JPS627191B2 - - Google Patents
Info
- Publication number
- JPS627191B2 JPS627191B2 JP24087683A JP24087683A JPS627191B2 JP S627191 B2 JPS627191 B2 JP S627191B2 JP 24087683 A JP24087683 A JP 24087683A JP 24087683 A JP24087683 A JP 24087683A JP S627191 B2 JPS627191 B2 JP S627191B2
- Authority
- JP
- Japan
- Prior art keywords
- melting point
- thiamine disulfide
- higher fatty
- fatty acids
- crystals
- 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.)
- Expired
Links
- 238000002844 melting Methods 0.000 claims description 38
- GFEGEDUIIYDMOX-BMJUYKDLSA-N n-[(4-amino-2-methylpyrimidin-5-yl)methyl]-n-[(z)-3-[[(z)-2-[(4-amino-2-methylpyrimidin-5-yl)methyl-formylamino]-5-hydroxypent-2-en-3-yl]disulfanyl]-5-hydroxypent-2-en-2-yl]formamide Chemical compound C=1N=C(C)N=C(N)C=1CN(C=O)C(\C)=C(CCO)/SSC(/CCO)=C(/C)N(C=O)CC1=CN=C(C)N=C1N GFEGEDUIIYDMOX-BMJUYKDLSA-N 0.000 claims description 34
- 230000008018 melting Effects 0.000 claims description 32
- 229960001385 thiamine disulfide Drugs 0.000 claims description 32
- 239000013078 crystal Substances 0.000 claims description 24
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 22
- 239000000194 fatty acid Substances 0.000 claims description 22
- 229930195729 fatty acid Natural products 0.000 claims description 22
- 150000004665 fatty acids Chemical class 0.000 claims description 22
- 239000002904 solvent Substances 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- 239000000155 melt Substances 0.000 claims description 2
- 239000000047 product Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 4
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 2
- 235000021314 Palmitic acid Nutrition 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 238000005187 foaming Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000007711 solidification Methods 0.000 description 2
- 230000008023 solidification Effects 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 150000003544 thiamines Chemical class 0.000 description 2
- -1 For example Substances 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000013081 microcrystal Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は特に微細結晶として得られる高融点型
チアミンジスルフイドの新規な製造法に関する。
チアミンジスルフイドはチアミン誘導体の１つ
として、その効力が評価されるものであるが、他
のチアミン誘導体及び塩類と同様に結晶多形の存
在することが知られており、溶融点領域が120〜
130℃の低融点型結晶及び170〜180℃の高融点型
結晶の２種が報告されている。しかしこれらの結
晶はいずれも溶融点で発泡分解を伴う場合が多い
ので、その測定値には多少の変動がみられる。こ
の低融点型結晶と高融点型結晶はビタミンB1効
力に差が認められないが、吸湿性が著しく相違す
る。すなわち低融点型結晶は吸湿しやすく、また
吸湿したものを脱水することはきわめて困難であ
るのに対し、高融点型結晶は比較的吸湿しないと
いう利点を有する。このため高融点型結晶を無水
物、低融点型結晶を含水物と呼ぶこともある。
ビタミンB1製剤の原料としては、吸湿性の低
い高融点型の微細結晶が、保存性や取扱い操作な
どの点で有利である。しかし市販のビタミンB1
製剤に用いられるチアミンジスルフイドは、一般
に低融点型結晶である。これは低融点型のチアミ
ンジスルフイドの方が製造が容易なためである。
低融点型結晶を高融点型結晶に変換する公知の方
法は、溶媒処理などの操作が繁雑であり、また技
術的にも熟練を要し、工業的利用が困難である。
本発明者らは、このような観点から高融点型チア
ミンジスルフイドの簡易な製造法を求めて研究し
た結果、本発明を完成した。
本発明は、低融点型チアミンジスルフイド１重
量部を、３重量部以上の炭素数10〜18の高級脂肪
酸の溶融物に溶解し、冷却固化させたのち、この
固化物をチアミンジスルフイドを溶解せず高級脂
肪酸を溶解する溶媒で処理して高級脂肪酸を除去
することを特徴とする、高融点型チアミンジスル
フイド結晶の製造法である。
本発明に用いられる低融点型チアミンジスルフ
イドとしては、一般市販の医薬品規格の製品が用
いられる。これらの製品は通常は６〜10％程度の
水分を含有しているが、本発明にそのまま用いる
ことができる。
炭素数10〜18の高級脂肪酸としては、例えばス
テアリン酸、パルミチン酸、ミリスチン酸、ラウ
リン酸、カプリン酸などが用いられる。これらの
高級脂肪酸は容易に入手することができ、室温で
固体状であるうえ、融点が比較的低いので実用的
である。炭素数19以上の高級脂肪酸は入手が困難
であり、また融点が高く、溶融するために高温に
加熱することが必要で経済的に不利である。また
炭素数９以下の高級脂肪酸は室温で液状のものが
多く、冷却固化させるための装置が必要となるの
で不適当である。なお室温で液状の高級脂肪酸に
チアミンジスルフイドを溶解したのち、これを固
化せずに有機溶媒で処理してもチアミンジスルフ
イドはあめ状に析出し、結晶として得ることがで
きない。
本発明を実施するに際しては、前記の高級脂肪
酸を溶融し、これに低融点型チアミンジスルフイ
ドを溶解する。
高級脂肪酸の使用量は、低融点型チアミンジス
ルフイド１重量部に対し３重量部以上好ましくは
５重量部までである。高級脂肪酸の量がこれより
少ないとチアミンジスルフイドを完全に溶解する
ことが困難であり、また５重量部より多くしても
格別な効果が得られず、経済的に不利となる。高
級脂肪酸の溶融法としては水浴、蒸気浴等による
方法が用いられる。
次いでチアミンジスルフイドの溶解物を冷却固
化させる。この場合、室温に放置してもよく、ま
た冷却装置などを用いた急激に冷却してもよい。
この段階でチアミンジスルフイドはすでに低融点
型から高融点型に変化していると考えられる。こ
うして得られた固化物を、チアミンジスルフイド
を溶解せず高級脂肪酸を溶解する溶媒で処理す
る。
このための溶媒としては、極性の小さい溶媒、
例えば石油ベンジン、ヘキサン、シクロヘキサ
ン、イソオクタンなどが好ましい。処理方法とし
ては例えば固化物に溶媒を加えて高級脂肪酸を溶
解する方法が用いられる。高級脂肪酸の溶解を促
進するため、固化物を粉砕して溶媒を加え、加熱
還流してもよい。減圧も用いられる。
固化物を溶媒で処理することにより、高級脂肪
酸が溶解し、チアミンジスルフイドはほぼ定量的
に残留する。残留するチアミンジスルフイドは
過、遠心分離などの方法により高級脂肪酸と分離
することができる。高級脂肪酸と溶媒の混合物
は、蒸留により分別して再使用することもでき
る。
残留物を常法により乾燥すると、白色の結晶性
粉末が得られる。この結晶性粉末は融点174〜179
℃を示し、高融点型チアミンジスルフイドである
ことが確認できる。この結晶性粉末は、顕微鏡下
の観察では透明な板状の結晶であることが認めら
れる。この結晶の長径は10μ以下で、きわめて微
細であるので、製剤原料として用いる際に粉砕の
必要がなく、また生体内の吸収の面でも優れてい
る。
本発明は、高融点型のチアミンジスルフイドを
特に微細な結晶として製造しうる点で工業上きわ
めて有利である。
実施例 １
ステアリン酸20ｇをマイヤーコルベンに入れ、
水浴上で加熱して溶融させる。これに市販のチア
ミンジスルフイド〔融点135〜136℃（発泡分
解）、水分5.3％〕５ｇを加え、加熱しながら振り
混ぜ溶解させる。チアミンジスルフイドが完全に
溶解したのち加熱をやめ、内容物が固化するまで
室温に放置する。固化終了後、これに石油ベンジ
ン500mlを加え、再び水浴上で加熱撹拌しながら
高級脂肪酸を溶解し、温時過する。残留物を加
温した石油ベンジン各50mlで２回洗浄したのち
過し得られた結晶をデシケーター中で減圧下に乾
燥し、白色結晶性粉末4.5ｇを得る。使用したチ
アミンジスルフイドに対して収率90％、水分を補
正すると収率95％となる。この結晶の融点は176
〜178℃（発泡分解）、大きさは長径10μ以下であ
る。
元素分析値：C24H34O4N8S2として
Ｃ Ｈ Ｎ Ｓ
計算値 51.23 6.09 19.91 11.39
実験値 51.28 6.02 19.88 11.27
実施例 ２
パルミチン酸30ｇをビーカーにとり、水浴上で
加熱して溶融させる。これに市販のチアミンジス
ルフイド〔融点135〜136℃（発泡分解）、水分5.3
％〕7.5ｇを加え、加熱撹拌しながら溶解させ
る。チアミンジスルフイドを完全に溶解したのち
加熱をやめ、室温で固化させる。固化終了後、固
化物を砕き、その2.5ｇずつを別のビーカーに移
し、それぞれに石油ベンジン、シクロヘキサン、
ヘキサン又はイソオクタン各200mlを加え、とき
どき静かにかき混ぜ、室温で２時間放置する。２
時間経過後、上清を除き、残留物にそれぞれの溶
媒100mlずつを加え、ときどき静かにかき混ぜ、
室温で30分間放置する。30分経過後、再び上清を
除き、この操作を２回くり返す。残留物を別々に
取し、それぞれの溶媒少量ずつで洗浄し、デシ
ケーター中で減圧下に乾燥する。いずれも白色の
結晶性粉末が得られる。収量、融点及び結晶の長
径を測定した結果は第１表のとおりである。
The present invention particularly relates to a novel method for producing high melting point thiamine disulfide obtained as fine crystals. Thiamine disulfide is one of the thiamine derivatives and is evaluated for its efficacy, but like other thiamine derivatives and salts, it is known that crystal polymorphism exists, and the melting point range is 120 ~
Two types of crystals have been reported: a low melting point crystal at 130°C and a high melting point crystal at 170-180°C. However, since all of these crystals are often accompanied by foaming and decomposition at the melting point, some fluctuations can be seen in the measured values. Although there is no difference in vitamin B 1 efficacy between the low-melting point crystal and the high-melting point crystal, there is a marked difference in hygroscopicity. In other words, low-melting point crystals easily absorb moisture and it is extremely difficult to dehydrate what has absorbed moisture, whereas high-melting point crystals have the advantage of relatively not absorbing moisture. For this reason, high melting point crystals are sometimes called anhydrous, and low melting point crystals are sometimes called hydrated. As a raw material for vitamin B 1 preparations, high melting point type microcrystals with low hygroscopicity are advantageous in terms of storage stability and handling operations. However, commercially available vitamin B 1
Thiamine disulfide used in formulations is generally a low melting point crystal. This is because low melting point thiamine disulfide is easier to manufacture.
Known methods for converting low-melting point crystals into high-melting point crystals require complicated operations such as solvent treatment, and require technical skill, making industrial use difficult.
From this viewpoint, the present inventors conducted research to find a simple method for producing high-melting-point thiamine disulfide, and as a result, completed the present invention. In the present invention, 1 part by weight of low melting point thiamine disulfide is dissolved in a melt of 3 parts by weight or more of higher fatty acids having a carbon number of 10 to 18, and after cooling and solidifying, this solidified product is converted into thiamine disulfide. This is a method for producing high-melting-point thiamine disulfide crystals, which is characterized by removing higher fatty acids by treating them with a solvent that dissolves higher fatty acids without dissolving them. As the low melting point type thiamine disulfide used in the present invention, a commercially available product of pharmaceutical standard is used. Although these products usually contain about 6 to 10% water, they can be used in the present invention as they are. Examples of higher fatty acids having 10 to 18 carbon atoms include stearic acid, palmitic acid, myristic acid, lauric acid, and capric acid. These higher fatty acids are easily available, solid at room temperature, and have a relatively low melting point, making them practical. Higher fatty acids having 19 or more carbon atoms are difficult to obtain and have a high melting point, requiring heating to high temperatures to melt them, which is economically disadvantageous. Further, higher fatty acids having carbon atoms of 9 or less are often liquid at room temperature and require equipment for cooling and solidifying, making them unsuitable. Note that even if thiamine disulfide is dissolved in a liquid higher fatty acid at room temperature and then treated with an organic solvent without solidifying it, thiamine disulfide precipitates in a candy-like shape and cannot be obtained as crystals. In carrying out the present invention, the above-described higher fatty acid is melted, and low melting point thiamine disulfide is dissolved therein. The amount of higher fatty acid used is 3 parts by weight or more, preferably up to 5 parts by weight, per 1 part by weight of low melting point thiamine disulfide. If the amount of higher fatty acid is less than this, it will be difficult to completely dissolve thiamine disulfide, and if it is more than 5 parts by weight, no particular effect will be obtained and this will be economically disadvantageous. As a method for melting higher fatty acids, a method using a water bath, a steam bath, etc. is used. Next, the thiamin disulfide solution is cooled and solidified. In this case, it may be left at room temperature, or it may be rapidly cooled using a cooling device or the like.
It is considered that at this stage, thiamine disulfide has already changed from a low melting point type to a high melting point type. The solidified product thus obtained is treated with a solvent that does not dissolve thiamine disulfide but dissolves higher fatty acids. Solvents for this include less polar solvents,
For example, petroleum benzene, hexane, cyclohexane, isooctane, etc. are preferred. As a treatment method, for example, a method is used in which a solvent is added to the solidified product to dissolve higher fatty acids. In order to promote dissolution of higher fatty acids, the solidified product may be crushed, a solvent may be added, and the mixture may be heated under reflux. Vacuum pressure may also be used. By treating the solidified product with a solvent, higher fatty acids are dissolved, and thiamine disulfide remains almost quantitatively. The remaining thiamine disulfide can be separated from higher fatty acids by methods such as filtration and centrifugation. The mixture of higher fatty acid and solvent can also be fractionated by distillation and reused. The residue is dried in a conventional manner to give a white crystalline powder. This crystalline powder has a melting point of 174-179
℃, confirming that it is a high melting point type thiamine disulfide. This crystalline powder is found to be transparent plate-like crystals when observed under a microscope. The long axis of these crystals is 10μ or less, which is extremely fine, so there is no need to grind them when used as a raw material for pharmaceutical preparations, and they are also excellent in terms of in vivo absorption. The present invention is industrially extremely advantageous in that high melting point thiamine disulfide can be produced in the form of particularly fine crystals. Example 1 Put 20g of stearic acid into Mayer Kolben,
Heat on a water bath to melt. To this was added 5 g of commercially available thiamine disulfide [melting point 135-136°C (foam decomposition), moisture 5.3%], and stirred while heating to dissolve. After the thiamine disulfide is completely dissolved, heating is stopped and the contents are left at room temperature until solidified. After solidification, add 500 ml of petroleum benzine, heat and stir on a water bath again to dissolve the higher fatty acids, and leave to warm. The residue was washed twice with 50 ml of warm petroleum benzine each time, and the crystals obtained were dried in a desiccator under reduced pressure to obtain 4.5 g of white crystalline powder. The yield is 90% based on the thiamine disulfide used, and the yield is 95% when corrected for moisture. The melting point of this crystal is 176
~178℃ (foaming decomposition), size is 10μ or less in major axis. Elemental analysis value: C 24 H 34 O 4 N 8 S 2 Calculated value 51.23 6.09 19.91 11.39 Experimental value 51.28 6.02 19.88 11.27 Example 2 30 g of palmitic acid is placed in a beaker and heated on a water bath to melt it. This was combined with commercially available thiamine disulfide [melting point 135-136°C (foam decomposition), water content 5.3].
%] Add 7.5g and dissolve while heating and stirring. After completely dissolving thiamine disulfide, stop heating and allow it to solidify at room temperature. After solidification, crush the solidified material, transfer 2.5g each to another beaker, and add petroleum benzine, cyclohexane,
Add 200 ml each of hexane or isooctane, stir gently from time to time, and leave at room temperature for 2 hours. 2
After a period of time, remove the supernatant, add 100 ml of each solvent to the residue, stir gently from time to time,
Leave at room temperature for 30 minutes. After 30 minutes, remove the supernatant again and repeat this operation twice. The residues are taken separately, washed with small portions of each solvent and dried under reduced pressure in a desiccator. In both cases, white crystalline powder is obtained. The results of measuring the yield, melting point, and major axis of the crystals are shown in Table 1.
【表】
本発明で得られた高融点型チアミンジスルフイ
ド（）と市販の低融点型チアミンジスルフイド
（）との吸湿性の比較を行つた。すなわち、チ
アミンジスルフイド及びを40℃で相対湿度70
％、80％、90％及び100％の条件下に放置し、そ
の重量増加から吸湿量を比較した。その結果を第
２〜５表に示す。本発明の高融点型チアミンジス
ルフイドは吸湿量も少なく、低融点型のものに比
べ臨界湿度も高い。[Table] The hygroscopic properties of the high melting point thiamine disulfide () obtained in the present invention and the commercially available low melting point thiamine disulfide (2) were compared. i.e. thiamine disulfide and 40°C with relative humidity of 70°C.
%, 80%, 90% and 100%, and the amount of moisture absorbed was compared based on the weight increase. The results are shown in Tables 2-5. The high melting point type thiamine disulfide of the present invention has a small amount of moisture absorption and has a higher critical humidity than the low melting point type.
【表】【table】
【表】【table】
【表】【table】
Claims (1)
３重量部以上の炭素数10〜18の高級脂肪酸の溶融
物に溶解し、冷却固化させたのち、この固化物を
チアミンジスルフイドを溶解せず高級脂肪酸を溶
解する溶媒で処理して高級脂肪酸を除去すること
を特徴とする、高融点型チアミンジスルフイド結
晶の製造法。1 1 part by weight of low melting point thiamine disulfide,
After dissolving in a melt of 3 parts by weight or more of higher fatty acids having 10 to 18 carbon atoms and solidifying by cooling, this solidified product is treated with a solvent that does not dissolve thiamine disulfide but dissolves higher fatty acids to obtain higher fatty acids. A method for producing high melting point thiamine disulfide crystals, characterized by removing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24087683A JPS60132965A (en) | 1983-12-22 | 1983-12-22 | Production of high-melting point thiamine disulfide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24087683A JPS60132965A (en) | 1983-12-22 | 1983-12-22 | Production of high-melting point thiamine disulfide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60132965A JPS60132965A (en) | 1985-07-16 |
| JPS627191B2 true JPS627191B2 (en) | 1987-02-16 |
Family
ID=17066007
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP24087683A Granted JPS60132965A (en) | 1983-12-22 | 1983-12-22 | Production of high-melting point thiamine disulfide |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60132965A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63145290U (en) * | 1987-03-16 | 1988-09-26 |
-
1983
- 1983-12-22 JP JP24087683A patent/JPS60132965A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63145290U (en) * | 1987-03-16 | 1988-09-26 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60132965A (en) | 1985-07-16 |
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