution, a sulfuric acid aqueous solution and a sodium hydroxide aqueous solution, and put the corrosion test piece without welding and the corrosion test piece with welding into the Teflon container. Was set at 80 ° C. and held for 1000 hours. The specific liquid amount at this time was 16.7 cc / cm ² (the liquid was 200 cc with respect to the sample surface area of 12 cm ² ).
After completion of the holding test, the Teflon container is cooled, and then the test piece is taken out. The element eluted in the corrosive solution after immersion is quantitatively analyzed (by ICP emission analysis), and the ions eluted per unit area of the test piece are analyzed. The total amount was measured, the total amount of ions eluted was divided by the surface area of the test piece, and the amount of elution per unit area was calculated. The values are shown in Tables 4-6.

From the results shown in Tables 1 to 6, the pharmaceutical production plant members 1 to 23 of the present invention are superior in deformability at high temperatures because they have a higher number of hot twists than the conventional pharmaceutical production plant members 1 and 2. Since the elution amount of metal ions per unit area of the test piece is small, and especially the elution amount of metal ions per unit area of the test piece with welding is particularly small, the pharmaceutical production plant members 1 to 23 of the present invention are It can be seen that, compared with the conventional pharmaceutical production plant members 1 and 2, the hot workability is excellent and the corrosion resistance including the welded portion is excellent. However, it can be seen that the test pieces of the comparative pharmaceutical production plant members 1 to 12 that deviate from the present invention have unfavorable characteristics such as cracking during hot rolling and a slightly large amount of metal ion elution.

Claims (4)

In mass%, Cr: 29 to less than 42%, Ta: more than 1 to 3%, Mg: 0.001 to 0.05%, N: 0.001 to 0.04%, Mn: 0.05 to 0.00. 5%, B: 0.0005-0.01% is contained, the balance is made of Ni and inevitable impurities, and is made of a Ni-based alloy having a composition in which the amount of C contained as inevitable impurities is adjusted to 0.05% or less. A pharmaceutical production plant member characterized by that . In mass%, Cr: 29 to less than 42%, Ta: more than 1 to 3%, Mg: 0.001 to 0.05%, N: 0.001 to 0.04%, Mn: 0.05 to 0.00. 5%, B: 0.0005 to 0.01%, further Mo: 0.1 to 2%, the balance is made of Ni and inevitable impurities, and the amount of C contained as inevitable impurities is 0.05. A pharmaceutical manufacturing plant member comprising a Ni-based alloy having a composition adjusted to not more than%. In mass%, Cr: 29 to less than 42%, Ta: more than 1 to 3%, Mg: 0.001 to 0.05%, N: 0.001 to 0.04%, Mn: 0.05 to 0.00. 5%, B: 0.0005-0.01%, Fe: 0.05-1.0% and Si: 0.01-0.1%, or one or two, the balance A pharmaceutical production plant member comprising: Ni and an inevitable impurity, and an Ni-based alloy having a composition in which the amount of C contained as an inevitable impurity is adjusted to 0.05% or less. In mass%, Cr: 29 to less than 42%, Ta: more than 1 to 3%, Mg: 0.001 to 0.05%, N: 0.001 to 0.04%, Mn: 0.05 to 0.00. 5%, B: 0.0005 to 0.01%, Mo: 0.1 to 2%, Fe: 0.05 to 1.0%, and Si: 0.01 to 0.3%. It is characterized by comprising 1% or 1 type of 1%, the balance being made of Ni and inevitable impurities, and a Ni-based alloy having a composition in which the amount of C contained as inevitable impurities is adjusted to 0.05% or less. Pharmaceutical manufacturing plant components .