JP5987102B1 - トリアリールメタン組成物,眼膜染色のための染色組成物 - Google Patents
トリアリールメタン組成物,眼膜染色のための染色組成物 Download PDFInfo
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- JP5987102B1 JP5987102B1 JP2015231303A JP2015231303A JP5987102B1 JP 5987102 B1 JP5987102 B1 JP 5987102B1 JP 2015231303 A JP2015231303 A JP 2015231303A JP 2015231303 A JP2015231303 A JP 2015231303A JP 5987102 B1 JP5987102 B1 JP 5987102B1
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- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 abstract description 15
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- 239000012046 mixed solvent Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052756 noble gas Inorganic materials 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229940001593 sodium carbonate Drugs 0.000 description 1
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical compound [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 229940086542 triethylamine Drugs 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- C09B67/00—Influencing the physical, e.g. the dyeing or printing properties of dyestuffs without chemical reactions, e.g. by treating with solvents grinding or grinding assistants, coating of pigments or dyes; Process features in the making of dyestuff preparations; Dyestuff preparations of a special physical nature, e.g. tablets, films
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Abstract
Description
そして,式(1)で示されるブリリアントブル−G(BBG)又はその薬学的に許容される塩を,
式(1)〜(3)で示されるトリアリールメタン誘導体,その薬学的に許容される塩中,90重量%以上100重量%以下含む。
式A1で示されるエチル−m−トリルアミン(ethyl−m−tolyl−amine)をベンジル化試薬と反応させ,式A2で示される化合物を得るベンジル化工程と,
式A2で示される化合物に三酸化硫黄又は硫酸を作用させ,
式A3で示されるベンジルエチル−m−トリルアミン誘導体を得る工程と,
式A3で示されるベンジルエチル−m−トリルアミン誘導体から,式(1)で示されるブリリアントブル−G(BBG)又はその薬学的に許容される塩を得る工程と,
を含む。
(上記式中X11は,水素原子,水酸基,アルカリ金属原子で水素原子が置換された水酸基,アルカリ金属原子又はハロゲン原子を示し,X12は,水素原子,水酸基,アルカリ金属原子で水素原子が置換された水酸基,アルカリ金属原子又はハロゲン原子を示す。)
式B1で示されるエチル−m−トリルアミン(ethyl−m−tolyl−amine)を,ハロゲン原子が付加したベンジル化試薬と反応させ,式B2で示されるハロゲン化化合物を得る工程と,
式B2で示されるハロゲン化化合物のハロゲン原子を置換して,式B3で示されるベンジルエチル−m−トリルアミン誘導体を得る工程と,
式B3で示されるベンジルエチル−m−トリルアミン誘導体とアルカリを反応させ,式B4で示されるベンジルエチル−m−トリルアミン誘導体を得る工程と,
式B4で示されるベンジルエチル−m−トリルアミン誘導体から,式1で示されるブリリアントブル−G(BBG)又はその薬学的に許容される塩を得る工程と,
を含む,
ブリリアントブル−G(BBG)又はその薬学的に許容される塩の製造方法に関する。
式B2で示されるハロゲン化化合物のハロゲン原子を置換して,式B3で示されるベンジルエチル−m−トリルアミン誘導体を得る工程は,
式B2で示されるハロゲン化化合物に硫化物を作用させ,式B2−1で示される化合物を得る工程と,
式B2−1で示される化合物に求電子試薬SO2Cl2を作用させ,式B3で示されるベンジルエチル−m−トリルアミン誘導体であってX2が塩素原子であるものを得る工程を含むものが好ましい。
式B2で示されるハロゲン化化合物とグリニャ−ル試薬を作用させ,SO2を作用させた後に,ハロゲンイオンと作用させることで,式B3で示されるベンジルエチル−m−トリルアミン誘導体を得る工程であるものが好ましい。
本発明のトリアリールメタン組成物は,式(1)〜(3)で示されるトリアリールメタン誘導体,その薬学的に許容される塩を少なくとも1つ含む。
91重量%以上99.99重量%以下含むものであり,91重量%以上99.9重量%以下含むものでもよく,91重量%以上99重量%以下含むものでもよく,91重量%以上98重量%以下含むものでもよく,91重量%以上97重量%以下含むものでもよく,91重量%以上95重量%以下含むものでもよく,
92重量%以上99.99重量%以下含むものであり,92重量%以上99.9重量%以下含むものでもよく,92重量%以上99重量%以下含むものでもよく,92重量%以上98重量%以下含むものでもよく,92重量%以上97重量%以下含むものでもよく,92重量%以上95重量%以下含むものでもよく,
93重量%以上99.99重量%以下含むものであり,93重量%以上99.9重量%以下含むものでもよく,93重量%以上99重量%以下含むものでもよく,93重量%以上98重量%以下含むものでもよく,93重量%以上97重量%以下含むものでもよく,93重量%以上95重量%以下含むものでもよく,
95重量%以上99.99重量%以下含むものであり,95重量%以上99.9重量%以下含むものでもよく,95重量%以上99重量%以下含むものでもよく,95重量%以上98重量%以下含むものでもよく,95重量%以上97重量%以下含むものでもよい。
上記のトリアリールメタン組成物は,眼膜除去を行う際の眼膜染色のための染色組成物の有効成分として用いることができる。すなわち,特許文献1に開示される通り,BBG又はその塩は,眼膜除去を行う際の眼膜染色のための染色組成物の有効成分(染料)として有効である。
次に,BBG又はその塩の製造方法を説明する。この基本となるBBG又はその塩の製造方法は,以下の3つの工程をこの順に含む。これらの工程の前後には,別の工程が含まれてもよい。
式A1で示されるエチル−m−トリルアミン(ethyl−m−tolyl−amine)をベンジル化試薬と反応させ,式A2で示される化合物を得る(ベンジル化工程)。
式A2で示される化合物に三酸化硫黄又は硫酸を作用させ,式A3で示されるベンジルエチル−m−トリルアミン誘導体を得る。
式A3で示されるベンジルエチル−m−トリルアミン誘導体から,式(1)で示されるブリリアントブル−G(BBG)又はその薬学的に許容される塩を得る。
まず,式A3で示される化合物を下記式A3−1で示される化合物を介して2つ結合する。
次に,BBG又はその塩を製造するための上記とは別の例を説明する。
この方法は,式B1で示されるエチル−m−トリルアミン(ethyl−m−tolyl−amine)を,ハロゲン原子が付加したベンジル化試薬と反応させ,式B2で示されるハロゲン化化合物を得る工程と,
式B2で示されるハロゲン化化合物のハロゲン原子を置換して,式B3で示されるベンジルエチル−m−トリルアミン誘導体を得る工程と,
式B3で示されるベンジルエチル−m−トリルアミン誘導体とアルカリを反応させ,式B4で示されるベンジルエチル−m−トリルアミン誘導体を得る工程と,
式B4で示されるベンジルエチル−m−トリルアミン誘導体から,式1で示されるブリリアントブル−G(BBG)又はその薬学的に許容される塩を得る工程と,
を含む。
X22は,ハロゲン原子を示。X22の好ましい例は,塩素原子又は臭素原子であり,塩素原子が好ましい。
X33は,水素原子,水酸基,アルカリ金属原子で水素原子が置換された水酸基,アルカリ金属原子又はハロゲン原子を示す。X23の好ましい例は,水素原子又はナトリウム塩である。
式B2で示されるハロゲン化化合物に硫化物を作用させ,式B2−1で示される化合物を得る工程と,
式B2−1で示される化合物に求電子試薬SO2Cl2を作用させ,式B3で示されるベンジルエチル−m−トリルアミン誘導体であってX2が塩素原子であるものを得る工程を含む。
(2)式B2で示されるハロゲン化化合物とグリニャ−ル試薬を作用させ,SO2を作用させた後に,ハロゲンイオンと作用させることで,式B3で示されるベンジルエチル−m−トリルアミン誘導体を得る工程である。ハロゲンイオンは,例えば,N−クロロスクシンイミドに由来する塩化物イオンである。この工程は,実施例3において説明されているものであり,実施例3に基づいて適宜調整すればよい。
Int. BBG−03は,精製効率が高くなかったため,精製効率を向上させることとした。ところで,Ca,Ba塩は無機塩だが水溶性が低いことが知られている。また,2価イオンとの塩は異性体間の物性差異が出やすいのではないかと考え,Caを含む数種の塩基を添加し,水溶性が減少した結晶が得られないか検討した。様々な塩基を用いて結晶化を試みた結果,Int. BBG−03をCs塩化すると水溶性が減少した塩が得られることが分かった。また,Cs塩化の段階で異性体比率が向上することも分かった(異性体:17.6%→1.1%)
Cs塩化の最適化:H2O(基質×35w/v),Cs2CO3(4.8当量),収率35%
なお,収率向上を目的にH2Oを減らした(基質×15w/v)ところ,回収率は向上した(77%)ものの,異性体が全く除去されなかった。
MeOH/IPA=1/10(×35v/w)・回収率:81%,異性体:1.1→0.5%
H2O懸洗(×5v/w)・・・・・・・回収率:50%,異性体:17.6→3.3%
H2O懸洗(×2.5v/w)・・・・・・回収率:81%,異性体:3.3→0.3%
結晶析出が見られないため,種晶(約50mg)を更に添加し,氷冷,終夜成り行き静置した(11時間)。
HPLCにて反応確認後,反応液を減圧濃縮(バス温:45〜50)した。濃縮残渣をメタノール:20mL×3回共沸した後,メタノール10mLを添加,不溶物をろ別した。
得られたろ液を減圧濃縮,乾燥し,粗体のInt. BBG−03−Na:776mg(白色固体,quant, LC88.0%,lot. 140526)を得た。
得られた有機層を水:50mL,塩水(brine):50mLで洗浄,Na2SO4乾燥,減圧濃縮(バス温:35〜45℃)した。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6431732A (en) * | 1987-07-22 | 1989-02-02 | Bayer Ag | Method of separating and removing impurities from organic substance |
US6057160A (en) * | 1997-08-06 | 2000-05-02 | Washington State University Research Foundation | Methods for preparation and use of a coomassie brilliant blue/protein complex |
JP2008522953A (ja) * | 2004-12-06 | 2008-07-03 | 国立大学法人九州大学 | 眼膜染色に用いる染色組成物 |
JP2011070171A (ja) * | 2009-08-26 | 2011-04-07 | Mitsubishi Chemicals Corp | カラーフィルタ用着色樹脂組成物、カラーフィルタ、液晶表示装置及び有機elディスプレイ |
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US1218232A (en) * | 1915-03-27 | 1917-03-06 | Synthetic Patents Co Inc | Blue triphenylmethane dye. |
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US5198558A (en) * | 1990-12-18 | 1993-03-30 | Basf Corporation | Process for the preparation of triphenylmethane dyes |
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- 2018-10-23 HK HK18113558.7A patent/HK1254472A1/zh unknown
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6431732A (en) * | 1987-07-22 | 1989-02-02 | Bayer Ag | Method of separating and removing impurities from organic substance |
US6057160A (en) * | 1997-08-06 | 2000-05-02 | Washington State University Research Foundation | Methods for preparation and use of a coomassie brilliant blue/protein complex |
JP2008522953A (ja) * | 2004-12-06 | 2008-07-03 | 国立大学法人九州大学 | 眼膜染色に用いる染色組成物 |
JP2011070171A (ja) * | 2009-08-26 | 2011-04-07 | Mitsubishi Chemicals Corp | カラーフィルタ用着色樹脂組成物、カラーフィルタ、液晶表示装置及び有機elディスプレイ |
Non-Patent Citations (1)
Title |
---|
JPN6016002242; Nazim Mekaoui, et al.: 'Purification of Coomassie Brilliant Blue G-250 by multiple dual modecountercurrent chromatography' Journal of Chromatography A Volume 1232, 2012, pp.134-141 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109721512A (zh) * | 2017-10-27 | 2019-05-07 | 江苏暨明医药科技有限公司 | 异硫蓝均相氧化合成方法及其合成的异硫蓝 |
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HK1254472A1 (zh) | 2019-07-19 |
WO2017090349A1 (ja) | 2017-06-01 |
US11534505B2 (en) | 2022-12-27 |
IL259418B2 (en) | 2023-04-01 |
US20230025076A1 (en) | 2023-01-26 |
JP2017095419A (ja) | 2017-06-01 |
CA3005714A1 (en) | 2017-06-01 |
IL259418A (en) | 2018-07-31 |
EP3381475A1 (en) | 2018-10-03 |
IL259418B (en) | 2022-12-01 |
EP3381475A4 (en) | 2019-07-31 |
CA3005714C (en) | 2022-07-26 |
US20180264142A1 (en) | 2018-09-20 |
CN108289968A (zh) | 2018-07-17 |
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