JPH09235232A - Skin damage-curing agent containing acetylsalicyclic acid - Google Patents
Skin damage-curing agent containing acetylsalicyclic acidInfo
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- JPH09235232A JPH09235232A JP34510396A JP34510396A JPH09235232A JP H09235232 A JPH09235232 A JP H09235232A JP 34510396 A JP34510396 A JP 34510396A JP 34510396 A JP34510396 A JP 34510396A JP H09235232 A JPH09235232 A JP H09235232A
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- acetylsalicylic acid
- skin damage
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- ointment
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- Prior art date
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Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明はアセチルサリチル酸
を含有する皮膚損傷治療剤に関する。TECHNICAL FIELD The present invention relates to a therapeutic agent for skin damage containing acetylsalicylic acid.
【０００２】[0002]
【従来の技術および発明が解決しようとする課題】アセ
チルサリチル酸は一般的にはアスピリンと呼称され、そ
の強力な鎮痛作用と緩和な解熱作用及び抗リウマチ作用
により、頭痛薬等に広く使用されている。一方、慢性的
な服用で消化性潰瘍を起こす作用やアスピリン喘息を招
くことがあり、胃潰瘍における動物病態モデルにアスピ
リン潰瘍が広く用いられているのもまた事実である。更
にサリチル酸誘導体には消炎鎮痛作用を持つ物が多く存
在し、これらは外用剤として打ち身、捻挫等に適用され
ている。このように、医療分野で多量に使用されている
アセチルサリチル酸ではあるが、その粘膜上皮傷害作用
のためか、創傷に適応することは過去においてなかっ
た。2. Description of the Related Art Acetylsalicylic acid is generally called aspirin, and is widely used as a headache drug due to its strong analgesic action, mild antipyretic action and antirheumatic action. . On the other hand, it is also a fact that aspirin ulcer is widely used as an animal pathological model for gastric ulcer, since it may cause peptic ulcer and aspirin asthma when chronically taken. Furthermore, there are many salicylic acid derivatives having anti-inflammatory and analgesic effects, and these are applied as external preparations for bruise, sprains and the like. Thus, although acetylsalicylic acid is used in large amounts in the medical field, it has not been applied to wounds in the past, probably due to its mucosal epithelial damage.
【０００３】一方、皮膚損傷は皮膚の創傷であり、創傷
の発生原因は物理的によるもの（熱傷、擦過傷、裂傷）
が主であるが、現在、その難治性のため注目されている
褥瘡を例に取り、その治療方法についての現状を見る
と、治療方法としては対症療法が主であり、褥瘡の発生
原因の除去や創面の洗浄、消毒、肉芽や表皮の形成環境
の整備といった面が主流である。肉芽や表皮組織の形成
を積極的に加速する薬物には幼牛血液抽出物（商品名ソ
ルコセリル）、ブグラデシンナトリウム、トレチノイン
トコフェリル等が開発されているものの、それらの効果
は充分とはいえないため、完治を見ない例が数多く存在
するのが現状である。従って、難治性の褥瘡に対しても
治癒を促進させ得る、作用の強い薬剤の出現が望まれて
いた。On the other hand, the skin damage is a wound of the skin, and the cause of the wound is physical (burn, abrasion, laceration).
However, taking pressure ulcers, which are currently attracting attention due to their intractability, as an example, and looking at the current state of treatment, the symptomatic treatment is the main treatment and the elimination of the cause of pressure ulcers. The mainstream areas are cleaning and disinfection of wounds, disinfection, and maintenance of the formation environment for granulation and epidermis. Although calf blood extract (trade name: solcoceryl), sodium bugladecin, tretinoin tocopheryl, etc. have been developed as drugs that positively accelerate the formation of granulation and epidermal tissue, their effects are not sufficient. Since there are no such cases, there are many cases in which a complete cure is not seen. Therefore, it has been desired to develop a drug having a strong action, which can promote healing even for intractable pressure ulcers.
【０００４】[0004]
【課題を解決するための手段】本発明者等はかかる現況
において、表皮組織の形成を強力に促進する化合物を検
索するべく研究を行ってきたが、アセチルサリチル酸が
この目的に完全に合致するものであることを見いだし、
本発明を完成した。すなわち、本発明はアセチルサリチ
ル酸を活性成分として含有することを特徴とする皮膚損
傷治療剤を提供するものである。Under the present circumstances, the present inventors have conducted research to find a compound that strongly promotes the formation of epidermal tissue, but acetylsalicylic acid completely meets this purpose. And found that
The present invention has been completed. That is, the present invention provides a therapeutic agent for skin damage, which comprises acetylsalicylic acid as an active ingredient.
【０００５】本発明者等は、アセチルサリチル酸を０.
１〜１０％濃度含有する局所適用製剤を作成し、この製
剤を皮膚損傷部位、具体的にはラットを用いた褥瘡モデ
ル、熱傷・火傷モデルに適用したところ、種々の皮膚損
傷状態において、顕著に組織修復の促進傾向が認めら
れ、筋層に達する深い皮膚損傷状態においても痂皮の形
成を抑制し肉芽組織の形成及び表皮形成を促進すること
を見いだした。更に、ラットを用いた皮膚欠損症モデル
に対してアセチルサリチル酸を１５ｍｇないしは７５ｍ
ｇ／ｋｇ／日の投与量で経口投与した場合にも、局所適
用製剤と同様の効果を見いだした。また、ヒトにおける
難治性の褥瘡に上記の局所適用製剤を用いたところ、ほ
とんどすべての例で創面面積の縮小更には治癒が認めら
れ、この効果は驚くべきものであった。熱傷・火傷につ
いてもアセチルサリチル酸の既知の作用である鎮痛効果
の他に皮膚損傷の著明な改善が得られ、この作用は皮膚
の損傷全般に適用できうることが見いだされた。The present inventors have added acetylsalicylic acid to
When a topical preparation containing 1 to 10% concentration was prepared and this preparation was applied to a skin damage site, specifically, a pressure ulcer model using rats, a burn / burn model, it was remarkably found in various skin damage states. It was found that there was a tendency to promote tissue repair and that it suppressed scab formation and promoted granulation tissue formation and epidermal formation even in the deep skin damage state reaching the muscular layer. Furthermore, 15 mg or 75 m of acetylsalicylic acid was used for a skin defect model using rats.
Even when orally administered at a dose of g / kg / day, the same effect as that of the topical preparation was found. Further, when the above-mentioned topical preparation was used for intractable pressure ulcer in humans, reduction in wound surface area and healing were observed in almost all cases, and this effect was surprising. With regard to burns and burns as well, in addition to the known analgesic effect of acetylsalicylic acid, significant improvement in skin damage was obtained, and it was found that this effect can be applied to skin damage in general.
【０００６】[0006]
【発明の実施の形態】上記作用は、局所適用製剤の場
合、製剤中のアセチルサリチル酸濃度に依存するため、
１５％を超える濃度の製剤ではかえって悪化傾向を示
し、０.０５％未満の濃度の製剤においては効果が見ら
れない。したがって、局所適用製剤中のアセチルサリチ
ル酸の含量は０.０５〜１５重量％、好ましくは０.１〜
１０重量％、最も好ましくは０.２〜８重量％の範囲で
ある。また、経口投与の場合にも至適投与量が存在し、
高用量では悪化傾向を示し、低用量では効果がみられな
い。したがって、本発明のアセチルサリチル酸の経口投
与での有効投与量は、１５〜７５ｍｇ／ｋｇ体重／日、
好ましくは２０〜６５ｍｇ／ｋｇ体重／日、最も好まし
くは３０〜６０ｍｇ／ｋｇ体重／日である。BEST MODE FOR CARRYING OUT THE INVENTION In the case of a preparation for topical application, the above action depends on the concentration of acetylsalicylic acid in the preparation.
A formulation having a concentration of more than 15% tends to worsen, and a formulation having a concentration of less than 0.05% has no effect. Therefore, the content of acetylsalicylic acid in the topical preparation is 0.05 to 15% by weight, preferably 0.1 to
It is in the range of 10% by weight, most preferably 0.2 to 8% by weight. There is also an optimal dose for oral administration,
High doses tend to worsen and low doses have no effect. Therefore, the effective dose for oral administration of acetylsalicylic acid of the present invention is 15-75 mg / kg body weight / day,
It is preferably 20 to 65 mg / kg body weight / day, most preferably 30 to 60 mg / kg body weight / day.
【０００７】本発明の皮膚損傷治療剤は、いずれの投与
剤型も採用され、局所適用製剤としては例えば軟膏剤、
クリーム剤、ゲル剤、ゲル軟膏剤、貼付剤、液剤、散剤
等の剤形を用いることができ、経口製剤としては錠剤、
丸剤、カプセル剤、散剤、顆粒剤、細粒剤、ドライシロ
ップ剤等の剤形を用いることができる。上記製剤の調製
は常法により、通常の賦形剤、希釈剤、担体等を用いて
行うことができる。The therapeutic agent for skin damage of the present invention may be used in any dosage form, and as a topical preparation, for example, an ointment,
Dosage forms such as creams, gels, gel ointments, patches, liquids, and powders can be used, and tablets as oral preparations,
Dosage forms such as pills, capsules, powders, granules, fine granules and dry syrups can be used. The above-mentioned preparation can be prepared by a conventional method using usual excipients, diluents, carriers and the like.
【０００８】例えば、軟膏剤の調製には、ワセリン、高
級アルコール類、ミツロウ、植物油、ポリエチレングリ
コール等を用いる。市販の軟膏基剤、例えば「プラスチ
ベース」を用いるのが好都合である。クリーム剤の調製
には、油脂類、ワックス類、高級脂肪酸類、高級アルコ
ール類、脂肪酸エステル類、精製水、乳化剤などが用い
られる。ゲル剤の調製には、ポリアクリル酸（ポリアク
リル酸ナトリウム等）、ヒドロキシプロピルセルロー
ス、ヒドロキシプロピルメチルセルロース、ポリビニル
アルコール、ポリビニルピロリドン、精製水、低級アル
コール、多価アルコール、ポリエチレングリコールなど
が用いられる。ゲル軟膏剤の調製には、上記ゲル剤に用
いられる基剤に加えて、乳化剤（好ましくは非イオン活
性剤）、油類（液体パラフィン等）が用いられる。局所
適用製剤には、さらに、パラフィン類、スクワラン、ラ
ノリン、コレステロールエステルなどを配合してもよ
く、またＢＨＡ、ＢＨＴなどの抗酸化剤なども適宜配合
される。For example, vaseline, higher alcohols, beeswax, vegetable oil, polyethylene glycol and the like are used for the preparation of ointments. It is convenient to use a commercially available ointment base, eg "Plastibase". For the preparation of the cream, oils and fats, waxes, higher fatty acids, higher alcohols, fatty acid esters, purified water, emulsifiers and the like are used. For the preparation of the gel agent, polyacrylic acid (sodium polyacrylate, etc.), hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone, purified water, lower alcohol, polyhydric alcohol, polyethylene glycol and the like are used. For the preparation of the gel ointment, an emulsifier (preferably a nonionic activator) and oils (liquid paraffin, etc.) are used in addition to the base used for the gel. The topical preparation may further contain paraffins, squalane, lanolin, cholesterol esters and the like, and antioxidants such as BHA and BHT may be appropriately added.
【０００９】錠剤の調製には、例えば乳糖、白糖、デン
プン、炭酸カルシウム、カオリン、結晶セルロースなど
の賦形剤、水、単シロップ、ブドウ糖液、デンプン液、
ゼラチン溶液、カルボキシメチルセルロース、セラッ
ク、メチルセルロース、ポリビニルピロリドンなどの結
合剤、乾燥デンプン、アルギン酸ナトリウム、カンテン
末、カルメロース、ポリオキシエチレンソルビタン脂肪
酸エステル類、ラウリル硫酸ナトリウム、ステアリン酸
モノグリセリドなどの崩壊剤、白糖、ステアリン、カカ
オバター、水素添加油などの崩壊抑制剤、グリセリン、
プロピレングリコールなどの保湿剤、デンプン、乳糖、
ベントナイト、コロイドケイ酸などの吸着剤、精製タル
ク、ステアリン酸塩、硫酸カルシウムなどの滑沢剤など
が用いられる。さらに錠剤は糖衣錠、ゼラチン被包錠、
腸溶被錠、フィルムコーティング錠あるいは二重錠、多
層錠とすることができる。For the preparation of tablets, for example, excipients such as lactose, sucrose, starch, calcium carbonate, kaolin, crystalline cellulose, water, simple syrup, glucose solution, starch solution,
Gelatin solution, carboxymethyl cellulose, shellac, methyl cellulose, binders such as polyvinylpyrrolidone, dry starch, sodium alginate, agar powder, carmellose, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, disintegrating agents such as stearic acid monoglyceride, sucrose, Disintegration inhibitors such as stearin, cocoa butter, hydrogenated oil, glycerin,
Moisturizers such as propylene glycol, starch, lactose,
Adsorbents such as bentonite and colloidal silicic acid, refined talc, stearates, and lubricants such as calcium sulfate are used. Furthermore, tablets are sugar-coated tablets, gelatin-coated tablets,
It may be an enteric coated tablet, a film-coated tablet, a double tablet, or a multilayer tablet.
【００１０】丸剤の調製には、ブドウ糖、乳糖、デンプ
ン、カカオ脂、硬化植物油、カオリン、タルクなどの賦
形剤、アラビアゴム末、トラガント末、ゼラチン、セタ
ノールなどの結合剤、ラミナラン、カンテンなどの崩壊
剤などが用いられる。顆粒剤および細粒剤は、上記賦形
剤、結合剤などを用い、常法により顆粒化または細粒化
して調製される。またカプセル剤は、アセチルサリチル
酸と上記担体類の混合物、好ましくは顆粒、細粒または
粉末の形態にて常法により硬カプセルまたは軟カプセル
に充填して調製される。For the preparation of pills, excipients such as glucose, lactose, starch, cocoa butter, hardened vegetable oil, kaolin and talc, gum arabic powder, tragacanth powder, binders such as gelatin and cetanol, laminaran, agar and the like. The disintegrant of the above is used. Granules and fine granules are prepared by using the above-mentioned excipients, binders and the like to granulate or finely granulate by a conventional method. A capsule is prepared by filling a hard capsule or a soft capsule in a conventional manner in the form of a mixture of acetylsalicylic acid and the above carriers, preferably in the form of granules, fine particles or powder.
【００１１】上記経口製剤では活性成分のアセチルサリ
チル酸の含量は製剤形によっても異なるが、錠剤、顆粒
剤、細粒剤、散剤などの固形製剤では、製剤全重量当た
り、３０〜７０重量％、好ましくは４０〜６０重量％で
あり、シロップ剤のような液剤では、製剤全重量当た
り、０.１〜１０重量％、好ましくは０.５〜５重量％で
ある。In the above oral preparation, the content of acetylsalicylic acid as an active ingredient varies depending on the dosage form, but in solid preparations such as tablets, granules, fine granules and powders, 30 to 70% by weight, preferably 30 to 70% by weight, based on the total weight of the preparation. Is 40 to 60% by weight, and in a liquid preparation such as syrup, it is 0.1 to 10% by weight, preferably 0.5 to 5% by weight, based on the total weight of the formulation.
【００１２】[0012]
【実施例】つぎに、実施例および試験例を用いて本発明
をさらに詳しく説明するが、本発明はこれらに限られる
ものではない。 実施例１ 下記に示す組成に従って、アセチルサリチル
酸を少量のエタノールに溶解した後、溶媒を揮散して微
粉末とし、これに界面活性剤を加えて均一に混和した。
これに軟膏基剤を加えて更に混和し、軟膏剤を得た。成 分 配 合 量 アセチルサリチル酸 ０.５ｇ Tween 80 ５.０ｇ プラスチベース ９４.５ｇエタノール 微量 EXAMPLES Next, the present invention will be described in more detail by way of examples and test examples, but the present invention is not limited to these. Example 1 According to the composition shown below, acetylsalicylic acid was dissolved in a small amount of ethanol, and then the solvent was volatilized to form a fine powder. A surfactant was added to this and mixed uniformly.
An ointment base was added to this and further mixed to obtain an ointment. Amount of ingredients combined Acetylsalicylic acid 0.5g Tween 80 5.0g Plastibase 94.5g Ethanol Trace amount
【００１３】実施例２ 下記に示す組成に従って、実施
例１と同様に操作し、軟膏剤を得た。成 分 配 合 量 アセチルサリチル酸 １.０ｇ Tween 80 ５.０ｇ プラスチベース ９４.０ｇエタノール 微量 Example 2 According to the composition shown below, the same operation as in Example 1 was carried out to obtain an ointment. Ingredients Blend amount acetylsalicylic acid 1.0 g Tween 80 5.0 g Plastibase 94.0g ethanol trace
【００１４】実施例３ 下記に示す組成に従って、実施
例１と同様に操作し、軟膏剤を得た。成 分 配 合 量 アセチルサリチル酸 ２.０ｇ Tween 80 ５.０ｇ プラスチベース ９３.０ｇエタノール 微量 Example 3 According to the composition shown below, the same operation as in Example 1 was carried out to obtain an ointment. Component Amount Acetylsalicylic acid 2.0g Tween 80 5.0g Plastibase 93.0g Ethanol Trace amount
【００１５】実施例４ 下記に示す組成に従って、実施
例１と同様に操作し、軟膏剤を得た。成 分 配 合 量 アセチルサリチル酸 ０.５ｇ Span 30 ５.０ｇ 白色ワセリン ９４.５gエタノール 微量 Example 4 According to the composition shown below, the same operation as in Example 1 was carried out to obtain an ointment. Amount of ingredients combined Acetylsalicylic acid 0.5g Span 30 5.0g White petrolatum 94.5g Ethanol
【００１６】実施例５ 下記に示す組成に従って、実施
例１と同様に操作し、軟膏剤を得た。成 分 配 合 量 アセチルサリチル酸 １.０ｇ HCO-60 ５.０ｇ プラスチベース ９４.０ｇエタノール 微量 Example 5 According to the composition shown below, the same operation as in Example 1 was carried out to obtain an ointment. Component Amount Acetylsalicylic acid 1.0g HCO-60 5.0g Plastibase 94.0g Ethanol Trace amount
【００１７】実施例６ 下記に示す組成に従って、実施
例１と同様に操作し、軟膏剤を得た。成 分 配 合 量 アセチルサリチル酸 ２.０ｇ HCO-60 ５.０ｇ 白色ワセリン ９３.０ｇエタノール 微量 Example 6 According to the composition shown below, the same operation as in Example 1 was carried out to obtain an ointment. Ingredients Blend amount acetylsalicylic acid 2.0 g HCO-60 5.0 g white vaseline 93.0g ethanol trace
【００１８】実施例７ 下記に示す組成に従って、実施
例１と同様に操作し、軟膏剤を得た。成 分 配 合 量 アセチルサリチル酸 １５.０ｇ Span 30 ５.０ｇ プラスチベース ８０.０ｇエタノール 微量 Example 7 An ointment was obtained in the same manner as in Example 1 according to the composition shown below. Amount of ingredients combined Acetylsalicylic acid 15.0g Span 30 5.0g Plastibase 80.0g Ethanol Trace amount
【００１９】実施例８ 下記に示す組成に従って、実施
例１と同様に操作し、軟膏剤を得た。成 分 配 合 量 アセチルサリチル酸 ０.０５ｇ Tween 80 ５.０ｇ プラスチベース ９４.９５ｇエタノール 微量 Example 8 An ointment was obtained in the same manner as in Example 1 according to the composition shown below. Component Amount Acetylsalicylic acid 0.05g Tween 80 5.0g Plastibase 94.95g Ethanol Trace amount
【００２０】実施例９ 下記に示す組成に従って、グリ
セリンにポリアクリル酸ナトリウムを均一に分散し、こ
れに水を加えて、透明なゲル状になるまで撹拌した。続
いて、アセチルサリチル酸をプロピレングリコールに均
一分散した液をこのゲル状物に加えて撹拌混合し、更に
水酸化アルミニウムの懸濁液に乳酸を加えたものを加え
て撹拌混合してゲルを得た。このゲルを布上に展延し、
表面をプラスチックフィルムで覆った後、適当なサイズ
に裁断して貼付剤を得た。成 分 配 合 量 ポリアクリル酸ナトリウム ６.０ｇ プロピレングリコール １０.０ｇ グリセリン ４０.０ｇ 水酸化アルミニウム ０.５ｇ 乳酸 １.５ｇ アセチルサリチル酸 １.０ｇ精製水 ４１.０ｇ Example 9 According to the composition shown below, sodium polyacrylate was uniformly dispersed in glycerin, water was added thereto, and the mixture was stirred until a transparent gel was formed. Subsequently, a liquid in which acetylsalicylic acid was uniformly dispersed in propylene glycol was added to this gel-like substance, and the mixture was stirred and mixed. Further, a suspension of aluminum hydroxide to which lactic acid was added was added and mixed with stirring to obtain a gel. . Spread this gel on a cloth,
After the surface was covered with a plastic film, it was cut into an appropriate size to obtain a patch. Component content Sodium polyacrylate 6.0 g Propylene glycol 10.0 g Glycerin 40.0 g Aluminum hydroxide 0.5 g Lactic acid 1.5 g Acetylsalicylic acid 1.0 g Purified water 41.0 g
【００２１】実施例１０ 下記に示す組成に従って、ポ
リアクリル酸ナトリウムをグリセリンに均一分散した後
加熱し、透明なゲル状になるまで撹拌した。これにアセ
チルサリチル酸をプロピレングリコールに均一分散した
懸濁液を加えて撹拌混合し、更にみょうばんをグリセリ
ンに均一分散した懸濁液を加えて撹拌混合した。こうし
て得たゲルを、布上に展延し、表面をプラスチックフィ
ルムで覆った後、適当なサイズに裁断して貼付剤を得
た。成 分 配 合 量 ポリアクリル酸ナトリウム ６.０ｇ プロピレングリコール １０.０ｇ グリセリン ８２.６ｇ アセチルサリチル酸 １.０ｇみょうばん ０.４ｇ Example 10 According to the composition shown below, sodium polyacrylate was uniformly dispersed in glycerin and then heated, and stirred until a transparent gel was formed. To this, a suspension in which acetylsalicylic acid was uniformly dispersed in propylene glycol was added and mixed with stirring, and further, a suspension in which alum was uniformly dispersed in glycerin was added and mixed with stirring. The gel thus obtained was spread on a cloth, the surface was covered with a plastic film, and then cut into a suitable size to obtain a patch. Sodium Ingredients Blend weight polyacrylic acid 6.0g Propylene glycol 10.0g glycerine 82.6g acetylsalicylic acid 1.0g alum 0.4g
【００２２】実施例１１ 下記に示す組成に従って、ア
セチルサリチル酸とコーンスターチ、結晶セルロースお
よび乳糖を混合し、１０％ヒドロキシプロピルセルロー
ス水溶液５４ｇを加えて練合し、常法に従って、０.７
ｍｍ孔あきスクリーンより押し出し造粒し、乾燥、破砕
整粒してアスピリン顆粒剤を得た。成 分 配 合 量 アセチルサリチル酸 １００.０ｇ 乳糖 ３６.０ｇ コーンスターチ ２４.０ｇ 結晶セルロース ３４.６ｇ ヒドロキシプロピルセルロース ５.４ｇ精製水 ４８.６ｇ Example 11 Acetylsalicylic acid, corn starch, crystalline cellulose and lactose were mixed according to the composition shown below, 54 g of a 10% aqueous solution of hydroxypropyl cellulose was added and kneaded, and then 0.7 according to a conventional method.
The mixture was extruded from a screen with a hole having a diameter of mm, granulated, dried, crushed and sized to obtain an aspirin granule. Ingredients Blend amount acetylsalicylic acid 100.0g lactose 36.0g corn starch 24.0g microcrystalline cellulose 34.6g hydroxypropyl cellulose 5.4g Purified water 48.6g
【００２３】実施例１２ 実施例１１で得た顆粒剤４９
０ｇにタルク１０ｇを加えて混合し、常法に従って、打
錠機を用いて圧縮成形し、１錠当たり０.５ｇ重量を持
つアスピリン錠剤を得た。Example 12 Granule 49 obtained in Example 11
10 g of talc was added to 0 g and mixed, and compression molding was carried out using a tableting machine according to a conventional method to obtain an aspirin tablet having a weight of 0.5 g per tablet.
【００２４】実施例１３ 下記に示す組成に従って、ア
セチルサリチル酸を精製水に溶解し、単シロップを加え
た後精製水を加えて全量を調整し、水剤を得た。 成 分 配 合 量 アセチルサリチル酸 １.５ｇ 単シロップ ８.０ｇ 精製水 適量 全 １００ｍｌ Example 13 According to the composition shown below, acetylsalicylic acid was dissolved in purified water, a single syrup was added, and then purified water was added to adjust the total amount to obtain a liquid preparation. Component Composition Acetylsalicylic acid 1.5g Single syrup 8.0g Purified water Appropriate amount 100ml
【００２５】実施例１４ 下記に示す組成に従って、ア
セチルサリチル酸を少量のエタノールに溶解した後、溶
媒を揮散して微粉末とし、これに軟膏基剤を加えて均一
に混和し、軟膏剤を得た。成 分 配 合 量 アセチルサリチル酸 ２.０ｇ プラスチベース ９８.０ｇエタノール 微量 Example 14 According to the composition shown below, acetylsalicylic acid was dissolved in a small amount of ethanol, and then the solvent was volatilized into a fine powder. An ointment base was added to this and uniformly mixed to obtain an ointment. . Ingredients Blend amount acetylsalicylic acid 2.0g plastibase 98.0g ethanol trace
【００２６】実施例１５ 下記に示す組成に従って、実
施例１４と同様に操作し、軟膏剤を得た。成 分 配 合 量 アセチルサリチル酸 ４.０ｇ プラスチベース ９６.０ｇエタノール 微量 Example 15 According to the composition shown below, the same operation as in Example 14 was carried out to obtain an ointment. Component Composition Acetylsalicylic acid 4.0 g Plastibase 96.0 g Ethanol Trace amount
【００２７】実施例１６ 下記に示す組成に従って、実
施例１４と同様に操作し、軟膏剤を得た。成 分 配 合 量 アセチルサリチル酸 ８.０ｇ プラスチベース ９２.０ｇエタノール 微量 Example 16 An ointment was obtained in the same manner as in Example 14 according to the composition shown below. Ingredients Blend amount acetylsalicylic acid 8.0g plastibase 92.0g ethanol trace
【００２８】本発明に従うアセチルサリチル酸含有製剤
の驚異的に有利な作用は例えば下記試験例に示すデータ
から明らかである。 試験例１ ラット褥瘡モデルに対する局所適用したアセ
チルサリチル酸の作用 体重４００ｇ〜４５０ｇのウィスターラットを１群５匹
で本試験に用いた。ラット右大腿部を除毛後ペントバル
ビタール麻酔下、大腿部に１ｋｇ／ｃｍ2の圧力がかか
るように円筒で１日６時間で６日間圧迫し、褥瘡を作成
した。薬剤投与は、褥瘡作成後１日目より１日１回アセ
チルサリチル酸０.２ｍｇ／部位、０.５ｍｇ／部位、１
ｍｇ／部位、２ｍｇ／部位、４ｍｇ／部位の投与量で１
４日間行った。効果判定は創傷部の長短径を測定して面
積を求め、創傷部位の面積変化を下記式により算出して
面積変化曲線を作成し、この面積変化曲線の曲線下面積
を算出し指標とした。また、対照薬としてはソルコセリ
ル（商品名）を用いた。その結果を図１に示す。図から
明らかなように、アセチルサリチル酸を０.５ｍｇ／部
位および１ｍｇ／部位適用した場合に顕著な治癒作用を
有することがわかる。 The surprisingly advantageous action of the acetylsalicylic acid-containing preparations according to the invention is evident, for example, from the data presented in the test examples below. Test Example 1 Effect of topically applied acetylsalicylic acid on rat pressure ulcer model Wistar rats having a body weight of 400 g to 450 g were used in this test in groups of 5 rats. After removing the hair from the right thigh of the rat, it was pressed under a pentobarbital anesthesia with a cylinder so that a pressure of 1 kg / cm 2 was applied to the thigh for 6 hours a day for 6 days to prepare a pressure ulcer. The drug was administered once a day from the first day after pressure ulcer preparation, 0.2 mg / site acetylsalicylic acid, 0.5 mg / site, 1
1 at a dose of mg / site, 2 mg / site, 4 mg / site
I went for 4 days. To determine the effect, the major and minor axes of the wound were measured to determine the area, the area change of the wound site was calculated by the following formula to create an area change curve, and the area under the curve of this area change curve was calculated and used as an index. Further, solcoceryl (trade name) was used as a control drug. The result is shown in FIG. As is clear from the figure, it is found that when acetylsalicylic acid is applied at 0.5 mg / site and 1 mg / site, it has a remarkable healing effect.
【００２９】試験例２ ラット欠損傷モデルに対する局
所適用したアセチルサリチル酸の作用 体重４００ｇ〜４５０ｇのウィスターラットを１群６匹
で本試験に用いた。ラット背部を除毛後消毒用イソジン
で消毒し、エーテル麻酔下ラット背部皮膚を内径１２ｍ
ｍの円形ポンチで打ち抜き、正中線に対称に２カ所の創
傷を作成した。創傷作成１日後よりアセチルサリチル酸
を０.５ｍｇ／部位、１ｍｇ／部位、２ｍｇ／部位の投
与量で１日１回１４日間投与した。効果判定は創傷部の
長短径を測定して面積を求め、創傷部位の面積変化曲線
を作成し、この面積変化曲線の曲線下面積を試験例１と
同様にして算出し指標とした。また、対照薬としてはソ
ルコセリル（商品名）を用いた。その結果を図２に示
す。図から明らかなように、アセチルサリチル酸を０.
５ｍｇ／部位、１ｍｇ／部位および２ｍｇ／部位適用し
た場合に顕著な治癒作用を有することがわかる。Test Example 2 Effect of Topically Applied Acetylsalicylic Acid on Rat Lacking Damage Model Wistar rats weighing 400 g to 450 g were used in this test in groups of 6 rats. After removing the hair from the back of the rat, disinfect it with Isodine for disinfection, and under ether anesthesia, the back skin of the rat has an inner diameter of 12 m.
It was punched out with a circular punch of m to make two wounds symmetrically with respect to the midline. One day after the wound was created, acetylsalicylic acid was administered once a day for 14 days at a dose of 0.5 mg / site, 1 mg / site, 2 mg / site. To determine the effect, the major and minor axes of the wound were measured to determine the area, an area change curve of the wound site was created, and the area under the curve of this area change curve was calculated as in Test Example 1 and used as an index. Further, solcoceryl (trade name) was used as a control drug. The result is shown in FIG. As is clear from the figure, acetylsalicylic acid was added to
It can be seen that when applied at 5 mg / site, 1 mg / site and 2 mg / site, it has a significant healing effect.
【００３０】試験例３ ラット熱傷モデルに対する局所
適用したアセチルサリチル酸の作用 体重４００〜４５０ｇのウィスター ラットを１群６匹
で用いた。ラット背部を除毛後消毒用イソジンで消毒
し、エーテル麻酔下、背部皮膚に２００℃の焼きごてを
５秒間接触させて熱傷を作成した。作成１日後より熱傷
部位にアセチルサリチル酸を１ｍｇ／部位、２ｍｇ／部
位の投与量で１日１回１７日間投与した。効果判定は熱
傷部の長短径を測定して面積を求め、熱傷部位の面積変
化曲線を作成し、この面積変化曲線の曲線下面積を試験
例１と同様にして算出し指標とした。また、対照薬とし
てはソルコセリル（商品名）を用いた。その結果を図３
に示す。図から明らかなように、１ｍｇ／部位および２
ｍｇ／部位においてアセチルサリチル酸が顕著な治癒作
用を有することがわかる。Test Example 3 Effect of Topically Applied Acetylsalicylic Acid on a Burn Model of Rats Wistar rats weighing 400 to 450 g were used in groups of 6 rats. After removing the hair from the rat, the back of the rat was disinfected with isodine for disinfection, and under ether anesthesia, the back skin was contacted with a 200 ° C. iron for 5 seconds to create a burn. One day after preparation, acetylsalicylic acid was administered to the burn site at a dose of 1 mg / site and 2 mg / site once a day for 17 days. To determine the effect, the major and minor diameters of the burned portion were measured to determine the area, an area change curve of the burned portion was created, and the area under the curve of this area change curve was calculated as in Test Example 1 and used as an index. Further, solcoceryl (trade name) was used as a control drug. The result is shown in FIG.
Shown in As is clear from the figure, 1 mg / site and 2
It can be seen that acetylsalicylic acid has a significant healing effect at mg / site.
【００３１】試験例４ ラット欠損症モデルに対するア
セチルサリチル酸の経口投与での作用 体重４００〜４５０ｇのウィスターラットを１群５匹で
本試験に用いた。ラット背部を除毛後消毒用イソジンで
消毒し、エーテル麻酔下ラット背部皮膚を内径１２ｍｍ
の円形ポンチで打ち抜き、正中線に対称に２カ所の創傷
を作成した。創傷作成１日後よりアセチルサリチル酸を
１５ｍｇ／ｋｇ／日、３０ｍｇ／ｋｇ／日、６０ｍｇ／
ｋｇ／日の投与量で１日１回１３日間投与した。効果判
定は創傷部の長短径を測定して面積を求め、創傷部位の
面積変化曲線を作成し、この面積変化曲線の曲線下面積
を試験例１と同様にして算出し指標とした。その結果を
図４に示す。図から明らかなように、３０ｍｇ／ｋｇ／
日、６０ｍｇ／ｋｇ／日においてアセチルサリチル酸が
顕著な治癒作用を有することがわかる。Test Example 4 Effect of Oral Administration of Acetylsalicylic Acid on Rat Defect Model A Wistar rat weighing 400 to 450 g was used in this test in groups of 5 rats. After removing the hair from the back of the rat, disinfect it with Isodine for disinfection, and under ether anesthesia, the back skin of the rat has an inner diameter of 12 mm.
It was punched out with a circular punch, and two wounds were created symmetrically with respect to the midline. Acetylsalicylic acid 15 mg / kg / day, 30 mg / kg / day, 60 mg /
It was administered at a dose of kg / day once a day for 13 days. To determine the effect, the major and minor axes of the wound were measured to determine the area, an area change curve of the wound site was created, and the area under the curve of this area change curve was calculated in the same manner as in Test Example 1 and used as an index. FIG. 4 shows the results. As is clear from the figure, 30 mg / kg /
It can be seen that acetylsalicylic acid has a remarkable healing effect at 60 mg / kg / day per day.
【００３２】試験例５ ヒト褥瘡における効果 アセチルサリチル酸を０.５重量％含有する軟膏製剤を
用い、従来の治療薬及び治療方法では治癒の見られなか
った難治性の褥瘡に対する治療効果を患者７名の９部位
に１ないし２週間投与し、著効、有効、やや有効、無効
の４段階で評価した結果、著効５例、有効２例、やや有
効１例、無効１例であった。やや有効及び無効例はポケ
ットを有する難治性褥瘡であり、本軟膏は解放性の創に
対して著効を示すことが判明した。Test Example 5 Effect on human pressure ulcer 7 patients were treated with an ointment formulation containing 0.5% by weight of acetylsalicylic acid to treat intractable pressure ulcer that could not be cured by conventional therapeutic agents and treatment methods. The drug was administered to 9 sites for 1 to 2 weeks and evaluated on a 4-grade scale of excellent, effective, moderately effective, and ineffective. The results were excellent in 5 cases, effective in 2 cases, slightly effective in 1 case, and ineffective in 1 case. It was found that the slightly effective and ineffective cases were intractable pressure ulcers with pockets, and that this ointment exhibited a remarkable effect on open wounds.
【００３３】試験例６ ラット欠損症モデルに対するア
セチルサリチル酸含有軟膏製剤の作用 体重３００〜３５０ｇのウィスターラットを１群５匹で
本試験に用いた。ラット背部を除毛後消毒用イソジンで
消毒し、エーテル麻酔下ラット背部皮膚を内径１０ｍｍ
の円形ポンチで打ち抜き、正中線に対称に２カ所の創傷
を作成した。創傷作成１日後より、実施例１４、１５お
よび１６で作製した軟膏製剤を０.２ｇ／部位の投与量
（アセチルサリチル酸として４ｍｇ／部位、８ｍｇ／部
位、および１６ｍｇ／部位）で１日１回１４日間投与し
た。効果判定は創傷部の長短径を測定して面積を求め、
創傷部位の面積変化曲線を作成し、この面積変化曲線の
曲線下面積を試験例１と同様にして算出し指標とした。
その結果を図５に示す。図から明らかなように、アセチ
ルサリチル酸２％、４％および８％含有軟膏製剤の適用
により、顕著な治癒作用を有することがわかる。Test Example 6 Action of ointment preparation containing acetylsalicylic acid on rat deficiency model Wistar rats weighing 300 to 350 g were used in this test in groups of 5 rats. After removing the hair from the back of the rat, disinfect it with Isodine for disinfection, and under ether anesthesia, the back skin of the rat has an inner diameter of 10 mm.
It was punched out with a circular punch, and two wounds were created symmetrically with respect to the midline. One day after the wound preparation, the ointment preparations prepared in Examples 14, 15 and 16 were administered once daily at a dose of 0.2 g / site (4 mg / site, 8 mg / site and 16 mg / site as acetylsalicylic acid). It was administered daily. To determine the effect, determine the area by measuring the major and minor diameters of the wound,
An area change curve of the wound site was created, and the area under the curve of this area change curve was calculated in the same manner as in Test Example 1 and used as an index.
The result is shown in FIG. As is clear from the figure, the application of the ointment formulations containing 2%, 4% and 8% acetylsalicylic acid has a remarkable healing effect.
【００３４】[0034]
【発明の効果】本発明により、これまで非常に治療が困
難であった褥瘡についての治癒が期待できる。更に、熱
傷、皮膚欠損症等についても治癒の促進が期待できる等
の効果を有する。EFFECTS OF THE INVENTION The present invention can be expected to cure pressure ulcers, which have been extremely difficult to treat until now. Further, it has an effect such that it can be expected to promote healing of burns and skin defects.
【図１】 ラットの褥瘡モデルに対する局所適用したア
セチルサリチル酸の作用を示す棒グラフである。FIG. 1 is a bar graph showing the effect of topically applied acetylsalicylic acid on a rat pressure ulcer model.
【図２】 ラット欠損傷モデルに対する局所適用したア
セチルサリチル酸の作用を示す棒グラフである。FIG. 2 is a bar graph showing the effect of topically applied acetylsalicylic acid on a rat defect model.
【図３】 ラットの熱傷モデルに対する局所適用したア
セチルサリチル酸の作用を示す棒グラフである。FIG. 3 is a bar graph showing the effect of topically applied acetylsalicylic acid on a rat burn model.
【図４】 ラット欠損症モデルに対する経口投与したア
セチルサリチル酸の作用を示す棒グラフである。FIG. 4 is a bar graph showing the effect of orally administered acetylsalicylic acid on a rat deficiency model.
【図５】 ラット欠損症モデルに対するアセチルサリチ
ル酸含有軟膏製剤の作用を示す棒グラフである。FIG. 5 is a bar graph showing the effect of an acetylsalicylic acid-containing ointment preparation on a rat deficiency model.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 畠瀬 修 香川県高松市春日町1687−24 (72)発明者 徳田 雅明 香川県高松市伏石町596 サラファン伏石 505 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Osamu Hatase 1687-24 Kasuga-cho, Takamatsu-shi, Kagawa (72) Masaaki Tokuda 596 Fushiishi-cho, Takamatsu-shi, Kagawa Sarafan Fushiishi 505
Claims (3)
有することを特徴とする皮膚損傷治療剤。1. A therapeutic agent for skin damage, which comprises acetylsalicylic acid as an active ingredient.
酸の含量が０.０５〜１５重量％、好ましくは０.１〜１
０重量％、最も好ましくは０.２〜８重量％である請求
項１に記載の皮膚損傷治療剤。2. A preparation for topical application, which has an acetylsalicylic acid content of 0.05 to 15% by weight, preferably 0.1 to 1.
The therapeutic agent for skin damage according to claim 1, which is 0% by weight, most preferably 0.2 to 8% by weight.
５〜７５ｍｇ／ｋｇ体重／日、好ましくは２０〜６５ｍ
ｇ／ｋｇ体重／日、最も好ましくは３０〜６０ｍｇ／ｋ
ｇ体重／日である請求項１に記載の皮膚損傷治療剤。3. An oral administration preparation, wherein the effective dose is 1
5-75 mg / kg body weight / day, preferably 20-65 m
g / kg body weight / day, most preferably 30-60 mg / k
The therapeutic agent for skin damage according to claim 1, which is g body weight / day.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP34510396A JP3979689B2 (en) | 1995-12-26 | 1996-12-25 | Acetylsalicylic acid-containing skin injury treatment agent |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP33874595 | 1995-12-26 | ||
| JP7-338745 | 1995-12-26 | ||
| JP34510396A JP3979689B2 (en) | 1995-12-26 | 1996-12-25 | Acetylsalicylic acid-containing skin injury treatment agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH09235232A true JPH09235232A (en) | 1997-09-09 |
| JP3979689B2 JP3979689B2 (en) | 2007-09-19 |
Family
ID=26576191
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP34510396A Expired - Fee Related JP3979689B2 (en) | 1995-12-26 | 1996-12-25 | Acetylsalicylic acid-containing skin injury treatment agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3979689B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998058652A1 (en) * | 1997-06-25 | 1998-12-30 | Teikoku Seiyaku Co., Ltd. | Stable aspirin ointment preparations |
| JP2004123551A (en) * | 2002-09-30 | 2004-04-22 | Teikoku Seiyaku Co Ltd | External preparation for suppressing formation of keloid or the like |
| US20110098256A1 (en) * | 2009-10-22 | 2011-04-28 | Hines Dixie J | Method for making and using a topical dermatological solution |
-
1996
- 1996-12-25 JP JP34510396A patent/JP3979689B2/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998058652A1 (en) * | 1997-06-25 | 1998-12-30 | Teikoku Seiyaku Co., Ltd. | Stable aspirin ointment preparations |
| US7029663B1 (en) | 1997-06-25 | 2006-04-18 | Teikoku Seiyaku Co., Ltd. | Stable ointment containing acetylsalicylic acid |
| JP2004123551A (en) * | 2002-09-30 | 2004-04-22 | Teikoku Seiyaku Co Ltd | External preparation for suppressing formation of keloid or the like |
| US20110098256A1 (en) * | 2009-10-22 | 2011-04-28 | Hines Dixie J | Method for making and using a topical dermatological solution |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3979689B2 (en) | 2007-09-19 |
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