JPS603363B2 - Injectable composition - Google Patents
Injectable compositionInfo
- Publication number
- JPS603363B2 JPS603363B2 JP10704780A JP10704780A JPS603363B2 JP S603363 B2 JPS603363 B2 JP S603363B2 JP 10704780 A JP10704780 A JP 10704780A JP 10704780 A JP10704780 A JP 10704780A JP S603363 B2 JPS603363 B2 JP S603363B2
- Authority
- JP
- Japan
- Prior art keywords
- cryptocyanin
- dimethyl sulfoxide
- present
- composition
- injection
- 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
- 239000007972 injectable composition Substances 0.000 title description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 24
- 238000002347 injection Methods 0.000 claims description 9
- 239000007924 injection Substances 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 1
- CEJANLKHJMMNQB-UHFFFAOYSA-M cryptocyanin Chemical compound [I-].C12=CC=CC=C2N(CC)C=CC1=CC=CC1=CC=[N+](CC)C2=CC=CC=C12 CEJANLKHJMMNQB-UHFFFAOYSA-M 0.000 description 14
- 239000000243 solution Substances 0.000 description 7
- 208000002193 Pain Diseases 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 239000003708 ampul Substances 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- MUDSDYNRBDKLGK-UHFFFAOYSA-N 4-methylquinoline Chemical compound C1=CC=C2C(C)=CC=NC2=C1 MUDSDYNRBDKLGK-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 231100000636 lethal dose Toxicity 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 208000010201 Exanthema Diseases 0.000 description 1
- 208000001034 Frostbite Diseases 0.000 description 1
- YDQJXVYGARVLRT-UHFFFAOYSA-N Lepidine Natural products C=1C=CC(CC=2NC=CN=2)=CC=1OC=1C(OC)=CC=CC=1CC1=NC=CN1 YDQJXVYGARVLRT-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010029333 Neurosis Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 206010053615 Thermal burn Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- XGZVPYGIUMLWIE-UHFFFAOYSA-N ethyl hypoiodite Chemical compound CCOI XGZVPYGIUMLWIE-UHFFFAOYSA-N 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 208000015238 neurotic disease Diseases 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Description
【発明の詳細な説明】
本発明は、神経痛、リュウマチ、振動病等の治療に著効
を奏する新規な注射剤組成物に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel injection composition that is highly effective in treating neuralgia, rheumatism, vibration disease, and the like.
さら詳しくいえば、本発明は、感光色素クリプトシアニ
ンとして知られている１，１′ージエチル−４，４′ー
トリメチンキノシアニンヨージド（以下クリプトシアニ
ンという）を有効成分とした注射剤組成物に関するもの
である。このクリプトシアニンは、構造式
で示される、融点２５７０（分解）をもつ金色針状結晶
で、例えばレピジンョードェチラートと正ギ酸エチルェ
ステルを、ピリジン中で反応させることによって得られ
る。More specifically, the present invention provides an injectable composition containing as an active ingredient 1,1'-diethyl-4,4'-trimethinequinocyanine iodide (hereinafter referred to as cryptocyanin), which is known as the photosensitive dye cryptocyanin. It is related to. This cryptocyanin is a golden needle-shaped crystal having a melting point of 2570 (decomposed) as shown by the structural formula, and can be obtained, for example, by reacting lepidine iodoethylate and orthoformic acid ethyl ester in pyridine.
このものは、水に灘溶であるがアルコール類には易溶で
、青色の溶液を与える。これまで、このクリプトシアニ
ン２８〜３の重量とネオシアニン〔１，１，１″−トリ
エチルー１１一（４−キノリル）−４，４″−ペンタメ
チンキノシアニンジョージド〕７０〜７２重量％から成
るシアニン色素複合体を、炭酸水素ナトリウムと緊密に
混和して、凍傷、熱湯、神経通、リュウマチ、難治性疾
患の治療に用いることは知られていた。This product is soluble in water but readily soluble in alcohols, giving a blue solution. Until now, cyanine consisting of 28-3% by weight of this cryptocyanine and 70-72% by weight of neocyanine [1,1,1''-triethyl-11-(4-quinolyl)-4,4''-pentamethine quinocyanine geordide] It was known to use dye complexes, in intimate admixture with sodium bicarbonate, for the treatment of frostbite, scalds, neuropathy, rheumatism, and intractable diseases.
しかし、この色素複合体は製造の際に一定組成のものが
得られにくく、安定した効果が得られないし、また水に
鱗漆のため注射剤としての製剤が困難であるという欠点
があった。本発明らは、このような欠点を克服し、安定
した薬理効果を奏する注射剤を開発するために、鋭意研
究を重ねた結果、クリプトシアニンは純粋な形で使用し
た場合においても良好な治療効果を奏しうろこと及びジ
メチルスルホキシドがその良好な溶剤であり、しかもこ
れらに溶かしたクリプトシアニンの溶液は水とよく混和
しうろことを見出し、この知見に基づいて本発明をなす
に至った。However, this dye complex has drawbacks in that it is difficult to obtain a constant composition during production, and a stable effect cannot be obtained, and it is difficult to formulate an injection as it is lacquered with scales in water. In order to overcome these drawbacks and develop an injection with stable pharmacological effects, the present inventors have conducted intensive research and found that cryptocyanin has good therapeutic effects even when used in its pure form. It was discovered that scales and dimethyl sulfoxide are good solvents for this purpose, and that a solution of cryptocyanin dissolved in these scales is highly miscible with water, and based on this knowledge, the present invention was accomplished.
すなわち、本発明は、前記構造式（１）で示されるクリ
プトシアニンを、ジメチルスルホキシドに溶解して成る
注射剤組成物を提供するものである。本発明において溶
剤として用いるジメチルスルホキシドは、通常注射剤溶
剤として１回の投与に使用される程度の量例え‘よ０．
５〜２の上では、人体に対し全く副作用を示さず、安全
に使用しうろことが認められている。That is, the present invention provides an injection composition prepared by dissolving cryptocyanin represented by the structural formula (1) in dimethyl sulfoxide. Dimethyl sulfoxide used as a solvent in the present invention is used in an amount of, for example, 0.00 to 0.0000, which is normally used as a solvent for injections in one administration.
If the drug is above 5-2, it is recognized that it shows no side effects to the human body and can be used safely.
本発明組成物は、有効成分であるクリプトシアニンを、
この溶剤中に濃度０．０５〜１．０％（Ｗ／Ｖ）になる
ような割合で溶解することによって調製される。本発明
組成物には、一般の注射剤に慣用されている添加剤を所
望に応じて添加することができる。The composition of the present invention contains cryptocyanin as an active ingredient,
It is prepared by dissolving it in this solvent at a ratio such that the concentration is 0.05 to 1.0% (W/V). Additives commonly used in general injections can be added to the composition of the present invention as desired.
このような添加剤としては、例えば安定剤、溶解補助剤
、緩衝剤、保存剤ト無痛化剤などがある。このようにし
て調製された本発明組成物、ガラスアンプルに１〜２の
【程度の量で詰めて、製品化される。Such additives include, for example, stabilizers, solubilizers, buffers, preservatives, and soothing agents. The composition of the present invention thus prepared is packed into a glass ampoule in an amount of about 1 to 2 to produce a product.
使用に際しては、この組成物をそのまま、もしくは同量
の蒸留水で希釈し、痔痛個所に注射器をを用いて投与さ
れる。本発明組成物の成人一日当りの投与量としては、
クリプトシアニン基準で、１〜５桝が適当であり、必要
に応じて２〜５回に分注することができる。In use, this composition is administered as is or diluted with the same amount of distilled water and administered to the hemorrhoidal area using a syringe. The daily dosage for adults of the composition of the present invention is as follows:
Based on cryptocyanin, 1 to 5 squares is appropriate, and it can be dispensed 2 to 5 times if necessary.
本発明によると、従来注射による投薬が困難であったク
リプトシアニンを、治療に必要な量だけ任意に投薬しう
るので、治療効果を向上しうる上に、アンプルとして広
く供給しうるので、容易に利用できるという利点がある
。According to the present invention, cryptocyanin, which has conventionally been difficult to administer by injection, can be administered arbitrarily in the amount required for treatment, improving the therapeutic effect, and can be widely supplied as ampoules, making it easy to administer. It has the advantage of being available.
次に実施例により本発明をさらに詳細に説明する。Next, the present invention will be explained in more detail with reference to Examples.
参考例
ジメチルスルホキシドの毒性を試験するために、次の動
物実験を行った。Reference Example The following animal experiment was conducted to test the toxicity of dimethyl sulfoxide.
体重１５〜２５夕のマウス１０匹（おす５匹、めす５匹
）と、体重１７０〜２３０夕のラット１０匹（おす５匹
、めす５匹）を１グループとし、各グループごとに異な
る量のジメチルスルホキシド（同仁薬化学研究所製、試
薬特級）を投与したのち、温度２２℃、湿度５５％に保
った飼育室内で標準飼料を用いて７日間飼育し、生存状
況を観察した。One group consisted of 10 mice (5 males, 5 females) weighing 15-25 mm and 10 rats (5 males, 5 females) weighing 170-230 mm, and each group received a different amount of After administering dimethyl sulfoxide (manufactured by Dojin Pharmaceutical Research Institute, reagent special grade), the animals were raised for 7 days using standard feed in a breeding room maintained at a temperature of 22°C and a humidity of 55%, and their survival status was observed.
前記のジメチルスルホキシドの投与は、これを０．９％
食塩水で、１０の‘／ｋ９になるように希釈したものを
それぞれの動物の尾に静脈注射することによって行った
。The administration of dimethyl sulfoxide mentioned above is 0.9%
Dilutions of 10'/k9 in saline were performed by intravenous injection into the tail of each animal.
このようにして、平均致死量を求めたところジメチルス
ルホキシド‘こ基づくｍ別は６．９泌／ｋ９であつた。In this way, the average lethal dose was determined to be 6.9 secretions/k9 based on dimethyl sulfoxide.
また、比較のために、全く同様にしてエチルアルコール
の平均致死量を求めたところＬＤ５ｏは２．８の【／ｋ
９であった。このことから、ジメチルスルホキシドは毒
性が著しく低いことが分る。Also, for comparison, when the average lethal dose of ethyl alcohol was determined in exactly the same way, the LD5o was 2.8 [/k
It was 9. This shows that dimethyl sulfoxide has extremely low toxicity.
実施例 １
ジメチルスルホキシド（同仁薬化学研究所製、試薬特級
）に、クリプトシアニン（東京化成工業株式会社製、純
度１００％）を加え、６０ｑｏでかきまぜながら溶解さ
せ、前者１の【中に後者１の９を含有する溶液を調製す
る。Example 1 Cryptocyanin (manufactured by Tokyo Kasei Kogyo Co., Ltd., purity 100%) was added to dimethyl sulfoxide (manufactured by Dojin Pharmaceutical Research Institute, reagent special grade) and dissolved while stirring at 60 qo. Prepare a solution containing 9.
この溶液を室温まで冷却し、ろ過して固形物を除いたの
ち、１の【ずつァルプルに充んし、溶融閉封し、さらに
常法に従って滅菌処理する。このようにしてアンプル入
注射剤を調製した。実施例 ２
実施例１で得たアンプルを開封し、クリプトシアニンの
ジメチルスルホキシド溶液を取り出し、蒸留水１の【で
希釈したのち、注射器を用いて、種々の症状を示す１０
人の患者の疹痛個所（ノイローゼの場合は筋肉注射）に
投与した。This solution is cooled to room temperature, filtered to remove solid matter, then filled into 1 cup, melted and sealed, and further sterilized according to a conventional method. In this way, an ampoule injection was prepared. Example 2 Open the ampoule obtained in Example 1, take out the dimethyl sulfoxide solution of cryptocyanin, dilute it with 1 part of distilled water, and use a syringe to inject 10 parts of the solution showing various symptoms.
It was administered to human patients at the site of pain (intramuscular injection in the case of neurosis).
クリプトシアニンの投薬量は３の３／日でこれを３回に
分注した。このようにして治療した１０日後の効果を第
１表に示す。十十十 箸効
十十 有効
十 やや有効
士 判定不能又は不変
症状悪化副作用
実施例 ３
実施例１で得たアンプルを開封し、クリプトシアニンの
ジメチルスルホキシド溶液を取り出し、蒸留水１私で希
釈したのち注射器を用いて、身体各部の筋肉の自発痛、
運動痛等の症状を示す５人の振動病患者の疹痛個所に数
回にわたって投与した。The dosage of cryptocyanin was 3/3/day, which was divided into three doses. The effects after 10 days of treatment in this manner are shown in Table 1. 110 Chopstick effect 10 Effective 10 Somewhat effective person Undeterminable or unchangeable symptom aggravation side effect Example 3 Open the ampoule obtained in Example 1, take out the dimethyl sulfoxide solution of cryptocyanin, dilute it with 1 part of distilled water, and then Spontaneous pain in muscles in various parts of the body using a syringe,
The drug was administered several times to the sore spots of five patients with vibration disease who exhibited symptoms such as movement pain.
このようにして治療した後の効果を第２表に示す。第２
表
１） 疹痛の改善度は投与終了後援痛の自覚症状の改善
の割合を示す。The effects after treatment in this manner are shown in Table 2. Second
Table 1) The degree of improvement in exanthema pain indicates the rate of improvement in subjective symptoms of pain behind the end of administration.
２） 持続日数は、疹痛の自覚症状改善の持続日数を示
す。2) The number of days of duration indicates the number of days that the subjective symptoms of eruption pain continue to improve.
３） 握力及びタッピングは、末梢運動機能の回復度を
示す指標として測定したものである。3) Grip strength and tapping were measured as indicators of the degree of recovery of peripheral motor function.
Claims (1)
キノシアニンヨージドを、ジメチルスルホキシドに溶解
して成る注射剤組成物。[Claims] 1. An injection prepared by dissolving 1,1'-diethyl-4,4'-trimethine quinocyanine iodide represented by the structural formula ▲ Numerical formula, chemical formula, table, etc. ▼ in dimethyl sulfoxide. agent composition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10704780A JPS603363B2 (en) | 1980-08-04 | 1980-08-04 | Injectable composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10704780A JPS603363B2 (en) | 1980-08-04 | 1980-08-04 | Injectable composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5731608A JPS5731608A (en) | 1982-02-20 |
| JPS603363B2 true JPS603363B2 (en) | 1985-01-28 |
Family
ID=14449164
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10704780A Expired JPS603363B2 (en) | 1980-08-04 | 1980-08-04 | Injectable composition |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS603363B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3858355A4 (en) * | 2018-09-26 | 2022-08-03 | Hayashibara Co., Ltd. | ANTI-NEURODEGENERATIVE DISEASE AGENT |
-
1980
- 1980-08-04 JP JP10704780A patent/JPS603363B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5731608A (en) | 1982-02-20 |
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