JPS6281365A - Guanidinoethanethiosulfonic acid, production thereof and cholesterol-lowering agent containing said derivative - Google Patents
Guanidinoethanethiosulfonic acid, production thereof and cholesterol-lowering agent containing said derivativeInfo
- Publication number
- JPS6281365A JPS6281365A JP21800985A JP21800985A JPS6281365A JP S6281365 A JPS6281365 A JP S6281365A JP 21800985 A JP21800985 A JP 21800985A JP 21800985 A JP21800985 A JP 21800985A JP S6281365 A JPS6281365 A JP S6281365A
- Authority
- JP
- Japan
- Prior art keywords
- guanidinoethanethiosulfonic
- cholesterol
- acid
- formula
- sulfur
- 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
- AAYSZAORPMDHDI-UHFFFAOYSA-N 2-(1-hydroxysulfonothioylethyl)guanidine Chemical compound OS(=S)(=O)C(C)N=C(N)N AAYSZAORPMDHDI-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 229940127226 anticholesterol agent Drugs 0.000 title claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 239000003529 anticholesteremic agent Substances 0.000 title claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 9
- 239000011593 sulfur Substances 0.000 claims abstract description 9
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 3
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 abstract description 25
- 150000001875 compounds Chemical class 0.000 abstract description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 13
- 235000012000 cholesterol Nutrition 0.000 abstract description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 6
- -1 lower alcohol Chemical compound 0.000 abstract description 3
- 239000002253 acid Substances 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 abstract description 2
- 102000015779 HDL Lipoproteins Human genes 0.000 abstract 2
- 108010010234 HDL Lipoproteins Proteins 0.000 abstract 2
- 239000000463 material Substances 0.000 abstract 1
- 235000019441 ethanol Nutrition 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- JKLRIMRKZBSSED-UHFFFAOYSA-N taurocyamine Chemical compound NC(=[NH2+])NCCS([O-])(=O)=O JKLRIMRKZBSSED-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000001766 physiological effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003518 caustics Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- VVIUBCNYACGLLV-UHFFFAOYSA-N hypotaurine Chemical compound [NH3+]CCS([O-])=O VVIUBCNYACGLLV-UHFFFAOYSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 235000021590 normal diet Nutrition 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- HSARCAKRDFJMNW-UHFFFAOYSA-N 1-aminoethanesulfonic acid;2-aminoethanesulfonic acid Chemical compound CC(N)S(O)(=O)=O.NCCS(O)(=O)=O HSARCAKRDFJMNW-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 108010023302 HDL Cholesterol Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000001166 anti-perspirative effect Effects 0.000 description 1
- 239000003213 antiperspirant Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- KYRKWKDNGQIWHP-UHFFFAOYSA-N hypotaurocyamine Chemical compound NC(=[NH2+])NCCS([O-])=O KYRKWKDNGQIWHP-UHFFFAOYSA-N 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- 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）
本発明は、新規な化合物であるグアニジノエタンチオス
ルホン酸（チオタウロシアミン）、その製法、及びそれ
を含有するコレステロール低下剤に関するものであって
、精密化学、医薬、動物医薬の各技術分野で重要な働き
をするものである。Detailed Description of the Invention (Field of Industrial Application) The present invention relates to a novel compound, guanidinoethanethiosulfonic acid (thiotaurocyamin), a method for producing the same, and a cholesterol-lowering agent containing the same. It plays an important role in the technical fields of fine chemistry, medicine, and veterinary medicine.
（従来の技術）
アミノエタンスルホン酸（タウリン）
Ｈ２ＮＣＨ２ＣＨ２Ｓ Ｏ３Ｈ
が胆汁分泌促進作用、制汗作用といった有用な生理活性
を有することは既知である。本発明者等は、この点に着
目して、アミノ基又はグアニジノ基とスルホン酸又はス
ルフィン酸とを併有する化合物、例えばアミノエタンス
ルフィン酸（ヒポタウリン）、グアニジノエタンスルホ
ン酸（タウロシアミン）、グアニジノエタンスルフィン
酸（ヒポタウロシアミン）について、その生理活性の検
討中に、これらの化合物が脂肪の代謝に関連があること
をつきとめ、脂質低下活性といった生理活性のすぐれた
化合物をデザインして各種の化合物を合成し、生理活性
の強力なものを更に選択して本発明を完成した。(Prior Art) It is known that aminoethanesulfonic acid (taurine) H2NCH2CH2S O3H has useful physiological activities such as bile secretion promoting action and antiperspirant action. Focusing on this point, the present inventors developed compounds having both an amino group or a guanidino group and a sulfonic acid or a sulfinic acid, such as aminoethanesulfinic acid (hypotaurine), guanidinoethanesulfonic acid (taurocyamine), and guanidinoethanesulfin. While investigating the physiological activity of acid (hypotaucyamin), we discovered that these compounds are related to fat metabolism, and designed compounds with excellent physiological activity such as lipid-lowering activity, and developed various compounds. The present invention was completed by synthesizing and selecting those with strong physiological activity.
本発明に係る化合物、つまり（１）式で示される化合物
は、文献に記載されたことのない新規なものであるし、
この化合物がコレステロールを低下させる医薬として使
用できることも全く知られておらず、新規な技術である
。The compound according to the present invention, that is, the compound represented by formula (1), is a novel compound that has not been described in the literature,
It is also completely unknown that this compound can be used as a medicine for lowering cholesterol, which is a new technology.
本発明に係る（１）式で示される化合物は文献未記載の
新規化合物であって、後記する実施例に示す元素分析、
ＩＲ吸収スペクトル、”ＩＩ−ＮＭＲ等の結果から、そ
の構造を次のように同定したものである。The compound represented by formula (1) according to the present invention is a new compound that has not been described in any literature, and the elemental analysis shown in the examples below,
The structure was identified as follows from the results of IR absorption spectrum, II-NMR, etc.
（１）式で示されるグアニジノエタンチオスルホン酸は
、ヒポタウロシアミン（グアニジノエタンスルフィン酸
）を塩基の存在下で硫黄と反応させて製造する。塩基と
しては、苛性ソーダ、苛性カリといった苛性アルカリを
使用する。硫黄としては粉末硫黄を使用するのが好適で
ある６溶媒は。Guanidinoethanethiosulfonic acid represented by formula (1) is produced by reacting hypotaurocyamine (guanidinoethanesulfinic acid) with sulfur in the presence of a base. As the base, a caustic alkali such as caustic soda or caustic potash is used. 6 It is preferable to use powdered sulfur as the sulfur solvent.
水ないしは苛性アルカリ水溶液でもよいが、アルコール
を使用するのが良く、中でも特にメチルアルコール、エ
チルアルコール、イソプロピルアルコールといった低級
アルコールが好適である。Although water or an aqueous caustic alkali solution may be used, alcohol is preferably used, and lower alcohols such as methyl alcohol, ethyl alcohol, and isopropyl alcohol are especially preferred.
本発明化合物は、下記する試験例からも明らかなように
、強力なコレステロール低下作用及び強力なＨＤＬ−コ
レステロール上昇作用を有する。The compound of the present invention has a strong cholesterol-lowering effect and a strong HDL-cholesterol-raising effect, as is clear from the test examples below.
試験例
ウィスター系雄性ラット（体重約ｔｏｏｇ）を１群５匹
とし、正常食群、コレステロール食対照群、コレステロ
ール食＋タウロシアミン投与群、コレステロール食＋チ
オタウロシアミン投与群の４群に分けた。正常食群には
日本タレア社製ＣＥ−２を他の３群にはＣＥ−２に１％
コレステロール、０．２％コール酸ナトリウムを含有し
た食餌を２週間自由摂取させた。タウロシアミン、チオ
タウロシアミンは２００ｍｇ／ｋｇの投与量で１日１回
コレステロール食負荷と同時に投与を開始し２週間連続
強制経口投与を続けた。Test Example Wistar male rats (weighing approximately 200 g) were divided into 4 groups: a normal diet group, a cholesterol diet control group, a cholesterol diet + taurocyamine administration group, and a cholesterol diet + thiotaurcyamine administration group. The normal diet group received CE-2 manufactured by Nippon Talea, and the other three groups received 1% CE-2.
The mice were given free access to a diet containing cholesterol and 0.2% sodium cholate for 2 weeks. Administration of taurocyanine and thiotaurocyanine at a dose of 200 mg/kg was started once a day at the same time as cholesterol food loading, and continuous forced oral administration was continued for 2 weeks.
その結果を下表に示す。The results are shown in the table below.
表に示すように、コレステロール食の２週間負荷により
血清総コレステロールは約５倍に上昇し、この上昇をチ
オタウロシアミンは対照群の５４．５％まで有意に低下
させ、タウロシアミンに比較しても作用は強力であった
。一方ＨＤＬ−コレステロールはコレステロール負荷に
より低下し、両薬物群で改善していた。従ってＨＤＬ−
コレステロール／総コレステロール（％）はチオタウロ
シアミンのみ顕著な改善を示していた。又血清コレステ
ロールの上昇はβ−リボ蛋白−コレスチロールの顕著な
増加によることが判明し、これに対してもチオタウロシ
アミンが対照群の５１％迄有意な低下を示しタウロシア
ミンに比較しても作用が強いことが判明した。 このよ
うに、本発明化合物は１強力なコレステロール低下作用
及びＩ（ＯＬ−コレステロール上昇作用を有するのみで
なく、タウリン等天然の生物体中に存在する化合物と構
造的にも類似していて、そのＬＤ５ｏは３０００ｍｇ／
ｋｇ （ラット）以上であって、毒性が極めて低いとい
うよりはむしろ毒性がないといっても過言ではないくら
い安全なものである。As shown in the table, serum total cholesterol increased approximately 5 times after 2 weeks of cholesterol food loading, and thiotaurocyamine significantly reduced this increase to 54.5% of the control group, compared to taucyamin. The effect was also strong. On the other hand, HDL-cholesterol decreased with cholesterol loading and improved in both drug groups. Therefore, HDL-
Regarding cholesterol/total cholesterol (%), only thiotaurocyamine showed a significant improvement. It was also found that the increase in serum cholesterol was due to a marked increase in β-riboprotein-cholestyol, and in contrast, thiotaurocyamine showed a significant decrease of 51% compared to the control group. It turned out to be very effective. As described above, the compound of the present invention not only has a strong cholesterol-lowering effect and an I(OL-cholesterol-raising effect), but also is structurally similar to compounds existing in natural organisms, such as taurine. LD5o is 3000mg/
kg (rat) or more, and it is so safe that it would not be an exaggeration to say that it has no toxicity, rather than extremely low toxicity.
したがって、抗コレステロール剤、抗動脈硬化剤として
人間ないし動物の治療ないし予防のために、安全且つ有
効に本発明化合物は使用できるものである。 ゛
本発明に係る有効成分化合物は、静脈内注射。Therefore, the compounds of the present invention can be used safely and effectively as anticholesterol agents and antiarteriosclerotic agents for the treatment or prevention of humans and animals.゛The active ingredient compound according to the present invention can be administered intravenously.
経口投与等の方法で投与することができる。成人に投与
する場合、その投与量は、投与経路、投与回数によって
も相違するが、１日１００〜５０００ｍｇとするのが好
適である。It can be administered by methods such as oral administration. When administered to adults, the dose is preferably 100 to 5000 mg per day, although it varies depending on the route of administration and the number of administrations.
経口投与する場合には、常法にしたがい、賦形剤、崩壊
剤、甘味料、着色料等を用いて錠剤、カプセル剤、液剤
その他の剤型に製剤化する。また、注射剤といった非経
口投与の場合には、単位用アンプルあるいは添加防腐剤
と共に多投与容器中に製剤化する。注射剤は、常法にし
たがって懸濁化剤、安定化剤、分散剤等と共に懸濁液、
溶液、油性又は水性ビヒクル中の乳液等に製剤化する。For oral administration, the drug is formulated into tablets, capsules, liquids, and other dosage forms using excipients, disintegrants, sweeteners, colorants, etc. in accordance with conventional methods. In the case of parenteral administration such as injections, it is formulated into unit ampoules or multi-dose containers with added preservatives. Injectables are prepared as suspensions, stabilizers, dispersants, etc. according to conventional methods.
Formulated as solutions, emulsions in oily or aqueous vehicles, and the like.
次に本発明に係る化合物の製造方法を例示する。Next, a method for producing the compound according to the present invention will be illustrated.
実施例１
０．２規定水酸化ナトリウム水溶液にヒポタウロシアミ
ン０．１８モルを完全に溶解し、さらにエチルアルコー
ル１．８００ｍ１、硫黄６．３ｇを加えたものを還流下
で攪拌しながら、硫黄が完全に溶解するまで、約５時間
加熱した。この反応液を一晩室温に放置し、析出した結
晶を濾過した。この粗結晶を二硫化炭素４５ｍ１で２回
、エチルアルコール適量にて洗浄した。これを熱水１８
０ｍ１にて完全に溶解し、エチルアルコール２７００ｍ
１を徐々に加えて、結晶を晶出させ、冷蔵庫で一晩冷却
し、濾過後エーテルにて洗浄した。Example 1 0.18 mol of hypotaurocyamine was completely dissolved in a 0.2N aqueous sodium hydroxide solution, and 1.800 ml of ethyl alcohol and 6.3 g of sulfur were added thereto, and the mixture was stirred under reflux to dissolve sulfur. The mixture was heated for approximately 5 hours until completely dissolved. This reaction solution was left at room temperature overnight, and the precipitated crystals were filtered. The crude crystals were washed twice with 45 ml of carbon disulfide and an appropriate amount of ethyl alcohol. Add this to hot water 18
Completely dissolve in 0 ml of ethyl alcohol and 2700 ml of ethyl alcohol.
1 was gradually added thereto to precipitate crystals, which were cooled in a refrigerator overnight, filtered, and washed with ether.
その結果、得られた製品は下記構造式
のグアニジノエタンチオスルボン酸で、収量は２６．４
ｇ（収率８０．１％）であった。また、この製品の融点
は、２０６〜２１０°Ｃ（分解）であり、元素分析値は
測定値Ｈ： ４．７８％、Ｃ： １９．５４％、 Ｎ
： ２２．８１％（理論値ＩＩ ： ４．９５％、Ｃ：
１９．６６％、Ｎ ： ２２．９３％）であった。As a result, the product obtained was guanidinoethanethiosulfonic acid with the following structural formula, and the yield was 26.4
g (yield 80.1%). In addition, the melting point of this product is 206-210°C (decomposed), and the elemental analysis values are measured H: 4.78%, C: 19.54%, N
: 22.81% (theoretical value II: 4.95%, C:
19.66%, N: 22.93%).
ＩＲｖＫＢｒｃｎ＋−’ ； ３４００．３３００．
３２００ （以上＝ＮＨ及ａｘ
び−Ｎｌ２）
１６７０、１６４０．１６２０ （以上−Ｃ＝Ｎ）ＩＩ
−ＮＭＲδＭｅ４”ｐｐｍ； ３．４〜３．９ （多
重線、２個の２Ｏ
−ＣＯＸ−）
次に１本発明に係る製剤の製造方法を例示する。IRvKBrcn+-'; 3400.3300.
3200 (or more = NH and -Nl2) 1670, 1640.1620 (or more -C=N) II
-NMRδMe4''ppm; 3.4 to 3.9 (multiplet, 2 2O -COX-) Next, a method for producing a preparation according to the present invention will be illustrated.
実施例２
チオタウロシアミン ２００ｇ乳糖
ｌｏｎｇ
トウモロコシ澱粉 ａｏｇ結晶セルロ
ース １００ｇポリビニルピロリドン
１５ｇステアリン酸マグネシウム
５ｇ００ｇ
常法に従って上記各成分を混和し、顆粒状とし圧縮成形
して１錠５００ｍｇの錠剤１０００錠を調製する。Example 2 Thiotaurocyamine 200g lactose
long corn starch aog crystalline cellulose 100g polyvinylpyrrolidone 15g magnesium stearate
5g00g The above ingredients are mixed according to a conventional method, granulated and compressed to prepare 1000 tablets each weighing 500 mg.
実施例３
チオタウロシアミン ２００ｇ乳糖
１５０ｇ
トウモロコシ澱粉 １００ｇ結晶セルロ
ース ４０ｇ軽質無水ケイ酸
５ｇステアリン酸マグネシウム
電００ｇ
常法に従って、上記各成分を混和し、顆粒状としたもの
をカプセル１０００個に充てんし、１個５００ｍｇのカ
プセル剤を調製する。Example 3 Thiotaurocyamine 200g lactose
150g corn starch 100g crystalline cellulose 40g light silicic anhydride
5g magnesium stearate
Electron 00g According to a conventional method, the above ingredients are mixed and granulated and filled into 1000 capsules to prepare capsules each weighing 500 mg.
Claims (3)
で硫黄と反応せしめることを特徴とする次の〔 I 〕式 ▲数式、化学式、表等があります▼〔 I 〕 で表わされるグアニジノエタンチオスルホン酸の製造方
法。(2) Guanidinoethanethiosulfonic acid represented by the following [I] formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ [I] characterized by reacting guanidinoethanethiosulfonic acid with sulfur in the presence of a base manufacturing method.
分として含有することを特徴とするコレステロール低下
剤。(3) A cholesterol-lowering agent characterized by containing guanidinoethanethiosulfonic acid represented by the following [ I ] formula ▼ Numerical formula, chemical formula, table, etc. ▼ [ I ] as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21800985A JPS6281365A (en) | 1985-10-02 | 1985-10-02 | Guanidinoethanethiosulfonic acid, production thereof and cholesterol-lowering agent containing said derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21800985A JPS6281365A (en) | 1985-10-02 | 1985-10-02 | Guanidinoethanethiosulfonic acid, production thereof and cholesterol-lowering agent containing said derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS6281365A true JPS6281365A (en) | 1987-04-14 |
Family
ID=16713195
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP21800985A Pending JPS6281365A (en) | 1985-10-02 | 1985-10-02 | Guanidinoethanethiosulfonic acid, production thereof and cholesterol-lowering agent containing said derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6281365A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2689396A1 (en) * | 1991-12-27 | 1993-10-08 | Sogo Pharm | Active oxygen scavenger. |
| US5543272A (en) * | 1993-02-17 | 1996-08-06 | Fuji Photo Film Co., Ltd. | Photographic composition having fixing capacity and a method for processing using the same |
| EP0823421A1 (en) * | 1995-04-21 | 1998-02-11 | Sogo Pharmaceutical Company Limited | Process for producing taurine analogues |
| EP0884307A3 (en) * | 1996-08-07 | 1999-12-15 | Sogo Pharmaceutical Company Limited | Process for producing taurine analogues, such as thiotaurine |
| KR100415962B1 (en) * | 1996-08-13 | 2004-05-14 | 소고 세이야꾸 가부시끼가이샤 | Process for producing taurine analogues |
-
1985
- 1985-10-02 JP JP21800985A patent/JPS6281365A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2689396A1 (en) * | 1991-12-27 | 1993-10-08 | Sogo Pharm | Active oxygen scavenger. |
| US5543272A (en) * | 1993-02-17 | 1996-08-06 | Fuji Photo Film Co., Ltd. | Photographic composition having fixing capacity and a method for processing using the same |
| EP0823421A1 (en) * | 1995-04-21 | 1998-02-11 | Sogo Pharmaceutical Company Limited | Process for producing taurine analogues |
| EP0884307A3 (en) * | 1996-08-07 | 1999-12-15 | Sogo Pharmaceutical Company Limited | Process for producing taurine analogues, such as thiotaurine |
| KR100415962B1 (en) * | 1996-08-13 | 2004-05-14 | 소고 세이야꾸 가부시끼가이샤 | Process for producing taurine analogues |
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