JP7450916B2 - surface anesthetic - Google Patents
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- JP7450916B2 JP7450916B2 JP2020032540A JP2020032540A JP7450916B2 JP 7450916 B2 JP7450916 B2 JP 7450916B2 JP 2020032540 A JP2020032540 A JP 2020032540A JP 2020032540 A JP2020032540 A JP 2020032540A JP 7450916 B2 JP7450916 B2 JP 7450916B2
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- 230000003444 anaesthetic effect Effects 0.000 title claims description 95
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- GLZPCOQZEFWAFX-UHFFFAOYSA-N Geraniol Chemical compound CC(C)=CCCC(C)=CCO GLZPCOQZEFWAFX-UHFFFAOYSA-N 0.000 claims description 30
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 24
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- 239000003193 general anesthetic agent Substances 0.000 claims description 11
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- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 2
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- NFLGAXVYCFJBMK-RKDXNWHRSA-N (+)-isomenthone Natural products CC(C)[C@H]1CC[C@@H](C)CC1=O NFLGAXVYCFJBMK-RKDXNWHRSA-N 0.000 description 1
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- CZVXBFUKBZRMKR-JTQLQIEISA-N (R)-lavandulol Natural products CC(C)=CC[C@@H](CO)C(C)=C CZVXBFUKBZRMKR-JTQLQIEISA-N 0.000 description 1
- CDOSHBSSFJOMGT-JTQLQIEISA-N (R)-linalool Natural products CC(C)=CCC[C@@](C)(O)C=C CDOSHBSSFJOMGT-JTQLQIEISA-N 0.000 description 1
- WEEGYLXZBRQIMU-UHFFFAOYSA-N Eucalyptol Chemical compound C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- NFLGAXVYCFJBMK-UHFFFAOYSA-N Menthone Chemical compound CC(C)C1CCC(C)CC1=O NFLGAXVYCFJBMK-UHFFFAOYSA-N 0.000 description 1
- GLZPCOQZEFWAFX-JXMROGBWSA-N Nerol Natural products CC(C)=CCC\C(C)=C\CO GLZPCOQZEFWAFX-JXMROGBWSA-N 0.000 description 1
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- PUFQVTATUTYEAL-UHFFFAOYSA-N cinchocaine Chemical compound C1=CC=CC2=NC(OCCCC)=CC(C(=O)NCCN(CC)CC)=C21 PUFQVTATUTYEAL-UHFFFAOYSA-N 0.000 description 1
- RFFOTVCVTJUTAD-UHFFFAOYSA-N cineole Natural products C1CC2(C)CCC1(C(C)C)O2 RFFOTVCVTJUTAD-UHFFFAOYSA-N 0.000 description 1
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- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 1
- 229940087305 limonene Drugs 0.000 description 1
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- INWLQCZOYSRPNW-UHFFFAOYSA-N mepivacaine Chemical compound CN1CCCCC1C(=O)NC1=C(C)C=CC=C1C INWLQCZOYSRPNW-UHFFFAOYSA-N 0.000 description 1
- 229930008383 myrcenol Natural products 0.000 description 1
- DUNCVNHORHNONW-UHFFFAOYSA-N myrcenol Chemical compound CC(C)(O)CCCC(=C)C=C DUNCVNHORHNONW-UHFFFAOYSA-N 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
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- RUVINXPYWBROJD-UHFFFAOYSA-N para-methoxyphenyl Natural products COC1=CC=C(C=CC)C=C1 RUVINXPYWBROJD-UHFFFAOYSA-N 0.000 description 1
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- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
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Description
本発明は、表面麻酔剤に関する。 The present invention relates to surface anesthetics.
外科治療ではほぼ毎日麻酔注射が行われているが、これと同様に、採血等で皮膚へ注射を行う回数も非常に多く、個人差はあれ、注射の痛みは辛いものである。痛みに感受性の高い患者(注射恐怖症や幼児など)に対して行う注射は、困難を来すことが多いことから、注射前に、局所的な表面麻酔が行われることがある。 In surgical treatment, anesthetic injections are performed almost every day, but similarly, injections into the skin are required very often for blood sampling, etc., and the pain of the injections can be painful, although it varies from person to person. Because injections are often difficult for patients who are sensitive to pain (such as those with injection phobia or young children), local topical anesthesia is sometimes administered before the injection.
例えば、エムラ（登録商標）クリーム等の外用局所麻酔剤や、ペンレステープ、リドカインテープ、エムラ（登録商標）パッチ等の貼付用局所表面麻酔剤が、透析時に頻用されている。しかしながら、これらの局所麻酔剤は、針の刺入時の痛みを軽減させるためには、１時間から２時間程度の時間を要するなど即効性に乏しく、また、その除痛効果も刺入時の痛みを感じさせないレベルではなく、満足できるものではない。さらに、頻回使用により皮膚がただれ、針の刺入時に血管が見えづらいという欠点もあるが、他の優れた選択肢がないために使用されているというのが実状である。 For example, external local anesthetics such as Emla (registered trademark) cream, and local surface anesthetics for pasting such as penless tape, lidocaine tape, and Emla (registered trademark) patch are frequently used during dialysis. However, these local anesthetics do not have a quick effect, requiring about 1 to 2 hours to reduce the pain at the time of needle insertion, and their pain-relieving effect does not last until the time of needle insertion. It's not at a pain-free level, and it's not satisfying. Furthermore, it has the disadvantage that the skin becomes sore due to frequent use, making it difficult to see blood vessels when the needle is inserted, but the reality is that it is used because there are no other excellent options.
一方、このような針の刺入時の痛みを軽減するための表面麻酔剤に関する各種研究が行われている（例えば、非特許文献１参照）。 On the other hand, various studies have been conducted on surface anesthetics for reducing pain during needle insertion (for example, see Non-Patent Document 1).
本発明の課題は、除痛効果の高い表面麻酔剤を提供することにある。 An object of the present invention is to provide a surface anesthetic with high pain relief effect.
本発明者らは、現場において求められる表面麻酔剤の高い除痛効果を得るべく鋭意研究した結果、リドカイン及びプロピトカインを含有する麻酔成分を、ゲラニオール等のテルペノイドと共に皮膚等に適用することにより、高い除痛効果を得ることができることを見出し、本発明を完成するに至った。また、本発明者らは、高い除痛効果に加えて、優れた即効性及び／又は優れた持続性を得ることができることを見いだした。 As a result of intensive research to obtain the high pain relief effect of surface anesthetics required in the field, the present inventors have found that by applying anesthetic ingredients containing lidocaine and propitocaine to the skin, etc. together with terpenoids such as geraniol, The present inventors have discovered that it is possible to obtain a pain relief effect, and have completed the present invention. Furthermore, the present inventors have discovered that in addition to a high pain relief effect, it is possible to obtain excellent immediate effect and/or excellent sustainability.
すなわち、本発明は、以下の通りのものである。
［１］リドカイン及びプロピトカインを含む麻酔成分と、テルペノイドとを含むことを特徴とする表面麻酔剤。
［２］さらに、イソプロピルアルコールを含むことを特徴とする［１］記載の表面麻酔剤。
［３］テルペノイドが、０．０００００１～２質量％含まれることを特徴とする［１］又は［２］記載の表面麻酔剤。
［４］テルペノイドが、ゲラニオールであることを特徴とする［１］～［３］のいずれか記載の表面麻酔剤。
［５］皮膚又は粘膜に適用されることを特徴とする［１］～［４］のいずれか記載の表面麻酔剤。
That is, the present invention is as follows.
[1] A surface anesthetic agent characterized by containing an anesthetic component including lidocaine and propitocaine, and a terpenoid.
[2] The surface anesthetic according to [1], further comprising isopropyl alcohol.
[3] The surface anesthetic according to [1] or [2], characterized in that the terpenoid is contained in an amount of 0.000001 to 2% by mass.
[4] The surface anesthetic according to any one of [1] to [3], wherein the terpenoid is geraniol.
[5] The surface anesthetic according to any one of [1] to [4], which is applied to the skin or mucous membranes.
本発明の表面麻酔剤は、高い除痛効果を有する。 The surface anesthetic of the present invention has a high pain relief effect.
本発明の表面麻酔剤としては、リドカイン及びプロピトカインを含む麻酔成分とテルペノイドとを含むことを特徴とする。
本発明の表面麻酔剤は、除痛効果が高く、例えば、針の刺入前に適用することにより、針刺入時の痛みを効果的に抑制することができる。したがって、痛みに感受性の高い患者に対して特に有効である。
The surface anesthetic of the present invention is characterized by containing an anesthetic component including lidocaine and propitocaine, and a terpenoid.
The surface anesthetic of the present invention has a high pain relief effect, and can effectively suppress pain during needle insertion, for example, by applying it before needle insertion. Therefore, it is particularly effective for patients who are highly sensitive to pain.
また、本発明の表面麻酔剤は、即効性に優れており、例えば、針刺入時の痛みを、表面麻酔剤の付与後１０分程度で、ほぼ痛みを感じないペインレベル１まで抑えることができる（実施例参照）。したがって、外科手術等において、手術に素早く着手できる等、治療時間の短縮を図ることができる。さらに、その効果の持続時間も長く、ペインレベル１程度を長期にわたって維持することができる。したがって、外科手術等において、手術等の処置時間を十分に確保できる点で有効である。 Furthermore, the surface anesthetic of the present invention has excellent immediate effects; for example, the pain during needle insertion can be reduced to pain level 1, where it is almost painless, within about 10 minutes after application of the surface anesthetic. Yes (see examples). Therefore, in a surgical operation or the like, it is possible to start the operation quickly, and the treatment time can be shortened. Furthermore, the effect lasts for a long time, and pain level 1 can be maintained for a long period of time. Therefore, it is effective in ensuring sufficient treatment time in surgical operations and the like.
本発明の表面麻酔剤は、例えば、外科、内科、歯科、眼科、耳鼻科、泌尿器科、皮膚科、麻酔科、小児科、産婦人科、整形外科等における治療、検査時などの外科的処置に用いることができる。外科的処置とは、例えば、皮膚、口腔内組織、鼻腔内組織、歯牙硬組織等に対する、注射、切開、切除、切削、縫合、刺入、器具の導入などの処置をいう。 The surface anesthetic of the present invention can be used, for example, in surgery, internal medicine, dentistry, ophthalmology, otolaryngology, urology, dermatology, anesthesiology, pediatrics, obstetrics and gynecology, orthopedics, and surgical procedures such as examinations. Can be used. Surgical treatment refers to, for example, treatment such as injection, incision, excision, cutting, suturing, insertion, and introduction of instruments to the skin, oral tissue, nasal cavity tissue, dental hard tissue, and the like.
好ましくは、注射前に、注射部位（皮膚、粘膜）に適用することができる。なお、注射とは、注射針（点滴針、留置針、透析用針等を含む）を用いた処理全般をいう。具体的には、手術等を行う場合の注射による浸潤麻酔や伝達麻酔に先立って針刺入時の痛みを軽減させる目的で用いることができる。その他、透析、採血、点滴、予防接種を行う場合の針刺入時の痛みを軽減する目的で用いることができる。 Preferably, it can be applied to the injection site (skin, mucous membranes) before injection. Note that injection refers to all treatments using injection needles (including drip needles, indwelling needles, dialysis needles, etc.). Specifically, it can be used for the purpose of reducing pain during needle insertion prior to infiltration anesthesia or delivery anesthesia by injection when performing surgery or the like. In addition, it can be used for the purpose of reducing pain during needle insertion during dialysis, blood sampling, intravenous drip, and vaccination.
また、内視鏡、大腸ファイバー、経鼻チューブ等の体内導入器具の使用前に、使用時の痛みを軽減する目的で、接触部位（皮膚、粘膜）に適用することができる。 Furthermore, before using an instrument introduced into the body such as an endoscope, colon fiber, or nasal tube, it can be applied to the contact area (skin, mucous membrane) for the purpose of reducing pain during use.
本発明の表面麻酔剤の適用方法（付与用法）としては、例えば、塗布、貼付、スプレー（噴霧）等を挙げることができる。 Examples of the application method (applying method) of the surface anesthetic of the present invention include coating, pasting, spraying, and the like.
本発明の麻酔成分は、リドカイン及びプロピトカインを含むものであれば特に制限されるものではなく、具体的に例えば、市販のエムラ（登録商標）クリームを挙げることができる。 The anesthetic component of the present invention is not particularly limited as long as it contains lidocaine and propitocaine, and a specific example thereof can include commercially available Emla (registered trademark) cream.
本発明の麻酔成分には、リドカイン及びプロピトカイン以外に、他の麻酔成分を組み合わせることもできる。他の麻酔成分としては、表面麻酔剤の麻酔成分として使用でき、本発明の効果を阻害するものでなければ特に制限されるものではなく、例えば、アミド型、エステル型などいずれの局所麻酔薬（表面麻酔薬）も組み合わせることができ、２種以上を組み合わせてもよい。 In addition to lidocaine and propitocaine, other anesthetic components can also be combined with the anesthetic component of the present invention. Other anesthetic ingredients can be used as an anesthetic ingredient for surface anesthetics and are not particularly limited as long as they do not inhibit the effects of the present invention. For example, any local anesthetics such as amide type and ester type ( Surface anesthetics) can also be combined, or two or more types may be combined.
アミド型の局所麻酔薬としては、例えば、メピバカイン，ジブカインを挙げることができる。エステル型の局所麻酔薬としては、例えば、テトラカイン、ベンゾカイン、アミノ安息香酸エチル、コカインを挙げることができる。麻酔成分は、塩酸塩等の塩であってもよく、本明細書において、例えばリドカインと称した場合は、リドカイン塩酸塩等を含む。これらの局所麻酔薬は市販されており、市販品を用いることができる。 Examples of amide-type local anesthetics include mepivacaine and dibucaine. Examples of ester-type local anesthetics include tetracaine, benzocaine, ethyl aminobenzoate, and cocaine. The anesthetic component may be a salt such as hydrochloride, and in this specification, for example, when lidocaine is referred to, it includes lidocaine hydrochloride and the like. These local anesthetics are commercially available, and commercially available products can be used.
テルペノイドは、香料成分や清涼成分として知られているが、本発明においては、麻酔成分の除痛効果を高め、さらにその効果の即効性及び／又は持続性を向上させる成分である。 Terpenoids are known as fragrance ingredients and refreshing ingredients, but in the present invention, they are ingredients that enhance the pain relief effect of the anesthetic ingredient and further improve the immediate effect and/or sustainability of the effect.
テルペノイドとしては、常温で油状のものが好ましく、例えば、ゲラニオール、メントン、リモネン、アネトール、ネロール、ミルセノール、リナロール、ラバンジュロール、シネオール、ピネン、テルピノレンを挙げることができ、これらの中でも、ゲラニオールが好ましい。これらのテルペノイドは、２種以上用いてもよい。 The terpenoid is preferably one that is oily at room temperature, and examples thereof include geraniol, menthone, limonene, anethole, nerol, myrcenol, linalool, lavandulol, cineole, pinene, and terpinolene. Among these, geraniol is preferable. . Two or more types of these terpenoids may be used.
本発明の表面麻酔剤は、１種又は２種以上の溶剤を含むことが好ましい。溶剤としては、例えば、エタノール、イソプロピルアルコール等のアルコールを挙げることができ、イソプロピルアルコールが好ましい。イソプロピルアルコールを含むことにより、麻酔成分及びテルペノイドの相溶性がより高くなり、本発明の効果をより有効に発揮することができる。イソプロピルアルコールは、医薬品としては消毒剤として使用されている物質であり、市販品を用いてもよい。 The surface anesthetic of the present invention preferably contains one or more solvents. Examples of the solvent include alcohols such as ethanol and isopropyl alcohol, with isopropyl alcohol being preferred. By including isopropyl alcohol, the compatibility between the anesthetic component and the terpenoid becomes higher, and the effects of the present invention can be more effectively exhibited. Isopropyl alcohol is a substance used as a disinfectant in medicine, and a commercially available product may be used.
本発明の表面麻酔剤における麻酔成分の含有量としては、表面麻酔剤としての効果を発揮できる量であれば特に制限されるものではなく、例えば、表面麻酔剤中、０．１質量％以上であり、０．５～７０質量％であることが好ましく、１～６０質量％であることがより好ましく、３～５０質量％であることがさらに好ましく、４～２０質量％であることが特に好ましく、５～２０質量％であることが最も好ましい。 The content of the anesthetic component in the surface anesthetic of the present invention is not particularly limited as long as it can exhibit the effect as a surface anesthetic; for example, the content of the anesthetic component in the surface anesthetic is 0.1% by mass or more. It is preferably 0.5 to 70% by mass, more preferably 1 to 60% by mass, even more preferably 3 to 50% by mass, and particularly preferably 4 to 20% by mass. , most preferably 5 to 20% by weight.
本発明の表面麻酔剤におけるテルペノイドの含有量としては、局所麻酔剤の除痛効果を高めることができる量であれば特に制限されるものではなく、例えば、表面麻酔剤中、０．０００００１～２質量％程度であり、０．０００００５～１質量％であることが好ましく、０．０００００８～０．５質量％であることがさらに好ましく、０．００００１～０．２質量％であることがさらに好ましく、０．０００１～０．１質量％であることが特に好ましい。 The content of terpenoid in the surface anesthetic of the present invention is not particularly limited as long as it can enhance the analgesic effect of the local anesthetic, and for example, 0.000001 to 2 It is about 0.000005 to 1% by mass, more preferably 0.000008 to 0.5% by mass, and even more preferably 0.00001 to 0.2% by mass. , 0.0001 to 0.1% by mass is particularly preferred.
本発明の表面麻酔剤は、従来公知の添加剤を含んでいてもよい。かかる添加剤としては、例えば、酸化防止剤、保存安定剤、増粘剤、香料等を挙げることができる。 The surface anesthetic of the present invention may contain conventionally known additives. Examples of such additives include antioxidants, storage stabilizers, thickeners, fragrances, and the like.
以下、本発明を実施例に基づき詳細に説明する。
［実施例１］
０．８ｇｍのエムラ（登録商標）クリームと、１６０μｌの０．００１％イソプロピルアルコール／ゲラニオール（ＩＰＡ／ＧＬ）溶液とを混合し、表面麻酔剤（ＥＭＬＡ０．８ｇｍ＋２０％ＩＰＡ／ＧＬ）を得た。
なお、エムラ（登録商標）クリームには、１ｇｍ当たり、リドカインが０.０２５ｇｍ、プロピトカインが０.０２５ｇｍ含まれる。また、表面麻酔剤中の麻酔成分（リドカイン及びプロピトカイン）の含有量は、４．３２質量％であり、表面麻酔剤中のゲラニオールの含有量は０．０００１３６質量％である。
Hereinafter, the present invention will be explained in detail based on examples.
[Example 1]
0.8 gm of Emla® cream and 160 μl of 0.001% isopropyl alcohol/geraniol (IPA/GL) solution were mixed to obtain a surface anesthetic (0.8 gm of EMLA+20% IPA/GL).
Note that Emla (registered trademark) cream contains 0.025 gm of lidocaine and 0.025 gm of propitocaine per 1 gm. Further, the content of anesthetic components (lidocaine and propitocaine) in the surface anesthetic is 4.32% by mass, and the content of geraniol in the surface anesthetic is 0.000136% by mass.
［実施例２］
１．０ｇｍのエムラ（登録商標）クリームと、２００μｌの０．００１％ＩＰＡ／ＧＬ溶液とを混合し、混合物の２０重量％を除去し、表面麻酔剤（（ＥＭＬＡ１．０ｇｍ＋２０％ＩＰＡ／ＧＬ）－２０％ｗｔ）を得た。
なお、表面麻酔剤中の麻酔成分（リドカイン及びプロピトカイン）の含有量は、４．３質量％であり、表面麻酔剤中のゲラニオールの含有量は０．０００１３６質量％である。
[Example 2]
Mix 1.0 gm of EMLA® cream and 200 μl of 0.001% IPA/GL solution, remove 20% by weight of the mixture, and apply the surface anesthetic ((EMLA 1.0 gm + 20% IPA/GL) - 20%wt) was obtained.
The content of anesthetic components (lidocaine and propitocaine) in the surface anesthetic is 4.3% by mass, and the content of geraniol in the surface anesthetic is 0.000136% by mass.
［比較例１］
０．８ｇｍのエムラ（登録商標）クリームを比較例１とした。
[Comparative example 1]
Comparative Example 1 was 0.8 gm of Emla (registered trademark) cream.
［実施例３］
１．２ｇｍのエムラ（登録商標）クリームと３０７．５μｌの０．００１％ＩＰＡ／ＧＬ溶液とを混合し、表面麻酔剤（ＥＭＬＡ１．２ｇｍ＋２０％ＩＰＡ／ＧＬ）を得た。
なお、表面麻酔剤中の麻酔成分（リドカイン及びプロピトカイン）の含有量は、４．１６質量％であり、表面麻酔剤中のゲラニオールの含有量は０．０００１６６質量％である。
[Example 3]
1.2 gm of Emla® cream and 307.5 μl of 0.001% IPA/GL solution were mixed to obtain a surface anesthetic (1.2 gm of EMLA+20% IPA/GL).
The content of anesthetic components (lidocaine and propitocaine) in the surface anesthetic is 4.16% by mass, and the content of geraniol in the surface anesthetic is 0.000166% by mass.
［比較例２］
１．２ｇｍのエムラ（登録商標）クリームを比較例２とした。
[Comparative example 2]
Comparative Example 2 was 1.2 gm of Emla (registered trademark) cream.
［実施例４］
１．５ｇｍのエムラ（登録商標）クリームと、３００μｌの０．００１％ＩＰＡ／ＧＬ溶液とを混合し、表面麻酔剤（ＥＭＬＡ１．５ｇｍ＋２０％ＩＰＡ／ＧＬ）を得た。
なお、表面麻酔剤中の麻酔成分（リドカイン及びプロピトカイン）の含有量は、４．３２質量％であり、表面麻酔剤中のゲラニオールの含有量は０．０００１３６質量％である。
[Example 4]
1.5 gm of Emla (registered trademark) cream and 300 μl of 0.001% IPA/GL solution were mixed to obtain a surface anesthetic (1.5 gm of EMLA + 20% IPA/GL).
The content of anesthetic components (lidocaine and propitocaine) in the surface anesthetic is 4.32% by mass, and the content of geraniol in the surface anesthetic is 0.000136% by mass.
［実施例５］
１．８７５ｇｍのエムラ（登録商標）クリームと、３７５μｌの０．００１％ＩＰＡ／ＧＬ溶液とを混合した後、混合物の２０重量％を除去し、表面麻酔剤（（ＥＭＬＡ１．８７５ｇｍ＋２０％ＩＰＡ／ＧＬ）－２０％ｗｔ）を得た。
なお、表面麻酔剤中の麻酔成分（リドカイン及びプロピトカイン）の含有量は、４．３２質量％であり、表面麻酔剤中のゲラニオールの含有量は０．０００１３６質量％である。
[Example 5]
After mixing 1.875 gm of EMLA® cream and 375 μl of 0.001% IPA/GL solution, 20% by weight of the mixture was removed and the surface anesthetic ((EMLA 1.875 gm + 20% IPA/GL) -20%wt) was obtained.
The content of anesthetic components (lidocaine and propitocaine) in the surface anesthetic is 4.32% by mass, and the content of geraniol in the surface anesthetic is 0.000136% by mass.
［比較例３］
１．５ｇｍのエムラ（登録商標）クリームを比較例３とした。
[Comparative example 3]
Comparative Example 3 was 1.5 gm of Emla (registered trademark) cream.
［鈍針の痛みの程度の評価］
調製した各表面麻酔剤を前腕部皮膚の約２．５ｃｍ×２．５ｃｍの範囲へ塗布し、所定時間経過後に、鈍針で皮膚を突くことによる痛みの程度について評価した。なお、表面麻酔剤は、試験開始２０分間経過後に拭き取り、評価を続けた。
[Evaluation of the degree of pain caused by blunt needles]
Each of the prepared surface anesthetics was applied to an area of about 2.5 cm x 2.5 cm on the skin of the forearm, and after a predetermined period of time, the degree of pain caused by poking the skin with a blunt needle was evaluated. Note that the surface anesthetic was wiped off 20 minutes after the start of the test, and the evaluation was continued.
その結果を図１～８に示す。図１は実施例１、図２は実施例２、図３は比較例１、図４は実施例３、図５は比較例２、図６は実施例４、図７は実施例５、図８は比較例３の結果を表す。図の横軸は塗布後の経過時間（分）であり、縦軸は痛みのレベル（ペインレベル）を表す。なお、縦軸のペインレベル５は中等度の痛みを表し、ペインレベル０は痛みなしを表す。ペインレベル１０が考えられる最大限の痛みである。 The results are shown in Figures 1-8. 1 is Example 1, FIG. 2 is Example 2, FIG. 3 is Comparative Example 1, FIG. 4 is Example 3, FIG. 5 is Comparative Example 2, FIG. 6 is Example 4, FIG. 7 is Example 5, 8 represents the results of Comparative Example 3. The horizontal axis of the figure represents the elapsed time (minutes) after application, and the vertical axis represents the level of pain (pain level). Note that pain level 5 on the vertical axis represents moderate pain, and pain level 0 represents no pain. A pain level of 10 is the maximum possible pain.
図１に示すように、実施例１に係る表面麻酔剤（ＥＭＬＡ０．８ｇｍ＋２０％ＩＰＡ／ＧＬ）では、ペインレベル１以下に塗布後１１分で到達し、その後、ペインレベル１以下の除痛効果は、塗布後３９分間継続した。また、塗布後１６分でペインレベル０の無痛となり、ペインレベル０の時間は、合計で７分間であった。 As shown in Figure 1, the surface anesthetic (EMLA 0.8 gm + 20% IPA/GL) according to Example 1 reached pain level 1 or below in 11 minutes after application, and thereafter the pain relief effect at pain level 1 or below was , continued for 39 minutes after application. Furthermore, the pain level was 0 and painless occurred 16 minutes after application, and the pain level 0 time was 7 minutes in total.
図２に示すように、実施例２に係る表面麻酔剤（（ＥＭＬＡ１．０ｇｍ＋２０％ＩＰＡ／ＧＬ）－２０％ｗｔ）では、ペインレベル１以下に塗布後１１分で到達し、その後、ペインレベル１以下の除痛効果は、塗布後３７分間継続した。また、塗布後１７分でペインレベル０の無痛となり、ペインレベル０の時間は、合計で７分間であった。 As shown in FIG. 2, the surface anesthetic according to Example 2 ((EMLA 1.0 gm + 20% IPA/GL) - 20% wt) reached pain level 1 or less in 11 minutes after application, and then reached pain level 1 or less after application. The following pain relief effect continued for 37 minutes after application. Moreover, the pain level was 0 and painless occurred 17 minutes after application, and the pain level 0 time was 7 minutes in total.
他方、図３に示すように、比較例１に係る表面麻酔剤（ＥＭＬＡ０．８ｇｍ）では、ペインレベル１以下に到達するのに塗布後２３分を要し、ペインレベル１以下の除痛効果は、塗布後１５分間しか持続しなかった。また、ペインレベル０の無痛に到達するのに塗布後３１分を要し、ペインレベル０の時間は、合計で２分間のみであった。 On the other hand, as shown in FIG. 3, with the surface anesthetic (EMLA 0.8 gm) according to Comparative Example 1, it took 23 minutes after application to reach pain level 1 or below, and the pain relief effect at pain level 1 or below was , lasted only 15 minutes after application. Furthermore, it took 31 minutes after application to reach pain level 0, which was pain-free, and the pain level 0 time was only 2 minutes in total.
図４に示すように、実施例３に係る表面麻酔剤（ＥＭＬＡ１．２ｇｍ＋２０％ＩＰＡ／ＧＬ）では、ペインレベル１以下に塗布後１１分で到達し、その後、ペインレベル１以下の除痛効果は、塗布後３８分間継続した。また、塗布後１６分でペインレベル０の無痛となり、ペインレベル０の時間は、合計で８分間であった。 As shown in Figure 4, the surface anesthetic (EMLA 1.2 gm + 20% IPA/GL) according to Example 3 reached pain level 1 or below in 11 minutes after application, and thereafter the pain relief effect at pain level 1 or below was , continued for 38 minutes after application. In addition, the pain level was 0 and painless 16 minutes after application, and the pain level was 0 for a total of 8 minutes.
他方、図５に示すように、比較例２に係る表面麻酔剤（ＥＭＬＡ１．２ｇｍ）では、ペインレベル１以下に到達するのに塗布後１６分を要し、ペインレベル１以下の除痛効果は、合計で塗布後１９分間持続したが、途中１分間はペインレベル２となった。また、ペインレベル０の無痛に到達するのに塗布後３１分を要し、ペインレベル０の時間は、合計で３分間のみであった。 On the other hand, as shown in FIG. 5, with the surface anesthetic (EMLA 1.2 gm) according to Comparative Example 2, it took 16 minutes after application to reach pain level 1 or below, and the pain relief effect at pain level 1 or below was It lasted a total of 19 minutes after application, but the pain level was 2 for 1 minute in the middle. Furthermore, it took 31 minutes after application to reach pain level 0, and the pain level 0 was only 3 minutes in total.
図６に示すように、実施例４に係る表面麻酔剤（ＥＭＬＡ１．５ｇｍ＋２０％ＩＰＡ／ＧＬ）では、ペインレベル１以下に塗布後１１分で到達し、その後、ペインレベル１以下の除痛効果は、塗布後３９分間継続した。また、塗布後１５分でペインレベル０の無痛となり、ペインレベル０の時間は、合計で９分間であった。 As shown in FIG. 6, the surface anesthetic according to Example 4 (EMLA 1.5 gm + 20% IPA/GL) reached pain level 1 or below in 11 minutes after application, and thereafter the pain relief effect at pain level 1 or below was , continued for 39 minutes after application. Furthermore, the pain level was 0 and painless occurred 15 minutes after application, and the pain level 0 time was 9 minutes in total.
図７に示すように、実施例５に係る表面麻酔剤（（ＥＭＬＡ１．８７５ｇｍ＋２０％ＩＰＡ／ＧＬ）－２０％ｗｔ）では、ペインレベル１以下に塗布後１１分で到達し、その後、ペインレベル１以下の除痛効果は、塗布後３８分間継続した。また、塗布後１６分でペインレベル０の無痛となり、ペインレベル０の時間は、合計で１０分間であった。 As shown in FIG. 7, the surface anesthetic according to Example 5 ((EMLA 1.875 gm + 20% IPA/GL) - 20% wt) reached pain level 1 or less in 11 minutes after application, and then reached pain level 1. The following pain relief effect continued for 38 minutes after application. Furthermore, the pain level was 0 and painless 16 minutes after application, and the pain level was 0 for a total of 10 minutes.
他方、図８に示すように、比較例３に係る表面麻酔剤（ＥＭＬＡ１．５ｇｍ）では、ペインレベル１以下に到達するのに塗布後１３分を要し、ペインレベル１以下の除痛効果は、合計で塗布後１９分間持続したが、途中５分間はペインレベル２となった。また、ペインレベル０の無痛に到達するのに塗布後２９分を要し、ペインレベル０の時間は、合計で３分間のみであった。 On the other hand, as shown in FIG. 8, with the surface anesthetic (EMLA 1.5 gm) according to Comparative Example 3, it took 13 minutes after application to reach pain level 1 or below, and the pain relief effect at pain level 1 or below was It lasted for a total of 19 minutes after application, but the pain level was 2 for 5 minutes in the middle. Furthermore, it took 29 minutes after application to reach pain level 0, which was pain-free, and the pain level 0 time was only 3 minutes in total.
［熱に対する痛みの評価］
調製した各表面麻酔剤を前腕部皮膚の約２．５ｃｍ×２．５ｃｍの範囲へ塗布し、表面麻酔剤を塗布した皮膚へ痛覚計（株式会社ユニークメディカル製：ＵＤＨ－１０５）を用いて熱刺激を与え、熱に対する痛みの評価を行った。痛覚計の設定温度は、３８～６０℃とした。表面麻酔剤は、試験開始２０分間経過後に拭き取り、評価を続けた。
[Evaluation of pain in response to heat]
Each prepared surface anesthetic was applied to an area of approximately 2.5 cm x 2.5 cm on the skin of the forearm, and heat was applied to the skin coated with the surface anesthetic using an algometer (manufactured by Unique Medical Co., Ltd.: UDH-105). Stimulation was applied, and pain in response to heat was evaluated. The temperature setting of the algometer was 38 to 60°C. The surface anesthetic was wiped off 20 minutes after the start of the test, and evaluation was continued.
その結果を図９～１６に示す。図９は実施例１、図１０は実施例２、図１１は比較例１、図１２は実施例３、図１３は比較例２、図１４は実施例４、図１５は実施例５、図１６は比較例３の結果を表す。図の横軸は塗布後の経過時間（分）であり、縦軸は痛みを感じる温度（℃）を表す。なお、皮膚に麻酔を塗布しない場合、３８℃では皮膚に痛みはなく、３９℃では非常に小さな痛みを示し、３９℃を超えると温度と共に痛みが増した。したがって、表面麻酔剤を塗布した後に、耐えられる温度が３９℃を超える場合に、麻酔が正常に機能していることを示す。 The results are shown in Figures 9-16. 9 shows Example 1, FIG. 10 shows Example 2, FIG. 11 shows Comparative Example 1, FIG. 12 shows Example 3, FIG. 13 shows Comparative Example 2, FIG. 14 shows Example 4, and FIG. 15 shows Example 5. 16 represents the results of Comparative Example 3. The horizontal axis of the figure represents the elapsed time (minutes) after application, and the vertical axis represents the temperature at which pain is felt (°C). Note that when no anesthesia was applied to the skin, there was no pain on the skin at 38°C, very little pain at 39°C, and the pain increased with temperature above 39°C. Therefore, if the tolerable temperature exceeds 39° C. after applying the topical anesthetic, it indicates that the anesthesia is functioning normally.
図９及び図１０に示すように、実施例１に係る表面麻酔剤（ＥＭＬＡ０．８ｇｍ＋２０％ＩＰＡ／ＧＬ）及び実施例２に係る表面麻酔剤（（ＥＭＬＡ１．０ｇｍ＋２０％ＩＰＡ／ＧＬ）－２０％ｗｔ）では、塗布後から急激に耐え得る温度（耐温度）の上昇がみられ、長期にわたって耐温度４３℃以上を維持していた。 As shown in FIGS. 9 and 10, the surface anesthetic according to Example 1 (EMLA 0.8 gm + 20% IPA/GL) and the surface anesthetic according to Example 2 ((EMLA 1.0 gm + 20% IPA/GL) - 20%wt ), a rapid rise in the withstandable temperature (temperature resistance) was observed after application, and the temperature resistance was maintained at 43° C. or higher for a long period of time.
他方、図１１に示すように、比較例１に係る表面麻酔剤（ＥＭＬＡ０．８ｇｍ）では、塗布後から緩やかに耐温度の上昇がみられ、耐温度が４３℃以上となることはなかった。 On the other hand, as shown in FIG. 11, with the surface anesthetic (EMLA 0.8 gm) according to Comparative Example 1, a gradual increase in temperature resistance was observed after application, and the temperature resistance did not exceed 43°C.
図１２に示すように、実施例３に係る表面麻酔剤（ＥＭＬＡ１．２ｇｍ＋２０％ＩＰＡ／ＧＬ）では、塗布後から急激に耐温度の上昇がみられ、長期にわたって耐温度４３℃以上を維持していた。 As shown in FIG. 12, the surface anesthetic according to Example 3 (EMLA 1.2 gm + 20% IPA/GL) showed a rapid increase in temperature resistance after application, and maintained a temperature resistance of 43°C or higher for a long period of time. Ta.
他方、図１３に示すように、比較例２に係る表面麻酔剤（ＥＭＬＡ１．２ｇｍ）では、塗布後から緩やかに耐温度の上昇がみられ、耐温度が４３℃以上となる時間は短時間であった。 On the other hand, as shown in Figure 13, with the surface anesthetic (EMLA 1.2 gm) according to Comparative Example 2, the temperature resistance gradually increased after application, and the time for the temperature resistance to exceed 43°C was short. there were.
図１４及び図１５に示すように、実施例４に係る表面麻酔剤（ＥＭＬＡ１．５ｇｍ＋２０％ＩＰＡ／ＧＬ）及び実施例５に係る表面麻酔剤（（ＥＭＬＡ１．８７５ｇｍ＋２０％ＩＰＡ／ＧＬ）－２０％ｗｔ）では、塗布後から急激に耐温度の上昇がみられ、長期にわたって耐温度４３℃以上を維持していた。特に実施例４では、長期にわたって耐温度４４℃程度を維持していた。 As shown in FIGS. 14 and 15, the surface anesthetic according to Example 4 (EMLA 1.5 gm + 20% IPA/GL) and the surface anesthetic according to Example 5 ((EMLA 1.875 gm + 20% IPA/GL) - 20% wt ), a rapid increase in temperature resistance was observed after application, and the temperature resistance was maintained at 43° C. or higher for a long period of time. In particular, in Example 4, a temperature resistance of about 44° C. was maintained for a long period of time.
他方、図１６に示すように、比較例３に係る表面麻酔剤（ＥＭＬＡ１．５ｇｍ）では、塗布後から緩やかに耐温度の上昇がみられ、耐温度が４３℃以上となる時間は短時間であった。 On the other hand, as shown in FIG. 16, with the surface anesthetic (EMLA 1.5 gm) according to Comparative Example 3, the temperature resistance gradually increased after application, and the time for the temperature resistance to reach 43°C or higher was short. there were.
以上のとおり、実施例に係る表面麻酔剤は、比較例に係る表面麻酔剤と比較して、除痛効果が高く、即効性、持続性の点でも優れていた。 As described above, the surface anesthetics according to the examples had a higher pain relief effect and were also superior in terms of immediate effect and sustainability, compared to the surface anesthetics according to the comparative examples.
本発明の表面麻酔剤は、除痛効果が高く、産業上有用である。
The surface anesthetic of the present invention has a high pain relief effect and is industrially useful.
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| WO2017164084A1 (en) | 2016-03-24 | 2017-09-28 | 株式会社メドレックス | Patch preparation having misuse prevention characteristics |
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| KOZIOL, Agata et al.，An Overview of the Pharmacological Properties and Potential Applications of Natural Monoterpenes，Mini-Reviews in Medicinal Chemistry，14，1156-1168，DOI: 10.2174/1389557514666141127145820 |
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