JPH0399053A - Production of granular cysteamine hydrochloride - Google Patents
Production of granular cysteamine hydrochlorideInfo
- Publication number
- JPH0399053A JPH0399053A JP23272089A JP23272089A JPH0399053A JP H0399053 A JPH0399053 A JP H0399053A JP 23272089 A JP23272089 A JP 23272089A JP 23272089 A JP23272089 A JP 23272089A JP H0399053 A JPH0399053 A JP H0399053A
- Authority
- JP
- Japan
- Prior art keywords
- cysteamine hydrochloride
- hydrogen sulfide
- ethyleneimine
- cooled
- hydrochloric acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 title claims abstract description 57
- 229940097265 cysteamine hydrochloride Drugs 0.000 title claims abstract description 57
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 27
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229910000037 hydrogen sulfide Inorganic materials 0.000 claims abstract description 17
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims abstract description 10
- 230000007797 corrosion Effects 0.000 claims abstract description 10
- 238000005260 corrosion Methods 0.000 claims abstract description 10
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 claims description 7
- 229960003151 mercaptamine Drugs 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 27
- 238000002844 melting Methods 0.000 abstract description 11
- 230000008018 melting Effects 0.000 abstract description 11
- 239000012299 nitrogen atmosphere Substances 0.000 abstract description 11
- 239000013078 crystal Substances 0.000 abstract description 10
- 239000000843 powder Substances 0.000 abstract description 9
- 238000001816 cooling Methods 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 8
- 239000002904 solvent Substances 0.000 abstract description 8
- 239000000758 substrate Substances 0.000 abstract description 7
- 238000010438 heat treatment Methods 0.000 abstract description 6
- 238000006243 chemical reaction Methods 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 239000002245 particle Substances 0.000 abstract description 5
- 239000004809 Teflon Substances 0.000 abstract description 4
- 229920006362 Teflon® Polymers 0.000 abstract description 4
- 239000007788 liquid Substances 0.000 abstract description 3
- 239000003905 agrochemical Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 150000007522 mineralic acids Chemical class 0.000 abstract 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 238000001035 drying Methods 0.000 description 5
- -1 acetone Chemical compound 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 238000010926 purge Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000007711 solidification Methods 0.000 description 3
- 230000008023 solidification Effects 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 238000005054 agglomeration Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 229920002449 FKM Polymers 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000000498 cooling water Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 229910000856 hastalloy Inorganic materials 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 206010041232 sneezing Diseases 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野ゴ
本発明は粒状システアミン塩酸塩の製造方法に関するも
のである．シスデアミン塩酸塩は、医薬、農薬などの原
料として有用な化合物であるが、本発明は微粉末発生が
少なく粒径のよくそろった、［従来の技術］
従来、システアミン塩酸塩は一般的にっぎのようにして
製造される。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing granular cysteamine hydrochloride. Cysteamine hydrochloride is a compound useful as a raw material for medicines, agricultural chemicals, etc., but the present invention is a compound that generates less fine powder and has a well-uniformed particle size. It is manufactured in this way.
（１）エチレイミンと硫化水素とからシステアミンを生
成させ、塩化水素を用いてシステアミン塩酸塩を生成さ
せる方法。(1) A method in which cysteamine is produced from ethyleimine and hydrogen sulfide, and cysteamine hydrochloride is produced using hydrogen chloride.
（２）２−ジメチルーチアゾリジンに塩酸を加えてシス
テアミン塩酸塩を生戊させる方法（特公昭５０−２９４
４４号）
（３）モノエタノールアミンを出発原料としてシステア
ミン塩酸塩を生成させる方法〈特開昭５７−８８１７１
号，特開昭５７−１４４２５２号，特公昭５５−１７０
１９号、特開昭５７−６４６８４号、特開昭５７−５３
４５８号、特開昭５７−６７５５５号、特開昭５７−６
４６６１号）従来、システアミン塩酸塩は粉体の形状で
取扱われているのが一般的である．しかしながら、シス
テアミン塩酸塩そのものは、人体に対して刺激性があり
、特に微粉末を吸入すると鼻腔、咽頭を刺激し、咳、く
しゃみがで、また皮膚に付着したまま放置すると炎症を
おこすなど好ましくない性質を有している。したがって
、このような微粉末を多量に含有している粉体状のシス
テアミン塩酸塩を取扱うに際しては、出来る限り皮膚へ
の接触をさけるよう厳重な注意を払う必要がある。(2) Method for producing cysteamine hydrochloride by adding hydrochloric acid to 2-dimethyl-thiazolidine (Japanese Patent Publication No. 50-294
No. 44) (3) Method for producing cysteamine hydrochloride using monoethanolamine as a starting material (JP-A-57-88171)
No., JP-A-57-144252, JP-A-55-170
No. 19, JP-A-57-64684, JP-A-57-53
No. 458, JP-A-57-67555, JP-A-57-6
No. 4661) Conventionally, cysteamine hydrochloride has generally been handled in the form of powder. However, cysteamine hydrochloride itself is irritating to the human body, and inhaling the fine powder can irritate the nasal cavity and pharynx, causing coughing and sneezing, and if left on the skin, it can cause inflammation, which is undesirable. It has properties. Therefore, when handling powdered cysteamine hydrochloride containing a large amount of such fine powder, strict care must be taken to avoid contact with the skin as much as possible.
また、粉体状のシステアミン塩酸塩は、貯蔵中に容器の
中で経時的に塊状化してしまい使用するにあたり、容器
から取り出すことができなくなったり、たとえ取り出し
たとしても再度、粉砕しなければ使用することができな
いなどの問題も有している。また塊状化したシステアミ
ン塩酸塩は溶解に長い時間を要するという問題をも有し
ている．この様に、粉体のシステアミン塩酸塩は極めて
問題の多い製品の形態であるといわざるをえない。In addition, powdered cysteamine hydrochloride aggregates over time in the container during storage, making it impossible to take it out of the container, or even if it is taken out, it must be crushed again before use. There are also problems such as not being able to do so. Another problem is that clumped cysteamine hydrochloride takes a long time to dissolve. Thus, it must be said that powdered cysteamine hydrochloride is an extremely problematic product form.
［発明が解決しようとする問題点］
このように、現存するシステアミン塩酸塩の粉状形態は
多くの問題点を有しており、特に工業的に多量に取扱う
に際して種々の不都合を生じている。そこで、本発明の
目的は、微粉末の発生が少なく、しかも貯蔵中において
も塊状化することなく長期間安定した製品形態を有する
システアミン塩酸塩を提供することにある．
かかる目的を達戒するために、本発明者等は鋭意検討し
た結果、極めて粒径のよくそろった粒状システアミン塩
酸塩類がえられ、このものは微粉末の発生も少なく、貯
蔵安定性及び溶解性にも優れていることを見い出し、本
発明を完成するにいたったのである。[Problems to be Solved by the Invention] As described above, the existing powdered form of cysteamine hydrochloride has many problems, especially when it is handled industrially in large quantities, causing various inconveniences. SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide cysteamine hydrochloride which has a stable product form for a long period of time without generating a small amount of fine powder and does not form agglomerates even during storage. In order to achieve this objective, the inventors of the present invention have made intensive studies and have obtained granular cysteamine hydrochloride with extremely uniform particle sizes, which generates little fine powder and has excellent storage stability and solubility. They discovered that it was also excellent, leading to the completion of the present invention.
［問題点を解決するための手段］
本発明は溶媒の存在下、硫化水素とエチレンイミンを反
応させ、得られたシステアミンを塩酸と反応させてシス
テアミン塩酸塩を生成させ、得られたシステアミン塩酸
塩の結晶を６８℃以上に加温してＦｉ敵し、温度６５℃
以下に冷却された耐蝕性の基材上に滴下し、冷却、凝固
せしめることを特徴とする粒状システアミン塩酸塩の製
法に関するものである。[Means for Solving the Problems] The present invention involves reacting hydrogen sulfide with ethyleneimine in the presence of a solvent, reacting the obtained cysteamine with hydrochloric acid to produce cysteamine hydrochloride, and producing the obtained cysteamine hydrochloride. By heating the crystal above 68°C, the temperature becomes 65°C.
The present invention relates to a method for producing granular cysteamine hydrochloride, which is characterized in that it is dropped onto a cooled corrosion-resistant substrate and allowed to cool and solidify.
また、本発明は溶媒の存在下、硫化水素を圧力６〜ｌ
ＯＫｇ／ｃｍ２Ｇ、温度Ｏ〜１０℃の範囲に保持したと
ころにエチレンイミンを連続添加して反応させ、ついで
加熱して硫化水素を分離した後、５℃以下に冷却して結
晶を析出させ、窒素雰囲気下で枦別、温度６５℃以下で
乾燥を行ない、再度他の溶媒中で塩酸を加えて再結晶を
析出させ、窒素雰囲気下で枦別、乾燥させながら６８℃
以上に加温して溶融し、得られたシステアミン塩酸塩を
温度６５゜Ｃ以下に冷却された耐蝕性の基材上に滴下し
、冷却、凝固せしめることを特徴とする粒状システアミ
ン塩酸塩の製法に関するものである。Furthermore, the present invention is capable of applying hydrogen sulfide at a pressure of 6 to 1 liters in the presence of a solvent.
OKg/cm2G, the temperature was maintained in the range of 0 to 10℃, and ethyleneimine was continuously added and reacted, then heated to separate hydrogen sulfide, cooled to below 5℃ to precipitate crystals, and nitrogen Separate in an atmosphere, dry at a temperature of 65°C or lower, add hydrochloric acid in another solvent to precipitate recrystallization, separate in a nitrogen atmosphere, and dry at 68°C while drying.
A method for producing granular cysteamine hydrochloride, which comprises heating and melting the obtained cysteamine hydrochloride dropwise onto a corrosion-resistant substrate cooled to a temperature of 65°C or less, cooling and solidifying it. It is related to.
本発明に用いる溶媒としては、メタノール、エタノール
、グロビルアルコールなどのアルコール類、アセトンな
どのケトン類および水などの溶媒が挙げられ、特にメタ
ノールまたはエタノールが好ましい．
本発明は溶媒の存在下、硫化水素を圧力６〜１０Ｋｇ／
ｃｍ２Ｇ、好ましくは圧力７〜１０Ｋｇ／ｃｍ２Ｇ．温
度０〜１０℃の範囲、好ましくは温度Ｏ〜５℃の範囲に
保持したところにエチレンイミンを連続添加して反応さ
せ、ついで温度６０〜７０℃で加熱して硫化水素を分離
した後、塩酸を加えて５℃以下、好ましくは温度０〜５
℃の範囲に冷却して結晶を析出させ、窒素雰囲気下で枦
別、乾燥させながら６８℃以上、好ましくは温度７０〜
１００℃の範囲に加温して溶融し、得られたシステアミ
ン塩酸塩を温度６５℃以下、好ましくは温度４０〜１０
゜Ｃの・範囲に冷却された耐蝕性の基材上に滴下し、冷
却、凝固せしめ、粒状システアミン塩酸塩が得られる．
本発明の方法により粒状化できるシステアミン塩酸塩は
常温で固体であり、その融点は約６８゜Ｃである．
システアミン塩酸塩の溶融加熱温度は、通常融点より高
い温度、好ましくは６８〜１５０℃、さらに好ましくは
７０〜１００℃の温度が採用される。Examples of the solvent used in the present invention include alcohols such as methanol, ethanol, and globil alcohol, ketones such as acetone, and solvents such as water, with methanol and ethanol being particularly preferred. The present invention uses hydrogen sulfide in the presence of a solvent at a pressure of 6 to 10 kg/
cm2G, preferably pressure 7-10Kg/cm2G. Ethyleneimine is continuously added and reacted while maintaining the temperature in the range of 0 to 10°C, preferably in the range of 0 to 5°C, and then heated at a temperature of 60 to 70°C to separate hydrogen sulfide, followed by addition of hydrochloric acid. to 5℃ or less, preferably at a temperature of 0 to 5℃.
The crystals are precipitated by cooling to a temperature of 68°C or higher, preferably 70°C or higher while being separated and dried in a nitrogen atmosphere.
The cysteamine hydrochloride obtained by heating to a temperature in the range of 100°C and melting is heated to a temperature of 65°C or lower, preferably a temperature of 40 to 10°C.
It is dropped onto a corrosion-resistant substrate cooled to a temperature in the range of °C, allowed to cool and solidify, and granular cysteamine hydrochloride is obtained. Cysteamine hydrochloride, which can be granulated by the method of the present invention, is solid at room temperature and has a melting point of about 68°C. The heating temperature for melting cysteamine hydrochloride is usually a temperature higher than the melting point, preferably 68 to 150°C, more preferably 70 to 100°C.
本発明のシステアミン塩酸塩の溶融の方法はジャケット
、コイルおよび／または電熱ヒーター等の加熱装置を備
えた耐蝕性の容器またはライン中で行なわれる．
またシステアミン塩酸塩は吸湿力が強く、高温で酸化を
受けやすいので除湿された不活性ガス、好ましくは窒素
雰囲気中で加温するのが好ましい．本発明において溶融
されたシステアミン塩酸塩は板状滴下型造粒機へ供給さ
れる．
本発明において板状滴下型造粒機とは溶融状態にある液
体を冷却された基板上たとえば搬送ベルト上に滴下して
冷却、凝固させて造粒物を作る機器を総称するものであ
る．
本発明では融点以上に加熱されたシステアミン塩酸塩の
溶融液は板状滴下型造粒機の６５℃以下に冷却された耐
蝕性の基材上に滴下し、急冷、固化、遣粒される．
本発明のシステアミン塩酸塩の遣粒物の粒径は滴下部分
の穴径、滴下温度、溶融液温度、耐蝕性基材の移動速度
によって決まるが、固化等の取り扱いおよび使用時の溶
解性により０．１〜２０ｍｍ、好ましくは直径１〜１５
ｍｍの粒状システアミン塩酸塩である．
本発明において板状滴下型造粒機のシステアミン塩酸塩
と接触する平板状ベルト基材として平滑でしかも耐蝕性
のものが使用される．たとえばステンレス、チタン、ハ
ステロイ等の金属類、テフロン、ポリプロピレン、ポリ
エチレン等の樹脂類、ネオグレン、バイトン等のゴム類
が挙げられる．本発明の板状滴下型造粒機のシステアミ
ン塩酸塩と接触する基材の冷却は一般的には、冷却水を
チラーや冷水塔などで冷却して循環使用する方法が採用
される．
システアミン塩酸塩の吸湿を防止するため板状滴下型造
粒機の滴下部分および冷却部分または全体を除湿された
空気、窒素等の不活性ガス雰囲気にするのが好ましい．
固化時間は特に限定するものではないが通常３０分以内
である．
本発明によって得られるシステアミン塩酸塩は径が０．
１〜２０ｍｍの半球状または半楕円球状の造粒物である
粒状システアミン塩酸塩である．システアミン塩酸塩を
融解し、冷却凝固せしめる方法は、通常常圧下に実施さ
れるが、場合により、減圧または加圧下に行うこともで
きる．｛作 用｝
本発明の溶媒の存在下、硫化水素を圧力６〜１０Ｋｇ／
ｃｍ２Ｇ、温度Ｏ〜１０℃の範囲に保持したところにエ
チレンイミンを連続添加して反応させ、ついで加熱して
硫化水素を分離した後、塩酸を加えて５℃以下に冷却し
て結晶を析出させ、窒素雰囲気下でｒ別、乾燥させなが
ら６８℃以上に加温して溶融し、得られたシステアミン
塩酸塩を温度６５℃以下に冷却された耐蝕性の基材上に
滴下し、冷却、凝固せしめることによって得られるシス
テアミン塩酸塩は高純度の品質ものが得られる．
［実 施 例コ
以下、実施例及び比較例で本発明を更に詳しく説明する
．
［溶解性テスト方法コ
粒状システアミン塩酸塩３０ｇを２００ｃｃ広口のガラ
ス製サンプルビン４本にとり、窒素置換後それぞれ密封
下、３０℃で０日、７日、１４日、３０日経過後開封し
た．
■ 窒素雰囲気下で１００ｍＪビーカー内の３５重量％
塩酸水溶液４０ｍＪに粒状システアミン塩酸塩をＬｏｇ
入れて、スターラーで２００ｒｐｍの回転数で混合して
、２５℃での溶解時間を測定した．
■ 窒素雰囲気下で１００ｍｊビーカー内のエタノール
２５ｍ１に粒状システアミン塩酸塩を８ｇ入れて、スタ
ーラーで２００ｒｐｍの回転数で混合して、２５℃で溶
解時間を測定した．［塊状化テスト方法］
粒状システアミン塩酸塩３０ｇを２００ｃｃ広口のガラ
ス製サンプルビン４本にとり、窒素置換ｆ＆でそれぞれ
密封下３０℃でＯ日、７日、１４日、３０日経過後、ビ
ンを１８０゜回転して上下を逆さにした時の粒子の移動
状態を肉眼で観察した．実施例 １
容量１ｊのオートクレープ中にメタノール２００ｃｃを
仕込み、系内を窒素置換した６この系の温度をＯ〜５℃
の範囲内に調節し、撹拌下に硫化水素１３６ｇ（４モル
）を仕込んだところ、系の圧力は８．６ｋｇ／ｃＪＧと
なった．系の温度を０〜５℃の範囲内に保ち、エチレン
イミン８６ｇ（２モル）をメタノール１００ｍＪに溶解
した溶液を撹拌下に２時間かけて連続添加し、反応させ
た．反応終了後の系の圧力は３．６ｋｇ／ｄＧであった
。The method of melting cysteamine hydrochloride of the present invention is carried out in a corrosion-resistant container or line equipped with a heating device such as a jacket, coil and/or electric heater. Cysteamine hydrochloride has strong hygroscopicity and is susceptible to oxidation at high temperatures, so it is preferable to heat it in a dehumidified inert gas, preferably nitrogen atmosphere. In the present invention, the molten cysteamine hydrochloride is supplied to a plate-like dropping granulator. In the present invention, a plate-like dropping granulator is a general term for equipment that produces granules by dropping a molten liquid onto a cooled substrate, such as a conveyor belt, and cooling and solidifying it. In the present invention, a molten solution of cysteamine hydrochloride heated above its melting point is dropped onto a corrosion-resistant base material cooled to below 65°C in a plate-shaped dropping granulator, and is rapidly cooled, solidified, and pelletized. The particle size of the cysteamine hydrochloride pellets of the present invention is determined by the hole diameter of the dropping part, the dropping temperature, the melt temperature, and the movement speed of the corrosion-resistant substrate, but it also depends on handling such as solidification and solubility during use. .1-20mm, preferably diameter 1-15
mm granular cysteamine hydrochloride. In the present invention, a smooth and corrosion-resistant material is used as the flat belt base material that comes into contact with cysteamine hydrochloride in the plate dropping type granulator. Examples include metals such as stainless steel, titanium, and Hastelloy, resins such as Teflon, polypropylene, and polyethylene, and rubbers such as Neoglen and Viton. To cool the base material that comes into contact with cysteamine hydrochloride in the plate-shaped dropping granulator of the present invention, a method is generally adopted in which cooling water is cooled in a chiller or a cooling tower and then used for circulation. In order to prevent cysteamine hydrochloride from absorbing moisture, it is preferable that the dropping section and cooling section of the plate-like dropping granulator, or the entirety thereof, be in an atmosphere of dehumidified air or an inert gas such as nitrogen. The solidification time is not particularly limited, but is usually within 30 minutes. Cysteamine hydrochloride obtained by the present invention has a diameter of 0.
This is granular cysteamine hydrochloride, which is a hemispherical or semiellipsoidal granule with a size of 1 to 20 mm. The method of melting cysteamine hydrochloride and cooling and solidifying it is usually carried out under normal pressure, but depending on the case, it can also be carried out under reduced pressure or increased pressure. {Function} In the presence of the solvent of the present invention, hydrogen sulfide is heated at a pressure of 6 to 10 kg/
cm2G and temperature maintained in the range of 0 to 10°C, ethyleneimine was continuously added and reacted, then heated to separate hydrogen sulfide, and then hydrochloric acid was added and cooled to below 5°C to precipitate crystals. , heated to 68°C or higher while drying in a nitrogen atmosphere to melt the resulting cysteamine hydrochloride was dropped onto a corrosion-resistant substrate cooled to a temperature of 65°C or lower, cooled, and solidified. High purity cysteamine hydrochloride can be obtained by this process. [Example] The present invention will be explained in more detail with reference to Examples and Comparative Examples below. [Solubility test method] 30 g of granular cysteamine hydrochloride was placed in four 200 cc wide-mouth glass sample bottles, and the bottles were opened after 0 days, 7 days, 14 days, and 30 days had elapsed at 30°C under nitrogen purging and sealed. ■ 35% by weight in a 100mJ beaker under nitrogen atmosphere
Log granular cysteamine hydrochloride in 40 mJ of hydrochloric acid aqueous solution
and mixed with a stirrer at a rotation speed of 200 rpm, and the dissolution time at 25°C was measured. (2) Under a nitrogen atmosphere, 8 g of granular cysteamine hydrochloride was added to 25 ml of ethanol in a 100 mj beaker, mixed with a stirrer at 200 rpm, and the dissolution time was measured at 25°C. [Agglomeration test method] 30 g of granular cysteamine hydrochloride was placed in four 200 cc wide-mouth glass sample bottles, and after 0 days, 7 days, 14 days, and 30 days had elapsed at 30° C. under nitrogen purging, the bottles were heated at 180°. The movement of the particles was observed with the naked eye when it was rotated and turned upside down. Example 1 200 cc of methanol was charged into an autoclave with a capacity of 1 j, and the system was purged with nitrogen. The temperature of the system was 0 to 5°C.
When 136 g (4 mol) of hydrogen sulfide was charged under stirring, the system pressure became 8.6 kg/cJG. The temperature of the system was maintained within the range of 0 to 5°C, and a solution of 86 g (2 mol) of ethyleneimine dissolved in 100 mJ of methanol was continuously added over 2 hours with stirring to cause a reaction. The system pressure after the reaction was completed was 3.6 kg/dG.
得られた反応混合物を窒素シール下にてメタノールが少
量留去されるまで加熱して硫化水素を追い出した６さら
に５℃に冷却して析出した結晶を窒素雰囲気下でろ別、
乾燥させて白色結晶性のシステアミンを得た。The resulting reaction mixture was heated under a nitrogen blanket until a small amount of methanol was distilled off to drive out hydrogen sulfide.6 It was further cooled to 5°C, and the precipitated crystals were filtered out under a nitrogen atmosphere.
After drying, white crystalline cysteamine was obtained.
得られたシステアミンをガラス性セパラグルフラスコに
移し、６００ｍＪのイソプロビルアルコールに溶解した
後、７３ｇの塩化水素ガスを吹き込みシステアミン塩酸
塩溶液を得た．該溶液を５℃に冷却して析出した結晶を
窒素雰囲気下でろ別、乾燥させながら８０℃に加温し、
完全に溶融させた後、口径２ｍｍのパスツールピペット
に吸い取り、水で反対面が冷却されて３０℃に保持され
ているテフロン板上に滴下した．テフロン板上で固化し
たシステアミン塩酸塩の白色固体は直径３−５ｍｍ、高
さ２〜３ｍｍの半球状であった．得られた粒状システア
ミン塩酸塩について、３０℃でＯ〜３０日間保存後、３
５重量％塩酸水溶液とエタノールに対する溶解性テスト
および塊状化テストをした．
溶解性テストの結果を表−１に示す．また塊状化テスト
の結果を表−２に示す．
表
１
比較例 １
容量１．１！のオートクレープ中にメタノール２０ＯＣ
Ｃを仕込み、系内を窒素置換した。この系の温度をＯ〜
５℃の範囲内に調節し、撹拌下に硫化水素１３６ｒ（４
モル〉を仕込んだところ、系の圧力は８．６ｋｒ／ｄＧ
となった．系の温度を０〜５゜Ｃの範囲内に保ち、エチ
レンイミン８６ｇ（’２モル）をメタノール１００ｍＪ
に溶解した溶液を撹拌下に２時間かけて連続添加し、反
応させた．反応終了後の系の圧力は３．６ｋｇ／ａａＧ
であった。The obtained cysteamine was transferred to a glass separaglu flask and dissolved in 600 mJ of isopropyl alcohol, and then 73 g of hydrogen chloride gas was blown into the flask to obtain a cysteamine hydrochloride solution. The solution was cooled to 5°C, the precipitated crystals were filtered off under a nitrogen atmosphere, and heated to 80°C while drying.
After completely melting, it was sucked into a Pasteur pipette with a diameter of 2 mm, and dropped onto a Teflon plate whose opposite side had been cooled with water and maintained at 30°C. The white solid of cysteamine hydrochloride solidified on the Teflon plate was hemispherical with a diameter of 3-5 mm and a height of 2-3 mm. After storing the obtained granular cysteamine hydrochloride at 30°C for 30 days,
Solubility tests and agglomeration tests were conducted in 5% by weight aqueous hydrochloric acid and ethanol. The results of the solubility test are shown in Table 1. Table 2 shows the results of the clumping test. Table 1 Comparative example 1 Capacity 1.1! methanol 20OC in autoclave
C was charged and the system was replaced with nitrogen. The temperature of this system is O~
Adjust the temperature within the range of 5℃ and add 136r (4 liters) of hydrogen sulfide while stirring.
mol>, the system pressure was 8.6 kr/dG.
It became. While maintaining the temperature of the system within the range of 0 to 5°C, 86 g ('2 mol) of ethyleneimine was mixed with 100 mJ of methanol.
A solution dissolved in was added continuously over 2 hours under stirring to cause a reaction. The pressure of the system after the reaction is 3.6 kg/aaG
Met.
得られた反応混合物を窒素シール下にてメタノールが少
量留去されるまで加熟して硫化水素を追い出した．さら
に５℃に冷却して析出した結晶を窒素雰囲気下でろ別、
乾燥させて白色結晶性のシステアミンを得た．
得られたシステアミンをガラス性セパラグルフラスコに
移し、６００ｍＪのイングロビルアルコールに溶解した
後、７３ｇの塩化水素ガスを吹き込みシステアミン塩酸
塩溶液を得た。該溶液を５℃に冷却して析出した結晶を
窒素雰囲気下でろ別、乾燥させて白色結晶性のシステア
ミン塩酸塩を得な。The resulting reaction mixture was heated under a nitrogen blanket until a small amount of methanol was distilled off to drive out hydrogen sulfide. After further cooling to 5°C, the precipitated crystals were filtered out under a nitrogen atmosphere.
After drying, white crystalline cysteamine was obtained. The obtained cysteamine was transferred to a glass separaglu flask and dissolved in 600 mJ of inglobil alcohol, and then 73 g of hydrogen chloride gas was blown into the flask to obtain a cysteamine hydrochloride solution. The solution was cooled to 5° C., and the precipitated crystals were filtered off and dried under a nitrogen atmosphere to obtain white crystalline cysteamine hydrochloride.
得られた白色結晶性の粉末のシステアミン塩酸塩につい
て、窒素置換後、３０℃で０〜３０日間保存後、溶融せ
ずにその状態で３５重量％塩酸水溶液とエタノールに対
する溶解性テストおよび塊状化テストをした。The obtained white crystalline powder of cysteamine hydrochloride was stored at 30°C for 0 to 30 days after purging with nitrogen, and then subjected to a solubility test and a clumping test in a 35% by weight aqueous hydrochloric acid solution and ethanol without melting. Did.
溶解性テストの結果を表−３に示す．また塊状化テスト
の結果を表−４に示す。The results of the solubility test are shown in Table 3. Table 4 shows the results of the clumping test.
表
３
表
４
実施例２
実施例１において固化造粒して得られた直径１０〜１
５ｍｍ、高さ５〜６ｍｍの半球状システアミン塩酸塩の
白色固体を用いる以外は実施例１と同様に行ない、３５
重量％塩酸水溶液に対する溶解性テストおよび塊状化テ
ストをした．溶解性テストの結果を表−５に示す．また
塊状化テストの結果を表−６に示す．
表
６
表−５
［効 果］
表から明らかな通り本発明の粒状システアミン塩酸塩の
製法は従来の粉末システアミン塩酸塩に比較し、貯蔵中
に容器の中で塊状化することがなく、また無Ｒ酸および
有機液体への溶解性に優れた効果を発揮するものである
。Table 3 Table 4 Example 2 Diameter 10 to 1 obtained by solidification and granulation in Example 1
The same procedure as in Example 1 was carried out except that a hemispherical white solid of cysteamine hydrochloride having a size of 5 mm and a height of 5 to 6 mm was used.
A solubility test and a clumping test in a wt% aqueous hydrochloric acid solution were conducted. The results of the solubility test are shown in Table 5. Table 6 shows the results of the clumping test. Table 6 Table-5 [Effects] As is clear from the table, the method for producing granular cysteamine hydrochloride of the present invention does not form lumps in a container during storage, and is free from clumping, compared to conventional powdered cysteamine hydrochloride. It exhibits excellent solubility in R acids and organic liquids.
Claims (1)
システアミンを塩酸と反応させてシステアミン塩酸塩を
生成させ、得られたシステアミン塩酸塩を６８℃以上に
加温して溶融し、溶融システアミン塩酸塩を温度６５℃
以下に冷却された耐蝕性の基材上に滴下し、冷却、凝固
せしめることを特徴とする粒状システアミン塩酸塩の製
法。(1) Hydrogen sulfide and ethyleneimine are reacted, and the resulting cysteamine is reacted with hydrochloric acid to produce cysteamine hydrochloride, and the resulting cysteamine hydrochloride is heated to 68°C or higher to melt it, and the resulting cysteamine hydrochloride is melted. Salt at a temperature of 65℃
A method for producing granular cysteamine hydrochloride, which is characterized by dropping it onto a cooled corrosion-resistant base material and allowing it to cool and solidify.
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23272089A JPH0399053A (en) | 1989-09-11 | 1989-09-11 | Production of granular cysteamine hydrochloride |
| KR1019900010687A KR0154328B1 (en) | 1989-07-14 | 1990-07-13 | Method for production of granular cysteamine hidrochloride |
| IE257290A IE67043B1 (en) | 1989-07-14 | 1990-07-13 | Granular cysteamine hydrochloride and method for production thereof |
| TW079105848A TW198696B (en) | 1989-07-14 | 1990-07-14 | |
| CN90107077A CN1031997C (en) | 1989-07-14 | 1990-07-14 | Granular cysteamine hydrochloride and method for production thereof |
| EP90307742A EP0408398B1 (en) | 1989-07-14 | 1990-07-16 | Granular cysteamine hydrochloride and method for production thereof |
| DE69018327T DE69018327D1 (en) | 1989-07-14 | 1990-07-16 | Granulated cysteamine hydrochloride and process for its preparation. |
| ES90307742T ES2070280T3 (en) | 1989-07-14 | 1990-07-16 | GRANULAR CISTEAMINE CHLORIDE AND METHOD FOR ITS PRODUCTION. |
| US07/703,744 US5256362A (en) | 1989-07-14 | 1991-05-21 | Method for production of granular cysteamine hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP23272089A JPH0399053A (en) | 1989-09-11 | 1989-09-11 | Production of granular cysteamine hydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0399053A true JPH0399053A (en) | 1991-04-24 |
Family
ID=16943731
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP23272089A Pending JPH0399053A (en) | 1989-07-14 | 1989-09-11 | Production of granular cysteamine hydrochloride |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0399053A (en) |
-
1989
- 1989-09-11 JP JP23272089A patent/JPH0399053A/en active Pending
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