JP5850453B2 - External skin analgesics, skin puncture pain relievers and subcutaneous vein vasodilators - Google Patents
External skin analgesics, skin puncture pain relievers and subcutaneous vein vasodilators Download PDFInfo
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Description
本発明は、皮膚外用鎮痛剤、皮膚穿刺時疼痛軽減剤、皮下静脈の血管拡張剤ならびに皮下静脈の血管拡張および皮膚穿刺時疼痛軽減剤に関する。 The present invention relates to an external skin analgesic, a pain reducing agent for skin puncture, a vasodilator for subcutaneous vein, and a pain reducing agent for vascular dilation of subcutaneous vein and skin puncture.
注射・採血・点滴等の針を穿刺する医療行為は、子供のみならず大人にも多大な苦痛をもたらす。その苦痛を軽減する従来の皮膚穿刺時疼痛軽減剤として、リドカインを主成分とし、粘着テープに付着させて成る貼付用テープ剤がある（例えば、特許文献１参照）。
また、従来の血管拡張剤として、ジアルキルフタリド誘導体を有効成分として含有するものがある（例えば、特許文献２参照）。
Medical practice of puncturing a needle such as injection, blood collection, and drip causes great pain not only for children but also for adults. As a conventional skin puncture pain relieving agent for reducing the pain, there is an adhesive tape agent comprising lidocaine as a main component and adhering to an adhesive tape (for example, see Patent Document 1).
Further, as a conventional vasodilator, there is one containing a dialkylphthalide derivative as an active ingredient (see, for example, Patent Document 2).
特許文献１に記載の皮膚穿刺時疼痛軽減剤では、鎮痛効果発現まで、静脈留置針穿刺予定部位に約３０分間貼付する必要があり、３０分前に準備するとともに、穿刺時まで貼付し続けなければならないという課題があった。また、特許文献１に記載の皮膚穿刺時疼痛軽減剤は、痛み緩和効果が小さいという課題があった。
特許文献２に記載の血管拡張剤の作用は、主に毛細血管を含む血管の全般に渡る拡張作用であり、穿刺部の皮下静脈のみを選択的に拡張させるものではない。また、原材料が入手しにくく、合成する必要があり、製造コストがかさむという課題があった。
With the pain reducing agent at the time of skin puncture described in Patent Document 1, it is necessary to apply it to the planned site of venous indwelling needle puncture for about 30 minutes until the analgesic effect appears. There was a problem that had to be done. Moreover, the pain reducing agent at the time of skin puncture described in Patent Document 1 has a problem that the pain relieving effect is small.
The action of the vasodilator described in Patent Document 2 is an expansion action mainly for blood vessels including capillaries, and does not selectively expand only the subcutaneous vein of the puncture site. In addition, it is difficult to obtain raw materials, it is necessary to synthesize them, and there is a problem that manufacturing costs increase.
本発明は、このような課題に着目してなされたもので、短時間で効果を発現するとともに痛み緩和効果が大きく、安価に製造可能な皮膚外用鎮痛剤、皮膚穿刺時疼痛軽減剤、皮下静脈の血管拡張剤ならびに皮下静脈の血管拡張および皮膚穿刺時疼痛軽減剤を提供することを目的としている。 The present invention has been made paying attention to such problems, and has an effect in a short time and has a large pain relieving effect, and can be manufactured at low cost. It is an object of the present invention to provide a vasodilator of the present invention and an agent for reducing pain during subcutaneous vein vasodilation and skin puncture.
本発明者は、デカン酸に皮膚知覚を鈍麻させる作用があること、およびデカン酸に皮下静脈のみを選択的に拡張させる作用があることを発見し、本発明に至った。
すなわち、本発明に係る皮下静脈の血管拡張剤ならびに皮下静脈の血管拡張および皮膚穿刺時疼痛軽減剤は、デカン酸を含むことを特徴とする。本発明に係る皮膚外用鎮痛剤および皮膚穿刺時疼痛軽減剤は、デカン酸およびカフェインを含むことを特徴とする。デカン酸は、CH3(CH2)8C(=O)OHで表される脂肪酸の一種である。本発明に係る皮下静脈の血管拡張剤ならびに皮下静脈の血管拡張および皮膚穿刺時疼痛軽減剤は、カフェインを含むことが好ましい。カフェインは無水カフェインであることが好ましい。本発明に係る皮膚外用鎮痛剤、皮膚穿刺時疼痛軽減剤、皮下静脈の血管拡張剤ならびに皮下静脈の血管拡張および皮膚穿刺時疼痛軽減剤（以下、「本発明」という）は、炭酸カルシウムを含むことが好ましい。本発明は、デカン酸と無水カフェインと炭酸カルシウムとを含むことがより好ましい。
The present inventor has found that decanoic acid has an action of obstructing skin perception, and that decanoic acid has an action of selectively expanding only a subcutaneous vein, leading to the present invention.
That is, the subcutaneous vein vasodilator and the subcutaneous vein vasodilator and skin puncture pain relieving agent according to the present invention contain decanoic acid. The external skin analgesic and skin pain reducing agent according to the present invention include decanoic acid and caffeine. Decanoic acid is a kind of fatty acid represented by CH 3 (CH 2 ) 8 C (═O) OH. The subcutaneous vein vasodilator and the subcutaneous vein vasodilator and skin puncture pain reducing agent according to the present invention preferably contain caffeine. The caffeine is preferably anhydrous caffeine. The external skin analgesic agent, skin puncture pain reducing agent, subcutaneous vein vasodilator and subcutaneous vein vasodilator and skin puncture pain reducing agent (hereinafter referred to as “the present invention”) according to the present invention contain calcium carbonate. It is preferable. The present invention more preferably contains decanoic acid, anhydrous caffeine, and calcium carbonate.
本発明は、皮膚に塗布などにより付着させることにより皮膚知覚を鈍麻させ、痛みを軽減させる。特に、注射針などの針を穿刺する際の痛みの軽減に効果的である。また、本発明は、皮下静脈付近の皮膚に塗布などにより付着させることにより皮下静脈のみを選択的に拡張させる。このため、注射針を皮下静脈に穿刺する際に、穿刺すべき皮下静脈を選択的に拡張させるとともに穿刺する際の痛みを軽減させるのに効果的である。本発明は、短時間に皮膚知覚に対する鈍麻効果および皮下静脈拡張効果を発現する。しかも、本発明は、皮膚から除去後、短時間でもとの皮膚知覚およびもとの血管の状態に戻る。 In the present invention, skin perception is blunted by attaching to the skin by application or the like, and pain is reduced. In particular, it is effective in reducing pain when a needle such as an injection needle is punctured. Further, according to the present invention, only the subcutaneous vein is selectively expanded by being attached to the skin near the subcutaneous vein by application or the like. Therefore, when the injection needle is punctured into the subcutaneous vein, it is effective to selectively expand the subcutaneous vein to be punctured and to reduce pain when puncturing. The present invention develops a dull effect and a subcutaneous vein dilation effect on skin perception in a short time. In addition, the present invention returns to the original skin condition and the original blood vessel state in a short time after removal from the skin.
本発明によれば、短時間で効果を発現するとともに痛み緩和効果が大きく、安価に製造可能な皮膚外用鎮痛剤、皮膚穿刺時疼痛軽減剤、皮下静脈の血管拡張剤ならびに皮下静脈の血管拡張および皮膚穿刺時疼痛軽減剤を提供することができる。 According to the present invention, an external skin pain relieving agent that exhibits an effect in a short time, has a large pain relieving effect, and can be manufactured at low cost, a pain reducing agent for skin puncture, a vasodilator for a subcutaneous vein, and a vasodilator for a subcutaneous vein An agent for reducing pain during skin puncture can be provided.
本発明の実施の形態に係る皮下静脈の血管拡張剤ならびに皮下静脈の血管拡張および皮膚穿刺時疼痛軽減剤は、デカン酸を含む。本発明の実施の形態に係る皮下静脈の血管拡張剤ならびに皮下静脈の血管拡張および皮膚穿刺時疼痛軽減剤は、デカン酸およびカフェインを含む。本発明の実施の形態に係る皮下静脈の血管拡張剤ならびに皮下静脈の血管拡張および皮膚穿刺時疼痛軽減剤は、カフェインを含むことが好ましい。カフェインは無水カフェインであることが好ましい。本発明の実施の形態に係る皮膚外用鎮痛剤、皮膚穿刺時疼痛軽減剤、皮下静脈の血管拡張剤ならびに皮下静脈の血管拡張および皮膚穿刺時疼痛軽減剤（以下、「本薬剤」という）は、炭酸カルシウムを含むことが好ましい。本薬剤は、デカン酸と無水カフェインと炭酸カルシウムとを含むことがより好ましい。
The subcutaneous vein vasodilator and the subcutaneous vein vasodilator and skin puncture pain relieving agent according to the embodiment of the present invention contain decanoic acid. The subcutaneous vein vasodilator and the subcutaneous vein vasodilator and skin puncture pain relieving agent according to the embodiment of the present invention include decanoic acid and caffeine. The subcutaneous vein vasodilator and the subcutaneous vein vasodilator and skin puncture pain reducing agent according to the embodiment of the present invention preferably contain caffeine. The caffeine is preferably anhydrous caffeine. The external skin painkiller, skin puncture pain reducing agent, subcutaneous vein vasodilator and subcutaneous vein vasodilation and skin puncture pain reducing agent (hereinafter referred to as “the present drug”) according to the embodiment of the present invention , Preferably it contains calcium carbonate. More preferably, the drug contains decanoic acid, anhydrous caffeine, and calcium carbonate.
本薬剤は、皮膚に塗布することにより皮膚知覚を鈍麻させ、痛みを軽減させる。特に、注射針などの針を穿刺する際の痛みの軽減に効果的である。本薬剤は、既存の皮膚外用鎮痛剤に比べて鎮痛効果が優れている。また、本薬剤は、皮下静脈付近の皮膚に塗布することにより皮下静脈のみを選択的に拡張させる。本薬剤は、超短時間（１分以内）に皮膚知覚に対する鈍麻効果を発現する。しかも、本薬剤は、塗布から１０〜２０分後には、もとの皮膚知覚に戻る。しかし、時間をかけて皮膚に浸透するよう選択した基剤に分散させることにより、鎮痛効果を持続させることもできる。 When applied to the skin, the drug reduces skin perception and reduces pain. In particular, it is effective in reducing pain when a needle such as an injection needle is punctured. This drug has an analgesic effect superior to existing skin external analgesics. In addition, this drug selectively expands only the subcutaneous vein by applying it to the skin near the subcutaneous vein. The drug exhibits a dull effect on skin perception in an extremely short time (within 1 minute). Moreover, this drug returns to the original skin perception 10 to 20 minutes after application. However, the analgesic effect can be sustained by dispersing in a base selected to penetrate the skin over time.
また、本薬剤は、超短時間（１分以内）に皮下静脈のみの選択的な拡張効果を発現する。本薬剤は、採血や点滴の際に皮下静脈付近の皮膚に塗布することにより、穿刺すべき皮下静脈を拡張させて血管をみつけやすくし、採血や点滴を容易にする。しかも、本薬剤は、塗布から１０〜２０分後には、もとの血管の状態に戻る。しかし、時間をかけて皮膚に浸透するよう選択した基剤に分散させることにより、血管拡張効果を持続させることもできる。 In addition, this drug exhibits a selective dilation effect of only the subcutaneous vein in an extremely short time (within 1 minute). This drug is applied to the skin in the vicinity of the subcutaneous vein at the time of blood collection or infusion, thereby expanding the subcutaneous vein to be punctured to make it easier to find the blood vessel and facilitate blood collection or infusion. In addition, the present drug returns to the original blood vessel state 10 to 20 minutes after application. However, the vasodilatory effect can also be sustained by dispersing in a base selected to penetrate the skin over time.
本薬剤の塗布量は、皮膚１平方センチメートルあたり０．００１ｇ乃至１ｇが好ましく、０．０５ｇ乃至０．８ｇがより好ましく、０．１ｇ乃至０．５ｇが特に好ましい。本薬剤は、軟膏、クリーム剤、ゲル剤、液剤、ローション剤などにすることができる。本薬剤は、粘着テープに付着させて成る貼付用テープ剤であってもよい。本薬剤は、種々の基剤に分散させて常法により製剤化することができる。その基剤としては、ワセリン、流動パラフィン、ミリスチン酸イソプロピル、ミリスチン酸オクチルドデシルなどの高級脂肪酸エステル、スクワラン、ラノリン、セタノールなどの高級アルコール、シリコーン油、動植物油脂などの油脂性基剤、エタノールなどの低級アルコール類、ポリエチレングリコール、プロピレングリコールなどの多価アルコール類、α−モノグリセリルエーテル、レシチン、ソルビタン脂肪酸エステル、デキストリン脂肪酸エステル、脂肪酸モノグリセリド、脂肪酸金属塩、硫酸マグネシウムなどの乳化又は乳化安定剤、芳香剤、防腐剤、色素、増粘剤、酸化防止剤、紫外線防御剤、創傷治癒剤、抗炎症剤、保湿剤などの各種薬効剤、デンプン、水などが挙げられる。デカン酸には、皮膚に対し刺激性があるため、緩和する目的で例えば、オリーブ油を使用することができる。本薬剤は、皮膚に付着させて使用され、塗布、噴霧、滴下などの方法で使用することができる。 The amount of the drug applied is preferably 0.001 to 1 g, more preferably 0.05 to 0.8 g, and particularly preferably 0.1 to 0.5 g per square centimeter of skin. The drug can be an ointment, cream, gel, liquid, lotion or the like. The drug may be an adhesive tape that is attached to an adhesive tape. The drug can be formulated in a conventional manner by dispersing in various bases. As the base, higher fatty acid esters such as petrolatum, liquid paraffin, isopropyl myristate, octyldodecyl myristate, higher alcohols such as squalane, lanolin and cetanol, oily bases such as silicone oil and animal and vegetable oils, ethanol etc. Lower alcohols, polyhydric alcohols such as polyethylene glycol and propylene glycol, α-monoglyceryl ether, lecithin, sorbitan fatty acid ester, dextrin fatty acid ester, fatty acid monoglyceride, fatty acid metal salt, emulsification stabilizer such as magnesium sulfate, aroma Agents, antiseptics, pigments, thickeners, antioxidants, UV protection agents, wound healing agents, anti-inflammatory agents, moisturizers and other various medicinal agents, starch, water and the like. Since decanoic acid is irritating to the skin, for example, olive oil can be used for relaxation. This drug is used by adhering to the skin, and can be used by methods such as application, spraying and dripping.
本薬剤がデカン酸とカフェインとを含む場合、カフェインはデカン酸に対して１００質量％乃至５０質量％含まれることが好ましい。デカン酸とカフェインとを含む場合、カフェインを含まない場合に比べて鎮痛効果を高めることができる。
本薬剤がデカン酸と炭酸カルシウムとを含む場合、炭酸カルシウムはデカン酸に対して１００質量％乃至５０質量％含まれることが好ましい。デカン酸と炭酸カルシウムとを含む場合、炭酸カルシウムを含まない場合に比べて鎮痛効果を高めることができる。
本薬剤がデカン酸とカフェインと炭酸カルシウムとを含む場合、デカン酸とカフェインと炭酸カルシウムとの配合比率は、２：１：２乃至３：１：２が好ましい。デカン酸とカフェインと炭酸カルシウムとを含む場合、カフェインを含まない場合や炭酸カルシウムを含まない場合に比べて、より高い鎮痛効果を示し、注射や点滴などの穿刺時の鋭い痛みにも十分に効果を発揮する。本薬剤は、その他、帯状疱疹やレーザー照射による痛みなど皮膚の種々の痛みの軽減に使用することができる。
When the drug contains decanoic acid and caffeine, caffeine is preferably contained in an amount of 100% by mass to 50% by mass with respect to decanoic acid. When decanoic acid and caffeine are included, the analgesic effect can be enhanced as compared with the case where caffeine is not included.
When the drug contains decanoic acid and calcium carbonate, the calcium carbonate is preferably contained in an amount of 100% by mass to 50% by mass with respect to the decanoic acid. When decanoic acid and calcium carbonate are included, the analgesic effect can be enhanced as compared with the case where calcium carbonate is not included.
When this drug contains decanoic acid, caffeine, and calcium carbonate, the blending ratio of decanoic acid, caffeine, and calcium carbonate is preferably 2: 1: 2 to 3: 1: 2. When decanoic acid, caffeine, and calcium carbonate are included, it shows a higher analgesic effect than when caffeine is not included or calcium carbonate is not included, and it is sufficient for sharp pain during puncture such as injection or infusion. To be effective. In addition, the drug can be used to reduce various types of skin pain such as shingles and pain caused by laser irradiation.
以下、デカン酸、無水カフェイン、炭酸カルシウムの急性毒性の試験結果は以下のとおりである。
デカン酸のラットを用いた経口投与試験のLD50値＝3,301mg/kg(JECFA(1998))である。デカン酸のウサギを用いた経皮投与試験のLD50値>5,000mg/kg(Patty(5th,2001))である。無水カフェインのラットを用いた経口投与試験のLD50値＝261mg/kgである。無水カフェインのラットを用いた経皮投与試験のLD50値>2,000mg/kgである。炭酸カルシウムのラットを用いた経口投与試験のLD50値＝6450mg/kgである。炭酸カルシウムのウサギを用いた皮膚腐食性・刺激性試験では、皮膚刺激500mg/24時間で中程度である。
本薬剤では、経口摂取でなく、皮膚への付着であり、しかも付着時間は１分乃至数分間と短時間で足りることから、副作用等の有害事象がほとんど認められず、安全性が確認された。
The test results of acute toxicity of decanoic acid, anhydrous caffeine and calcium carbonate are as follows.
LD50 value of oral administration test using decanoic acid rats = 3,301 mg / kg (JECFA (1998)). LD50 value of dermal administration test using rabbits of decanoic acid> 5,000 mg / kg (Patty (5th, 2001)). LD50 value of oral administration test using rats of anhydrous caffeine = 261 mg / kg. LD50 value of dermal administration test using anhydrous caffeine rats> 2,000 mg / kg. LD50 value of oral administration test using rats of calcium carbonate = 6450 mg / kg. In skin corrosion / irritation tests using calcium carbonate rabbits, skin irritation is moderate at 500 mg / 24 hours.
With this drug, it was not taken orally but was attached to the skin, and the attachment time was only 1 minute to several minutes, so there were almost no adverse events such as side effects, and safety was confirmed. .
以下に実施例をあげて本発明をさらに具体的に説明するが、本発明はこれらにより限定されるものではない。 The present invention will be described more specifically with reference to the following examples, but the present invention is not limited thereto.
［試験例１］
本発明のデカン酸とカフェインとの配合比率による鎮痛効果を検討するため、以下の試験を行った。
デカン酸１００質量％のもの（１：０試料）、デカン酸２質量部に対して無水カフェイン１質量部の割合で混合したもの（２：１試料）、デカン酸１質量部に対して無水カフェイン１質量部の割合で混合したもの（１：１試料）、無水カフェイン１００質量％のもの（０：１試料）の４種類の試料を作製した。
[Test Example 1]
In order to examine the analgesic effect depending on the blending ratio of decanoic acid and caffeine of the present invention, the following test was conducted.
100% by weight of decanoic acid (1: 0 sample), 2 parts by weight of decanoic acid mixed with 1 part by weight of anhydrous caffeine (2: 1 sample), 1 part by weight of anhydrous decanoic acid Four types of samples were prepared, one mixed at a ratio of 1 part by weight of caffeine (1: 1 sample) and 100% by weight anhydrous caffeine (0: 1 sample).
成人１０名（男５名，女５名）から成る被験者の両前腕皮膚に約０．４ｇの各試料を塗布し、疼痛試験を行った。疼痛試験は、ピンプリック法により行った。すなわち、直径０．２mmのステンレス製の針を手甲皮膚に押し当て、激しい痛みを伴う点（痛点）を予め選定した。この部位に試料を塗布し、３分経過後に試料を除去して直後に予め選定した痛点にステンレス製の針を押し当て、この時の痛みを問診した。
その結果、鈍麻作用は大きい順に、（２：１試料）＞（１：１試料）＞（１：０試料）＞（０：１試料）であった。（０：１試料）には、皮膚知覚に対する鈍麻作用は全く認められなかった。
About 0.4 g of each sample was applied to both forearm skins of subjects consisting of 10 adults (5 men and 5 women), and a pain test was performed. The pain test was performed by the pin prick method. That is, a stainless needle having a diameter of 0.2 mm was pressed against the back skin, and a point with severe pain (pain point) was selected in advance. A sample was applied to this site, and after 3 minutes had passed, the sample was removed, and immediately after that, a stainless steel needle was pressed against a preselected pain point, and the pain at this time was interrogated.
As a result, the blunt action was (2: 1 sample)> (1: 1 sample)> (1: 0 sample)> (0: 1 sample) in descending order. (0: 1 sample) showed no blunt action on skin perception.
［試験例２］
本発明のデカン酸と炭酸カルシウムとの配合比率による鎮痛効果を検討するため、以下の試験を行った。
デカン酸１００質量％のもの（１：０試料）、デカン酸２質量部に対して炭酸カルシウム１質量部の割合で混合したもの（２：１試料）、デカン酸１質量部に対して炭酸カルシウム１質量部の割合で混合したもの（１：１試料）、デカン酸１質量部に対して炭酸カルシウム２質量部の割合で混合したもの（１：２試料）、炭酸カルシウム１００質量％のもの（０：１試料）の５種類の試料を作製した。
[Test Example 2]
In order to examine the analgesic effect by the blending ratio of decanoic acid and calcium carbonate of the present invention, the following test was conducted.
Decanoic acid 100% by weight (1: 0 sample), decanoic acid 2 parts by weight mixed with calcium carbonate 1 part by weight (2: 1 sample), decanoic acid 1 part by weight calcium carbonate Mixed at a ratio of 1 part by mass (1: 1 sample), mixed at a ratio of 2 parts by mass of calcium carbonate to 1 part by mass of decanoic acid (1: 2 sample), 100% by mass of calcium carbonate ( 0: 1 sample) were prepared.
成人１０名（男５名，女５名）から成る被験者の両前腕皮膚に約０．４ｇの各試料を塗布し、疼痛試験を行った。疼痛試験は、前述のピンプリック法により行った。
その結果、鈍麻作用は大きい順に、（１：１試料）＞（２：１試料）＞（１：０試料）＞（１：２試料）＞（０：１試料）であった。（０：１試料）には、皮膚知覚に対する鈍麻作用は全く認められなかった。
About 0.4 g of each sample was applied to both forearm skins of subjects consisting of 10 adults (5 men and 5 women), and a pain test was performed. The pain test was performed by the pin prick method described above.
As a result, the blunt action was (1: 1 sample)> (2: 1 sample)> (1: 0 sample)> (1: 2 sample)> (0: 1 sample) in descending order. (0: 1 sample) showed no blunt action on skin perception.
［軟膏の作製］
試験１と試験２の結果から、鈍麻作用が最も大きいデカン酸：カフェイン：炭酸カルシウムの配合比率は２：１：２となるが、デカン酸の濃度を高めて３：１：２の配合比率の軟膏を作製することとした。デカン酸３質量部、無水カフェイン１質量部、炭酸カルシウム２質量部の割合で配合したものは常温では固形状態となるため、それらに対して２質量部のマクロゴール軟膏および０．５質量部のオリーブ油を混合して粘度を調節し、皮膚外用鎮痛剤、皮膚穿刺時疼痛軽減剤、皮下静脈の血管拡張剤ならびに皮下静脈の血管拡張および皮膚穿刺時疼痛軽減剤の軟膏（以下、「本軟膏」という）を作製した。なお、本軟膏には、０．０５質量部のヒドロキシ安息香酸メチルを保存用の防腐剤として添加してもよい。
[Preparation of ointment]
From the results of Test 1 and Test 2, the mixing ratio of decanoic acid: caffeine: calcium carbonate having the largest blunt action was 2: 1: 2, but the mixing ratio of 3: 1: 2 was increased by increasing the concentration of decanoic acid. An ointment was prepared. Since those blended at a ratio of 3 parts by weight of decanoic acid, 1 part by weight of anhydrous caffeine and 2 parts by weight of calcium carbonate are in a solid state at room temperature, 2 parts by weight of macrogol ointment and 0.5 parts by weight with respect to them The oil was mixed with olive oil to adjust the viscosity, and the topical analgesic, skin puncture pain relieving agent, subcutaneous vein vasodilator and subcutaneous vein vasodilator and skin puncture pain relieving ointment (hereinafter “this ointment”) "). In addition, you may add 0.05 mass part methyl hydroxybenzoate to this ointment as a preservative for preservation | save.
［疼痛試験］
作製した本軟膏の鎮痛効果を検討するため、以下の試験を行った。
成人２０名（男１０名・女１０名）から成る被験者の一方の上腕の内側に、３０ｍｇの膏体中に１８ｍｇのリドカインを有効成分として含む市販の局所麻酔用テープ剤（日東電工株式会社製「ペンレステープ１８ｍｇ」（商標））（以下、「比較例」という）を貼り付け、他方の上腕の内側に、本軟膏約０．４ｇを塗布した。比較例では貼り付けてから３０分後に、本軟膏では塗布してから１分後に、前述のピンプリック法により疼痛試験を行った。
その結果、すべての被験者が、本軟膏の方が比較例より鎮痛効果が優れており、本軟膏を塗布した箇所の痛みは比較例を貼り付けた箇所の痛みの１／２以下であると判定した。本軟膏では、副作用や有害事象は全く認められなかったが、比較例では発赤が３名に、掻痒が１名に認められた。
[Pain test]
In order to examine the analgesic effect of the produced ointment, the following test was conducted.
A commercially available tape for local anesthesia containing 18 mg of lidocaine as an active ingredient in a 30 mg paste on the inside of one upper arm of a subject consisting of 20 adults (10 males and 10 females) (manufactured by Nitto Denko Corporation) “Penless tape 18 mg” (trademark)) (hereinafter referred to as “comparative example”) was applied, and about 0.4 g of the present ointment was applied to the inner side of the other upper arm. In the comparative example, a pain test was performed by the above-described pin prick method 30 minutes after application and 1 minute after application with the present ointment.
As a result, all subjects determined that the ointment had better analgesic effect than the comparative example, and the pain at the place where the ointment was applied was determined to be 1/2 or less of the pain at the place where the comparative example was applied. did. In this ointment, no side effects or adverse events were observed, but redness was observed in 3 persons and pruritus was observed in 1 person in the comparative example.
［治験例］
被験者による治験の結果、本軟膏の有効性および安全性が確認されたため、実際の皮膚穿刺例において鎮痛効果を検討した。
方法：22Ｇの太さのテフロン針（注射器がついた金属の内針とポリテトラフルオロエチレン製の外套管とを持った二重針）で点滴のため穿刺を予定された成人１００名を対象とした。対象の成人は、３ヶ月以内に複数回、同針で点滴を施行された経験を持つものとした。
本軟膏使用の同意が得られた上で、穿刺部に本軟膏を貼布（0.4ｇ程度）し、１分後にアルコール綿で拭き取り穿刺行為を行った。
[Clinical trial example]
The effectiveness and safety of this ointment were confirmed as a result of clinical trials by subjects, and the analgesic effect was examined in actual skin puncture cases.
Method: Targeting 100 adults scheduled to puncture with a 22G Teflon needle (double needle with a metal inner needle with a syringe and an outer tube made of polytetrafluoroethylene). did. Subject adults had experience in instilling multiple times with the same needle within 3 months.
After obtaining consent to use this ointment, this ointment was applied to the puncture site (about 0.4 g), and after 1 minute, it was wiped with alcohol cotton and puncture was performed.
穿刺時の痛みの程度を以前の穿刺時の痛みと比較し、ａ．著効：痛みは以前の1/2以下、ｂ．有効：痛みは以前の1/2以上１以下、ｃ．痛みは以前と同程度、ｄ．以前の穿刺より痛い、の４段階に分け、痛みを問診した。また、穿刺部の皮下静脈の血管拡張状態や副作用等の有害な事象の有無についても問診とともに視認した。 Comparing the degree of pain at the time of puncture with the pain at the time of previous puncture; a. Remarkable: Pain is less than 1/2 of the previous level, b. Effective: Pain is 1/2 or more and 1 or less, c. Pain is the same as before, d. The patient was questioned for pain in four stages, which were more painful than the previous puncture. In addition, the presence or absence of adverse events such as vasodilation of the subcutaneous vein at the puncture site and side effects were also visually confirmed.
結果：成人100名の平均年齢は64.5才で、男性55名（平均67.1才）、女性45名（平均61.3才）であった。
ａ．著効の症例が８８名（８８％：男性５２名・女性３６名）
ｂ．有効の症例が１２名（１２％：男性３名・女性９名）
ｃ．以前と同様の痛みの症例は全く無く０名（０％）
ｄ．の以前より痛いの症例は全く無く０名（０％）
という問診結果であった。
穿刺部の皮下静脈の血管拡張は全例でみられ、特に血管拡張が２倍にもなった症例が１４例も出現した。副作用等の有害事象は全く認められなかった。
穿刺から２０分後には、全ての被験者で、もとの皮膚知覚に戻り、拡張した血管ももとの状態に戻った。
Results: The average age of 100 adults was 64.5 years, 55 men (average 67.1 years) and 45 women (average 61.3 years).
a. 88 cases (88%: 52 men, 36 women)
b. 12 effective cases (12%: 3 males, 9 females)
c. There were no pain cases as before, and there were 0 (0%)
d. There were no cases of pain than before (0%)
It was an interview result.
Vasodilation of the subcutaneous vein at the puncture site was observed in all cases, and in particular, 14 cases in which vasodilation was doubled appeared. There were no adverse events such as side effects.
Twenty minutes after the puncture, all subjects returned to their original skin perception and dilated blood vessels also returned to their original state.
Claims (14)
The pain reducing agent at the time of skin puncture according to claim 12 or 13 , comprising calcium carbonate.
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