JP5322207B2 - New synthetic hydrotalcite particles and production method thereof. - Google Patents
New synthetic hydrotalcite particles and production method thereof. Download PDFInfo
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- JP5322207B2 JP5322207B2 JP2008168100A JP2008168100A JP5322207B2 JP 5322207 B2 JP5322207 B2 JP 5322207B2 JP 2008168100 A JP2008168100 A JP 2008168100A JP 2008168100 A JP2008168100 A JP 2008168100A JP 5322207 B2 JP5322207 B2 JP 5322207B2
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- 239000002245 particle Substances 0.000 title claims abstract description 99
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 title claims abstract description 77
- 229960001545 hydrotalcite Drugs 0.000 title claims abstract description 76
- 229910001701 hydrotalcite Inorganic materials 0.000 title claims abstract description 76
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 13
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims abstract description 23
- 239000001095 magnesium carbonate Substances 0.000 claims abstract description 23
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims abstract description 23
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims abstract description 10
- 239000007900 aqueous suspension Substances 0.000 claims abstract description 8
- 239000003518 caustics Substances 0.000 claims abstract description 8
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 239000011777 magnesium Substances 0.000 claims abstract description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 230000032683 aging Effects 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- 229940069428 antacid Drugs 0.000 claims description 8
- 239000003159 antacid agent Substances 0.000 claims description 8
- 229940024545 aluminum hydroxide Drugs 0.000 claims description 7
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 6
- 229940024546 aluminum hydroxide gel Drugs 0.000 claims description 6
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 claims description 6
- 230000001458 anti-acid effect Effects 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 230000018044 dehydration Effects 0.000 claims description 5
- 238000006297 dehydration reaction Methods 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- 238000004438 BET method Methods 0.000 claims description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical group [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical group [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 2
- 239000011541 reaction mixture Substances 0.000 abstract 2
- 230000015572 biosynthetic process Effects 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- 239000000243 solution Substances 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 5
- 238000002156 mixing Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000003463 adsorbent Substances 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical group [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000000635 electron micrograph Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000002431 foraging effect Effects 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000007863 gel particle Substances 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 229920005672 polyolefin resin Polymers 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Compounds Of Alkaline-Earth Elements, Aluminum Or Rare-Earth Metals (AREA)
Abstract
Description
本発明は新規で、特殊な形状、すなわち内部に空洞を有さない柱状を有する合成ハイドロタルサイト粒子及びその製法に関する。 The present invention relates to a synthetic hydrotalcite particle having a novel and special shape, that is, a columnar shape having no cavity inside, and a method for producing the same.
合成ハイドロタルサイト粒子は、陰イオン交換による酸の不活性化や優れた酸中和能を有しており、更に、構成元素の置換及び陰イオンの種類を変換できる等の特異な性質を活用し、医薬用制酸剤（特許文献１，２）、吸着剤（特許文献３，４）、ポリオレフィン系樹脂の触媒残分の中和剤（特許文献５）、塩素系樹脂の安定剤（特許文献６）等多岐にわたる分野で利用されている。しかしながら、従来のハイドロタルサイト粒子は、カサが３．０〜６．０ｍＬ／ｇと高いために、作業性や輸送効率が悪く、更に錠剤とした時の厚みが厚くなり服用しにくいという問題があり、カサが低い合成ハイドロタルサイトが求められてきたが、上記課題を解決するまでには至ってない。
本発明の目的は、カサが低い合成ハイドロタルサイト粒子を提供することである。すなわち、新規形状を有し、カサが低く、特に錠剤にした時の錠剤の厚みを薄く出来るハイドロタルサイト粒子及びその製造方法を提供することである。
An object of the present invention is to provide synthetic hydrotalcite particles with low bulk. That is, it is to provide a hydrotalcite particle having a novel shape, low mass, and particularly capable of reducing the thickness of the tablet when made into a tablet, and a method for producing the same.
前記のように、合成ハイドロタルサイト粒子については多くの検討がなされているが、いづれもカサが高く、特に医薬用制酸剤錠剤用に利用するに当たっては服用しにくいものであった。従って、カサが低く錠剤にした時の錠剤厚みが薄い合成ハイドロタルサイト粒子が嘱望されている。
本発明者らは前記課題を解決するために鋭意研究を重ねた結果、ハイドロタルサイト製造時の原料を特定することにより、目的の合成ハイドロタルサイト粒子が得られることを、すなわち、形状が内部に空洞を有さない柱状の合成ハイドロタルサイト粒子が得られ、従来の合成ハイドロタルサイト粒子に比べカサが低く、例えば錠剤とした時の厚みが薄く、更に、比較的安価に目的の合成ハイドロタルサイト粒子が得られることを見出し本発明を完成した。
As described above, many studies have been made on the synthetic hydrotalcite particles, but all of them are high in weight and are particularly difficult to take when used for pharmaceutical antacid tablets. Therefore, synthetic hydrotalcite particles having a low bulk and a thin tablet thickness when formed into tablets are desired.
As a result of intensive research to solve the above problems, the present inventors have determined that the desired synthetic hydrotalcite particles can be obtained by specifying the raw materials during the production of hydrotalcite, that is, the shape is internal. Columnar synthetic hydrotalcite particles that do not have cavities are obtained, and the synthetic hydrotalcite particles are lower than conventional synthetic hydrotalcite particles. For example, they are thinner when made into tablets, and the target synthetic hydrotalcite particles are relatively inexpensive. The present invention has been completed by finding that talcite particles can be obtained.
本発明で得られた合成ハイドロタルサイト粒子は、下記式化１で表わされる形状が内部に空洞を有さない柱状である合成ハイドロタルサイト粒子である。
本発明の形状が内部に空洞を有さない柱状である合成ハイドロタルサイト粒子は、日本薬局方外医薬品規格２００２年収載規格に適合することを特徴とし、更に、該ハイドロタルサイト粒子はカサが低く、錠剤とした時の厚みが薄いものとなるので制酸剤として有効で、さらにその他利用範囲の広いものとなる。 The synthetic hydrotalcite particles having the shape of the present invention in the form of a column having no cavity inside are characterized by conforming to the Japanese Pharmacopoeia Standards Listed in 2002, and the hydrotalcite particles are made of Since it is low and has a thin thickness when it is made into a tablet, it is effective as an antacid and has a wide range of other uses.
本発明の製造方法は、下記である。
〈製造方法〉
本発明の形状が内部に空洞を有さない柱状の合成ハイドロタルサイト粒子は以下の工程により製造することができる。
（１）塩基性炭酸マグネシウム粒子の水懸濁液と水酸化アルミニウムの水懸濁液とを、マグネシウム原子とアルミニウム原子との比（Ｍｇ／Ａｌ）が２．６〜３．２となる割合で混合し、さらに苛性アルカリを加えて該液ｐＨ８．５〜１１．５の反応液を得る工程、および
（２）反応液を５０〜１００℃で０．５〜２０時間加熱熟成する工程、
（３）熟成後液からハイドロタルサイト粒子を固液分離、洗浄、脱水および乾燥する工程。
The production method of the present invention is as follows.
<Production method>
The columnar synthetic hydrotalcite particles having the shape of the present invention having no cavity inside can be produced by the following steps.
(1) An aqueous suspension of basic magnesium carbonate particles and an aqueous suspension of aluminum hydroxide at a ratio such that the ratio of magnesium atom to aluminum atom (Mg / Al) is 2.6 to 3.2. Mixing, further adding a caustic alkali to obtain a reaction solution having a pH of 8.5 to 11.5, and (2) aging the reaction solution at 50 to 100 ° C. for 0.5 to 20 hours,
(3) A step of solid-liquid separation, washing, dehydration and drying of hydrotalcite particles from the solution after aging.
（反応）
水酸化アルミニウム粒子は、日本薬局方第十五改正適合の乾燥水酸化アルミニウムゲル粒子であり、乾燥品または乾燥前スラリーであってもよい。炭酸マグネシウム粒子は、形状が短冊状であり、長辺の平均長さが１０〜１００μｍ、短辺の平均長さが５〜２０μｍ、長辺／短辺比の平均が２〜２０であり、さらに日本薬局方第十五改正適合の塩基性炭酸マグネシウムである。長辺の長さについては、特に限定するものではないが１０μｍ以下のものは合成できなく、また１００μｍ以上のものも合成できない。短辺の長さについては５μｍ以下であれば得られるハイドロタルサイト粒子の形状が内部に空洞を有さない柱状にならなく、１００μｍ以上のものは合成できない。
また、用いるマグネシウム原子とアルミニウム原子の混合比率（Ｍｇ／Ａｌ）２．６〜３．２は、得られたハイドロタルサイト粒子が日本薬局方外医薬品規格のモル比規格に適合する範囲である。
上記苛性アルカリとしては、水酸化ナトリウム、水酸化カリウムおよび水酸化アンモニウムなる群から選ばれる少なくとも１種を用いることが好ましい。
反応ｐＨは、８．５〜１１．５、好ましくは９．５〜１０．５である。反応ｐＨが８．５以下であると、ハイドロタルサイト生成率が低くなり、また後工程の熟成に多大のエネルギーを必要とするので不利である。逆に反応ｐＨ１１．５
以上では、ｐＨ調整のための苛性アルカリの使用量が多大となりこれもまた不利である。
なお、反応温度に関しては特に限定するものでないが、１５〜３０℃の範囲内であればよい。
(reaction)
The aluminum hydroxide particles are dry aluminum hydroxide gel particles conforming to the 15th revision of the Japanese Pharmacopoeia, and may be a dried product or a slurry before drying. The magnesium carbonate particles have a strip shape, the average length of the long side is 10 to 100 μm, the average length of the short side is 5 to 20 μm, and the average of the long side / short side ratio is 2 to 20, Basic magnesium carbonate compatible with the 15th revision of the Japanese Pharmacopoeia. The length of the long side is not particularly limited, but those having a length of 10 μm or less cannot be synthesized, and those having a length of 100 μm or more cannot be synthesized. If the length of the short side is 5 μm or less, the shape of the obtained hydrotalcite particles does not have a columnar shape without a cavity inside, and a particle having a length of 100 μm or more cannot be synthesized.
Moreover, the mixing ratio (Mg / Al) 2.6-3.2 of the magnesium atom and aluminum atom to be used is a range in which the obtained hydrotalcite particles meet the molar ratio standard of the Japanese Pharmacopoeia pharmaceutical standards.
As the caustic alkali, it is preferable to use at least one selected from the group consisting of sodium hydroxide, potassium hydroxide and ammonium hydroxide.
The reaction pH is 8.5 to 11.5, preferably 9.5 to 10.5. If the reaction pH is 8.5 or less, the hydrotalcite production rate is low, and a large amount of energy is required for aging in the subsequent process, which is disadvantageous. Conversely, reaction pH 11.5
In the above, the amount of caustic alkali used for pH adjustment becomes large, which is also disadvantageous.
In addition, although it does not specifically limit regarding reaction temperature, What is necessary is just in the range of 15-30 degreeC.
（熟成）
熟成は、得られた反応液を５０〜１００℃、好ましくは７０〜９０℃で維持することにより行う。
また、熟成時間は０．５〜２０時間、好ましくは１〜３時間である。
（固液分離、洗浄、脱水および乾燥）
熟成後反応液を、ろ過、洗浄、脱水および乾燥させる。
(Aging)
The aging is performed by maintaining the obtained reaction solution at 50 to 100 ° C, preferably 70 to 90 ° C.
The aging time is 0.5 to 20 hours, preferably 1 to 3 hours.
(Solid-liquid separation, washing, dehydration and drying)
After aging, the reaction solution is filtered, washed, dehydrated and dried.
すなわち本発明は、
１.顕微鏡観察下における形状が内部に空洞を有さない柱状であり、且つ下記式化２を満足する新規合成ハイドロタルサイト粒子、
２.上記内部に空洞を有さない柱状粒子の高さが１０〜１００μｍ、柱の直径が５〜２０μｍ、高さ／直径の比（アスペクト比）が２〜２０である前項１記載の合成ハイドロタルサイト粒子、
３.見掛け比容が２〜３ｍＬ／ｇである前項１記載の合成ハイドロタルサイト粒子、
４.ＢＥＴ法で測定された比表面積が、３０〜２００ｍ２／ｇである前項１記載の合成ハイドロタルサイト粒子、
５.合成ハイドロタルサイト粒子が、日本薬局方外医薬品規格２００２年収載規格に適合する前項１記載の合成ハイドロタルサイト粒子、
６.前項１記載の新規合成ハイドロタルサイト粒子を有効成分とする制酸剤、
７.（１）炭酸マグネシウム粒子の水懸濁液と水酸化アルミニウムの水懸濁液とを、マグネシウム原子とアルミニウム原子との比（Ｍｇ／Ａｌ）が２．６〜３．２となる割合で混合し、さらに苛性アルカリを加えて該液ｐＨ８．５〜１１．５の反応液を得る工程、および
（２）反応液を５０〜１００℃で０．５〜２０時間加熱熟成する工程、
（３）熟成後液からハイドロタルサイト粒子を固液分離、洗浄、脱水および乾燥することからなる形状が内部に空洞を有さない柱状の合成ハイドロタルサイト粒子の製造方法、
８.水酸化アルミニウム粒子が、日本薬局方第十五改正適合の乾燥水酸化アルミニウムゲルである前項７記載の製造方法、
９.炭酸マグネシウム粒子は形状が短冊状であり、長辺の長さが１０〜１００μｍ、短辺の長さが５〜２０μｍ、長辺／短辺の比が２〜２０であり、さらに日本薬局方第十五改正適合の塩基性炭酸マグネシウムである前項７記載の製造方法、
１０.苛性アルカリが水酸化ナトリウムである前項７記載の製造方法、
である。
That is, the present invention
1. New synthetic hydrotalcite particles having a columnar shape with no cavity inside and satisfying the following formula 2
2. The synthetic hydrogel according to item 1 above, wherein the columnar particles having no cavity inside have a height of 10 to 100 μm, a column diameter of 5 to 20 μm, and a height / diameter ratio (aspect ratio) of 2 to 20. Talcite particles,
3. Synthetic hydrotalcite particles according to item 1, wherein the apparent specific volume is 2 to 3 mL / g,
4. The synthetic hydrotalcite particles according to item 1, wherein the specific surface area measured by the BET method is 30 to 200 m 2 / g,
5. Synthetic hydrotalcite particles according to paragraph 1 above, wherein the synthetic hydrotalcite particles conform to the standards listed in the Japanese Pharmacopoeia Pharmaceutical Standards 2002
6. An antacid containing the newly synthesized hydrotalcite particles described in the preceding item 1 as an active ingredient,
7. (1) An aqueous suspension of magnesium carbonate particles and an aqueous suspension of aluminum hydroxide at a ratio such that the ratio of magnesium atoms to aluminum atoms (Mg / Al) is 2.6-3.2. Mixing, further adding a caustic alkali to obtain a reaction solution having a pH of 8.5 to 11.5, and (2) aging the reaction solution at 50 to 100 ° C. for 0.5 to 20 hours,
(3) A method for producing columnar synthetic hydrotalcite particles having a shape that does not have a cavity inside, comprising solid-liquid separation, washing, dehydration and drying of hydrotalcite particles from the liquid after aging,
8. The method according to item 7 above, wherein the aluminum hydroxide particles are dried aluminum hydroxide gel conforming to the 15th revision of the Japanese Pharmacopoeia.
9. Magnesium carbonate particles have a strip shape, the length of the long side is 10 to 100 μm, the length of the short side is 5 to 20 μm, the ratio of the long side / short side is 2 to 20, and The manufacturing method according to 7 above, which is basic magnesium carbonate conforming to the fifteenth revision,
10. The method according to item 7 above, wherein the caustic alkali is sodium hydroxide,
It is.
本発明により、形状が内部に空洞を有さない柱状で日本薬局方外医薬品規格２００２に適合し、更にカサが低いため作業性が良く、打錠した時、錠剤の厚みが薄い剤形となる合成ハイドロタルサイト粒子が得られる。 According to the present invention, it is a columnar shape that does not have a cavity inside, conforms to the Japanese Pharmacopoeia Standard for Drugs 2002, and has low workability so that it has good workability. When tableted, the tablet is thin. Synthetic hydrotalcite particles are obtained.
本発明の合成ハイドロタルサイト粒子は、上式化２で示され、形状が内部に空洞を有さない柱状であることを特徴とし、医薬用制酸剤として利用する合成ハイドロタルサイト粒子である。
本発明の方法によれば、上式化２におけるｘの範囲が上記範囲外の既知のハイドロタルサイトであっても形状を内部に空洞を有さない柱状とすることが可能である。更に、Ｍｇの一部を他のＭ２＋イオンで置換したり、Ａｌを他のＭ３＋イオンと置換することが可能であり、ＣＯ３と他の陰イオンとのイオン交換も可能である。
したがって、本発明の方法によれば、医薬用制酸剤のみならず、多岐にわたる用途、例えば、吸着剤、樹脂用安定剤および担体等に使用可能な内部に空洞を有さない柱状ハイドロタルサイトを合成することができる。
The synthetic hydrotalcite particle of the present invention is a synthetic hydrotalcite particle represented by the above formula 2, characterized in that the shape is a columnar shape without a cavity inside, and is used as a pharmaceutical antacid .
According to the method of the present invention, even if the range of x in the above formula 2 is a known hydrotalcite outside the above range, the shape can be a columnar shape without a cavity inside . Further, a part of Mg can be replaced with other M 2+ ions, Al can be replaced with other M 3+ ions, and ion exchange between CO 3 and other anions is also possible.
Therefore, according to the method of the present invention, columnar hydrotalcite having no internal cavity that can be used not only for pharmaceutical antacids but also for various applications such as adsorbents, stabilizers for resins and carriers. Can be synthesized.
本発明の合成ハイドロタルサイト粒子は、
２０００倍の電子顕微鏡による拡大写真で観察して、全粒子の７０％以上、好ましくは８０％以上の個数の粒子が内部に空洞を有さない柱状であればよい。その内部に空洞を有さない柱状粒子の高さと直径
は、平均高さが１０〜１００μｍ、平均直径が５〜２０μｍであり、高さ／直径の平均が２〜２０である。高さについては、特に限定するものではないが １０μｍ以下のものは合成できなく、また１００μｍ以上のものも合成できない。直径についても、特に限定するものでないが５μｍ以下のものは合成できな
く、２０μｍ以上のものも合成できない。高さと直径の比は、高さと直径に支配されるので、おのずと上記範囲となる。
The synthetic hydrotalcite particles of the present invention are
Observed by a magnified photograph with a 2000-fold electron microscope, 70% or more, preferably 80% or more of the total number of particles may be a column having no cavity inside . As for the height and diameter of the columnar particles having no cavities inside , the average height is 10 to 100 μm, the average diameter is 5 to 20 μm, and the average height / diameter is 2 to 20. The height is not particularly limited, but those having a thickness of 10 μm or less cannot be synthesized, and those having a height of 100 μm or more cannot be synthesized. The diameter is not particularly limited, but a diameter of 5 μm or less cannot be synthesized, and a diameter of 20 μm or more cannot be synthesized. Since the ratio of height to diameter is governed by height and diameter, it naturally falls within the above range.
見掛け比容については、２〜３ｍＬ／ｇであり低い側については特に限定しないが、２ｍＬ／ｇ以下のものは得ることができない。３ｍＬ／ｇ以上については、本発明の目的と異なるものである。 The apparent specific volume is 2 to 3 mL / g, and there is no particular limitation on the lower side, but it cannot be obtained below 2 mL / g. About 3 mL / g or more, it is different from the object of the present invention.
ＢＥＴ法で測定された比表面積は３０〜２００ｍ２／ｇであるが、３０ｍ２／ｇ以下とするとハイドロタルサイト粒子の制酸剤としての特徴である酸反応性が悪くなると同時に、これもハイドロタルサイトの特徴である圧縮した時の錠剤の硬度が低いものとなる。また、２００ｍ２／ｇ以上のものは合成できない。 Although the measured specific surface area by the BET method is 30~200m 2 / g, 30m 2 / g or less to the the characteristic acid reactivity is as antacid hydrotalcite particles becomes poor at the same time, this also Hydro The tablet hardness when compressed is a characteristic of talcite. Moreover, the thing 200 m < 2 > / g or more cannot be synthesize | combined.
また本発明のハイドロタルサイト粒子は、表１に示すように日本薬局方外医薬品規格２００２に適合するものである。更に、本発明のハイドロタルサイト粒子は、粉末Ｘ線回折法による測定に基づいて、ハイドロタルサイト粒子と同じパターンを示し、これ以外のパターンを示さない。 In addition, as shown in Table 1, the hydrotalcite particles of the present invention conform to the Japanese Pharmacopoeia Pharmaceutical Standard 2002. Furthermore, the hydrotalcite particles of the present invention show the same pattern as the hydrotalcite particles based on the measurement by the powder X-ray diffraction method, and show no other patterns.
以下の合成例および比較例に基づき本発明をより詳細に説明するが、本発明はこれに限定されるものではない。また、ハイドロタルサイト粒子の特性は以下の方法により測定した。
（１）粒子形状：走査型電子顕微鏡（ＪＳＭ−６３００／日本電子）で倍率２０００倍の写真を取り、その写真中の粒子の長辺、短辺、高さおよび直径を測定した。
（２）日本薬局方外医薬品規格２００２合成ハイドロタルサイト規格：日本薬局法外医薬品合成ハイドロタルサイトに準じて測定した。
（３）ＣＯ３：ＪＩＳ Ｒ ９１０１のＡＧＫ法に準じて測定した。
（４）見かけ比容：ＪＩＳ Ｋ ５１０１に準じて測定した。
（５）比表面積：ハイドロタルサイト粒子を真空圧１００ｍｍＴｏｒｒで、１０５℃×３時間処理し、ＱＵＡＮＴＡ ＣＨＲＯＭＥ社製ＮＯＶＡ２０００を用いてＢＥＴ法により測定した。
（６）打錠試験：（株）前川試験機製作所製 ＴＹＰＥ Ｍ 型静的圧縮機を用いて、錠剤
径１０ｍｍ、試料量２００ｍｇ、打錠圧０．２５ｔで打錠した。錠剤の厚みはＭｉｔｕｔｏｙｏ製ノギス６５を用いて測定し、錠剤の硬度はフロイント産業 （株）製Ｔａｂｌｅ Ｔｅｓｔｅｒ ８Ｍを用いて測定した。
（７）Ｘ線回折：理学電気（株）製ＲＩＮＴ２２００Ｖを用いてＣＵ−Ｋαにて測定した。
（８）合成例において使用した形状が短冊状の塩基性炭酸マグネシウムは、協和化学工業（株）製炭酸マグネシウム（商品名：シタ）を用いた。
なお、走査型電子顕微鏡で倍率２０００倍の写真を取り、その写真で粒子の長辺および短辺を測定したところ表２のような結果が得られた。５個の塩基性炭酸マグネシウム粒子の平均は長辺３８．６μｍ、短辺１０.５μｍ、長辺／短辺＝３．７であった。
（９）比較例において使用した塩基性炭酸マグネシウムは、株式会社トクヤマ製の塩基性炭酸マグネシウム（トクヤマ製）を用いた。なお、同塩基性炭酸マグネシウムの形状は不定形であった。
（１０）合成例、比較例においては水酸化アルミニウムとして、協和化学工業（株）製乾燥水酸化アルミニウムゲル（商品名：Ｓ−１００）をもちいた。
The present invention will be described in more detail based on the following synthesis examples and comparative examples, but the present invention is not limited thereto. The characteristics of the hydrotalcite particles were measured by the following method.
(1) Particle shape: A photograph with a magnification of 2000 times was taken with a scanning electron microscope (JSM-6300 / JEOL), and the long side, short side, height and diameter of the particles in the photo were measured.
(2) Japanese Pharmacopoeia Pharmaceutical Standard 2002 Synthetic Hydrotalcite Standard: Measured according to Japanese Pharmacopoeia Pharmaceutical Hydrotalcite.
(3) CO 3 : Measured according to the AGK method of JIS R 9101.
(4) Apparent specific volume: Measured according to JIS K 5101.
(5) Specific surface area: Hydrotalcite particles were treated at 105 ° C. for 3 hours at a vacuum pressure of 100 mmTorr, and measured by BET method using NOVA2000 manufactured by QUANTA CHROME.
(6) Tableting test: Tableting was performed using a TYPE M type static compressor manufactured by Maekawa Test Co., Ltd., with a tablet diameter of 10 mm, a sample amount of 200 mg, and a tableting pressure of 0.25 t. The thickness of the tablet was measured using a caliper 65 manufactured by Mitutoyo, and the hardness of the tablet was measured using a Table Tester 8M manufactured by Freund Sangyo Co., Ltd.
(7) X-ray diffraction: Measured with CU-Kα using RINT2200V manufactured by Rigaku Corporation.
(8) Kyowa Chemical Industry Co., Ltd. magnesium carbonate (trade name: Shita) was used as the basic magnesium carbonate having a strip shape used in the synthesis examples.
In addition, when the photograph of magnification 2000 times was taken with the scanning electron microscope and the long side and the short side of the particle were measured with the photograph, the results shown in Table 2 were obtained. The average of the 5 basic magnesium carbonate particles was 38.6 μm long side, 10.5 μm short side, and long side / short side = 3.7.
(9) As the basic magnesium carbonate used in the comparative example, basic magnesium carbonate (manufactured by Tokuyama Corporation) manufactured by Tokuyama Corporation was used. The shape of the basic magnesium carbonate was indefinite.
(10) In the synthesis example and the comparative example, dry aluminum hydroxide gel (trade name: S-100) manufactured by Kyowa Chemical Industry Co., Ltd. was used as aluminum hydroxide.
（合成例１）
６Ｌ容ステンレス製反応容器に水道水３．８Ｌを投入し、攪拌下に、前記協和化学工業（株）製塩基性炭酸マグネシウムを４２４ｇ（ＭｇＯとして４．５モル）投入し、炭酸マグネシウム懸濁液を作成する。続いて攪拌下に、前記乾燥水酸化アルミニウムゲル１４０ｇ（Ａｌ２Ｏ３と
して０．７４モル）および３．３５ｍｏｌ／Ｌ水酸化ナトリウム水溶液１．７９Ｌを投入した。得られた混合液の液温は２５℃、液ｐＨは１０．６５であった。 続いて、液温を５０℃に昇温し、５０℃で２４時間熟成した。冷後、ヌッチエを用いて減圧下に吸引ろ過し、洗浄、脱水しケーキを得た。得られたケーキに、固
形分濃度として２００ｇ／Ｌとなるように水を加えて攪拌しスラリー化し、ラボスケールスプレードライヤーを用いて乾燥することにより、ハイドロタルサイト 粒子を得た。得られたハイドロタルサイト粒子の、電子顕微鏡による倍率２０００倍での観察下における粒子形状は、全粒子の７０％以上が内部に空洞を有さない柱状であり、高さおよび直径および高さ／直径の比を測定したところ表３のような結果が得られた。５個のハイドロタルサイト粒子の平均値は高さ３９．６μｍ、直径１０．０μｍ、高さ／直径＝３．９であった。
なお、得られたハイドロタルサイト粒子のその他の特性を表６に示す。
(Synthesis Example 1)
3.8 L of tap water was charged into a 6 L stainless steel reaction vessel, and 424 g (4.5 mol of MgO) of basic magnesium carbonate manufactured by Kyowa Chemical Industry Co., Ltd. was charged with stirring, and the magnesium carbonate suspension Create Subsequently, 140 g (0.74 mol as Al 2 O 3 ) of the dried aluminum hydroxide gel and 1.79 L of a 3.35 mol / L aqueous sodium hydroxide solution were added under stirring. The liquid temperature of the obtained liquid mixture was 25 degreeC, and liquid pH was 10.65. Subsequently, the liquid temperature was raised to 50 ° C. and aged at 50 ° C. for 24 hours. After cooling, suction filtration was performed under reduced pressure using Nuccie, washing and dehydration to obtain a cake. Hydrotalcite particles were obtained by adding water to the obtained cake so as to have a solid concentration of 200 g / L, stirring to make a slurry, and drying using a lab scale spray dryer. The particle shape of the obtained hydrotalcite particles under observation with an electron microscope at a magnification of 2000 times is a columnar shape in which 70% or more of all particles do not have cavities inside , and the height, diameter and height / When the ratio of diameters was measured, the results shown in Table 3 were obtained. The average value of the five hydrotalcite particles was 39.6 μm in height, 10.0 μm in diameter, and height / diameter = 3.9.
In addition, Table 6 shows other characteristics of the obtained hydrotalcite particles.
（合成例２）
合成例１において、熟成温度を７０℃とし、熟成時間を７時間とした以外は合成例１と同操作を行いハイドロタルサイト粒子を得た。なお、塩基性炭酸マグネシウム、乾燥水酸化アルミニウムゲルおよび水酸化ナトリウム水溶液を混合した液のｐＨは
１０．５７であった。得られたハイドロタルサイト粒子の、電子顕微鏡による倍率２０００倍での観察下における粒子形状は、全粒子の７０％以上が内部に空洞を有さない柱状であり、高さおよび直径および高さ／直径の比を測定したところ表４のような結果が得られた。５個のハイドロタルサイト粒子の平均値は高さ３７．０μｍ、直径９．２μｍ、高さ／直径＝４．２であった。
なお、得られたハイドロタルサイト粒子のその他の特性を表６に示す。
(Synthesis Example 2)
Hydrotalcite particles were obtained in the same manner as in Synthesis Example 1 except that the aging temperature was 70 ° C. and the aging time was 7 hours in Synthesis Example 1. In addition, pH of the liquid which mixed basic magnesium carbonate, dry aluminum hydroxide gel, and sodium hydroxide aqueous solution was 10.57. The particle shape of the obtained hydrotalcite particles under observation with an electron microscope at a magnification of 2000 times is a columnar shape in which 70% or more of all particles do not have cavities inside , and the height, diameter and height / When the ratio of diameters was measured, the results shown in Table 4 were obtained. The average value of the five hydrotalcite particles was 37.0 μm in height, 9.2 μm in diameter, and height / diameter = 4.2.
In addition, Table 6 shows other characteristics of the obtained hydrotalcite particles.
（合成例３）
合成例１において、熟成温度を９０℃とし、熟成時間を２時間とした以外は
合成例１と同操作を行いハイドロタルサイト粒子を得た。なお、塩基性炭酸マグネシウム、乾燥水酸化アルミニウムゲルおよび水酸化ナトリウム水溶液を混合した液のｐＨは１０．２０であった。得られたハイドロタルサイト粒子の、電子顕微鏡による倍率 ２０００倍での観察下における粒子形状は、全粒子の７０％以上が内部に空洞を有さない柱状であり、高さおよび直径および高さ／直径の比を測定したところ表５のような結果が得ら
れた。５個のハイドロタルサイト粒子の平均値は高さ４４．２μｍ、直径１０．１μｍ、高さ／直径＝４．４であった。
なお、得られたハイドロタルサイト粒子のその他の特性を表６に、電子顕微鏡写真を図１に、およびＸ線回折パターンを図３に示す。
(Synthesis Example 3)
In Synthesis Example 1, hydrotalcite particles were obtained in the same manner as in Synthesis Example 1 except that the aging temperature was 90 ° C. and the aging time was 2 hours. In addition, pH of the liquid which mixed basic magnesium carbonate, dry aluminum hydroxide gel, and sodium hydroxide aqueous solution was 10.20. The particle shape of the obtained hydrotalcite particles under an observation with an electron microscope at a magnification of 2000 times is a columnar shape in which 70% or more of all particles do not have cavities inside , and the height, diameter and height / When the ratio of diameters was measured, the results shown in Table 5 were obtained. The average value of the five hydrotalcite particles was 44.2 μm in height, 10.1 μm in diameter, and height / diameter = 4.4.
The other characteristics of the obtained hydrotalcite particles are shown in Table 6, an electron micrograph is shown in FIG. 1, and an X-ray diffraction pattern is shown in FIG.
（比較例１）
合成例３において、塩基性炭酸マグネシウムを前記株式会社トクヤマ製炭酸
マグネシウムとした以外は合成例３と同操作を行いハイドロタルサイト粒子を得た。なお、塩基性炭酸マグネシウム、乾燥水酸化アルミニウムゲルおよび水酸化 ナトリウム水溶液を混合した液のｐＨは１０．３５であった。得られたハイドロタルサイト粒子の、電子顕微鏡観察下における粒子形状は不定形であった。なお、得られたハイドロタルサイト粒子のその他の特性を表６に、電子顕微鏡写真を図２に示す。
(Comparative Example 1)
In Synthesis Example 3, hydrotalcite particles were obtained by performing the same operation as in Synthesis Example 3 except that basic magnesium carbonate was changed to magnesium carbonate manufactured by Tokuyama Corporation. The pH of the solution obtained by mixing basic magnesium carbonate, dry aluminum hydroxide gel and aqueous sodium hydroxide solution was 10.35. The particle shape of the obtained hydrotalcite particles under an electron microscope observation was indefinite. The other characteristics of the obtained hydrotalcite particles are shown in Table 6, and an electron micrograph is shown in FIG.
（参考例１）
参考例として、市販品ハイドロタルサイト粒子（商標名：アルカマックＳＨ／協和化学工業（株）製）の特性を表６に示す。
(Reference Example 1)
As a reference example, Table 6 shows the characteristics of commercially available hydrotalcite particles (trade name: Alkamak SH / manufactured by Kyowa Chemical Industry Co., Ltd.).
本発明のハイドロタルサイト粒子は形状が内部に空洞を有さない柱状で、見かけ比容が低く、日本薬局方外医薬品規格２００２に適合し、さらに、打錠された錠剤の厚みが薄いものであることが分かる。 The hydrotalcite particles of the present invention are columnar in shape and do not have cavities inside, have a low apparent specific volume, conform to the Japanese Pharmacopoeia Standard 2002, and have a thin tablet tablet. I understand that there is.
Claims (10)
（２）反応液を５０〜１００℃で０．５〜２０時間加熱熟成する工程、
（３）熟成後液からハイドロタルサイト粒子を固液分離、洗浄、脱水および乾燥することからなる形状が内部に空洞を有さない柱状の合成ハイドロタルサイト粒子の製造方法。 (1) An aqueous suspension of magnesium carbonate particles and an aqueous suspension of aluminum hydroxide are mixed at a ratio such that the ratio of magnesium atoms to aluminum atoms (Mg / Al) is 2.6 to 3.2. A step of further adding caustic alkali to obtain a reaction solution having a pH of 8.5 to 11.5, and (2) a step of heating and aging the reaction solution at 50 to 100 ° C. for 0.5 to 20 hours,
(3) A method for producing columnar synthetic hydrotalcite particles having a shape that does not have a cavity inside, comprising solid-liquid separation, washing, dehydration, and drying of hydrotalcite particles from a solution after aging.
The process according to claim 7, wherein the caustic is sodium hydroxide.
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