JP4360229B2 - Pharmaceutical manufacturing plant components - Google Patents

Description

The present invention relates to a pharmaceutical production plant member made of a Ni-based alloy that is excellent in high-temperature processability and has an excellent corrosion resistance in which metal ion elution is extremely small in an environment exposed to a relatively weak acid or strong alkaline environment.

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 materials for multipurpose equipment to perform batch processes without contamination under a wide range of operating conditions (corrosive environment).

  On the other hand, currently used pharmaceutical manufacturing plants generally have a structure in which contamination of 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, Since the conductivity is poor, delicate control of the process is difficult, and since it is vulnerable to hydrogen fluoride and alkali, operating in such an environment may cause contamination of the product.

  In order to overcome these drawbacks, as a material of a pharmaceutical manufacturing plant, for example, Hastelloy C-22 (trade name) (UNS No. 06022) having excellent high-temperature processability and far superior corrosion resistance compared to stainless steel and stainless steel. Nickel-based alloys with excellent corrosion resistance, such as standardized alloys, are being selected and 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 pharmaceutical manufacturing plant. However, although the conventional stainless steel and Hastelloy C-22 can be judged as excellent, the amount of elution of metal ions is large, and the eluted metal ions cause contamination. In order to carry out a batch process without contamination even if different processes are carried out in the same equipment in order to carry out a manufacturing method according to GMP validation to ensure safety and to produce a variety of products in small quantities, a wider range of operating conditions A material having further excellent corrosion resistance against (corrosive environment) has been required.

As a material with little 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: 0.1 2%, and if necessary, (i) Cu: 0.1 to 2%, (ii) Ca: 0.001 to 0.01%, (iii) Of Zr, Nb, Ta and Hf 1 type or 2 types or more: 0.1 to 3%, (iv) 1 type or 2 types or more of Y and rare earth elements: 0.001 to 0.01%, among the above (i) to (iv) 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: 0.04% Further, as other inevitable impurities, Fe: 0.3% or less, Mn: 0.3% or less, Ti: 0.3% or less, Al: 0 .3% or less, Mg: 0.05% or less of corrosion-resistant Ni—Cr alloy having excellent bending workability is known (see Patent Document 1), and this Ni—Cr alloy is used in a pharmaceutical production plant. It has begun to attract attention as a material.
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 the deformability at high temperatures that is an index of hot extrudability is low, for example, Corrosion resistance degradation in welds due to difficulties in imparting shapes such as seamless pipes, difficult fabrication of complex-shaped machine parts that need to be processed at high temperatures, and poor phase stability that causes them. Therefore, there is a problem that the elution of metal ions from the welded part and the heat-affected part becomes large.

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: 43% to 50% by mass% (hereinafter,% represents mass%) is Mo: 0.1-2%, Mg: 0.001-0.05% , N: 0.001-0.04%, Mn: 0.05-0.5%, B: 0.0005-0.01%, and Fe: 0.05- 1.0% and Si: 0.01 to 0.1% containing 1 type or 2 types, the remainder is composed of Ni and inevitable impurities, and the composition in which C as an inevitable impurity is adjusted to 0.05% or less Since the Ni-based alloy has excellent high-temperature workability, the corrosion rate (mm / year) in a relatively weak acid or strong alkaline environment is less than 0.1 mm / year, and the elution of metal ions is remarkably small. Ni-Cr alloys having this component composition are relatively weak acids and strong. Having a more excellent effect as a material, such as pharmaceutical manufacturing plants under alkaline environment, it was obtained a finding that.

This invention has been made based on such knowledge,
(1) Cr: more than 43-50%, Mo: 0.1-2%, Mg: 0.001-0.05%, N: 0.001-0.04%, Mn: 0.05-0. 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. Pharmaceutical manufacturing plant components ,
(2) Cr: More than 43-50%, Mo: 0.1-2%, Mg: 0.001-0.05%, N: 0.001-0.04%, Mn: 0.05-0. 5%, B: 0.0005-0.01%, Fe: 0.05-1.0% and Si: 0.01-0.1% of one or two The remainder is composed of Ni and inevitable impurities, and is characterized by a pharmaceutical manufacturing plant member 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.

Next, the reason for limitation of each element in a pharmaceutical manufacturing plant member made of a Ni-based alloy having excellent high-temperature workability and a remarkably small metal ion elution amount according to the present invention will be described in detail.

Cr:
In a relatively weak acid or strong alkali environment such as a pharmaceutical manufacturing plant, Cr concentrates on the surface and forms a thin and dense passive film mainly composed of Cr ₂ O ₃ to suppress elution of metal ions. Add it. In that case, elution of metal ions can be remarkably suppressed when the cation ratio in the surface coating is 95% or more. For that purpose, Cr needs to contain over 43%, but if it contains over 50%, processing becomes difficult. Therefore, Cr contained in the pharmaceutical manufacturing plant member made of the Ni-based alloy of the present invention is determined to be more than 43 to 50%. More preferably, it is 43.1 to 47%.

Mo:
Mo has an effect of promoting the formation of a passive film mainly composed of Cr ₂ O ₃ . In that case, the effect is shown by containing 0.1% or more, but if it exceeds 2%, the phase stability is deteriorated and it becomes difficult to solidify the Cr-bcc phase. Since a microbattery was formed between the -fcc phase and the Cr-bcc phase, resulting in an increase in the elution amount of metal ions, the Mo content was determined to be 0.1 to 2%. More preferably, it is more than 0.1 to less than 0.5%.

N, Mn and Mg:
By making N, Mn, and Mg coexist, phase stability can be improved. That is, N, Mn, and Mg all 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 suppression of deterioration of corrosion resistance of welds, while 0.5% If the content 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%).
It has been found that these three elements have no effect unless the three elements are simultaneously contained within 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 content of B is set to 0.0005 to 0.01%. A more preferable range is 0.001 to 0.01%.

Fe and Si:
Both Fe and Si have the effect of improving the 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. However, if the content exceeds 0.1%, the phase stability is deteriorated. Therefore, 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 members of the present invention are excellent in high-temperature processability, making it possible to manufacture seamless pipes by hot extrusion, which is the most difficult to process, making it possible to manufacture machine parts with complex shapes, and the amount of metal ion elution is extremely small. excellent properties from the point in corrosion resistance, quality control is exposed to particularly severe and relatively weak acids and strong alkaline environment, it is effective as a pharmaceutical manufacturing plants member dislike contamination by metal ion elution.

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. 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 to 2 are partially cut to produce a 30 mm thick plate, which is 1200 ° C. The solution was solidified by holding 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) The present invention was made in hot torsion test destination pharmaceutical manufacturing plants member 1 to 23, Comparative drug manufacturing plants member 12 and a thickness comprised a conventional pharmaceutical production plants member 1 to 2: machining a thick plate of 30mm 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 this hot twist test piece at temperatures of 1050 ° C. and 1150 ° C. for 15 minutes, respectively, the hot twist test was carried out by adjusting the rotational speed of the twist so that the strain rate was 2.0 / sec. The number of rotations until measurement was measured, and the results were shown in Tables 4 to 6 to evaluate the deformability at high temperatures.

(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 alkalis used in pharmaceutical production, pH: 1 hydrochloric acid aqueous solution, pH: 1 sulfuric acid aqueous solution, pH: 2 It was prepared by preparing a hydrofluoric acid aqueous solution and a 25% sodium hydroxide aqueous solution at room temperature. Furthermore, a pressure vessel is prepared, and the pressure vessel is filled with the hydrochloric acid aqueous solution, the sulfuric acid aqueous solution, the hydrofluoric acid aqueous solution and the sodium hydroxide aqueous solution, and the corrosion test piece without welding and the corrosion test piece with welding are put into the pressure vessel, The temperature in the pressure vessel was set to 150 ° C. and held for 100 hours. The ratio liquid volume at this time was (a liquid 200cc to a sample surface area of 12cm ²⁾ and 16.7cc ^/ cm 2.
After completion of the holding test, the pressure vessel is cooled, and then the test piece is taken out. The element eluted in the corroded solution after immersion is analyzed quantitatively (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 (2)

In mass%, Cr: more than 43-50%, Mo: 0.1-2%, Mg: 0.001-0.05%, N: 0.001-0.04%, Mn: 0.05-0 0.5%, B: 0.005% to 0.01%, with the balance being 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 A pharmaceutical production plant member characterized by comprising: In mass%, Cr: more than 43-50%, Mo: 0.1-2%, Mg: 0.001-0.05%, N: 0.001-0.04%, Mn: 0.05-0 0.5%, B: 0.0005 to 0.01%, and Fe: 0.05 to 1.0% and Si: 0.01 to 0.1% A pharmaceutical manufacturing 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.