JP2011088930A - Carbon dioxide percutaneous and transmucosal absorption composition - Google Patents

Carbon dioxide percutaneous and transmucosal absorption composition Download PDF

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JP2011088930A
JP2011088930A JP2011008226A JP2011008226A JP2011088930A JP 2011088930 A JP2011088930 A JP 2011088930A JP 2011008226 A JP2011008226 A JP 2011008226A JP 2011008226 A JP2011008226 A JP 2011008226A JP 2011088930 A JP2011088930 A JP 2011088930A
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carbon dioxide
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carbonate
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Masaya Tanaka
雅也 田中
Masato Hioki
正人 日置
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Medion Research Laboratories Inc
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Medion Research Laboratories Inc
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a kit for manufacturing a composition for cosmetic/treatment of skin/mucous. <P>SOLUTION: The carbon dioxide percutaneous and transmucosal absorption composition kit is composed of a basic composition containing water, a hydroxyethyl cellulose and a carbonate, and a carbon dioxide generating granule agent (I) containing an acid at least equivalent to 10% or more of the molar number of the carbonate contained in the basic composition. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

本発明は、二酸化炭素経皮・経粘膜吸収用組成物、該組成物の製造用キット、該組成物を含む皮膚粘膜疾患もしくは皮膚粘膜障害に伴うかゆみ、末梢循環障害に基づく皮膚潰瘍、冷感、しびれ感;歯科疾患、皮膚粘膜損傷、化膿性皮膚疾患、角化異常症、筋骨格系疾患及び神経系疾患からなる群から選ばれるいずれかの疾患の予防ないし治療剤及び化粧料に関する。   The present invention relates to a composition for carbon dioxide percutaneous / transmucosal absorption, a kit for producing the composition, a skin mucosal disease containing the composition or itching associated with skin mucosal disorder, skin ulcer based on peripheral circulation disorder, cooling sensation , Numbness; a preventive or therapeutic agent and cosmetic for a disease selected from the group consisting of dental diseases, cutaneous mucosal damage, purulent skin diseases, keratoses, musculoskeletal diseases and nervous system diseases.

痒みの治療に対して、局所療法として外用の抗ヒスタミン剤や抗アレルギー剤などが一般に使用される。これらは痒みが発生したときに使用され、一時的にある程度痒みを抑える。湿疹に伴う痒みに対しては外用の非ステロイド抗炎症剤やステロイド剤の使用が一般的であり、これらは炎症を抑えることにより痒みの発生を防ごうとするものである。   For the treatment of pruritus, external antihistamines and antiallergic agents are generally used as local therapies. These are used when itching occurs and temporarily suppress itching to some extent. For itching associated with eczema, non-steroidal anti-inflammatory agents and steroids for external use are generally used, and these are intended to prevent the occurrence of itching by suppressing inflammation.

しかしながら、外用の抗ヒスタミン剤や抗アレルギー剤はアトピー性皮膚炎、水虫や虫さされの痒みにはほとんど効果がない。外用の非ステロイド抗炎症剤やステロイド剤は、痒みに対する効果は弱く、即効性もない。また、ステロイド剤は副作用が強いため、使用が容易でない。   However, topical antihistamines and antiallergic agents have little effect on atopic dermatitis, athlete's foot and insect bite. Non-steroidal anti-inflammatory agents and steroids for external use have a weak effect on itching and are not immediately effective. Steroids are not easy to use because they have strong side effects.

炭酸ガスは血行をよくすることが知られており、炭酸ガスを含む湿布剤が提案されている(特許文献1)。しかしながら、特許文献1の湿布剤は、炭酸塩と有機酸を用いて発生させた炭酸ガスを水に溶かして溶存炭酸ガスとして利用するものであり、水に溶解する炭酸ガスの絶対量は極めて少ないため、実質的に効果は期待できない。   Carbon dioxide is known to improve blood circulation, and a poultice containing carbon dioxide has been proposed (Patent Document 1). However, the poultice of Patent Document 1 dissolves carbon dioxide gas generated using carbonate and organic acid in water and uses it as dissolved carbon dioxide gas, and the absolute amount of carbon dioxide gas dissolved in water is extremely small. Therefore, the effect cannot be expected substantially.

特許文献2は、各々コーティングを施したアスコルビン酸と炭酸塩を含有する発泡性固形組成物を開示するが、該組成物は使用時までにアスコルビン酸と炭酸塩が反応して炭酸ガスを発生しないように安定化したものであり、その用途は、該文献の4頁左上欄及び実施例に記載されるように発泡性の粉末飲料、錠剤等の食品、発泡性浴剤、コンタクトレンズ、トイレ、浴槽などの洗浄剤に用いられるものであり、発生した炭酸ガスを保持する技術的課題は存在しない。   Patent Document 2 discloses an effervescent solid composition containing ascorbic acid and carbonate each coated, but the composition does not generate carbon dioxide by the reaction of ascorbic acid and carbonate before use. As described in the upper left column on page 4 of the literature and examples, foods such as effervescent powder drinks, tablets and other foods, effervescent baths, contact lenses, toilets, It is used for cleaning agents such as bathtubs, and there is no technical problem of retaining the generated carbon dioxide gas.

特許文献3は、爪のクチクラに対し軟化作用を有する気泡性水溶液の製造方法を開示し、気泡性は製品を気持ちよく快適にさせるものであると記載されており、発生する二酸化炭素の作用については何ら記載されていない。また、二酸化炭素の発生のための酸成分として、その塩が尿素の軟化作用を補完するピロリドンカルボン酸を用いており、他の酸は一切開示されていない。また、その実施例1〜5で得られる溶液はいずれも発生する炭酸ガスを保持するのに十分な粘性はなく、発生した炭酸ガスは速やかに空気中に拡散するものである。   Patent Document 3 discloses a method for producing a cellular aqueous solution having a softening action on the nail cuticle, and it is described that the cellularity makes the product comfortable and comfortable. It is not described at all. Further, pyrrolidone carboxylic acid whose salt complements the softening action of urea is used as an acid component for generating carbon dioxide, and no other acid is disclosed. Further, any of the solutions obtained in Examples 1 to 5 does not have sufficient viscosity to hold the generated carbon dioxide gas, and the generated carbon dioxide gas diffuses rapidly into the air.

特許文献4は、性交時の潤滑性及び膣の乾燥防止のためのムース状潤滑剤を開示する。該潤滑剤には高分子凝集剤であるポリアクリルアミド、グリセリン、ビタミンE及び炭酸ガスが含まれているが、該ムース状潤滑剤は容器から取り出したときの容積を大きくするために炭酸ガスを使用するものであり、容器から出されたムース状潤滑剤は速やかに炭酸ガスを失い、性器に塗布する時点では炭酸ガスはほぼ完全に消失している。また、潤滑剤用途のためには非常に薄く塗布する必要があり、炭酸ガスを保持することができないものである。   Patent Document 4 discloses a mousse-like lubricant for lubrication during sexual intercourse and prevention of vaginal dryness. The lubricant contains polymer flocculants polyacrylamide, glycerin, vitamin E and carbon dioxide, but the mousse lubricant uses carbon dioxide to increase the volume when taken out of the container. The mousse-like lubricant taken out of the container quickly loses carbon dioxide, and the carbon dioxide disappears almost completely when applied to the genitals. Moreover, it is necessary to apply | coat very thinly for a lubricant use, and cannot hold | maintain a carbon dioxide gas.

特許文献5は、酸、炭酸塩、増粘剤または沈殿防止剤とともに、水不溶性またはマイクロカプセル化された薬剤を含む固形医薬組成物であり、該組成物に水を加えると薬剤が懸濁するものである。該公報の4頁左下欄〜右下欄に記載されるように、酸性物質及び塩基の処方への添加は増粘剤の水和は促進するが、発泡が生じないような量で行われ、二酸化炭素の発泡により増粘剤で被覆した顆粒は浮かんだ状態のままとなる傾向があり、この物質の溶解を遅らせ、所望の効果に対し反対の効果を生じさせることに留意する必要がある。すなわち、特許文献5は、酸と炭酸塩を有する固形医薬組成物を開示するが、該組成物を水に溶かせたときに、二酸化炭素による発泡は実質的に起こらないものである。
特開昭62−286922号公報 特開昭61−207322号公報 特開平3−227910号公報 特開平4−312521号公報 特表平5−501421号公報
Patent Document 5 is a solid pharmaceutical composition containing a water-insoluble or microencapsulated drug together with an acid, carbonate, thickener or suspending agent. When water is added to the composition, the drug is suspended. Is. As described in page 4, lower left column to lower right column of the publication, addition of acidic substances and bases to the formulation promotes hydration of the thickener, but is performed in such an amount that foaming does not occur, It should be noted that granules coated with a thickener due to carbon dioxide foam tend to remain floating, delaying the dissolution of this material and producing the opposite effect to the desired effect. That is, Patent Document 5 discloses a solid pharmaceutical composition having an acid and a carbonate. However, when the composition is dissolved in water, foaming due to carbon dioxide does not substantially occur.
JP-A-62-286922 Japanese Patent Application Laid-Open No. 61-207322 JP-A-3-227910 Japanese Patent Laid-Open No. 4-312521 Japanese National Patent Publication No. 5-501421

本発明の目的は、水虫、虫さされ、アトピー性皮膚炎、貨幣状湿疹、乾皮症、脂漏性湿疹、蕁麻疹、痒疹、主婦湿疹、尋常性ざ瘡、膿痂疹、毛包炎、癰、せつ、蜂窩織炎、膿皮症、乾癬、魚鱗癬、掌蹠角化症、苔癬、粃糠疹、創傷、熱傷、き裂、びらん、凍瘡などの皮膚粘膜疾患もしくは皮膚粘膜障害に伴う痒みに有効な組成物を提供することにある。   The object of the present invention is athlete's foot, insect bite, atopic dermatitis, monetary eczema, dry skin, seborrheic eczema, hives, urticaria, housewife eczema, acne vulgaris, impetigo, folliculitis For skin mucosal diseases or skin mucosal disorders such as phlegm, phlegm, cellulitis, pyoderma, psoriasis, ichthyosis, palmokeratosis, lichen, rash, wounds, burns, cracks, erosions, and cryoma The object is to provide a composition effective for itch.

また本発明は、褥創、創傷、熱傷、口角炎、口内炎、皮膚潰瘍、き裂、びらん、凍瘡、壊疽などの皮膚粘膜損傷;移植皮膚片、皮弁などの生着不全;歯肉炎、歯槽膿漏、義歯性潰瘍、黒色化歯肉、口内炎などの歯科疾患;閉塞性血栓血管炎、閉塞性動脈硬化症、糖尿病性末梢循環障害、下肢静脈瘤などの末梢循環障害に基づく皮膚潰瘍や冷感、しびれ感;慢性関節リウマチ、頸肩腕症候群、筋肉痛、関節痛、腰痛症などの筋骨格系疾患;神経痛、多発性神経炎、スモン病などの神経系疾患;乾癬、鶏眼、たこ、魚鱗癬、掌蹠角化症、苔癬、粃糠疹などの角化異常症;尋常性ざ瘡、膿痂疹、毛包炎、癰、せつ、蜂窩織炎、膿皮症、化膿性湿疹などの化膿性皮膚疾患;除毛後の再発毛抑制(むだ毛処理);そばかす、肌荒れ、肌のくすみ、肌の張りや肌の艶の衰え、髪の艶の衰えなどの皮膚や毛髪などの美容上の問題及び部分肥満に有効な二酸化炭素経皮・経粘膜吸収用組成物、該組成物製造用キットを提供することを目的とする。   In addition, the present invention relates to skin mucosal damage such as wounds, wounds, burns, stomatitis, stomatitis, skin ulcers, cracks, erosions, frostbite, gangrene; graft failure such as graft skin pieces, flaps; gingivitis, alveoli Dental illnesses such as pyorrhea, denture ulcers, blackened gingiva, stomatitis; obstructive thromboangitis, obstructive arteriosclerosis, diabetic peripheral circulatory disturbance, peripheral circulatory disturbance such as varicose veins, cold sensation Numbness; musculoskeletal diseases such as rheumatoid arthritis, cervical shoulder arm syndrome, muscle pain, joint pain, low back pain; nervous system diseases such as neuralgia, polyneuritis, SMON's disease; psoriasis, chicken eyes, octopus, fish scales Keratosis abnormalities such as psoriasis, palmokeratosis, lichen, urticaria; acne vulgaris, impetigo, folliculitis, hemorrhoids, bruise, cellulitis, pyoderma, purulent eczema, etc. Purulent skin disease; suppression of recurrent hair after hair removal (dead hair treatment); freckles, rough skin, dull skin, skin tension A composition for carbon dioxide transdermal and transmucosal absorption, which is effective for cosmetic problems such as skin and hair, such as the deterioration of skin gloss and hair gloss, and partial obesity, and a kit for producing the composition For the purpose.

項1. 水、増粘剤及び気泡状二酸化炭素を含有し、二酸化炭素を持続的に経皮・経粘膜吸収させることができる組成物。
項2. 水及び増粘剤の合計量に対し、水60〜99.9重量%、増粘剤0.1〜40重量%を含有する項1に記載の組成物。
項3. 保湿剤をさらに含有する項1又は2に記載の組成物。
項4. 保湿剤の含量が0.1〜25重量%である項3に記載の組成物。
項5. 親油性物質をさらに含有する項1〜4のいずれかに記載の組成物。
項6. 親油性物質の含量が0.01〜10重量%である項5に記載の組成物。
項7. 界面活性剤をさらに含有する項1〜6のいずれかに記載の組成物。
項8. 界面活性剤の含量が0.01〜10重量%である項7に記載の組成物。
項9. 気泡状二酸化炭素を0.1容量%以上、好ましくは1容量%以上、より好ましくは2容量%以上、さらに好ましくは3容量%以上、特に好ましくは4容量%以上、最も好ましくは5容量%以上含む項1〜8のいずれかに記載の組成物。
項10. 組成物中に保持されている気泡状二酸化炭素の40容量%以上、好ましくは60容量%以上、より好ましくは80容量%以上を気泡状で5分間以上、好ましくは30分間以上、より好ましくは1時間以上、特に2時間以上保持することができる項1〜9のいずれかに記載の組成物。
項11. 表面が滑らかな長さ40cmのガラス板の端に、その1gを直径1cmの円盤状に塗り、その円盤が上に来るように水平面に対して60度の角度で立てたとき、5秒後の円盤の移動距離が30cm以内、好ましくは25cm以内、より好ましくは20cm以内、特に15cm以内である項1〜10のいずれかに記載の組成物。
項12. 水、増粘剤及び炭酸塩を含有する塩基性組成物と、塩基性組成物に含まれる炭酸塩のモル数に対して少なくとも10%以上の酸を含有する二酸化炭素発生補助剤(I)からなり、使用時にこれらを混合して得られた組成物中に発生した二酸化炭素を保持し、発泡後の最大容積時の組成物中に保持されている二酸化炭素の40容量%以上、好ましくは60容量%以上、より好ましくは80容量%以上を気泡状で5分間以上、好ましくは30分間以上、より好ましくは1時間以上、特に2時間以上保持することができる二酸化炭素経皮・経粘膜吸収用組成物の製造キット。
項13. 塩基性組成物が、水、増粘剤及び炭酸塩の合計量に対し、水60〜99.8重量%、増粘剤0.1〜30重量%、炭酸塩0.1〜10重量%を含有する項12記載のキット。
項14. 塩基性組成物と二酸化炭素発生補助剤(I)を混合したときの体積増加率が、塩基性組成物と二酸化炭素発生補助剤の合計容量の0.1容量%以上、好ましくは1容量%以上、より好ましくは3容量%以上、特に好ましくは5容量%以上、最も好ましくは7容量%以上である項12または13に記載のキット。
項15. 塩基性組成物に保湿剤0.1〜25重量%を含む項12〜14のいずれかに記載のキット。
項16. 塩基性組成物に界面活性剤0.01〜10重量%を含む項12〜15のいずれかに記載のキット。
項17. 塩基性組成物に親油性物質0.01〜10重量%を含む項12〜16のいずれかに記載のキット。
項18. 表面が滑らかな長さ40cmのガラス板の端に、その1gを直径1cmの円盤状に塗り、その円盤が上に来るように水平面に対して60度の角度で立てたとき、5秒後の円盤の移動距離が30cm以内、好ましくは25cm以内、より好ましくは20cm以内、特に15cm以内である項12〜17のいずれかに記載の二酸化炭素経皮・経粘膜吸収用組成物の製造キットから製造される組成物。
項19. 水、増粘剤及び酸を含有する酸性組成物と、酸性組成物に含まれる酸のモル数に対して少なくとも10%以上の炭酸塩を含有する二酸化炭素発生補助剤(II)からなり、使用時にこれらを混合して得られた組成物中に発生した二酸化炭素を保持し、発泡後の最大容積時の組成物中に保持されている二酸化炭素の40容量%以上、好ましくは60容量%以上、より好ましくは80容量%以上を気泡状で5分間以上、好ましくは30分間以上、より好ましくは1時間以上、特に2時間以上保持することができる二酸化炭素経皮・経粘膜吸収用組成物の製造キット。
項20. 酸性組成物が、水、増粘剤及び酸の合計量に対し、水60〜99.8重量%、増粘剤0.1〜30重量%、酸0.1〜10重量%を含有する項19に記載のキット。
項21. 酸性組成物と二酸化炭素発生補助剤(II)を混合したときの体積増加率が、酸性組成物と二酸化炭素発生補助剤(II)の合計容量の0.1容量%以上、好ましくは1容量%以上、より好ましくは3容量%以上、特に好ましくは5容量%以上、最も好ましくは7容量%以上である項19または20に記載のキット。
項22. 酸性組成物に保湿剤0.1〜25重量%を含む項19〜21のいずれかに記載のキット。
項23. 酸性組成物に界面活性剤0.01〜10重量%を含む項19〜22のいずれかに記載のキット。
項24. 酸性組成物に親油性物質0.01〜10重量%を含む項19〜23のいずれかに記載のキット。
項25. 表面が滑らかな長さ40cmのガラス板の端に、その1gを直径1cmの円盤状に塗り、その円盤が上に来るように水平面に対して60度の角度で立てたとき、5秒後の該組成物の円盤の移動距離が30cm以内、好ましくは25cm以内、より好ましくは20cm以内、特に15cm以内である項19〜24のいずれかに記載の二酸化炭素経皮・経粘膜吸収用組成物の製造キットから製造される組成物。
項26. 項1〜11のいずれかの組成物、或いは、項18または25の組成物を含む、皮膚粘膜疾患もしくは皮膚粘膜障害に伴うかゆみ;末梢循環障害に基づく皮膚潰瘍、冷感、しびれ感;歯科疾患;皮膚粘膜損傷;化膿性皮膚疾患;角化異常症;筋骨格系疾患;及び神経系疾患からなる群から選ばれるいずれかの疾患の予防ないし治療剤。
項27.項1〜11のいずれかの組成物、或いは、項18または25の組成物を含む、しみやそばかすを減少ないし目立たなくさせる作用、美白作用、肌の若返り作用、肌の引き締め作用、顔、脚、腕、腹部、脇腹、背中、首、顎などの部分肥満を改善する作用、肌質改善作用及び除毛後の再発毛抑制作用のいずれかの作用を有する化粧料。
項28. 化粧料がクリーム、パック、ジェル、ペーストまたはマスクである請求項27に記載の化粧料。
項29. 炭酸塩と酸と増粘剤と水を実質的に二酸化炭素を発生しない状態で含み、炭酸塩と酸と増粘剤と水を混合することにより気泡状の二酸化炭素を含有する二酸化炭素経皮・経粘膜吸収用組成物を得ることができる下記の(i)〜(iv)のいずれかのキット:
(i)水、増粘剤及び炭酸塩を含有する塩基性組成物と水、増粘剤及び酸を含有する酸性組成物を含むキット。
(ii)炭酸塩及び固体酸(顆粒、細粒、粉末)、並びに水及び増粘剤から成る粘性組成物を含むキット。
(iii)水及び増粘剤から成る粘性組成物、及び炭酸塩と酸の複合顆粒(細粒、粉末)剤を含むキット。
(iv)炭酸塩と酸と増粘剤と水を含むキット。
Item 1. A composition containing water, a thickening agent and cellular carbon dioxide, and capable of continuously absorbing carbon dioxide through the skin and transmucosally.
Item 2. Item 2. The composition according to Item 1, comprising 60 to 99.9% by weight of water and 0.1 to 40% by weight of the thickener with respect to the total amount of water and the thickener.
Item 3. Item 3. The composition according to Item 1 or 2, further comprising a humectant.
Item 4. Item 4. The composition according to Item 3, wherein the content of the humectant is 0.1 to 25% by weight.
Item 5. Item 5. The composition according to any one of Items 1 to 4, further comprising a lipophilic substance.
Item 6. Item 6. The composition according to Item 5, wherein the content of the lipophilic substance is 0.01 to 10% by weight.
Item 7. Item 7. The composition according to any one of Items 1 to 6, further comprising a surfactant.
Item 8. Item 8. The composition according to Item 7, wherein the surfactant content is 0.01 to 10% by weight.
Item 9. 0.1% by volume or more of cellular carbon dioxide, preferably 1% by volume or more, more preferably 2% by volume or more, further preferably 3% by volume or more, particularly preferably 4% by volume or more, and most preferably 5% by volume or more. Item 9. The composition according to any one of Items 1 to 8.
Item 10. 40% by volume or more, preferably 60% by volume or more, more preferably 80% by volume or more of the cellular carbon dioxide retained in the composition is foamed for 5 minutes or more, preferably 30 minutes or more, more preferably 1%. Item 10. The composition according to any one of Items 1 to 9, which can be maintained for at least 2 hours, particularly at least 2 hours.
Item 11. When 1 g of a 1 cm diameter disk was applied to the edge of a glass plate with a smooth surface of 40 cm in length and the disk was placed at an angle of 60 degrees with respect to a horizontal plane so that the disk would be on top, 5 seconds later Item 11. The composition according to any one of Items 1 to 10, wherein the moving distance of the disk is within 30 cm, preferably within 25 cm, more preferably within 20 cm, and particularly within 15 cm.
Item 12. From a basic composition containing water, a thickener and a carbonate, and a carbon dioxide generating aid (I) containing at least 10% or more acid with respect to the number of moles of carbonate contained in the basic composition The carbon dioxide generated in the composition obtained by mixing them at the time of use is retained, and 40% by volume or more of the carbon dioxide retained in the composition at the maximum volume after foaming, preferably 60 For transdermal and transmucosal absorption of carbon dioxide capable of holding volume% or more, more preferably 80 volume% or more in the form of bubbles for 5 minutes or more, preferably 30 minutes or more, more preferably 1 hour or more, especially 2 hours or more Composition production kit.
Item 13. 60 to 99.8 wt% water, 0.1 to 30 wt% thickener, 0.1 to 10 wt% carbonate with respect to the total amount of water, thickener and carbonate. Item 13. A kit according to item 12.
Item 14. The volume increase rate when the basic composition and the carbon dioxide generating auxiliary (I) are mixed is 0.1% by volume or more of the total volume of the basic composition and the carbon dioxide generating auxiliary, preferably 1% by volume or more. The kit according to Item 12 or 13, more preferably 3% by volume or more, particularly preferably 5% by volume or more, and most preferably 7% by volume or more.
Item 15. Item 15. The kit according to any one of Items 12 to 14, wherein the basic composition contains 0.1 to 25% by weight of a humectant.
Item 16. Item 16. The kit according to any one of Items 12 to 15, wherein the basic composition contains 0.01 to 10% by weight of a surfactant.
Item 17. Item 17. The kit according to any one of Items 12 to 16, wherein the basic composition contains 0.01 to 10% by weight of a lipophilic substance.
Item 18. When 1 g of a 1 cm diameter disk was applied to the edge of a glass plate with a smooth surface of 40 cm in length and the disk was placed at an angle of 60 degrees with respect to a horizontal plane so that the disk would be on top, 5 seconds later Item 20. The production of the carbon dioxide transdermal / transmucosal absorption composition production kit according to any one of Items 12 to 17, wherein the disc travel distance is within 30 cm, preferably within 25 cm, more preferably within 20 cm, and particularly within 15 cm. Composition.
Item 19. Consists of an acidic composition containing water, a thickener and an acid, and a carbon dioxide generating aid (II) containing at least 10% or more of a carbonate with respect to the number of moles of acid contained in the acidic composition. Sometimes the carbon dioxide generated in the composition obtained by mixing these is retained, and the volume of carbon dioxide retained in the composition at the maximum volume after foaming is preferably 40% by volume or more, preferably 60% by volume or more More preferably, the composition for carbon dioxide transdermal / transmucosal absorption capable of holding 80% by volume or more in the form of bubbles for 5 minutes or more, preferably 30 minutes or more, more preferably 1 hour or more, particularly 2 hours or more. Production kit.
Item 20. The term in which the acidic composition contains 60 to 99.8% by weight of water, 0.1 to 30% by weight of the thickener, and 0.1 to 10% by weight of the acid with respect to the total amount of water, the thickener and the acid. 19. The kit according to 19.
Item 21. The volume increase rate when the acidic composition and the carbon dioxide generating auxiliary (II) are mixed is 0.1% by volume or more, preferably 1% by volume of the total capacity of the acidic composition and the carbon dioxide generating auxiliary (II). Item 21. The kit according to Item 19 or 20, more preferably 3% by volume or more, particularly preferably 5% by volume or more, and most preferably 7% by volume or more.
Item 22. Item 22. The kit according to any one of Items 19 to 21, wherein the acidic composition contains 0.1 to 25% by weight of a humectant.
Item 23. Item 23. The kit according to any one of Items 19 to 22, wherein the acidic composition contains 0.01 to 10% by weight of a surfactant.
Item 24. Item 24. The kit according to any one of Items 19 to 23, wherein the acidic composition contains 0.01 to 10% by weight of a lipophilic substance.
Item 25. When 1 g of a 1 cm diameter disk was applied to the edge of a glass plate with a smooth surface of 40 cm in length and the disk was placed at an angle of 60 degrees with respect to a horizontal plane so that the disk would be on top, 5 seconds later Item 25. The composition for carbon dioxide transdermal / transmucosal absorption according to any one of Items 19 to 24, wherein the moving distance of the disk of the composition is within 30 cm, preferably within 25 cm, more preferably within 20 cm, particularly preferably within 15 cm. A composition produced from a production kit.
Item 26. The composition according to any one of Items 1 to 11, or the itch associated with skin mucosal disease or skin mucosal disorder, comprising the composition according to Item 18 or 25; skin ulcer based on peripheral circulation disorder, cooling sensation, numbness; dental disease An agent for preventing or treating any disease selected from the group consisting of: mucocutaneous damage; purulent skin disease; keratosis disorder; musculoskeletal disease; and nervous system disease.
Item 27. The composition according to any one of Items 1 to 11, or the composition according to Item 18 or 25, which reduces or makes stains and freckles less noticeable, whitening action, skin rejuvenation action, skin tightening action, face and legs Cosmetics having any of the effects of improving partial obesity such as arms, abdomen, flank, back, neck, chin, etc., improving skin quality, and suppressing hair recurrence after hair removal.
Item 28. The cosmetic according to claim 27, wherein the cosmetic is a cream, a pack, a gel, a paste or a mask.
Item 29. Carbon dioxide transcutaneous containing carbonate, acid, thickener and water in a state that does not substantially generate carbon dioxide, and containing foamy carbon dioxide by mixing carbonate, acid, thickener and water -Any of the following kits (i) to (iv) capable of obtaining a composition for transmucosal absorption:
(i) A kit comprising a basic composition containing water, a thickener and a carbonate, and an acidic composition containing water, a thickener and an acid.
(ii) A kit comprising a viscous composition comprising carbonate and solid acid (granule, fine granule, powder) and water and a thickener.
(iii) A kit comprising a viscous composition comprising water and a thickener, and a composite granule (fine granule, powder) agent of carbonate and acid.
(iv) A kit comprising carbonate, acid, thickener and water.

かゆみを伴う皮膚粘膜疾患もしくは皮膚粘膜障害としては、水虫、虫さされ、アトピー性皮膚炎、貨幣状湿疹、乾皮症、脂漏性湿疹、蕁麻疹、痒疹、主婦湿疹、尋常性ざ瘡、膿痂疹、毛包炎、癰、せつ、蜂窩織炎、膿皮症、乾癬、魚鱗癬、掌蹠角化症、苔癬、粃糠疹、創傷、熱傷、き裂、びらん、凍瘡などが挙げられる。   Itchy skin dermatosis or mucocutaneous disorders include athlete's foot, insect bites, atopic dermatitis, monetary eczema, dry skin, seborrheic eczema, hives, urticaria, housewife eczema, acne vulgaris, Impetigo, folliculitis, fistula, phlegm, cellulitis, pyoderma, psoriasis, ichthyosis, palmokeratosis, lichen, rash, wounds, burns, cracks, erosions, cryops, etc. It is done.

皮膚粘膜損傷としては、褥創、創傷、熱傷、口角炎、口内炎、皮膚潰瘍、き裂、びらん、凍瘡、壊疸などが挙げられる。   Skin mucosal damage includes wounds, wounds, burns, stomatitis, stomatitis, skin ulcers, cracks, erosions, frostbite, gangrene and the like.

化膿性皮膚疾患としては、尋常性ざ瘡、膿痂疹、毛包炎、癰、せつ、蜂窩織炎、膿皮症、化膿性湿疹などが挙げられる。   Examples of purulent skin diseases include acne vulgaris, impetigo, folliculitis, hemorrhoids, cough, cellulitis, pyoderma, purulent eczema and the like.

角化異常症としては、乾癬、鶏眼、たこ、魚鱗癬、掌蹠角化症、苔癬、粃糠疹などが挙げられる。   Examples of keratosis include psoriasis, chicken eyes, octopus, ichthyosis, palmokeratosis, lichen, and urticaria.

筋骨格系疾患としては、慢性関節リウマチ、頸肩腕症候群、筋肉痛、関節痛、腰痛症などが挙げられる。   Examples of musculoskeletal diseases include rheumatoid arthritis, cervical shoulder arm syndrome, muscle pain, joint pain, and back pain.

歯科疾患としては、歯肉炎、歯槽膿漏、義歯性潰瘍、黒色化歯肉、口内炎などが挙げられる。   Examples of dental diseases include gingivitis, alveolar pyorrhea, denture ulcer, blackened gingiva, stomatitis and the like.

皮膚潰瘍や冷感、しびれ感を生じる末梢循環障害としては、閉塞性血栓血管炎、閉塞性動脈硬化症、糖尿病性末梢循環障害、下肢静脈瘤などが挙げられる。   Examples of peripheral circulatory disorders that cause skin ulcers, cold sensations, and numbness include obstructive thromboangitis, obstructive arteriosclerosis, diabetic peripheral circulatory disorders, and lower limb varices.

神経系疾患としては、神経痛、多発性神経炎、スモン病などが挙げられる。   Examples of nervous system diseases include neuralgia, polyneuritis, and SMON disease.

本発明の組成物は、水虫、虫さされ、アトピー性皮膚炎、貨幣状湿疹、乾皮症、脂漏性湿疹、蕁麻疹、痒疹、主婦湿疹、尋常性ざ瘡、膿痂疹、毛包炎、癰、せつ、蜂窩織炎、膿皮症、乾癬、魚鱗癬、掌蹠角化症、苔癬、粃糠疹、創傷、熱傷、き裂、びらん、凍瘡などの皮膚粘膜疾患もしくは皮膚粘膜障害に伴うかゆみ;褥創、創傷、熱傷、口角炎、皮膚潰瘍、き裂、びらん、凍瘡、壊疽などの皮膚粘膜損傷;移植皮膚片、皮弁などの生着不全;歯肉炎、歯槽膿漏、義歯性潰瘍、黒色化歯肉、口内炎などの歯科疾患;閉塞性血栓血管炎、閉塞性動脈硬化症、糖尿病性末梢循環障害、下肢静脈瘤などの末梢循環障害に基づく皮膚潰瘍や冷感、しびれ感;慢性関節リウマチ、頸肩腕症候群、筋肉痛、関節痛、腰痛症などの筋骨格系疾患;神経痛、多発性神経炎、スモン病などの神経系疾患;乾癬、鶏眼、たこ、魚鱗癬、掌蹠角化症、苔癬、粃糠疹などの角化異常症;尋常性ざ瘡、膿痂疹、毛包炎、癰、せつ、蜂窩織炎、膿皮症、化膿性湿疹などの化膿性皮膚疾患;除毛後の再発毛抑制(むだ毛処理);そばかす、肌荒れ、肌のくすみ、肌の張りや肌の艶の衰え、髪の艶の衰えなどの皮膚や毛髪などの美容上の問題などを副作用をほとんどともなわずに治療及び予防あるいは改善でき、また所望する部位に使用すれば、その部位を痩せさせられる。   The composition of the present invention is athlete's foot, insect bite, atopic dermatitis, monetary eczema, dry skin, seborrheic eczema, urticaria, urticaria, housewife eczema, acne vulgaris, impetigo, hair follicle Skin mucosal diseases or skin mucosal disorders such as inflammation, hemorrhoids, fertility, cellulitis, pyoderma, psoriasis, ichthyosis, palmokeratosis, lichen, rash, wounds, burns, cracks, erosions, cryoma Itching: cutaneous wounds, burns, stomatitis, cutaneous ulcers, cracks, erosions, frostbite, gangrene and other mucous membrane damage; graft failure, graft graft failure, gingivitis, alveolar pus Dental diseases such as denture ulcers, blackened gingiva, stomatitis; skin ulcers, cold sensation, numbness based on peripheral circulatory disorders such as obstructive thromboangitis, obstructive arteriosclerosis, diabetic peripheral circulatory disorder, varicose veins Musculoskeletal disorders such as rheumatoid arthritis, cervical shoulder-arm syndrome, muscle pain, joint pain, low back pain; Nervous system diseases such as pneumonia, chicken eye, octopus, ichthyosis, keratokeratosis, lichen, rash, etc .; acne vulgaris, impetigo, hair Purulent skin diseases such as folliculitis, wrinkles, bruises, cellulitis, pyoderma, purulent eczema; suppression of recurring hair after hair removal (dead hair treatment); freckles, rough skin, dull skin, skin tension and It can treat, prevent, or improve skin and hair cosmetic problems such as deteriorating skin gloss and hair gloss with almost no side effects. Be made.

本発明の二酸化炭素経皮・経粘膜吸収用組成物を水虫、虫さされ、アトピー性皮膚炎、貨幣状湿疹、乾皮症、脂漏性湿疹、蕁麻疹、痒疹、主婦湿疹、尋常性ざ瘡、膿痂疹、毛包炎、癰、せつ、蜂窩織炎、膿皮症、乾癬、魚鱗癬、掌蹠角化症、苔癬、粃糠疹、創傷、熱傷、き裂、びらん、凍瘡などの皮膚粘膜疾患もしくは皮膚粘膜障害に伴うかゆみの治療に使用する場合は、患部を完全に覆うように0.2mm以上、好ましくは0.5mm以上、より好ましくは1.0mm以上、さらに好ましくは1.5mm以上、最も好ましくは2.0mm以上の厚さに、2分以上、好ましくは3分以上、より好ましくは5分以上、さらに好ましくは10分以上、最も好ましくは15分以上塗布する。このとき該組成物の上を食品用合成樹脂ラップフィルムやビニールなどの気体不透過性物質で覆えば一層効果が高まる。本発明の組成物は1回のみの塗布でも効果が得られるが、1日1回〜数回を週1回以上、好ましくは3日に1回、より好ましくは2日に1回、最も好ましくは毎日、痒みが消失するまで塗布する。塗布終了後は拭き取るか、水などで洗い流すか、あるいはその両方を行ってもよい。   The composition for carbon dioxide transdermal / transmucosal absorption of the present invention is athlete's foot, insect bite, atopic dermatitis, monetary eczema, xeroderma, seborrheic eczema, hives, urticaria, housewife eczema, acne vulgaris Acne, impetigo, folliculitis, phlegm, bruise, cellulitis, pyoderma, psoriasis, ichthyosis, palmokeratosis, lichen, urticaria, wound, burns, cracks, erosions, cryopus, etc. When used for the treatment of dermal mucosal diseases or itching associated with mucocutaneous disorders, 0.2 mm or more, preferably 0.5 mm or more, more preferably 1.0 mm or more, more preferably 1 so as to completely cover the affected area. It is applied to a thickness of 0.5 mm or more, most preferably 2.0 mm or more, for 2 minutes or more, preferably 3 minutes or more, more preferably 5 minutes or more, still more preferably 10 minutes or more, most preferably 15 minutes or more. At this time, if the composition is covered with a gas-impermeable material such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. The composition of the present invention is effective even when applied only once, but once a day to several times once a week or more, preferably once every 3 days, more preferably once every 2 days, most preferably Apply daily until itching disappears. After the application is completed, it may be wiped off, washed away with water, or both.

本発明の二酸化炭素経皮・経粘膜吸収用組成物を褥創、創傷、熱傷、口角炎、皮膚潰瘍、き裂、びらん、凍瘡、壊疽などの皮膚粘膜損傷の治療に使用する場合は、患部を完全に覆うように0.5mm以上、好ましくは1.0mm以上、より好ましくは1.5mm以上、さらに好ましくは2.0mm以上、最も好ましくは3.0mm以上の厚さに、5分以上、好ましくは10分以上、より好ましくは15分以上、最も好ましくは20分以上、損傷が治癒するまで塗布する。損傷部位が周囲皮膚粘膜より陥没している症例に対しては、損傷部位を該組成物で埋めて周囲皮膚粘膜組織と同じ高さに、好ましくは周囲皮膚粘膜組織より0.5mm以上高く、より好ましくは周囲皮膚粘膜組織より1.0mm以上高く、さらに好ましくは周囲皮膚粘膜組織より1.5mm以上高く、最も好ましくは周囲皮膚粘膜組織より2.0mm以上高く該組成物を損傷部位上に盛り上げる。フィルムドレッシング材などの、粘着性が強く気体透過性の劣る素材でできた膜などで該組成物を覆って周囲皮膚に接着させ、該組成物を密閉すれば一層効果が高まるが、食品用合成樹脂ラップフィルムやビニールなどの気体不透過性物質で覆っても効果は増大する。24時間持続的に塗布しても問題はなく、褥創などの場合は長時間の連続塗布により効果が高まるだけでなく、看護の大幅な省力化が可能である。本発明の組成物は1日1回〜数回を週1回以上、好ましくは3日に1回、より好ましくは2日に1回、最も好ましくは毎日、皮膚粘膜損傷が治癒するまで塗布する。塗布終了後は生理的食塩水などで洗い流すか、清潔なガーゼなどで部分的に除去した後生理的食塩水などで洗い流し、創傷被覆材などで患部を保護すればよいが、連続投与する場合には部分的に組成物を除去した後に、残った組成物の上から新しい本発明の組成物を追加投与してもよい。   When the composition for carbon dioxide transdermal / transmucosal absorption of the present invention is used for the treatment of cutaneous mucosal damage such as wounds, wounds, burns, stomatitis, skin ulcers, cracks, erosions, frostbite, gangrene, etc. 0.5 mm or more, preferably 1.0 mm or more, more preferably 1.5 mm or more, further preferably 2.0 mm or more, and most preferably 3.0 mm or more for 5 minutes or more so as to completely cover Preferably, it is applied for 10 minutes or more, more preferably 15 minutes or more, and most preferably 20 minutes or more until the damage has healed. For cases where the damaged site is depressed from the surrounding skin mucous membrane, the damaged site is filled with the composition and is flush with the surrounding skin mucosal tissue, preferably more than 0.5 mm higher than the surrounding skin mucosal tissue, Preferably, the composition is raised above the injury site by 1.0 mm or more above the surrounding skin mucosal tissue, more preferably at least 1.5 mm above the surrounding skin mucosal tissue, most preferably at least 2.0 mm above the surrounding skin mucosal tissue. If the composition is covered with a film made of a material having high tackiness and poor gas permeability, such as a film dressing material, and adhered to the surrounding skin, and the composition is sealed, the effect is further enhanced. The effect increases even if it is covered with a gas-impermeable material such as a resin wrap film or vinyl. Even if it is applied continuously for 24 hours, there is no problem, and in the case of wounds and the like, not only is the effect improved by continuous application for a long time, but also significant labor saving of nursing is possible. The composition of the present invention is applied once to several times a day once or more a week, preferably once every 3 days, more preferably once every 2 days, most preferably every day until the mucocutaneous injury is healed. . After application is complete, rinse with physiological saline, etc., or remove with a piece of clean gauze and then rinse with physiological saline to protect the affected area with wound dressing, etc. After partially removing the composition, a new composition of the present invention may be additionally administered over the remaining composition.

本発明の二酸化炭素経皮・経粘膜吸収用組成物を生着不全状態にある移植皮膚片、皮弁などの生着促進に使用する場合、もしくは移植皮膚片、皮弁などの生着不全の防止に使用する場合は、患部を完全に覆うように0.5mm以上、好ましくは1.0mm以上、より好ましくは1.5mm以上、さらに好ましくは2.0mm以上、最も好ましくは3.0mm以上の厚さに、5分以上、好ましくは10分以上、より好ましくは15分以上、最も好ましくは20分以上塗布する。フィルムドレッシング材などの粘着性が強く気体透過性の劣る素材でできた膜などで該組成物を覆って周囲皮膚に接着させ、該組成物を密閉すれば一層効果が高まるが、食品用合成樹脂ラップフィルムやビニールなどの気体不透過性物質で覆っても効果は増大する。24時間以上持続的に塗布しても問題はなく、むしろ長時間の連続塗布により効果が高まる。本発明の組成物は1日1回〜数回を週1回以上、好ましくは3日に1回、より好ましくは2日に1回、最も好ましくは毎日、生着が完成するまで塗布する。塗布終了後は生理的食塩水などで洗い流すか、清潔なガーゼなどで部分的に除去した後生理的食塩水などで洗い流し、創傷被覆材などで患部を保護すればよいが、連続投与する場合には部分的に組成物を除去した後に、残った組成物の上から新しい本発明の組成物を追加投与してもよい。   When the composition for carbon dioxide percutaneous / transmucosal absorption of the present invention is used for promoting the survival of transplanted skin pieces and flaps in the state of graft failure, or the graft failure of graft grafts and flaps, etc. When used for prevention, it is 0.5 mm or more, preferably 1.0 mm or more, more preferably 1.5 mm or more, further preferably 2.0 mm or more, most preferably 3.0 mm or more so as to completely cover the affected area. The thickness is applied for 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, and most preferably 20 minutes or more. If the composition is covered with a film made of a material having high adhesiveness and poor gas permeability, such as a film dressing material, and adhered to the surrounding skin, and the composition is sealed, the effect is further enhanced. The effect increases even if it is covered with a gas-impermeable material such as a wrap film or vinyl. Even if it is applied continuously for 24 hours or more, there is no problem. Rather, the effect is enhanced by continuous application for a long time. The composition of the present invention is applied once to several times a day once or more a week, preferably once every 3 days, more preferably once every 2 days, most preferably every day until engraftment is completed. After application is complete, rinse with physiological saline, etc., or remove with a piece of clean gauze and then rinse with physiological saline to protect the affected area with wound dressing, etc. After partially removing the composition, a new composition of the present invention may be additionally administered over the remaining composition.

本発明の二酸化炭素経皮・経粘膜吸収用組成物を歯肉炎、歯槽膿漏、義歯性潰瘍、黒色化歯肉、口内炎などの歯科疾患の治療もしくは予防に使用する場合は、通常患部もしくは疾患の発生が予想される部位を完全に覆うように0.5mm以上、好ましくは1.0mm以上、より好ましくは1.5mm以上、さらに好ましくは2.0mm以上、最も好ましくは3.0mm以上の厚さに、5分以上、好ましくは10分以上、より好ましくは15分以上、最も好ましくは20分以上、1日1回〜数回を週1回以上、好ましくは3日に1回、より好ましくは2日に1回、最も好ましくは毎日、患部の治癒が認められるか、疾患の発生兆候がなくなるまで塗布する。塗布終了後はうがいなどで口内の組成物を洗い流せばよいが、完全に洗い流せずに口内に残り、飲み込んでも問題はない。また本発明の組成物で非常に流動性の高いもの、例えば試験例35(組成物の流動性の評価試験)の試験方法で組成物の円盤の5秒間の移動距離が30cm以上の本発明の組成物の場合は、含漱剤として使用することも可能である。その場合は、本発明の組成物5g以上、好ましくは10g以上、より好ましくは15g以上、さらに好ましくは20g以上、最も好ましくは30g以上を、3分以上、好ましくは5分以上、より好ましくは10分以上、さらに好ましくは15分以上、最も好ましくは20分以上所望する部位を覆うように口に含む。所定の時間が過ぎれば組成物を吐き出し、水などでうがいして洗い流してもよいし、そのまま放置しても特に問題はない。   When the composition for carbon dioxide transdermal / transmucosal absorption of the present invention is used for treatment or prevention of dental diseases such as gingivitis, alveolar pyorrhea, denture ulcer, blackened gingiva, stomatitis, etc. A thickness of 0.5 mm or more, preferably 1.0 mm or more, more preferably 1.5 mm or more, further preferably 2.0 mm or more, and most preferably 3.0 mm or more so as to completely cover the site where the occurrence is expected. 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, most preferably 20 minutes or more, once a day to several times once a week or more, preferably once every 3 days, more preferably Apply once every two days, most preferably daily until healing of the affected area is observed or there are no signs of disease. After application, the composition in the mouth may be washed away by gargle or the like, but it remains in the mouth without being completely washed away, and there is no problem even if swallowed. Further, the composition of the present invention having very high fluidity, for example, the test method of Test Example 35 (Evaluation Test for Fluidity of Composition), wherein the moving distance of the composition disk for 5 seconds is 30 cm or more. In the case of a composition, it can also be used as a gargle. In that case, the composition of the present invention is 5 g or more, preferably 10 g or more, more preferably 15 g or more, further preferably 20 g or more, most preferably 30 g or more, 3 minutes or more, preferably 5 minutes or more, more preferably 10 More than 15 minutes, more preferably 15 minutes or more, and most preferably 20 minutes or more. When the predetermined time has passed, the composition may be discharged, rinsed with water or the like, or left as it is without any particular problem.

本発明の二酸化炭素経皮・経粘膜吸収用組成物を閉塞性血栓血管炎、閉塞性動脈硬化症、糖尿病性末梢循環障害、下肢静脈瘤などの末梢循環障害に基づく皮膚潰瘍や冷感、しびれ感などの予防もしくは治療に使用する場合は、末梢循環障害部位を完全に覆うように0.2mm以上、好ましくは0.5mm以上、より好ましくは1.0mm以上、さらに好ましくは1.5mm以上、最も好ましくは2.0mm以上の厚さに、5分以上、好ましくは10分以上、より好ましくは15分以上、さらに好ましくは20分以上、最も好ましくは30分以上塗布する。このとき該組成物の上を食品用合成樹脂ラップフィルムやビニールなどの気体不透過性物質などで覆えば一層効果が高まる。本発明の組成物は1日1回〜数回を週1回以上、好ましくは3日に1回、より好ましくは2日に1回、最も好ましくは毎日、患部の治癒が認められるか、疾患の発生兆候がなくなるまで塗布する。塗布終了後は拭き取るか、水などで洗い流すか、あるいはその両方を行ってもよい。   The composition for carbon dioxide transdermal / transmucosal absorption of the present invention is used for skin ulcer, cold sensation, numbness based on peripheral circulatory disorders such as obstructive thromboangitis, obstructive arteriosclerosis, diabetic peripheral circulatory disorder, lower limb varices When used for prevention or treatment of feeling, etc., 0.2 mm or more, preferably 0.5 mm or more, more preferably 1.0 mm or more, further preferably 1.5 mm or more, so as to completely cover the peripheral circulatory disturbance site. Most preferably, it is applied to a thickness of 2.0 mm or more for 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, still more preferably 20 minutes or more, and most preferably 30 minutes or more. At this time, if the composition is covered with a gas-impermeable material such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. The composition of the present invention is used once or several times a day, once a week or more, preferably once every 3 days, more preferably once every 2 days, most preferably every day. Apply until signs of After the application is completed, it may be wiped off, washed away with water, or both.

本発明の二酸化炭素経皮・経粘膜吸収用組成物を慢性関節リウマチ、頸肩腕症候群、筋肉痛、関節痛、腰痛症などの筋骨格系疾患、もしくは神経痛、多発性神経炎、スモン病などの神経系疾患の治療もしくは予防に使用する場合は、患部もしくは疾患発生が予想される部位を完全に覆うように0.2mm以上、好ましくは0.5mm以上、より好ましくは1.0mm以上、さらに好ましくは1.5mm以上、最も好ましくは2.0mm以上の厚さに、5分以上、好ましくは10分以上、より好ましくは15分以上、さらに好ましくは20分以上、最も好ましくは30分以上塗布する。このとき該組成物の上を食品用合成樹脂ラップフィルムやビニールなどの気体不透過性物質などで覆えば一層効果が高まる。本発明の組成物は1日1回〜数回を週1回以上、好ましくは3日に1回、より好ましくは2日に1回、最も好ましくは毎日、患部の治癒が認められるか、疾患の発生兆候がなくなるまで塗布する。塗布終了後は拭き取るか、水などで洗い流すか、あるいはその両方を行ってもよい。   The composition for carbon dioxide transdermal / transmucosal absorption of the present invention is used for musculoskeletal diseases such as rheumatoid arthritis, cervical-shoulder-arm syndrome, muscle pain, joint pain, low back pain, or neuralgia, polyneuritis, summon disease, etc. When used for the treatment or prevention of nervous system diseases, 0.2 mm or more, preferably 0.5 mm or more, more preferably 1.0 mm or more, more preferably so as to completely cover the affected area or the site where disease occurrence is expected. Is applied to a thickness of 1.5 mm or more, most preferably 2.0 mm or more, for 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, still more preferably 20 minutes or more, most preferably 30 minutes or more. . At this time, if the composition is covered with a gas-impermeable material such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. The composition of the present invention is used once or several times a day, once a week or more, preferably once every 3 days, more preferably once every 2 days, most preferably every day. Apply until signs of After the application is completed, it may be wiped off, washed away with water, or both.

本発明の二酸化炭素経皮・経粘膜吸収用組成物を乾癬、鶏眼、たこ、魚鱗癬、掌蹠角化症、苔癬、粃糠疹などの角化異常症の治療に使用する場合は、患部を完全に覆うように0.2mm以上、好ましくは0.5mm以上、より好ましくは1.0mm以上、さらに好ましくは1.5mm以上、最も好ましくは2.0mm以上の厚さに、5分以上、好ましくは10分以上、より好ましくは15分以上、さらに好ましくは20分以上、最も好ましくは30分以上塗布する。このとき該組成物の上を食品用合成樹脂ラップフィルムやビニールなどの気体不透過性物質などで覆えば一層効果が高まる。本発明の組成物は1日1回〜数回を週1回以上、好ましくは3日に1回、より好ましくは2日に1回、最も好ましくは毎日、治癒が確認できるまで塗布する。塗布終了後は拭き取るか、水などで洗い流すか、あるいはその両方を行ってもよい。   When the carbon dioxide transdermal / mucosal absorption composition of the present invention is used for the treatment of keratosis disorders such as psoriasis, chicken eyes, octopus, ichthyosis, palmokeratosis, lichen, rash, 0.2 mm or more, preferably 0.5 mm or more, more preferably 1.0 mm or more, further preferably 1.5 mm or more, most preferably 2.0 mm or more, and 5 minutes or more so as to completely cover the affected area. It is preferably applied for 10 minutes or more, more preferably for 15 minutes or more, still more preferably for 20 minutes or more, and most preferably for 30 minutes or more. At this time, if the composition is covered with a gas-impermeable material such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. The composition of the present invention is applied once to several times a day, once a week or more, preferably once every three days, more preferably once every two days, most preferably every day until healing can be confirmed. After the application is completed, it may be wiped off, washed away with water, or both.

本発明の二酸化炭素経皮・経粘膜吸収用組成物を尋常性ざ瘡、膿痂疹、毛包炎、癰、せつ、蜂窩織炎、膿皮症、化膿性湿疹などの化膿性皮膚疾患の治療に使用する場合は、患部を完全に覆うように0.5mm以上、好ましくは1.0mm以上、より好ましくは1.5mm以上、さらに好ましくは2.0mm以上、最も好ましくは3.0mm以上の厚さに、5分以上、好ましくは10分以上、より好ましくは15分以上、さらに好ましくは20分以上、最も好ましくは30分以上塗布する。このとき該組成物の上を食品用合成樹脂ラップフィルムやビニールなどの気体不透過性物質などで覆えば一層効果が高まる。本発明の組成物は1日1回〜数回を週1回以上、好ましくは3日に1回、より好ましくは2日に1回、最も好ましくは毎日、治癒が確認できるまで塗布する。塗布終了後は拭き取るか、水などで洗い流すか、あるいはその両方を行ってもよい。   The composition for transdermal and transmucosal absorption of carbon dioxide according to the present invention is used for purulent skin diseases such as acne vulgaris, impetigo, folliculitis, hemorrhoids, cough, cellulitis, pyoderma, purulent eczema and the like. When used for treatment, it is 0.5 mm or more, preferably 1.0 mm or more, more preferably 1.5 mm or more, further preferably 2.0 mm or more, and most preferably 3.0 mm or more so as to completely cover the affected area. The thickness is applied for 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, still more preferably 20 minutes or more, and most preferably 30 minutes or more. At this time, if the composition is covered with a gas-impermeable material such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. The composition of the present invention is applied once to several times a day, once a week or more, preferably once every three days, more preferably once every two days, most preferably every day until healing can be confirmed. After the application is completed, it may be wiped off, washed away with water, or both.

本発明の二酸化炭素経皮・経粘膜吸収用組成物を除毛後の再発毛抑制(むだ毛処理)に使用する場合は、剃刀等で所望の部位のむだ毛を剃るか、あるいは除毛剤等で除毛した後に、除毛部位を完全に覆うように0.5mm以上、好ましくは1.0mm以上、より好ましくは1.5mm以上、さらに好ましくは2.0mm以上、最も好ましくは3.0mm以上の厚さに、5分以上、好ましくは10分以上、より好ましくは15分以上、さらに好ましくは20分以上、最も好ましくは30分以上塗布する。このとき該組成物の上を食品用合成樹脂ラップフィルムやビニールなどの気体不透過性物質などで覆えば一層効果が高まる。本発明の組成物は1日1回〜数回を週1回以上、好ましくは3日に1回、より好ましくは2日に1回、最も好ましくは毎日、総塗布回数が10回以上、好ましくは15回以上、より好ましくは20回以上、最も好ましくは30回以上塗布する。塗布終了後は拭き取るか、水などで洗い流すか、あるいはその両方を行ってもよい。   When the composition for carbon dioxide transdermal / transmucosal absorption according to the present invention is used for the suppression of recurrent hair after hair removal (dead hair treatment), the unwanted hair at a desired site is shaved with a razor or the hair remover. After removing the hair, etc., 0.5 mm or more, preferably 1.0 mm or more, more preferably 1.5 mm or more, further preferably 2.0 mm or more, most preferably 3.0 mm so as to completely cover the hair removal site. The above thickness is applied for 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, still more preferably 20 minutes or more, and most preferably 30 minutes or more. At this time, if the composition is covered with a gas-impermeable material such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. The composition of the present invention is once to several times a day, once a week or more, preferably once every 3 days, more preferably once every 2 days, most preferably every day, the total number of application is 10 times or more, preferably Is applied 15 times or more, more preferably 20 times or more, most preferably 30 times or more. After the application is completed, it may be wiped off, washed away with water, or both.

本発明の二酸化炭素経皮・経粘膜吸収用組成物をそばかすを減少させる、もしくは目立たなくさせる目的で使用する場合は、所望の部位のみを覆うよう塗布してもよいが、美白作用や部分肥満を改善する作用などが塗布部位に同時に現れるため、できる限り広範囲に、例えば顔の場合は顔全体に0.5mm以上、好ましくは1.0mm以上、より好ましくは1.5mm以上、さらに好ましくは2.0mm以上、最も好ましくは3.0mm以上の厚さに、5分以上、好ましくは10分以上、より好ましくは15分以上、さらに好ましくは20分以上、最も好ましくは30分以上塗布する。このとき該組成物の上を食品用合成樹脂ラップフィルムやビニールなどの気体不透過性物質などで覆えば一層効果が高まる。本発明の組成物は1日1回〜数回を週1回以上、好ましくは3日に1回、より好ましくは2日に1回、最も好ましくは毎日、総塗布回数が10回以上、好ましくは15回以上、より好ましくは20回以上、最も好ましくは30回以上塗布する。塗布終了後は拭き取るか、水などで洗い流すか、あるいはその両方を行ってもよい。   When the carbon dioxide transdermal / transmucosal absorption composition of the present invention is used for the purpose of reducing freckles or making it inconspicuous, it may be applied to cover only the desired site, but it may be used for whitening or partial obesity. In the case of a face, for example, the entire face is 0.5 mm or more, preferably 1.0 mm or more, more preferably 1.5 mm or more, more preferably 2 It is applied to a thickness of 0.0 mm or more, most preferably 3.0 mm or more for 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, still more preferably 20 minutes or more, and most preferably 30 minutes or more. At this time, if the composition is covered with a gas-impermeable material such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. The composition of the present invention is once to several times a day, once a week or more, preferably once every 3 days, more preferably once every 2 days, most preferably every day, the total number of application is 10 times or more, preferably Is applied 15 times or more, more preferably 20 times or more, most preferably 30 times or more. After the application is completed, it may be wiped off, washed away with water, or both.

本発明の二酸化炭素経皮・経粘膜吸収用組成物を美白や肌の引き締め、肌質改善目的で使用する場合は、所望の部位を覆うように0.2mm以上、好ましくは0.5mm以上、より好ましくは1.0mm以上、さらに好ましくは1.5mm以上、最も好ましくは2.0mm以上の厚さに、5分以上、好ましくは10分以上、より好ましくは15分以上、さらに好ましくは20分以上、最も好ましくは30分以上塗布する。このとき該組成物の上を食品用合成樹脂ラップフィルムやビニールなどの気体不透過性物質で覆えば一層効果が高まる。本発明で言う肌質改善とは、滑らかできめが細かく、透明感があって化粧乗りのよい肌にすることを言う。美白効果や肌の引き締め効果、肌質改善効果は本発明の組成物を1回塗布するだけでも得られるが、1日1回〜数回を週1回以上、好ましくは3日に1回、より好ましくは2日に1回、最も好ましくは毎日、可能な限り継続する。塗布終了後は拭き取るか、水などで洗い流すか、あるいはその両方を行ってもよい。   When using the composition for carbon dioxide transdermal / transmucosal absorption according to the present invention for the purpose of whitening or tightening the skin and improving the skin quality, it is 0.2 mm or more, preferably 0.5 mm or more so as to cover a desired site. More preferably, the thickness is 1.0 mm or more, more preferably 1.5 mm or more, most preferably 2.0 mm or more, 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, still more preferably 20 minutes. As described above, it is most preferably applied for 30 minutes or more. At this time, if the composition is covered with a gas-impermeable material such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. The skin quality improvement referred to in the present invention means that the skin is smooth, fine, transparent, and has good makeup. The whitening effect, skin tightening effect, and skin quality improving effect can be obtained by applying the composition of the present invention only once, but once a day to several times once a week or more, preferably once every 3 days, More preferably once every two days, most preferably every day as long as possible. After the application is completed, it may be wiped off, washed away with water, or both.

本発明の二酸化炭素経皮・経粘膜吸収用組成物を肌の若返り目的で使用する場合は、所望の部位を覆うように0.2mm以上、好ましくは0.5mm以上、より好ましくは1.0mm以上、さらに好ましくは1.5mm以上、最も好ましくは2.0mm以上の厚さに、5分以上、好ましくは10分以上、より好ましくは15分以上、さらに好ましくは20分以上、最も好ましくは30分以上塗布する。このとき該組成物の上を食品用合成樹脂ラップフィルムやビニールなどの気体不透過性物質で覆えば一層効果が高まる。本発明で言う肌の若返りとは、微視的皮膚表面の形状において皮溝、皮丘が消失もしくは不明瞭で、部分的もしくは広範囲に角質の剥離が生じている皮膚を皮溝、皮丘が明瞭で整った肌にすることを言う。本発明の組成物は1日1回〜数回、3日に1回以上、より好ましくは2日に1回以上、最も好ましくは毎日、総塗布回数が10回以上、好ましくは15回以上、より好ましくは20回以上、最も好ましくは30回以上塗布する。塗布終了後は拭き取るか、水などで洗い流すか、あるいはその両方を行ってもよい。   When the carbon dioxide transdermal / mucosal absorption composition of the present invention is used for the purpose of skin rejuvenation, it is 0.2 mm or more, preferably 0.5 mm or more, more preferably 1.0 mm so as to cover a desired site. More preferably, the thickness is 1.5 mm or more, most preferably 2.0 mm or more, 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, still more preferably 20 minutes or more, most preferably 30 Apply for at least minutes. At this time, if the composition is covered with a gas-impermeable material such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. Skin rejuvenation as referred to in the present invention means that skin grooves and dermis disappear or are unclear in the shape of the surface of the microscopic skin, and skin or dermis is skin that has partially or extensively exfoliated keratin. Say to make your skin clear and tidy. The composition of the present invention is once to several times a day once or more, once every three days, more preferably once every two days, most preferably every day, the total application number is 10 times or more, preferably 15 times or more, More preferably, it is applied 20 times or more, most preferably 30 times or more. After the application is completed, it may be wiped off, washed away with water, or both.

本発明の二酸化炭素経皮・経粘膜吸収用組成物を顔、脚、腕、腹部、脇腹、背中、首、顎などの部分肥満を改善する目的で使用する場合は、所望の部位を覆うように0.2mm以上、好ましくは0.5mm以上、より好ましくは1.0mm以上、さらに好ましくは1.5mm以上、最も好ましくは2.0mm以上の厚さに、5分以上、好ましくは10分以上、より好ましくは15分以上、さらに好ましくは20分以上、最も好ましくは30分以上、1日1回〜数回、3日に1回以上、より好ましくは2日に1回以上、最も好ましくは毎日、総塗布回数が20回以上、好ましくは25回以上、最も好ましくは30回以上塗布する。このとき該組成物の上を食品用合成樹脂ラップフィルムやビニールなどの気体不透過性物質で覆えば一層効果が高まる。塗布終了後は拭き取るか、水などで洗い流すか、あるいはその両方を行ってもよい。   When using the carbon dioxide transdermal / transmucosal absorption composition of the present invention for the purpose of improving partial obesity on the face, legs, arms, abdomen, flank, back, neck, chin, etc., it should cover the desired site. 0.2 mm or more, preferably 0.5 mm or more, more preferably 1.0 mm or more, more preferably 1.5 mm or more, and most preferably 2.0 mm or more, 5 minutes or more, preferably 10 minutes or more. More preferably 15 minutes or more, still more preferably 20 minutes or more, most preferably 30 minutes or more, once to several times a day, once or more every 3 days, more preferably once or more every 2 days, most preferably Each day, the total number of applications is 20 times or more, preferably 25 times or more, most preferably 30 times or more. At this time, if the composition is covered with a gas-impermeable material such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. After the application is completed, it may be wiped off, washed away with water, or both.

本発明の組成物は肌のくすみを取る作用があり、1回の塗布で美白効果が得られるが、該組成物を唇や乳頭などに塗布すれば色素沈着等でくすんだ色のこれらの部位を健康的な色にできる。この場合、本発明の組成物を所望の部位を完全に覆うように0.2mm以上、好ましくは0.5mm以上、より好ましくは1.0mm以上、さらに好ましくは1.5mm以上、最も好ましくは2.0mm以上の厚さに、5分以上、好ましくは10分以上、より好ましくは15分以上、さらに好ましくは20分以上、最も好ましくは30分以上、1日1回〜数回、3日に1回以上、より好ましくは2日に1回以上、最も好ましくは毎日、効果が現れるまで塗布する。このとき該組成物の上を食品用合成樹脂ラップフィルムやビニールなどの気体不透過性物質で覆えば一層効果が高まる。塗布終了後は拭き取るか、水などで洗い流すか、あるいはその両方を行ってもよい。   The composition of the present invention has a function of removing dullness of the skin, and a whitening effect can be obtained by a single application. However, if the composition is applied to the lips, the nipple, etc., these parts having a dull color due to pigmentation or the like. Can be a healthy color. In this case, the composition of the present invention is 0.2 mm or more, preferably 0.5 mm or more, more preferably 1.0 mm or more, further preferably 1.5 mm or more, and most preferably 2 so as to completely cover a desired site. 0.05 mm or more, 5 minutes or more, preferably 10 minutes or more, more preferably 15 minutes or more, more preferably 20 minutes or more, most preferably 30 minutes or more, once to several times a day, 3 days Apply once or more, more preferably once every two days, most preferably every day until the effect appears. At this time, if the composition is covered with a gas-impermeable material such as a synthetic resin wrap film for food or vinyl, the effect is further enhanced. After the application is completed, it may be wiped off, washed away with water, or both.

試験例42の結果に示されているように、ハーブエキスを加えた本発明の二酸化炭素経皮・経粘膜吸収用組成物は、それを加えない組成物と比較して美白効果が強いことから、ハーブエキスの吸収促進効果があると考えられる。このことから生理活性物質を本発明組成物に加えることにより、経皮吸収可能な成分は一層吸収効率が向上し、効果が得られやすくなるとともに、従来経皮吸収が困難とされていた生理活性物質の経皮吸収が可能になると期待できる。この場合の経皮吸収には経粘膜吸収も含む。生理活性物質の吸収効率の向上により投与量低減が期待されるために副作用の低減も期待される。また、本発明の組成物は従来の経皮吸収製剤のように角質を破壊することなく生理活性物質の吸収を促進するのみならず、破壊もしくは損傷された皮膚粘膜の治癒促進作用を持つため、生理活性物質を配合した本発明の組成物を含む経皮吸収製剤は、従来の製品に見られるかぶれなどの副作用が軽減もしくは回避されると期待される。本発明の組成物を含む経皮吸収製剤には生理活性物質としてフルオシノロンアセトニド、フルオシノニド、吉草酸ベタメタゾン、ジプロピオン酸ベタメタゾン、酪酸プロピオン酸ベタメタゾン、酢酸ヒドロコルチゾン、プレドニゾロン、メチルプレドニゾロン、酢酸メチルプレドニゾロン、酢酸メチルプレドニゾロン、デキサメタゾン、吉草酸デキサメタゾン、プロピオン酸デキサメタゾン、フルドロキシコルチド、ピバル酸フルメタゾン、プロンピオン酸ベクロメタゾン、酪酸ヒドロコルチゾン、プロピオン酸クロベタゾール、トリアムシノロンアセトニド吉草酸ジフルコルトロン、ハルシノニド、吉草酸酢酸プレドニゾロン、アムシノニド、酪酸プロピオン酸ヒドロコルチゾン、酪酸クロベタゾン、酢酸ジフロラゾン、ジフルプレドナート、プロピオン酸アルクロメタゾン、ブデソニド、プロピオン酸デプロドン、フランカルボン酸モメタゾンなどのステロイドを0.01〜5重量%、硫酸カナマイシン、硫酸フラジオマイシン、硫酸ゲンタマイシン、エリスロマイシン、塩酸テトラサイクリン、塩酸オキシテトラサイクリン、クロラムフェニコール、バシトラシン、オフロキサシン、ナジフロキサシンなどの抗生物質を0.1〜10重量%、ナイスタチン、トリコマイシン、トルナフタート、硝酸イソコナゾール、トルシクラート、チオコナゾール、硝酸スルコナゾール、硝酸オキシコナゾール、塩酸クロコナゾール、ビフォナゾール、ケトコナゾール、塩酸ブテナフィン、塩酸ネチコナゾール、塩酸テルビナフィン、ラノコナゾール、塩酸アモロルフィン、硝酸エコナゾール、クロトリマゾール、ピマリシン、硝酸ミコナゾール、トルナフタート、シクロピロクスオラミンなどの抗真菌薬を0.01〜5重量%、塩酸オキシブプロカイン、アミノ安息香酸エチル、塩酸コカイン、塩酸リドカイン、塩酸ジブカインなどの局所麻酔薬を0.1〜10重量%、トコレチナートやブクラデシンなどの細胞賦活薬を0.1〜20重量%、ニトログリセリンや硝酸イソソルビドなどの冠血管拡張薬、ニフェジピンなどのカルシウム拮抗薬を0.1〜10重量%、エピネフィリン、塩酸エフェドリン、塩酸メトキシフェナミン、硫酸イソプレナリン、塩酸イソプレナリン、硫酸オルシプレナリン、塩酸クロルプレナリン、塩酸トリメトキノール、硫酸サルブタモール、硫酸テルブタリン、塩酸プロカテロール、塩酸ピルブテロール、臭化水素酸フェノテロール、フマル酸フォルモテロール、塩酸クレンブテロール、塩酸マブテロール、ジプロフィリンなどのβー刺激薬を0.1〜10重量%、シャゼンソウエキス、オウヒエキス、キョウニンエキス、マオウエキスなどの鎮咳去痰薬を1〜15重量%配合できるが、ここに例示した以外の生理活性物質でも経皮吸収が可能、もしくは経皮吸収が期待される生理活性物質であれば本発明の組成物に配合することにより効率的な経皮吸収が期待される。   As shown in the results of Test Example 42, the carbon dioxide transdermal / mucosal absorption composition of the present invention to which the herb extract is added has a strong whitening effect compared to the composition to which it is not added. It is considered that there is an effect of promoting absorption of the herb extract. Therefore, by adding a physiologically active substance to the composition of the present invention, the percutaneously absorbable component is further improved in absorption efficiency and more effective, and the physiological activity that has been conventionally difficult to percutaneously absorb. Expected to enable transdermal absorption of substances. Transdermal absorption in this case includes transmucosal absorption. Since the dose reduction is expected by improving the absorption efficiency of the physiologically active substance, side effects are also expected to be reduced. In addition, the composition of the present invention not only promotes the absorption of a physiologically active substance without destroying the stratum corneum as in the conventional percutaneous absorption preparation, but also has the effect of promoting the healing of the destroyed or damaged skin mucosa, The transdermally absorbable preparation containing the composition of the present invention containing a physiologically active substance is expected to reduce or avoid side effects such as irritation found in conventional products. The transdermally absorbable preparation containing the composition of the present invention includes fluocinolone acetonide, fluocinonide, betamethasone valerate, betamethasone dipropionate, betamethasone butyrate propionate, hydrocortisone acetate, prednisolone, methylprednisolone acetate, methylprednisolone acetate , Methylprednisolone acetate, dexamethasone, dexamethasone valerate, dexamethasone propionate, fludroxycortide, flumetasone pivalate, beclomethasone propionate, hydrocortisone butyrate, clobetasol propionate, diflucortron triamcinolone acetonide diflucortron valinate, , Amsinonide, hydrocortisone butyrate propionate, clobetasone butyrate, diflorazone acetate, diflupredone , 0.01-5% by weight of steroid such as alcromethasone propionate, budesonide, deprodon propionate, mometasone furanate, kanamycin sulfate, fradiomycin sulfate, gentamicin sulfate, erythromycin, tetracycline hydrochloride, oxytetracycline hydrochloride, chloramphenicol 0.1-10% by weight of antibiotics such as bacitracin, ofloxacin, nadifloxacin, nystatin, tricomycin, tolnaphthalate, isoconazole nitrate, tolcyclate, thioconazole, sulconazole nitrate, oxyconazole nitrate, croconazole hydrochloride, bifonazole, ketoconazole, butenafine hydrochloride , Neticonazole hydrochloride, terbinafine hydrochloride, lanoconazole, amorolfine hydrochloride, econazol nitrate 0.01 to 5% by weight of an antifungal agent such as clotrimazole, pimaricin, miconazole nitrate, tolnaphthalate, cyclopyroxolamine, oxybuprocaine hydrochloride, ethyl aminobenzoate, cocaine hydrochloride, lidocaine hydrochloride, dibucaine hydrochloride, etc. 0.1 to 10% by weight of local anesthetics, 0.1 to 20% by weight of cell activators such as tocolatinate and bucladecin, coronary vasodilators such as nitroglycerin and isosorbide nitrate, and calcium antagonists such as nifedipine. 1 to 10% by weight, epinephrine, ephedrine hydrochloride, methoxyphenamine hydrochloride, isoprenaline sulfate, isoprenaline hydrochloride, orciprenaline sulfate, chlorprenalin hydrochloride, trimethquinol hydrochloride, salbutamol sulfate, terbutaline sulfate, procaterol hydrochloride, pyrbuterol hydrochloride 0.1 to 10% by weight of β-stimulant such as water, fenoterol hydrobromide, formoterol fumarate, clenbuterol hydrochloride, mabuterol hydrochloride, diprofilin, etc., antitussive expectorant such as chasenso extract, prawn extract, kyonin extract, mao extract The drug can be blended in an amount of 1 to 15% by weight. However, any physiologically active substance other than those exemplified here can be percutaneously absorbed or expected to be percutaneously absorbed. Efficient transdermal absorption is expected.

本発明の組成物は、正常であるか、何らかの疾患や損傷による異常があるかを問わず、血管系を有する皮膚や粘膜組織、皮下組織などに適用される。皮膚としては、手掌や足底、頭皮を含む外皮全てが含まれる。粘膜組織としては、鼻粘膜や口腔粘膜、歯周組織粘膜、口唇粘膜、外性器粘膜、肛門周囲粘膜などが含まれる。皮下組織としては、筋膜、皮下脂肪、真皮などが含まれる。   The composition of the present invention is applied to skin having a vascular system, mucosal tissue, subcutaneous tissue or the like regardless of whether it is normal or abnormal due to some disease or injury. The skin includes all outer skins including palms, soles and scalp. Examples of mucosal tissues include nasal mucosa, oral mucosa, periodontal mucosa, lip mucosa, external genital mucosa, and perianal mucosa. Subcutaneous tissues include fascia, subcutaneous fat, dermis and the like.

二酸化炭素は、炭酸飲料や発泡性製剤のように短時間、例えば数秒から数分以内に消失するものではなく、本発明の組成物に気泡状態で保持され、持続的に放出される。   Carbon dioxide does not disappear within a short time, for example within a few seconds to a few minutes, like carbonated beverages and effervescent preparations, but is retained in the state of bubbles in the composition of the present invention and released continuously.

本発明において、「二酸化炭素を持続的に経皮・経粘膜吸収させることができる組成物」とは、好ましい具体例では、二酸化炭素を5分以上、好ましくは20分以上、より好ましくは30分以上、さらに好ましくは1時間以上、特に好ましくは1.5時間以上、最も好ましくは2時間以上二酸化炭素を経皮・経粘膜吸収させることができる組成物を意味する。   In the present invention, the “composition capable of continuously absorbing carbon dioxide percutaneously and transmucosally” is a specific example, in which carbon dioxide is 5 minutes or longer, preferably 20 minutes or longer, more preferably 30 minutes. As mentioned above, it means a composition capable of absorbing carbon dioxide percutaneously and transmucosally, more preferably 1 hour or more, particularly preferably 1.5 hours or more, and most preferably 2 hours or more.

本発明において、「気泡状二酸化炭素」とは、例えば炭酸塩と酸を反応させて二酸化炭素を発生させた場合や、二酸化炭素ボンベから二酸化炭素を吹き込んだ場合に、組成物中に気泡として含まれる二酸化炭素を意味し、該気泡は二酸化炭素のみからなっていてもよく、二酸化炭素とともに空気などを含んでいてもよい。「気泡状二酸化炭素」中の二酸化炭素の割合は30容量%以上、好ましくは50容量%以上、さらに好ましくは70容量%以上、特に好ましくは90容量%以上、最も好ましくは100容量%である。   In the present invention, “bubble carbon dioxide” is included as bubbles in the composition when carbon dioxide is generated by reacting a carbonate and an acid, or when carbon dioxide is blown from a carbon dioxide cylinder, for example. The bubble may consist of only carbon dioxide, and may contain air or the like together with carbon dioxide. The ratio of carbon dioxide in the “bubble carbon dioxide” is 30% by volume or more, preferably 50% by volume or more, more preferably 70% by volume or more, particularly preferably 90% by volume or more, and most preferably 100% by volume.

本発明のキットにおいて、二酸化炭素発生補助剤(I)は、酸のみからなっていてもよく、酸とともに、水、増粘剤、結合剤、崩壊剤、賦形剤、界面活性剤、保湿剤、親油性物質、pH調整剤などを含んでいてもよい。二酸化炭素発生補助剤(I)は、塩基性組成物中に含まれる炭酸塩のモル数に対して少なくとも10%、好ましくは10〜300%程度、より好ましくは50〜200%程度の酸を含む。   In the kit of the present invention, the carbon dioxide generating auxiliary agent (I) may consist of an acid alone, and together with the acid, water, thickener, binder, disintegrant, excipient, surfactant, moisturizer. , Lipophilic substances, pH adjusters and the like. The carbon dioxide generating auxiliary agent (I) contains at least 10%, preferably about 10 to 300%, more preferably about 50 to 200% of acid with respect to the number of moles of carbonate contained in the basic composition. .

本発明のキットにおいて、二酸化炭素発生補助剤(II)は、炭酸塩のみからなっていてもよく、炭酸塩とともに、水、増粘剤、結合剤、崩壊剤、賦形剤、界面活性剤、保湿剤、親油性物質、pH調整剤などを含んでいてもよい。二酸化炭素発生補助剤(II)は、酸性組成物中に含まれる炭酸塩のモル数に対して少なくとも10%、好ましくは10〜300%程度、より好ましくは50〜200%程度の炭酸塩を含む。   In the kit of the present invention, the carbon dioxide generating auxiliary agent (II) may consist of carbonate alone, together with carbonate, water, thickener, binder, disintegrant, excipient, surfactant, It may contain a humectant, a lipophilic substance, a pH adjuster and the like. The carbon dioxide generating auxiliary agent (II) contains at least 10%, preferably about 10 to 300%, more preferably about 50 to 200% of carbonate with respect to the number of moles of carbonate contained in the acidic composition. .

本発明の組成物は二酸化炭素の持続的経皮・経粘膜吸収が目的であるので、組成物を対象部位に適用する際には組成物中に気泡状二酸化炭素がより多く含まれていることが好ましく、組成物で対象部位を完全に覆うように厚めに塗布することが好ましい。流動性が低い組成物の場合にはガーゼや不織布などの吸収性素材などに吸収させて組成物の塗布時の厚みを持たせればよい。塗布する厚さは対象疾患や目的によって異なるが、0.2mm以上、好ましくは0.5mm以上、より好ましくは1.0mm以上、さらに好ましくは1.5mm以上、最も好ましくは2.0mm以上である。ただし、厚みがありすぎては組成物の適用が困難になるため、塗布する組成物もしくは組成物を含浸する吸収体の厚みは5cm以下、より好ましくは4cm以下、さらに好ましくは2cm以下、最も好ましくは1cm以下である。   Since the composition of the present invention is intended for continuous percutaneous and transmucosal absorption of carbon dioxide, when the composition is applied to a target site, the composition should contain more bubble carbon dioxide. It is preferable to apply a thick layer so as to completely cover the target site with the composition. In the case of a composition having low fluidity, it may be absorbed in an absorbent material such as gauze or a nonwoven fabric so as to have a thickness when the composition is applied. The thickness to be applied varies depending on the target disease and purpose, but is 0.2 mm or more, preferably 0.5 mm or more, more preferably 1.0 mm or more, further preferably 1.5 mm or more, and most preferably 2.0 mm or more. . However, since it is difficult to apply the composition if there is too much thickness, the thickness of the composition to be applied or the absorber impregnated with the composition is 5 cm or less, more preferably 4 cm or less, more preferably 2 cm or less, and most preferably Is 1 cm or less.

本発明の組成物は、広範囲の皮膚もしくは粘膜組織に適用してもよく、例えば足全体を本発明組成物中に浸けることにより、水虫の痒みの治療を含むフットケア用途に用いてもよいし、ふくらはぎや下腿等を本発明組成物中に浸しておけば、所望する部位の部分的な美肌効果などが得られ、部分痩せも可能である。   The composition of the present invention may be applied to a wide range of skin or mucosal tissues, and may be used for foot care applications including treatment of athlete's foot itch by, for example, immersing the entire foot in the composition of the present invention. If a calf, a lower leg or the like is immersed in the composition of the present invention, a partial skin-beautifying effect at a desired site can be obtained, and partial skin thinning is also possible.

さらに、全身熱傷あるいは部分熱傷の場合、熱傷部分を全体的に本発明組成物に浸けることにより、熱傷治療を行うことができる。同様に、本発明組成物を全身に適用することにより、全身の肌のケアを行うことができる。   Furthermore, in the case of whole body burns or partial burns, burn treatment can be performed by immersing the burned part entirely in the composition of the present invention. Similarly, whole body skin can be cared for by applying the composition of the present invention to the whole body.

本発明の組成物を皮膚粘膜疾患もしくは皮膚粘膜障害の治療や予防目的、又は皮膚や粘膜に対する美容目的で使用する場合は、該組成物を直接使用部位に塗布することもできるし、あるいはガーゼやスポンジ等の吸収性素材に含浸させるか、またはこれらの素材を袋状に成形してその中に該組成物を入れて使用部位に貼付してもよい。該組成物を塗布又は貼付した部位を通気性の乏しいフィルム、ドレッシング材などで覆う閉鎖療法を併用すれば更に高い効果が期待できる。また該組成物を満たした容器に所望部位を浸すことも有効である。その場合、二酸化炭素ボンベなどを用いて該組成物に二酸化炭素を補給すればより効果が持続する。   When the composition of the present invention is used for treatment or prevention of skin mucosal disease or skin mucosal disorder, or for cosmetic purposes for skin or mucosa, the composition can be applied directly to the site of use, or gauze or An absorbent material such as a sponge may be impregnated, or these materials may be formed into a bag shape, and the composition may be put in the bag and attached to a use site. A higher effect can be expected by using in combination with a closed therapy in which the site where the composition is applied or affixed is covered with a film or dressing material having poor air permeability. It is also effective to immerse the desired site in a container filled with the composition. In that case, the effect will be more sustained if the composition is supplemented with carbon dioxide using a carbon dioxide cylinder or the like.

本発明の二酸化炭素経皮・経粘膜吸収用組成物は、密閉容器等に保存することにより、長期間有効性を失うことなく使用が可能である。また、用時調製により使用することも可能である。用時調製では二酸化炭素の発生に伴う吸熱反応により二酸化炭素経皮・経粘膜吸収用組成物が冷たくなるため、電子レンジや湯煎などにより調製用の材料を体温付近の温度など適当な暖かさに暖めておくか、又は調製後に該組成物を暖めてもよい。   The carbon dioxide transdermal / mucosal absorption composition of the present invention can be used without losing its effectiveness for a long period of time by storing it in a sealed container or the like. It can also be used by preparation at the time of use. In preparation for use, the endothermic reaction accompanying the generation of carbon dioxide causes the composition for carbon dioxide transdermal / transmucosal absorption to cool, so the preparation material can be heated to a suitable temperature such as a temperature around the body temperature using a microwave oven or a hot water bath. It may be warmed or the composition may be warmed after preparation.

本発明の二酸化炭素経皮・経粘膜吸収用組成物は、損傷組織と粘膜に対してはpH5〜8で用いることが好ましい。該組成物のpHが5以下では酸の刺激により痛みを生じ、pH8以上ではアルカリによる蛋白変性作用により組織が損傷されるおそれがある。損傷のない皮膚に対して本発明の組成物はpH3〜pH9で用いることが好ましい。該組成物のpHが3未満では酸の皮膚刺激により痛みやかぶれなどの副作用を起こすおそれがあり、pHが9超ではアルカリによる蛋白変性作用により組織が損傷されるおそれがある。   The carbon dioxide transdermal / mucosal absorption composition of the present invention is preferably used at a pH of 5 to 8 for damaged tissues and mucous membranes. When the pH of the composition is 5 or less, pain is caused by acid stimulation, and when the pH is 8 or more, tissue may be damaged due to protein denaturation by alkali. The composition of the present invention is preferably used at pH 3 to pH 9 with respect to intact skin. If the pH of the composition is less than 3, side effects such as pain and rash may occur due to acid skin irritation, and if the pH exceeds 9, the tissue may be damaged by protein denaturation by alkali.

本発明の組成物の製造は、常圧又は加圧の二酸化炭素雰囲気下に行うのが、気泡状二酸化炭素中の二酸化炭素の割合を高めるため好ましい。   The production of the composition of the present invention is preferably carried out in an atmospheric pressure or pressurized carbon dioxide atmosphere in order to increase the proportion of carbon dioxide in the bubble carbon dioxide.

本発明の組成物には、二酸化炭素の気泡を効率よく組成物中に含ませるために界面活性剤を加えることができる。界面活性剤としては、以下のものが例示される。
・ノニオン界面活性剤:ジグリセロールジオレイン酸エステル、ソルビタン脂肪酸エステル、モノオレイン酸グリセリン、モノステアリン酸グリセリン、プロピレングリコールモノステアリン酸エステル、ポリオキシエチレンアルキルエーテル、ポリオキシエチレンソルビタン脂肪酸エステル、ポリオキシエチレン・ポリオキシプロピレンブロックポリマー、ポリオキシエチレン硬化ヒマシ油エステルなど。
・カチオン界面活性剤:ステアリルトリメチルアンモニウムクロライド、セチルメチルアンモニウムクロライド、ステアリルジメチルベンジルアンモニウムクロライド、ミリスチルベンジルアンモニウムクロライド、塩化ベンザルコニウム、アシルグルタメート、DL-2-Pyrrolidone-5-Carboxylic Acid Salt of Ethyl N-Cocoyl-L-Arginateなど。
・アニオン界面活性剤:アシルN−メチルタウリン塩、アルキルエーテルリン酸エステル塩、アルキル硫酸ナトリウム、N−アシルアミノ酸塩、高級脂肪酸石鹸、ポリオキシエチレンアルキルエーテル硫酸塩など。
・両性界面活性剤:アルキルジメチルアミノ酢酸ベタイン、アルキルアミドジメチルアミノ酢酸ベタイン、2−アルキル−N−カルボキシ−N−ヒドロキシイミダゾリニウムベタインなど。
・非イオン界面活性剤:ポリオキシエチレンラウリルエーテル、プロピレングリコール脂肪酸エステル、ソルビタン脂肪酸エステル、グリセリン脂肪酸エステル、ポリオキシエチレンステアリルエーテル、ポリオキシエチレンオレイルエーテル、ポリオキシエチレンノニルフェニルエーテル、ポリオキシエチレンポリオキシプロピレンアルキルエーテル、エチレンオキシド・プロピレンオキシドブロック共重合体など。
・天然界面活性剤:レシチン、ラノリン、コレステロール、サポニンなど。
A surfactant can be added to the composition of the present invention in order to efficiently incorporate carbon dioxide bubbles in the composition. Examples of the surfactant include the following.
Nonionic surfactant: Diglycerol dioleate, sorbitan fatty acid ester, glyceryl monooleate, glyceryl monostearate, propylene glycol monostearate, polyoxyethylene alkyl ether, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene・ Polyoxypropylene block polymer, polyoxyethylene hydrogenated castor oil ester, etc.
Cationic surfactants: stearyl trimethyl ammonium chloride, cetyl methyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride, myristyl benzyl ammonium chloride, benzalkonium chloride, acyl glutamate, DL-2-Pyrrolidone-5-Carboxylic Acid Salt of Ethyl N- Cocoyl-L-Arginate etc.
Anionic surfactant: acyl N-methyltaurine salt, alkyl ether phosphate ester salt, sodium alkyl sulfate, N-acyl amino acid salt, higher fatty acid soap, polyoxyethylene alkyl ether sulfate and the like.
Amphoteric surfactants: alkyldimethylaminoacetic acid betaines, alkylamidodimethylaminoacetic acid betaines, 2-alkyl-N-carboxy-N-hydroxyimidazolinium betaines, and the like.
Nonionic surfactant: polyoxyethylene lauryl ether, propylene glycol fatty acid ester, sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene stearyl ether, polyoxyethylene oleyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene polyoxy Propylene alkyl ether, ethylene oxide / propylene oxide block copolymer, etc.
・ Natural surfactants: lecithin, lanolin, cholesterol, saponin, etc.

界面活性剤の量は、水、増粘剤及び界面活性剤の合計量あるいは組成物全量に対し、0.01〜10重量%、好ましくは0.05〜7重量%、より好ましくは0.01〜5重量%、最も好ましくは0.1〜2重量%である   The amount of the surfactant is 0.01 to 10% by weight, preferably 0.05 to 7% by weight, more preferably 0.01% with respect to the total amount of water, thickener and surfactant or the total amount of the composition. ~ 5 wt%, most preferably 0.1-2 wt%

界面活性剤は、最初から二酸化炭素を気泡状で含む組成物のみならず、用時調製型の二酸化炭素経皮・経粘膜吸収用組成物の製造キットの場合でも、塩基性組成物もしくは酸性組成物に界面活性剤を含んでいればの発泡性がよくなるために、気泡状二酸化炭素の含有量が増えるために好ましい。   The surfactant is not only a composition containing carbon dioxide in the form of bubbles from the beginning, but also a basic composition or an acidic composition in the case of a kit for preparation of a carbon dioxide transdermal / mucosal absorption composition prepared at the time of use. If the product contains a surfactant, the foaming property is improved and the content of cellular carbon dioxide is increased, which is preferable.

本発明の組成物の増粘剤としては、天然高分子、半合成高分子、合成高分子、無機物からなる群の中から選ばれる1種または2種以上を使用できる。増粘剤の使用量は、本発明の組成物に0.1〜40重量%、好ましくは1〜15重量%、より好ましくは3〜10重量%含まれる。   As the thickener of the composition of the present invention, one or more selected from the group consisting of natural polymers, semi-synthetic polymers, synthetic polymers, and inorganic substances can be used. The amount of the thickener used is 0.1 to 40% by weight, preferably 1 to 15% by weight, more preferably 3 to 10% by weight in the composition of the present invention.

本発明で増粘剤に用いる天然高分子の中の植物系高分子としてはアラビアゴム、カラギーナン、ガラクタン、寒天、クインスシード、グアガム、トラガントガム、ペクチン、マンナン、ローカストビーンガム、小麦澱粉、米澱粉、トウモロコシ澱粉、馬鈴薯澱粉などがあげられる。   Among the natural polymers used for the thickener in the present invention, the plant polymers include gum arabic, carrageenan, galactan, agar, quince seed, guar gum, tragacanth gum, pectin, mannan, locust bean gum, wheat starch, rice starch, Examples include corn starch and potato starch.

本発明で増粘剤に用いる天然高分子の中の微生物系高分子としてはカードラン、キサンタンガム、サクシノグルカン、デキストラン、ヒアルロン酸、プルランなどがあげられる。   Examples of the microbial polymer among the natural polymers used for the thickener in the present invention include curdlan, xanthan gum, succinoglucan, dextran, hyaluronic acid, and pullulan.

本発明で増粘剤に用いる天然高分子の中の蛋白系高分子としてはアルブミン、カゼイン、コラーゲン、ゼラチン、フィブロインなどがあげられる。   Examples of the protein polymer among the natural polymers used for the thickener in the present invention include albumin, casein, collagen, gelatin, and fibroin.

本発明で増粘剤に用いる半合成高分子の中のセルロース系高分子としてはエチルセルロース、カルボキシメチルセルロース及びその塩類、カルボキシメチルエチルセルロース及びその塩類、カルボキシメチルスターチ及びその塩類、クロスカルメロース及びその塩類、結晶セルロース、酢酸セルロース、酢酸フタル酸セルロース、ヒドロキシエチルセルロース、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、ヒドロキシプロピルメチルセルロースフタレート、粉末セルロース、メチルセルロース、メチルヒドロキシプロピルセルロースなどがあげられる。   Cellulosic polymers among the semi-synthetic polymers used for the thickener in the present invention include ethyl cellulose, carboxymethyl cellulose and salts thereof, carboxymethyl ethyl cellulose and salts thereof, carboxymethyl starch and salts thereof, croscarmellose and salts thereof, Examples thereof include crystalline cellulose, cellulose acetate, cellulose acetate phthalate, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, powdered cellulose, methylcellulose, and methylhydroxypropylcellulose.

本発明で増粘剤に用いる半合成高分子の中の澱粉系高分子としてはアルファー化澱粉、部分アルファー化澱粉、カルボキシメチル澱粉、デキストリン、メチル澱粉などがあげられる。   Examples of the starch polymer in the semi-synthetic polymer used in the present invention include pregelatinized starch, partially pregelatinized starch, carboxymethyl starch, dextrin, and methyl starch.

本発明で増粘剤に用いる半合成高分子の中のアルギン酸系高分子としてはアルギン酸ナトリウム、アルギン酸プロピレングリコールエステルなどがあげられる。   Examples of the alginic acid polymer in the semi-synthetic polymer used in the present invention as a thickener include sodium alginate and propylene glycol alginate.

本発明で増粘剤に用いる半合成高分子の中のその他の多糖類系高分子としてはコンドロイチン硫酸ナトリウム、ヒアルロン酸ナトリウムなどがあげられる。   Other polysaccharide polymers in the semi-synthetic polymer used for the thickener in the present invention include sodium chondroitin sulfate and sodium hyaluronate.

本発明で増粘剤に用いる合成高分子としては、カルボキシビニルポリマー、ポリアクリル酸ナトリウム、ポリビニルアセタールジエチルアミノアセテート、ポリビニルアルコール、ポリビニルピロリドン、メタアクリル酸−アクリル酸エチルコポリマー、メタアクリル酸−メタアクリル酸エチルコポリマー、メタアクリル酸エチル・メタアクリル酸塩化トリメチルアンモニウムエチルコポリマー、メタアクリル酸ジメチルアミノエチル・メタアクリル酸メチルコポリマーなどがあげられる。   The synthetic polymer used for the thickener in the present invention includes carboxyvinyl polymer, sodium polyacrylate, polyvinyl acetal diethylaminoacetate, polyvinyl alcohol, polyvinyl pyrrolidone, methacrylic acid-ethyl acrylate copolymer, methacrylic acid-methacrylic acid. Examples thereof include an ethyl copolymer, an ethyl methacrylate / methacrylic acid trimethylammonium ethyl copolymer, and a dimethylaminoethyl methacrylate / methyl methacrylate copolymer.

本発明で増粘剤に用いる無機物としては含水二酸化ケイ素、軽質無水ケイ酸、コロイダルアルミナ、ベントナイト、ラポナイトなどがあげられる。   Examples of the inorganic substance used for the thickener in the present invention include hydrous silicon dioxide, light anhydrous silicic acid, colloidal alumina, bentonite, and laponite.

水は、本発明の組成物に60〜99.9重量%程度、好ましくは75〜99重量%程度、より好ましくは85〜97重量%程度含まれる。   Water is contained in the composition of the present invention at about 60 to 99.9% by weight, preferably about 75 to 99% by weight, more preferably about 85 to 97% by weight.

本発明の組成物に気泡状の二酸化炭素を含有、保持させる方法としては、水と増粘剤を含む組成物に炭酸ガスボンベなどを用いて二酸化炭素を直接吹き込む方法がある。   As a method for containing and retaining cellular carbon dioxide in the composition of the present invention, there is a method in which carbon dioxide is directly blown into a composition containing water and a thickener using a carbon dioxide gas cylinder or the like.

また、反応により二酸化炭素を発生する物質を水と増粘剤を含む組成物中で反応させて二酸化炭素を発生させるか、又は本発明のキットの各成分を混合することにより本発明の組成物中に二酸化炭素を含有、保持させることができる。   Also, the composition of the present invention can be produced by reacting a substance that generates carbon dioxide by reaction in a composition containing water and a thickener to generate carbon dioxide, or by mixing the components of the kit of the present invention. Carbon dioxide can be contained and retained therein.

本発明に用いる炭酸塩としては、酸と反応して二酸化炭素を発生するものであれば特に限定されないが、好ましくは炭酸アンモニウム、炭酸水素アンモニウム、炭酸カリウム、炭酸水素カリウム、セスキ炭酸カリウム、炭酸ナトリウム、炭酸水素ナトリウム、セスキ炭酸ナトリウム、炭酸リチウム、炭酸水素リチウム、セスキ炭酸リチウム、炭酸セシウム、炭酸水素セシウム、セスキ炭酸セシウム、炭酸マグネシウム、炭酸水素マグネシウム、炭酸水素カルシウム、炭酸カルシウム、炭酸水酸化マグネシウム、炭酸バリウムなどのアルカリ金属またはアルカリ土類金属の炭酸塩、炭酸水素塩、セスキ炭酸塩、塩基性炭酸塩があげられこれらの1種または2種以上が用いられる。   The carbonate used in the present invention is not particularly limited as long as it reacts with an acid to generate carbon dioxide, but is preferably ammonium carbonate, ammonium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, sesqui potassium carbonate, sodium carbonate. , Sodium bicarbonate, sodium sesquicarbonate, lithium carbonate, lithium bicarbonate, sesquilithium carbonate, cesium carbonate, cesium bicarbonate, cesium carbonate cesium carbonate, magnesium carbonate, magnesium bicarbonate, calcium bicarbonate, calcium carbonate, magnesium carbonate hydroxide, Examples include alkali metal or alkaline earth metal carbonates such as barium carbonate, bicarbonates, sesquicarbonates, and basic carbonates, and one or more of these are used.

本発明に用いる酸としては、有機酸、無機酸のいずれでもよく、これらの1種または2種以上が用いられる。   The acid used in the present invention may be either an organic acid or an inorganic acid, and one or more of these are used.

有機酸としては、ギ酸、酢酸、プロピオン酸、酪酸、吉草酸等の直鎖脂肪酸、シュウ酸、マロン酸、コハク酸、グルタル酸、アジピン酸、ピメリン酸、フマル酸、マレイン酸、フタル酸、イソフタル酸、テレフタル酸等のジカルボン酸、グルタミン酸、アスパラギン酸等の酸性アミノ酸、グリコール酸、リンゴ酸、酒石酸、クエン酸、乳酸、ヒドロキシアクリル酸、α−オキシ酪酸、グリセリン酸、タルトロン酸、サリチル酸、没食子酸、トロパ酸、アスコルビン酸、グルコン酸等のオキシ酸などがあげられる。   Organic acids include linear fatty acids such as formic acid, acetic acid, propionic acid, butyric acid, valeric acid, oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, fumaric acid, maleic acid, phthalic acid, isophthalic acid Acids, dicarboxylic acids such as terephthalic acid, acidic amino acids such as glutamic acid and aspartic acid, glycolic acid, malic acid, tartaric acid, citric acid, lactic acid, hydroxyacrylic acid, α-oxybutyric acid, glyceric acid, tartronic acid, salicylic acid, gallic acid And oxyacids such as tropic acid, ascorbic acid and gluconic acid.

無機酸としてはリン酸、リン酸二水素カリウム、リン酸二水素ナトリウム、亜硫酸ナトリウム、亜硫酸カリウム、ピロ亜硫酸ナトリウム、ピロ亜硫酸カリウム、酸性へキサメタリン酸ナトリウム、酸性ヘキサメタリン酸カリウム、酸性ピロリン酸ナトリウム、酸性ピロリン酸カリウム、スルファミン酸などがあげられる。   Inorganic acids include phosphoric acid, potassium dihydrogen phosphate, sodium dihydrogen phosphate, sodium sulfite, potassium sulfite, sodium pyrosulfite, potassium pyrosulfite, acidic sodium hexametaphosphate, acidic potassium hexametaphosphate, acidic sodium pyrophosphate, acidic Examples thereof include potassium pyrophosphate and sulfamic acid.

本発明の組成物は化粧料としては、美白、肌質改善、そばかす改善、肌の若返り、肌の引き締め、部分痩せ、除毛後の再発毛抑制、髪の艶改善効果などがあり、クリーム、ジェル、ペースト、パック、マスクなどの形状で使用できる。また、香料や色材が添加でき、香料としては天然香料、合成香料、調合香料などがあげられる。   The composition of the present invention includes cosmetics such as whitening, skin quality improvement, freckles improvement, skin rejuvenation, skin tightening, partial thinning, recurring hair suppression after hair removal, hair gloss improvement effect, cream, Can be used in the form of gel, paste, pack, mask, etc. Moreover, a fragrance | flavor and a coloring material can be added and a natural fragrance | flavor, a synthetic | combination fragrance | flavor, a compound fragrance | flavor, etc. are mention | raise | lifted as a fragrance | flavor.

パックに配合できる添加物としては、パック時の清涼感を付加するために揮発性アルコールとしてエタノールなどを0.1〜20重量%配合できる。また皮膚に潤いを与える目的などでポリエチレングリコール、グリセリン、プロピレングリコール、ジプロピレングリコール、1,3−ブチレングリコール、ソルビトールなどの糖類を0.1〜15重量%、コンドロイチン硫酸ナトリウムなどのムコ多糖類などを保湿剤として0.1〜25重量%配合できる。皮膚を軟化させる目的でオリーブ油、マカデミアナッツ油、ホホバ油、流動パラフィン、スクワラン、オレイン酸オクチルドデシルなどの油脂類を0.01〜10重量%配合できる。美白、美肌、肌の若返り効果等を増強する目的でビタミンCとその誘導体やアルブチン、コウジ酸などの美白剤を0.01〜15重量%、パントテニールエチルエーテルやプラセンタエキスなどの細胞賦活剤などを0.01〜20重量%配合できる。アラントインやグリチルリチン塩などの消炎剤を0.01〜10重量%、クロルヘキシジンやアクリノールなどの殺菌剤を0.1〜20重量%、メチルパラベンや1,2−ペンタンジオールなどの防腐剤などを0.1〜25重量%配合することもできる。油脂類の分離を防ぐ目的でポリキシエチレンノニルフェニルエーテルやソルビタンモノステアレートなどの界面活性剤を0.01〜10重量%配合できる。   As an additive that can be blended in the pack, 0.1 to 20% by weight of ethanol or the like can be blended as a volatile alcohol in order to add a refreshing feeling when packed. Also, for the purpose of moisturizing the skin, 0.1-15% by weight of sugars such as polyethylene glycol, glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, sorbitol, mucopolysaccharides such as sodium chondroitin sulfate, etc. Can be blended in an amount of 0.1 to 25% by weight as a humectant. For the purpose of softening the skin, 0.01 to 10% by weight of oils and fats such as olive oil, macadamia nut oil, jojoba oil, liquid paraffin, squalane and octyldodecyl oleate can be blended. 0.01-15% by weight of whitening agents such as vitamin C and its derivatives, arbutin and kojic acid, and cell activators such as pantotenyl ethyl ether and placenta extract for the purpose of enhancing whitening, skin rejuvenation and skin rejuvenation In an amount of 0.01 to 20% by weight. 0.01 to 10% by weight of an anti-inflammatory agent such as allantoin or glycyrrhizin salt, 0.1 to 20% by weight of a fungicide such as chlorhexidine or acrinol, 0.1% of a preservative such as methylparaben or 1,2-pentanediol -25 wt% can also be blended. In order to prevent separation of oils and fats, a surfactant such as polyoxyethylene nonylphenyl ether and sorbitan monostearate can be blended in an amount of 0.01 to 10% by weight.

クリームに配合できる成分としては、クリームは油相成分、水相成分、界面活性剤を主な成分として構成されるが、油相成分としては例えばスクワラン、ワセリン、流動パラフィン、セレシン、マイクロクリスタリンワックスなどの炭化水素、オリーブ油、マカデミアナッツ油、アーモンド油、ホホバ油、アボカド油、硬化パーム油、ひまし油、月見草油、合成トリグリセライドなどの油脂、オレイン酸、ステアリン酸、イソステアリン酸、ミリスチン酸、パルミチン酸、ベヘニン酸などの脂肪酸、ミツロウ、ラノリン、カルナバロウ、キャンデリラロウなどのロウ、セタノール、ステアリルアルコール、ベヘニルアルコール、オクチルドデシアルコール、コレステロールなどの高級アルコール、グリセリントリエステル、ペンタエリスリトールテトラエステル、コレステリルエステルなどの合成エステルなどが0.01〜10重量%配合できる。水相成分としてはグリセリン、プロピレングリコール、ポリエチレングリコール、1,3−ブチレングリコール、ジグリセリン、ジプロピレングリコール、ソルビトール、マンニトールなどの保湿剤を0.1〜25重量%、クインスシード、ペクチン、キサンタンガム、アルギン酸ナトリウム、カルボキシビニルポリマーなどの粘液質を0.1〜40重量%、エタノール、イソプロパノールなどのアルコールを0.1〜20重量%を配合できる。界面活性剤としてはモノステアリン酸グリセリン、ポリオキシエチレンソルビタン脂肪酸エステル、ソルビタン脂肪酸エステル、ポリオキシエチレンアルキルエーテルなどの非イオン性界面活性剤、脂肪酸石鹸、アルキル硫酸ナトリウムなどの陰イオン性界面活性剤などを0.01〜10重量%配合できる。香料、色素も特に制限なく通常の化粧料に使用される範囲の配合量で配合できる。ビタミンEやジブチルヒドロキシトルエンなどの酸化防止剤を0.1〜10重量%、ビタミンCとその誘導体やアルブチン、コウジ酸などの美白剤を0.01〜15重量%、パントテニールエチルエーテルやプラセンタエキスなどの細胞賦活剤を0.01〜15重量%、アラントインやグリチルリチン塩などの消炎剤を0.01〜10重量%、クロルヘキシジンやアクリノールなどの殺菌剤を0.1〜20重量%、メチルパラベンや1,2−ペンタンジオールなどの防腐剤を0.1〜25重量%を配合することもできる。   As ingredients that can be blended into the cream, the cream is composed mainly of an oil phase component, an aqueous phase component, and a surfactant. Examples of the oil phase component include squalane, petrolatum, liquid paraffin, ceresin, and microcrystalline wax. Oils such as olive oil, macadamia nut oil, almond oil, jojoba oil, avocado oil, hydrogenated palm oil, castor oil, evening primrose oil, synthetic triglyceride, oleic acid, stearic acid, isostearic acid, myristic acid, palmitic acid, behenic acid Fatty acids such as beeswax, lanolin, carnauba wax, candelilla wax, cetanol, stearyl alcohol, behenyl alcohol, octyldodecyl alcohol, cholesterol and other higher alcohols, glycerin triester, pentaerythrito Le tetraester, and synthetic esters such as cholesteryl esters can 0.01-10 wt% blend. As an aqueous phase component, 0.1 to 25% by weight of a humectant such as glycerin, propylene glycol, polyethylene glycol, 1,3-butylene glycol, diglycerin, dipropylene glycol, sorbitol, mannitol, quince seed, pectin, xanthan gum, 0.1 to 40% by weight of mucus such as sodium alginate and carboxyvinyl polymer and 0.1 to 20% by weight of alcohol such as ethanol and isopropanol can be blended. Surfactants include non-ionic surfactants such as glyceryl monostearate, polyoxyethylene sorbitan fatty acid ester, sorbitan fatty acid ester, polyoxyethylene alkyl ether, anionic surfactants such as fatty acid soap, sodium alkyl sulfate, etc. 0.01 to 10% by weight. A fragrance | flavor and a pigment | dye can also be mix | blended with the compounding quantity of the range used for normal cosmetics without a restriction | limiting in particular. 0.1 to 10% by weight of antioxidants such as vitamin E and dibutylhydroxytoluene, 0.01 to 15% by weight of whitening agents such as vitamin C and its derivatives, arbutin and kojic acid, pantotenyl ethyl ether and placenta extract 0.01 to 15% by weight of a cell activator such as 0.01 to 10% by weight of an anti-inflammatory agent such as allantoin or glycyrrhizin salt, 0.1 to 20% by weight of a bactericide such as chlorhexidine or acrinol, methylparaben or 1 , 2-pentanediol and other preservatives can be blended in an amount of 0.1 to 25% by weight.

本発明の組成物には、これまでに述べた成分もしくは原料以外に、例えばセラミドやコメ発酵エキス、ワインもしくはワイン抽出液、マリーゴールドエキスなどの保湿剤を0.1〜25重量%、カフェインやコラエキス、アルゴエキスなどの脂肪代謝促進剤を0.1〜10重量%、フルーツ酸、イオウ、サリチル酸、レゾルシンなどの角質除去成分を0.1〜10重量%、β−グリチルレチン酸、グリチルリチン酸誘導体、アラントイン、アズレン、ε−アミノカプロン酸、ヒノキチオール、ハイドロコーチゾンなどの抗炎症剤を0.01〜10重量%、酸化亜鉛、硫酸亜鉛、アラントインヒドロキシアルミニウム、塩化アルミニウム、硫酸アルミニウム、スルホ石炭酸亜鉛、タンニン酸、クエン酸、乳酸などの収斂剤を0.1〜10重量%、メントール、カンフルなどの清涼化剤を0.1〜10重量%、ビタミンA、ビタミンB群、ビタミンD、ビタミンE、パントテン酸カルシウム、パントテン酸エチルエーテル、ビオチンなどのビタミン類を0.01〜10重量%、エストラジオール、エストロン、エチニルエストラジオール、コルチゾン、プレドニゾン、プレドニゾロンなどのホルモン類を0.01〜5重量%、塩酸ジフェンヒドラミン、マレイン酸クロルフェニラミン、グリチルリチン酸誘導体などの抗ヒスタミン剤を0.01〜10重量%、アロエエキス、カミツレエキス、カンゾウエキス、オオバクエキス、ビワ抽出液などの植物性抗炎症、細胞賦活作用物質を0.01〜10重量%、カンファー、メントールなどの鎮痒剤を0.01〜5重量%、アミリス、イランイラン、エレミ、カユプテ、グアヤックウッド、クラリセージ、クローブ、コパイバ、コリアンダー、サイプレス、サンダルウッド、サントキシラム、シダーウッド、シトロネラ、シナモン、ジャスミン、スターアニス、スパイクラベンダー、スペアミント、セージ、ゼラニウムローズ、ティーツリー、ディル、ニアウリ、ネロリ、パイン、バジル、パチュリー、パルマローザ、ファー、フェンネル、プチグレン、フランキンセンス、フレンチマリーゴールド、ペパーミント、ベルガモット、ベンゾイン、マージョラム、マートル、マンダリン、ミルラ、ライム、ラバンジン、ラベンダー、リツェア、レモン、レモングラス、ローズ、ローズウッド、ユーカリなどのアロマテラピーなどに用いられるハーブエッセンスを0.01〜5重量%配合できる。ここに例示した以外にも、通常化粧料に配合される成分は特に制限なく本発明組成物に配合できる。   The composition of the present invention contains 0.1 to 25% by weight of a humectant such as ceramide, fermented rice extract, wine or wine extract, marigold extract, etc. 0.1 to 10% by weight of a fat metabolism promoter such as fruit extract, cora extract, and algo extract, 0.1 to 10% by weight of exfoliating ingredients such as fruit acid, sulfur, salicylic acid and resorcin, β-glycyrrhetinic acid, glycyrrhizic acid derivative 0.01-10% by weight of anti-inflammatory agents such as allantoin, azulene, ε-aminocaproic acid, hinokitiol, hydrocortisone, zinc oxide, zinc sulfate, allantoin hydroxyaluminum, aluminum chloride, aluminum sulfate, zinc sulfocolate, tannic acid 0.1 to 10% by weight of an astringent such as citric acid and lactic acid, 0.1-10% by weight of refreshing agents such as menthol and camphor, 0.01-10% of vitamins such as vitamin A, vitamin B group, vitamin D, vitamin E, calcium pantothenate, ethyl pantothenate, biotin % By weight, hormones such as estradiol, estrone, ethinylestradiol, cortisone, prednisone, prednisolone 0.01 to 5% by weight, antihistamines such as diphenhydramine hydrochloride, chlorpheniramine maleate and glycyrrhizic acid derivatives 0.01 to 10% by weight %, Aloe extract, chamomile extract, licorice extract, oat extract, loquat extract and other plant anti-inflammatory and cell activator substances 0.01 to 10% by weight, camphor, menthol and other antipruritic agents 0.01 to 5% %, Amiris, Ylang Yi , Elemi, Cayupute, Guayac Wood, Clarisage, Clove, Copaiba, Coriander, Cypress, Sandalwood, Santoxilam, Cedarwood, Citronella, Cinnamon, Jasmine, Star Anise, Spike Lavender, Spearmint, Sage, Geranium Rose, Tea Tree, Dill, Niouri, Neroli, Pine, Basil, Patchouli, Palmarosa, Fur, Fennel, Petit Glen, Frankincense, French Marigold, Peppermint, Bergamot, Benzoin, Marjoram, Myrtle, Mandarin, Myrrh, Lime, Lavandin, Lavender, Lyzea, Lemon, Lemongrass Contains 0.01 to 5% by weight of herbal essence used in aromatherapy such as rose, rosewood and eucalyptus Kill. In addition to those exemplified here, components that are usually blended in cosmetics can be blended in the composition of the present invention without any particular limitation.

本発明の二酸化炭素経皮・経粘膜吸収用組成物及び二酸化炭素経皮・経粘膜吸収用組成物の製造キットの塩基性組成物または酸性組成物は製造に必要な全ての成分を一つの容器中で同時に混合攪拌するだけでも製造できるが、増粘剤が粉体等の固形物の場合は、延びがよく使いやすいものとするためには、増粘剤をあらかじめ液体の保湿剤で分散させておき、それ以外の成分を溶解もしくは分散させた液に徐々に加えてゆっくり混合攪拌することが好ましい。保湿剤の量としては、増粘剤との混合液が入った容器を傾けたときに流れ出る程度の流動性を持つような量を選べばよいが、増粘剤の重量に対して60〜500重量%、好ましくは80〜400重量%、より好ましくは100〜300重量%、さらに好ましくは120〜250重量%、最も好ましくは130〜200重量%である。保湿剤としてはグリセリン、1,3−ブチレングリコール、プロピレングリコール、ポリエチレングリコール、ジプロピレングリコール、ジグリセリンなどがあげられる。   The basic composition or acidic composition of the carbon dioxide transdermal / transmucosal absorption composition and the kit for manufacturing the carbon dioxide transdermal / mucosal absorption composition of the present invention contains all components necessary for production in one container. It can also be produced by mixing and stirring at the same time. However, if the thickener is a solid substance such as a powder, the thickener should be dispersed in advance with a liquid moisturizer in order to make it easy to use. In addition, it is preferable that the other components are gradually added to the solution in which the other components are dissolved or dispersed, and then slowly mixed and stirred. The amount of the moisturizing agent may be selected such that it has fluidity enough to flow when the container containing the mixture with the thickener is tilted, but 60 to 500 based on the weight of the thickener. % By weight, preferably 80 to 400% by weight, more preferably 100 to 300% by weight, still more preferably 120 to 250% by weight, and most preferably 130 to 200% by weight. Examples of the humectant include glycerin, 1,3-butylene glycol, propylene glycol, polyethylene glycol, dipropylene glycol, diglycerin and the like.

保湿剤の量としては、組成物全体量を基準として0.1〜25重量%程度、好ましくは1〜20重量%程度、より好ましくは3〜15重量%程度である。本発明の組成物が特に水、増粘剤、保湿剤と二酸化炭素からなる場合には、組成物全体の重量に対して水60〜99.8重量%、増粘剤0.1〜20重量%、保湿剤0.1〜20重量%が好ましい。   The amount of the humectant is about 0.1 to 25% by weight, preferably about 1 to 20% by weight, more preferably about 3 to 15% by weight based on the total amount of the composition. When the composition of the present invention is composed of water, a thickener, a humectant and carbon dioxide, 60 to 99.8% by weight of water and 0.1 to 20% by weight of the thickener based on the total weight of the composition. %, Moisturizer 0.1 to 20% by weight is preferred.

本発明の二酸化炭素経皮・経粘膜吸収用組成物は、例えば真空乳化機などの密閉式攪拌混合機内で容器内の空気を二酸化炭素に置換することにより、原料を混合攪拌するだけで製造できるが、原料に界面活性剤を加えることにより、多くの気泡状二酸化炭素を短時間で含有保持させることができる。界面活性剤の該組成物中の含有量としては、10重量%以下、好ましくは0.01〜7重量%、より好ましくは0.1〜5重量%、最も好ましくは0.5〜3重量%である。   The carbon dioxide percutaneous / transmucosal absorption composition of the present invention can be produced simply by mixing and stirring the raw materials, for example, by replacing the air in the container with carbon dioxide in a closed stirring mixer such as a vacuum emulsifier. However, a lot of cellular carbon dioxide can be contained and held in a short time by adding a surfactant to the raw material. The content of the surfactant in the composition is 10% by weight or less, preferably 0.01 to 7% by weight, more preferably 0.1 to 5% by weight, most preferably 0.5 to 3% by weight. It is.

本発明の二酸化炭素経皮・経粘膜吸収用組成物及び二酸化炭素経皮・経粘膜吸収用組成物の製造用キットの塩基性もしくは酸性組成物は、親油性物質を加えることにより美肌効果や創傷治癒促進効果等の有効性を損なうことなく皮膚粘膜から除去しやすい組成物にできる。親油性物質としては天然油脂、半合成油脂、合成油脂のいずれも制限なく使える。親油性物質の該組成物中の含有量としては、0.01〜10重量%、より好ましくは0.3〜5重量%、最も好ましくは0.5〜3重量%である。   The basic or acidic composition of the carbon dioxide transdermal / transmucosal absorption composition and the kit for producing the carbon dioxide transdermal / mucosal absorption composition of the present invention can be used to improve skin beautification and wounds by adding lipophilic substances. The composition can be easily removed from the skin mucosa without impairing the effectiveness such as the healing promoting effect. As the lipophilic substance, any of natural fats, semi-synthetic fats and synthetic fats can be used without limitation. The content of the lipophilic substance in the composition is 0.01 to 10% by weight, more preferably 0.3 to 5% by weight, and most preferably 0.5 to 3% by weight.

親油性物質としては、アボカド油、アーモンド油、オリーブ油、カカオ脂、硬化パーム油、合成トリグリセライド、月見草油、ヒマシ油、ヒマワリ油、ホホバ油、マカデミアナッツ油などの油脂、スクワラン、セレシン、固形パラフィン、マイクロクリスタリンワックス、流動パラフィン、ワセリンなどの炭化水素、カルナバロウ、キャンデリラロウ、ミツロウ、ラノリンなどのロウ、イソステアリルアルコール、2−オクチルドデカノール、ステアリルアルコール、セタノール、コレステロール、ヘキサデシルアルコール、ベヘニルアルコールなどの高級アルコール、イソステアリン酸、オレイン酸、ステアリン酸、パルミチン酸、ベヘニン酸、ミリスチン酸などの脂肪酸、イソプロピルミリステート、2−エチルヘキサン酸セチル、グリセリントリエステル、コレステリルエステル、ペンタエリスリトールテトラエステル、リンゴ酸ジイソステアリルなどの合成エステル、シクロメチコン、ジメチルポリシロキサン、メチルポリシロキサン、メチルフェニルポリシロキサンなどのシリコーン油などが挙げられる。   Examples of lipophilic substances include avocado oil, almond oil, olive oil, cocoa butter, hydrogenated palm oil, synthetic triglyceride, evening primrose oil, castor oil, sunflower oil, jojoba oil, macadamia nut oil and other oils, squalane, ceresin, solid paraffin, micro Higher grades such as hydrocarbons such as crystallin wax, liquid paraffin, petrolatum, carnauba wax, candelilla wax, beeswax, lanolin, etc., isostearyl alcohol, 2-octyldodecanol, stearyl alcohol, cetanol, cholesterol, hexadecyl alcohol, behenyl alcohol Fatty acids such as alcohol, isostearic acid, oleic acid, stearic acid, palmitic acid, behenic acid, myristic acid, isopropyl myristate, cetyl 2-ethylhexanoate, glycerin Phosphoric triester, cholesteryl ester, pentaerythritol tetraester, synthetic esters such as diisostearyl malate, cyclomethicone, dimethyl polysiloxane, methyl polysiloxane and silicone oils such as methyl phenyl polysiloxane.

本発明の組成物はチューブや広口容器に入れて使用することができる。容器は本発明組成物に含まれる気泡状二酸化炭素が減少もしくは消失しないように完全密閉式が好ましい。容器の材質は容器の形状に応じてナイロンPA、ポリエチレン、ポリプロピレン、ポリスチレン、AS樹脂、ABS樹脂、ポリエチレンテレフタレート、ポリ塩化ビニル、エチレン−ビニルアルコール共重合樹脂、ポリアセタールなどプラスチックやアルミニウム、鉄、真鍮、ステンレスなどの金属、ソーダ石灰ガラス、カリ鉛ガラス、乳白ガラスなどのガラスなどから適宜選んで使用できる。本発明のキットの塩基性組成物もしくは酸性組成物はチューブや広口容器に入れて使用できるが、チューブの場合は空の広口容器に出して二酸化炭素発生補助剤と混合して使う。広口容器の場合は底の角が丸い容器が二酸化炭素発生補助剤と混合攪拌しやすく好ましい。また広口容器の場合は本発明のキットから製造される組成物の体積が塩基性組成物もしくは酸性組成物と二酸化炭素発生補助剤との合計よりも増加するため、これら組成物の体積の1.5倍以上、好ましくは1.6倍以上、より好ましくは1.7倍以上、最も好ましくは1.8倍以上の容量の容器を使用する。容器の材質は塩基性組成物の場合は耐アルカリ性、酸性組成物の場合は耐酸性の材質であればいずれも制限なく使えるが、ナイロンPA、ポリエチレン、ポリプロピレン、ポリスチレン、AS樹脂、ABS樹脂、ポリエチレンテレフタレート、ポリ塩化ビニル、エチレン−ビニルアルコール共重合樹脂、ポリアセタールなどプラスチックやアルミニウム、鉄、真鍮、ステンレスなどの金属などを容器の形状に応じて適宜使用する。酸性組成物の場合はさらにソーダ石灰ガラス、カリ鉛ガラス、乳白ガラスなどのガラスも使える。塩基性組成物もしくは酸性組成物と二酸化炭素発生補助剤の混合攪拌は手指でも可能であるが、バターナイフやヘラなどを使えば攪拌とともに塗布にも使える。   The composition of the present invention can be used in a tube or a wide-mouthed container. The container is preferably a completely sealed type so that the bubbled carbon dioxide contained in the composition of the present invention does not decrease or disappear. The material of the container depends on the shape of the container, such as nylon PA, polyethylene, polypropylene, polystyrene, AS resin, ABS resin, polyethylene terephthalate, polyvinyl chloride, ethylene-vinyl alcohol copolymer resin, polyacetal, plastic, aluminum, iron, brass, It can be appropriately selected from metals such as stainless steel, soda lime glass, potassium lead glass, milk white glass and the like. The basic composition or acidic composition of the kit of the present invention can be used in a tube or a wide-mouth container, but in the case of a tube, it is put out into an empty wide-mouth container and mixed with a carbon dioxide generating auxiliary agent. In the case of a wide-mouthed container, a container having a rounded bottom corner is preferable because it can be easily mixed and stirred with a carbon dioxide generating auxiliary agent. In the case of a wide-mouthed container, the volume of the composition produced from the kit of the present invention increases from the total of the basic composition or acidic composition and the carbon dioxide generating auxiliary agent. A container having a capacity of 5 times or more, preferably 1.6 times or more, more preferably 1.7 times or more, and most preferably 1.8 times or more is used. The material of the container can be used without limitation as long as it is an alkali-resistant material in the case of a basic composition and an acid-resistant material in the case of an acidic composition, but nylon PA, polyethylene, polypropylene, polystyrene, AS resin, ABS resin, polyethylene Plastics such as terephthalate, polyvinyl chloride, ethylene-vinyl alcohol copolymer resin, polyacetal, and metals such as aluminum, iron, brass, and stainless steel are appropriately used according to the shape of the container. In the case of an acidic composition, glass such as soda lime glass, potassium lead glass, and milk white glass can also be used. Mixing and stirring of the basic composition or acidic composition and the carbon dioxide generating auxiliary agent can be performed with fingers, but if a butter knife or a spatula is used, it can be used for coating as well as stirring.

実施例を示して本発明を更に詳しく説明するが、本発明はこれらの実施例に限定されるものではない。尚、表中の数字は特にことわらない限り重量部を表す。
実施例1〜84
塩基性組成物と酸との組み合わせよりなる本発明の二酸化炭素経皮・経粘膜吸収用組成物を表1〜表7に示す。
〔製造方法〕
増粘剤と精製水、炭酸塩を表1〜表7のように組み合わせ、塩基性組成物をあらかじめ調製する。酸は、固形の場合はそのまま、又は粉砕して、又は適当な溶媒に溶解又は分散させて、液体の場合はそのまま、又は適当な溶媒で希釈して用いる。塩基性組成物と酸を混合し、二酸化炭素経皮・経粘膜吸収用組成物を得る。
<塩基性組成物の製造>
ビーカー等の容器中で精製水に増粘剤を溶解又は膨潤させ、炭酸塩を溶解又は分散させる。このとき必要であれば精製水を加熱して増粘剤の溶解、膨潤を促進してもよいし、増粘剤を適当な溶媒に溶解又は分散させておいて用いてもよい。必要に応じてこれに適当な添加剤や薬効物質等を加えてもよい。
〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕
<発泡性>
塩基性組成物50gと酸1gを直径5cm、高さ10cmのカップに入れ、その体積を測定する。これを10秒間に20回攪拌混合し二酸化炭素経皮・経粘膜吸収用組成物を得る。攪拌混合1分後の該組成物の体積を測定し、攪拌混合前の体積からの増加率をパーセントで求め、評価基準1に従い発泡性を評価する。
EXAMPLES The present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples. The numbers in the table represent parts by weight unless otherwise specified.
Examples 1-84
Tables 1 to 7 show the carbon dioxide transdermal and transmucosal absorption compositions of the present invention comprising a combination of a basic composition and an acid.
〔Production method〕
Thickener, purified water, and carbonate are combined as shown in Tables 1 to 7, and a basic composition is prepared in advance. The acid is used as it is in the case of a solid, or is pulverized or dissolved or dispersed in a suitable solvent, and is used as it is in the case of a liquid or diluted with a suitable solvent. A basic composition and an acid are mixed to obtain a carbon dioxide transdermal / mucosal absorption composition.
<Manufacture of basic composition>
In a container such as a beaker, the thickener is dissolved or swollen in purified water, and the carbonate is dissolved or dispersed. If necessary, purified water may be heated to promote dissolution and swelling of the thickener, or the thickener may be dissolved or dispersed in a suitable solvent. If necessary, an appropriate additive or medicinal substance may be added thereto.
[Evaluation of composition for transdermal and transmucosal absorption of carbon dioxide]
<Foaming properties>
50 g of the basic composition and 1 g of acid are put into a cup having a diameter of 5 cm and a height of 10 cm, and the volume is measured. This is stirred and mixed 20 times in 10 seconds to obtain a carbon dioxide transdermal / mucosal absorption composition. The volume of the composition after 1 minute of stirring and mixing is measured, the rate of increase from the volume before stirring and mixing is obtained as a percentage, and foamability is evaluated according to Evaluation Criteria 1.

<評価基準1>
増加率 発泡性
70%以上 +++
50%〜70% ++
30%〜50% +
30%以下 0
体積の測定は、各々の測定時点での二酸化炭素経皮・経粘膜吸収用組成物の高さをカップに記し、該組成物を除去した後でそれらの高さまで水を入れ、それらの水の体積をメスシリンダーで測定する。
<気泡の持続性>
塩基性組成物50gと酸1gを直径5cm、高さ10cmのカップに入れ、10秒間に20回攪拌混合し二酸化炭素経皮・経粘膜吸収用組成物を得る。攪拌混合1分後の該組成物の体積を測定し、その2時間後の体積を測定して体積の減少率をパーセントで求め、評価基準2に従い、気泡の持続性を評価する。
<Evaluation criteria 1>
Increase rate More than 70% foaming +++
50% to 70% ++
30% to 50% +
30% or less 0
For the volume measurement, the height of the carbon dioxide transdermal / mucosal absorption composition at the time of each measurement is recorded on the cup, and after removing the composition, water is added to those heights. Measure the volume with a graduated cylinder.
<Bubble persistence>
50 g of the basic composition and 1 g of acid are placed in a cup having a diameter of 5 cm and a height of 10 cm, and are stirred and mixed 20 times for 10 seconds to obtain a composition for transdermal absorption of carbon dioxide. The volume of the composition 1 minute after stirring and mixing is measured, the volume after 2 hours is measured to determine the volume reduction rate in percent, and the persistence of bubbles is evaluated according to Evaluation Criteria 2.

<評価基準2>
減少率 気泡の持続性
20%以下 +++
20%〜40% ++
40%〜60% +
60%以上 0
体積の測定は、各々の測定時点での二酸化炭素経皮・経粘膜吸収用組成物の高さをカップに記し、該組成物を除去した後でそれらの高さまで水を入れ、それらの水の体積をメスシリンダーで測定する。
<Evaluation criteria 2>
Reduction rate Bubble persistence 20% or less ++++
20% to 40% ++
40% -60% +
60% or more 0
For the volume measurement, the height of the carbon dioxide transdermal / mucosal absorption composition at the time of each measurement is recorded on the cup, and after removing the composition, water is added to those heights. Measure the volume with a graduated cylinder.

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

実施例85〜108
酸性組成物と炭酸塩の組み合わせよりなる二酸化炭素経皮・経粘膜吸収用組成物を表8〜表9に示す。
〔製造方法〕
増粘剤と精製水、酸(有機酸及び/又は無機酸)を表8、表9のように組み合わせ、酸性組成物をあらかじめ調製する。炭酸塩はそのまま、又は結晶の場合は粉砕して、又は適当な溶媒に溶解又は分散させて用いることもできる。酸性組成物と炭酸塩を混合し、二酸化炭素経皮・経粘膜吸収用組成物を得る。
<酸性組成物の製造>
ビーカー等の容器中で精製水に増粘剤を溶解又は膨潤させ、酸を溶解又は分散させる。このとき必要であれば精製水を加熱して増粘剤の溶解、膨潤を促進してもよいし、増粘剤を適当な溶媒に溶解又は分散させておいて用いてもよい。必要に応じてこれに適当な添加剤や薬効物質等を加えてもよい。
〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕
<発泡性>
酸性組成物50gと炭酸塩1.2gを直径5cm、高さ10cmのカップに入れ、その体積を測定する。これを10秒間に20回攪拌混合し二酸化炭素経皮・経粘膜吸収用組成物を得る。攪拌混合1分後の該組成物の体積を測定し、攪拌混合前の体積からの増加率をパーセントで求め、評価基準1に従い、発泡性を評価する。
体積の測定は、実施例1〜84の〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕の<発泡性>に記載の方法に従い測定する。
<気泡の持続性>
酸性組成物50gと炭酸塩1.2gを直径5cm、高さ10cmのカップに入れ、10秒間に20回攪拌混合し二酸化炭素経皮・経粘膜吸収用組成物を得る。攪拌混合1分後の該組成物の体積を測定し、その2時間後の体積を測定して体積の減少率をパーセントで求め、評価基準2に従い、気泡の持続性を評価する。体積の測定は、実施例1〜84の〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕の<気泡の持続性>に記載の方法に従い測定する。
Examples 85-108
Tables 8 to 9 show carbon dioxide transdermal / mucosal absorption compositions comprising a combination of an acidic composition and carbonate.
〔Production method〕
A thickener, purified water, and an acid (organic acid and / or inorganic acid) are combined as shown in Tables 8 and 9, and an acidic composition is prepared in advance. The carbonate can be used as it is, or in the case of crystals, pulverized, or dissolved or dispersed in an appropriate solvent. An acidic composition and carbonate are mixed to obtain a carbon dioxide transdermal / mucosal absorption composition.
<Production of acidic composition>
A thickener is dissolved or swollen in purified water in a container such as a beaker, and the acid is dissolved or dispersed. If necessary, purified water may be heated to promote dissolution and swelling of the thickener, or the thickener may be dissolved or dispersed in a suitable solvent. If necessary, an appropriate additive or medicinal substance may be added thereto.
[Evaluation of composition for transdermal and transmucosal absorption of carbon dioxide]
<Foaming properties>
50 g of the acidic composition and 1.2 g of carbonate are put into a cup having a diameter of 5 cm and a height of 10 cm, and the volume is measured. This is stirred and mixed 20 times in 10 seconds to obtain a carbon dioxide transdermal / mucosal absorption composition. The volume of the composition after 1 minute of stirring and mixing is measured, the rate of increase from the volume before stirring and mixing is obtained as a percentage, and foamability is evaluated according to Evaluation Criteria 1.
The volume is measured according to the method described in <Foaming properties> in [Evaluation of composition for carbon dioxide transdermal / transmucosal absorption] in Examples 1 to 84.
<Bubble persistence>
50 g of the acidic composition and 1.2 g of carbonate are put in a cup having a diameter of 5 cm and a height of 10 cm, and stirred and mixed 20 times in 10 seconds to obtain a composition for transdermal absorption of carbon dioxide. The volume of the composition 1 minute after stirring and mixing is measured, the volume after 2 hours is measured to determine the volume reduction rate in percent, and the persistence of bubbles is evaluated according to Evaluation Criteria 2. The volume is measured in accordance with the method described in <Evaluation of composition for carbon dioxide transdermal / transmucosal absorption> in Examples 1 to 84 in <Persistence of bubbles>.

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

実施例109〜144
塩基性組成物と酸の顆粒剤との組み合わせよりなる二酸化炭素経皮・経粘膜吸収用組成物を表10〜表12に示す。
〔製造方法〕
増粘剤と精製水、炭酸塩と酸(有機酸及び/又は無機酸)、マトリックス基剤を表10〜表12のように組み合わせ、塩基性組成物と酸の顆粒剤をあらかじめ調製する。この顆粒剤は徐放性であってもよい。塩基性組成物と酸の顆粒剤を混合し、二酸化炭素経皮・経粘膜吸収用組成物を得る。本発明でいうマトリックス基剤とは、溶媒による溶解や膨潤、加熱による溶融などにより流動化し、他の化合物を包含した後、溶媒除去又は冷却等により固化し、粉砕等により顆粒を形成する化合物、もしくは他の化合物と混合、圧縮して固化し、粉砕等により顆粒を形成する化合物で水により溶解もしくは崩壊するものすべてをいう。マトリックス基剤としては、エチルセルロース、エリスリトール、カルボキシメチルスターチ及びその塩、カルボキシメチルセルロース及びその塩、含水二酸化ケイ素、キシリトール、クロスカルメロースナトリウム、軽質無水ケイ酸、結晶セルロース、合成ケイ酸アルミニウム、合成ヒドロタルサイト、ステアリルアルコール、セタノール、ソルビトール、デキストリン、澱粉、乳糖、白糖、ヒドロキシエチルセルロース、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、ヒドロキシプロピルメチルセルロースアセテートサクシネート、ヒドロキシプロピルメチルセルロースフタレート、プルラン、ポリエチレングリコール、ポリビニルアルコール、ポリビニルピロリドン、マンノース、メチルセルロースなどがあげられ、これらの1種又は2種以上が用いられる。
<塩基性組成物の製造>
実施例1〜84に記載の塩基性組成物の製造方法に従い製造する。
<酸の顆粒剤の製造>
マトリックス基剤に低融点化合物を使用する場合は、ビーカー等の容器中で加熱により溶融させた低融点マトリックス基剤に酸を加えて十分攪拌、混合する。必要に応じてこれに適当な添加剤や薬効物質等を加えてもよい。これを室温で徐々に冷やしながら更に攪拌し、固まるまで放置する。ある程度固まってきたら冷蔵庫等で急速に冷却してもよい。マトリックス基剤に低融点化合物を用いない場合は、ビーカー等の容器中でマトリックス基剤を水又はエタノールのような適当な溶媒に溶解又は分散させ、これに酸を溶解又は分散させて十分混合した後にオーブン等で加熱して溶媒を除去し、乾燥させる。完全に固まったら粉砕し顆粒とする。このとき顆粒の大きさを揃えるために篩過してもよい。
Examples 109-144
Tables 10 to 12 show carbon dioxide transdermal and transmucosal absorption compositions comprising a combination of a basic composition and an acid granule.
〔Production method〕
Thickener, purified water, carbonate, acid (organic acid and / or inorganic acid), and matrix base are combined as shown in Tables 10 to 12, and a basic composition and acid granules are prepared in advance. The granules may be sustained release. A basic composition and acid granules are mixed to obtain a carbon dioxide transdermal / mucosal absorption composition. The matrix base referred to in the present invention is a compound that is fluidized by dissolution or swelling with a solvent, melted by heating, etc., includes other compounds, solidifies by solvent removal or cooling, and forms granules by pulverization, Alternatively, it refers to all compounds that are mixed with other compounds, compressed and solidified, and formed into granules by pulverization or the like and dissolved or disintegrated with water. Matrix bases include ethyl cellulose, erythritol, carboxymethyl starch and salts thereof, carboxymethyl cellulose and salts thereof, hydrous silicon dioxide, xylitol, croscarmellose sodium, light anhydrous silicic acid, crystalline cellulose, synthetic aluminum silicate, synthetic hydrotal Sight, stearyl alcohol, cetanol, sorbitol, dextrin, starch, lactose, sucrose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose acetate succinate, hydroxypropylmethylcellulose phthalate, pullulan, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone , Mannose, methylcellulose, etc. Is, these one or more is used.
<Manufacture of basic composition>
Manufacture according to the method for manufacturing the basic composition described in Examples 1 to 84.
<Manufacture of acid granules>
In the case of using a low melting point compound for the matrix base, an acid is added to the low melting point matrix base melted by heating in a container such as a beaker, and the mixture is sufficiently stirred and mixed. If necessary, an appropriate additive or medicinal substance may be added thereto. The mixture is further stirred while being cooled at room temperature, and left to solidify. If it hardens to some extent, it may be cooled rapidly in a refrigerator or the like. When a low melting point compound is not used for the matrix base, the matrix base is dissolved or dispersed in a suitable solvent such as water or ethanol in a container such as a beaker, and the acid is dissolved or dispersed therein and mixed well. Thereafter, the solvent is removed by heating in an oven or the like, and drying is performed. When it is completely solidified, it is crushed into granules. At this time, sieving may be performed in order to equalize the size of the granules.

なお、本発明において上記の酸の顆粒剤の製造方法は本実施例に限定されることはなく、乾式破砕造粒法や湿式破砕造粒法、流動層造粒法、高速攪拌造粒法、押し出し造粒法などの常法に従い製造できる。
〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕
<発泡性>
塩基性組成物50gと酸1g相当量の酸の顆粒剤を直径5cm、高さ10cmのカップに入れ、その体積を測定する。これを10秒間に20回攪拌混合し二酸化炭素経皮・経粘膜吸収用組成物を得る。攪拌混合1分後の該組成物の体積を測定し、攪拌混合前の体積からの増加率をパーセントで求め、評価基準1に従い、発泡性を評価する。
In the present invention, the method for producing the above-mentioned acid granule is not limited to this example, dry crush granulation method or wet crush granulation method, fluidized bed granulation method, high-speed stirring granulation method, It can be produced according to conventional methods such as extrusion granulation.
[Evaluation of composition for transdermal and transmucosal absorption of carbon dioxide]
<Foaming properties>
50 g of the basic composition and an acid granule equivalent to 1 g of acid are placed in a cup having a diameter of 5 cm and a height of 10 cm, and the volume is measured. This is stirred and mixed 20 times in 10 seconds to obtain a carbon dioxide transdermal / mucosal absorption composition. The volume of the composition after 1 minute of stirring and mixing is measured, the rate of increase from the volume before stirring and mixing is obtained as a percentage, and foamability is evaluated according to Evaluation Criteria 1.

体積の測定は、実施例1〜84の〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕の<発泡性>に記載の方法に従い測定する。
<気泡の持続性>
塩基性組成物50gと酸1g相当量の酸の顆粒剤を直径5cm、高さ10cmのカップに入れ、10秒間に20回攪拌混合し二酸化炭素経皮・経粘膜吸収用組成物を得る。攪拌混合1分後の該組成物の体積を測定し、その2時間後の体積を測定して体積の減少率をパーセントで求め、評価基準2に従い、気泡の持続性を評価する。
The volume is measured according to the method described in <Foaming properties> in [Evaluation of composition for carbon dioxide transdermal / transmucosal absorption] in Examples 1 to 84.
<Bubble persistence>
50 g of the basic composition and an acid granule equivalent to 1 g of acid are placed in a cup having a diameter of 5 cm and a height of 10 cm, and stirred and mixed 20 times for 10 seconds to obtain a composition for transdermal absorption of carbon dioxide. The volume of the composition 1 minute after stirring and mixing is measured, the volume after 2 hours is measured to determine the volume reduction rate in percent, and the persistence of bubbles is evaluated according to Evaluation Criteria 2.

体積の測定は、実施例1〜84の〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕の<気泡の持続性>に記載の方法に従い測定する。   The volume is measured in accordance with the method described in <Evaluation of composition for carbon dioxide transdermal / transmucosal absorption> in Examples 1 to 84 in <Persistence of bubbles>.

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

実施例145〜179
酸性組成物と炭酸塩の顆粒剤との組み合わせよりなる二酸化炭素経皮・経粘膜吸収用組成物を表13〜表15に示す。
〔製造方法〕
増粘剤と精製水、炭酸塩と酸(有機酸及び/又は無機酸)、マトリックス基剤を表13〜表15のように組み合わせ、酸性組成物と炭酸塩の顆粒剤をあらかじめ調製する。この顆粒剤は徐放性でもよい。酸性組成物と炭酸塩の顆粒剤を混合し、二酸化炭素経皮・経粘膜吸収用組成物を得る。
<酸性組成物の製造>
実施例85〜108に記載の酸性組成物の製造方法に従い製造する。
<炭酸塩の顆粒剤の製造>
マトリックス基剤に低融点化合物を使用する場合は、ビーカー等の容器中で加熱により溶融させた低融点マトリックス基剤に炭酸塩を加えて十分攪拌、混合する。必要に応じてこれに適当な添加剤や薬効物質を加えてもよい。これを室温で徐々に冷やしながら更に攪拌し、固まるまで放置する。ある程度固まってきたら冷蔵庫等で急速に冷却してもよい。マトリックス基剤に低融点化合物を用いない場合は、ビーカー等の容器中でマトリックス基剤を水又はエタノールのような適当な溶媒に溶解又は分散させ、これに炭酸塩を溶解又は分散させて十分混合した後にオーブン等で加熱して溶媒を除去し、乾燥させる。完全に固まったら粉砕し、顆粒とする。このとき顆粒の大きさを揃えるために篩過してもよい。
Examples 145-179
Tables 13 to 15 show carbon dioxide transdermal / mucosal absorption compositions comprising a combination of an acidic composition and a carbonate granule.
〔Production method〕
Thickener, purified water, carbonate and acid (organic acid and / or inorganic acid), and matrix base are combined as shown in Tables 13 to 15, and an acidic composition and carbonate granule are prepared in advance. The granules may be sustained release. An acidic composition and a carbonate granule are mixed to obtain a composition for carbon dioxide transdermal and transmucosal absorption.
<Production of acidic composition>
Manufactured according to the method for producing an acidic composition described in Examples 85-108.
<Manufacture of carbonate granules>
When a low melting point compound is used for the matrix base, carbonate is added to the low melting point matrix base melted by heating in a container such as a beaker, and the mixture is sufficiently stirred and mixed. If necessary, an appropriate additive or medicinal substance may be added thereto. The mixture is further stirred while being cooled at room temperature, and left to solidify. If it hardens to some extent, it may be cooled rapidly in a refrigerator or the like. When a low melting point compound is not used for the matrix base, the matrix base is dissolved or dispersed in an appropriate solvent such as water or ethanol in a container such as a beaker, and the carbonate is dissolved or dispersed therein and mixed thoroughly. After that, the solvent is removed by heating in an oven or the like and dried. When it is completely solidified, it is crushed into granules. At this time, sieving may be performed in order to equalize the size of the granules.

なお、本発明において上記の炭酸塩の顆粒剤の製造方法は本実施例に限定されることはなく、乾式破砕造粒法や湿式破砕造粒法、流動層造粒法、高速攪拌造粒法、押し出し造粒法などの常法に従い製造できる。
〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕
<発泡性>
酸性組成物50gと炭酸塩1.2g相当量の炭酸塩の顆粒剤を直径5cm、高さ10cmのカップに入れ、その体積を測定する。これを10秒間に20回攪拌混合し二酸化炭素経皮・経粘膜吸収用組成物を得る。攪拌混合1分後の該組成物の体積を測定し、攪拌混合前の体積からの増加率をパーセントで求め、評価基準1に従い、発泡性を評価する。
In the present invention, the method for producing the above-mentioned carbonate granule is not limited to this example, and dry crushing granulation method, wet crushing granulation method, fluidized bed granulation method, high speed stirring granulation method It can be produced according to a conventional method such as extrusion granulation.
[Evaluation of composition for transdermal and transmucosal absorption of carbon dioxide]
<Foaming properties>
An acidic composition 50 g and a carbonate granule equivalent to 1.2 g carbonate are put in a cup having a diameter of 5 cm and a height of 10 cm, and the volume is measured. This is stirred and mixed 20 times in 10 seconds to obtain a carbon dioxide transdermal / mucosal absorption composition. The volume of the composition after 1 minute of stirring and mixing is measured, the rate of increase from the volume before stirring and mixing is obtained as a percentage, and foamability is evaluated according to Evaluation Criteria 1.

体積の測定は、実施例1〜84の〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕の<発泡性>に記載の方法に従い測定する。
<気泡の持続性>
酸性組成物50gと炭酸塩1.2g相当量の炭酸塩の顆粒剤を直径5cm、高さ10cmのカップに入れ、10秒間に20回攪拌混合し二酸化炭素経皮・経粘膜吸収用組成物を得る。攪拌混合1分後の該組成物の体積を測定し、その2時間後の体積を測定して体積の減少率をパーセントで求め、評価基準2に従い、気泡の持続性を評価する。
The volume is measured according to the method described in <Foaming properties> in [Evaluation of composition for carbon dioxide transdermal / transmucosal absorption] in Examples 1 to 84.
<Bubble persistence>
50g of acidic composition and carbonate granule equivalent to 1.2g of carbonate are put in a cup with a diameter of 5cm and a height of 10cm and stirred and mixed 20 times for 10 seconds to obtain a composition for transdermal absorption of carbon dioxide. obtain. The volume of the composition 1 minute after stirring and mixing is measured, the volume after 2 hours is measured to determine the volume reduction rate in percent, and the persistence of bubbles is evaluated according to Evaluation Criteria 2.

体積の測定は、実施例1〜84の〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕の<気泡の持続性>に記載の方法に従い測定する。   The volume is measured in accordance with the method described in <Evaluation of composition for carbon dioxide transdermal / transmucosal absorption> in Examples 1 to 84 in <Persistence of bubbles>.

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

実施例180〜226
酸性組成物と塩基性組成物の組み合わせよりなる二酸化炭素経皮・経粘膜吸収用組成物を表16〜表19に示す。
〔製造方法〕
増粘剤と精製水、炭酸塩と酸(有機酸及び/又は無機酸)を表16〜表19のように組み合わせ、酸性組成物と塩基性組成物を予め調製する。
酸性組成物と塩基性組成物を混合し、二酸化炭素経皮・経粘膜吸収用組成物を得る。
<酸性組成物の製造>
実施例85〜108に記載の酸性組成物の製造方法に従い製造する。
<塩基性組成物の製造>
実施例1〜84に記載の塩基性組成物の製造方法に従い製造する。
〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕
<発泡性>
酸性組成物25gと塩基性組成物25gとを直径5cm、高さ10cmのカップに入れ、その体積を測定する。これを10秒間に20回攪拌混合し二酸化炭素経皮・経粘膜吸収用組成物を得る。攪拌混合1分後の該組成物の体積を測定し、攪拌混合前の体積からの増加率をパーセントで求め、評価基準1に従い、発泡性を評価する。
Examples 180-226
Tables 16 to 19 show carbon dioxide transdermal / mucosal absorption compositions comprising a combination of an acidic composition and a basic composition.
〔Production method〕
Thickener, purified water, carbonate and acid (organic acid and / or inorganic acid) are combined as shown in Tables 16 to 19, and an acidic composition and a basic composition are prepared in advance.
An acidic composition and a basic composition are mixed to obtain a carbon dioxide transdermal / transmucosal absorption composition.
<Production of acidic composition>
Manufactured according to the method for producing an acidic composition described in Examples 85-108.
<Manufacture of basic composition>
Manufacture according to the method for manufacturing the basic composition described in Examples 1 to 84.
[Evaluation of composition for transdermal and transmucosal absorption of carbon dioxide]
<Foaming properties>
25 g of the acidic composition and 25 g of the basic composition are put into a cup having a diameter of 5 cm and a height of 10 cm, and the volume is measured. This is stirred and mixed 20 times in 10 seconds to obtain a carbon dioxide transdermal / mucosal absorption composition. The volume of the composition after 1 minute of stirring and mixing is measured, the rate of increase from the volume before stirring and mixing is obtained as a percentage, and foamability is evaluated according to Evaluation Criteria 1.

体積の測定は、実施例1〜84の〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕の<発泡性>に記載の方法に従い測定する。
<気泡の持続性>
酸性組成物25gと塩基性組成物25gとを直径5cm、高さ10cmのカップに入れ、10秒間に20回攪拌混合し二酸化炭素経皮・経粘膜吸収用組成物を得る。攪拌混合1分後の該組成物の体積を測定し、その2時間後の体積を測定して体積の減少率をパーセントで求め、評価基準2に従い、気泡の持続性を評価する。
The volume is measured according to the method described in <Foaming properties> in [Evaluation of composition for carbon dioxide transdermal / transmucosal absorption] in Examples 1 to 84.
<Bubble persistence>
25 g of the acidic composition and 25 g of the basic composition are put into a cup having a diameter of 5 cm and a height of 10 cm, and are stirred and mixed 20 times for 10 seconds to obtain a composition for carbon dioxide transdermal / transmucosal absorption. The volume of the composition 1 minute after stirring and mixing is measured, the volume after 2 hours is measured to determine the volume reduction rate in percent, and the persistence of bubbles is evaluated according to Evaluation Criteria 2.

体積の測定は、実施例1〜84の〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕の<気泡の持続性>に記載の方法に従い測定する。   The volume is measured in accordance with the method described in <Evaluation of composition for carbon dioxide transdermal / transmucosal absorption> in Examples 1 to 84 in <Persistence of bubbles>.

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

実施例227〜249
炭酸塩と酸の複合顆粒剤と含水粘性組成物の組み合わせよりなる二酸化炭素経皮・経粘膜吸収用組成物を表20〜表21に示す。
〔製造方法〕
増粘剤と精製水、炭酸塩と酸(有機酸及び/又は無機酸)、マトリックス基剤を表20〜表21のように組み合わせ、炭酸塩と酸の複合顆粒剤と含水粘性組成物をあらかじめ調製する。炭酸塩と酸の複合顆粒剤と含水粘性組成物を混合し、二酸化炭素経皮・経粘膜吸収用組成物を得る。炭酸塩と酸の複合顆粒剤は炭酸塩と酸が徐放性であってもよい。
<炭酸塩と酸の複合顆粒剤の製造>
マトリックス基剤に低融点化合物を使用する場合は、ビーカー等の容器中で加熱により溶融させた低融点マトリックス基剤に炭酸塩と酸を加えて十分攪拌、混合する。必要に応じてこれに適当な添加剤や薬効物質等を加えてもよい。これを室温で徐々に冷やしながら更に攪拌し、固まるまで放置する。ある程度固まってきたら冷蔵庫等で急速に冷却してもよい。マトリックス基剤に低融点化合物を用いない場合はビーカー等の容器中でマトリックス基剤を無水エタノールのような適当な溶媒に溶解又は分散させ、炭酸塩と酸を溶解又は分散させ、十分混合した後にオーブン等で加熱して溶媒を除去し、乾燥させる。完全に固まったら粉砕し、顆粒とする。このとき顆粒の大きさを揃えるために篩過してもよい。
<含水粘性組成物の製造>
ビーカー等の容器中で増粘剤を精製水に溶解又は膨潤させる。このとき必要であれば精製水を加熱して増粘剤の溶解又は膨潤を促進してもよいし、増粘剤を適当な溶媒に溶解又は分散させておいて用いてもよい。必要に応じてこれに適当な添加剤や薬効物質等を加えてもよい。
Examples 227-249
Tables 20 to 21 show carbon dioxide transdermal and transmucosal absorption compositions comprising a combination of a carbonate and acid composite granule and a hydrous viscous composition.
〔Production method〕
Thickener and purified water, carbonate and acid (organic acid and / or inorganic acid), matrix base are combined as shown in Table 20 to Table 21, and carbonate and acid composite granule and water-containing viscous composition are prepared beforehand. Prepare. A composite granule of carbonate and acid and a hydrous viscous composition are mixed to obtain a carbon dioxide transdermal / transmucosal absorption composition. The composite granule of carbonate and acid may be a sustained release of carbonate and acid.
<Production of carbonate and acid composite granules>
When a low melting point compound is used for the matrix base, a carbonate and an acid are added to the low melting point matrix base melted by heating in a container such as a beaker, and the mixture is sufficiently stirred and mixed. If necessary, an appropriate additive or medicinal substance may be added thereto. The mixture is further stirred while being cooled at room temperature, and left to solidify. If it hardens to some extent, it may be cooled rapidly in a refrigerator or the like. If a low melting point compound is not used for the matrix base, dissolve or disperse the matrix base in an appropriate solvent such as absolute ethanol in a container such as a beaker, dissolve or disperse the carbonate and acid, and mix well. Heat in an oven to remove the solvent and dry. When it is completely solidified, it is crushed into granules. At this time, sieving may be performed in order to equalize the size of the granules.
<Production of hydrous viscous composition>
A thickener is dissolved or swollen in purified water in a container such as a beaker. At this time, if necessary, purified water may be heated to promote dissolution or swelling of the thickener, or the thickener may be dissolved or dispersed in an appropriate solvent. If necessary, an appropriate additive or medicinal substance may be added thereto.

なお、本発明において上記の炭酸塩と酸の複合顆粒の製造方法は本実施例に限定されることはなく、乾式破砕造粒法や流動層造粒法、高速攪拌造粒法、押し出し造粒法などの常法に従い製造できる。
〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕
<発泡性>
含水粘性組成物50gと炭酸塩1.2g相当量の炭酸塩と酸の複合顆粒剤とを直径5cm、高さ10cmのカップに入れ、その体積を測定する。含水粘性組成物と炭酸塩と酸の複合顆粒剤の混合物を10秒間に20回攪拌混合し二酸化炭素経皮・経粘膜吸収用組成物を得る。攪拌混合1分後の該組成物の体積を測定し、攪拌混合前の体積からの増加率をパーセントで求め攪拌混合前の体積からの増加率をパーセントで求め、評価基準1に従い、発泡性を評価する。
In the present invention, the method for producing the composite granule of carbonate and acid described above is not limited to this example, and dry crushing granulation method, fluidized bed granulation method, high-speed stirring granulation method, extrusion granulation method, It can be produced according to a conventional method such as a method.
[Evaluation of composition for transdermal and transmucosal absorption of carbon dioxide]
<Foaming properties>
50 g of a hydrous viscous composition and a carbonate and acid composite granule equivalent to 1.2 g of carbonate are put into a cup having a diameter of 5 cm and a height of 10 cm, and the volume is measured. A mixture of a hydrous viscous composition, a carbonate and acid composite granule is stirred and mixed 20 times in 10 seconds to obtain a composition for carbon dioxide transdermal / transmucosal absorption. The volume of the composition after 1 minute of stirring and mixing is measured, the rate of increase from the volume before stirring and mixing is determined as a percentage, the rate of increase from the volume before stirring and mixing is calculated as a percentage, evaluate.

体積の測定は、実施例1〜84の〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕の<発泡性>に記載の方法に従い測定する。
<気泡の持続性>
含水粘性組成物50gと炭酸塩1.2g相当量の炭酸塩と酸の複合顆粒剤とを直径5cm、高さ10cmのカップに入れ、10秒間に20回攪拌混合し二酸化炭素経皮・経粘膜吸収用組成物を得る。攪拌混合1分後の該組成物の体積を測定し、その2時間後の体積を測定して体積の減少率をパーセントで求め、評価基準2に従い、気泡の持続性を評価する。
The volume is measured according to the method described in <Foaming properties> in [Evaluation of composition for carbon dioxide transdermal / transmucosal absorption] in Examples 1 to 84.
<Bubble persistence>
50 g of hydrous viscous composition and carbonate and acid composite granule equivalent to 1.2 g of carbonate are placed in a cup with a diameter of 5 cm and a height of 10 cm, and stirred and mixed 20 times for 10 seconds. An absorbent composition is obtained. The volume of the composition 1 minute after stirring and mixing is measured, the volume after 2 hours is measured to determine the volume reduction rate in percent, and the persistence of bubbles is evaluated according to Evaluation Criteria 2.

体積の測定は、実施例1〜84の〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕の<気泡の持続性>に記載の方法に従い測定する。   The volume is measured in accordance with the method described in <Evaluation of composition for carbon dioxide transdermal / transmucosal absorption> in Examples 1 to 84 in <Persistence of bubbles>.

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

実施例250〜272
塩基性組成物と酸含有シートの組み合わせよりなる二酸化炭素経皮・経粘膜吸収用組成物を表22〜表23に示す。
〔製造方法〕
炭酸塩と酸(有機酸及び/又は無機酸)、増粘剤、マトリックス基剤、精製水を表22〜表23のように組み合わせ、塩基性組成物と酸含有シートをあらかじめ調製する。塩基性組成物と酸含有シートを接触させ、二酸化炭素経皮・経粘膜吸収用組成物を得る。
<塩基性組成物の製造>
実施例1〜84に記載の塩基性組成物の製造方法に従い製造する。
<酸含有シートの製造>
ビーカー等の容器中でマトリックス基剤を水又はエタノール等の溶媒で溶解又は分散させ、そこに酸を溶解又は分散させ、ガラス板上に均一な厚さで必要に応じて適当な大きさに広げ、オーブン等で乾燥させて酸含有シートを得る。必要に応じてこれに適当な添加剤や薬効物質等を加えてもよい。また、不織布や織布、高分子フィルム等を支持体としてもよく、支持体の周囲に粘着剤を塗布して貼付材とすることも可能である。
〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕
<発泡性>
塩基性組成物50gをガラス板上に一辺10cmの均一な厚みの正方形にのばし、その上に酸1gを含有する一辺10cmの正方形の酸含有シートを乗せる。5分後に該シートと該塩基性組成物の界面に気泡の認められたものを発泡性「○」、認められなかったものを発泡性「×」と評価する。
<気泡の持続性>
塩基性組成物50gをガラス板上に一辺10cmの均一な厚みの正方形にのばし、その上に酸1gを含有する一辺10cmの正方形の酸含有シートを乗せる。5分後と2時間後の両方で該シートと該塩基性組成物の界面に気泡の認められたものを気泡の持続性「○」、5分後には気泡が認められたが、2時間後には認められなかったものを気泡の持続性「×」と評価する。
Examples 250-272
Tables 22 to 23 show carbon dioxide transdermal / mucosal absorption compositions comprising a combination of a basic composition and an acid-containing sheet.
〔Production method〕
Carbonate and acid (organic acid and / or inorganic acid), thickener, matrix base, and purified water are combined as shown in Tables 22 to 23, and a basic composition and an acid-containing sheet are prepared in advance. A basic composition and an acid-containing sheet are contacted to obtain a composition for carbon dioxide transdermal / transmucosal absorption.
<Manufacture of basic composition>
Manufacture according to the method for manufacturing the basic composition described in Examples 1 to 84.
<Manufacture of acid-containing sheet>
Dissolve or disperse the matrix base with a solvent such as water or ethanol in a container such as a beaker, dissolve or disperse the acid there, and spread it on the glass plate to an appropriate size as needed with a uniform thickness. And drying in an oven or the like to obtain an acid-containing sheet. If necessary, an appropriate additive or medicinal substance may be added thereto. Further, a nonwoven fabric, a woven fabric, a polymer film, or the like may be used as a support, and an adhesive may be applied around the support to form a patch.
[Evaluation of composition for transdermal and transmucosal absorption of carbon dioxide]
<Foaming properties>
50 g of the basic composition is spread on a glass plate into a square having a uniform thickness of 10 cm on a side, and a 10 cm side acid-containing sheet containing 1 g of acid is placed thereon. After 5 minutes, the case where bubbles were observed at the interface between the sheet and the basic composition was evaluated as foaming “◯”, and the case where bubbles were not observed was evaluated as foaming “X”.
<Bubble persistence>
50 g of the basic composition is spread on a glass plate into a square having a uniform thickness of 10 cm on a side, and a 10 cm side acid-containing sheet containing 1 g of acid is placed thereon. In both 5 minutes and 2 hours, bubbles were observed at the interface between the sheet and the basic composition. The bubble persistence was “Good”. After 5 minutes, bubbles were observed. Those that were not recognized were evaluated as “×”.

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

実施例273〜294
酸性組成物と炭酸塩含有シートの組み合わせよりなる二酸化炭素経皮・経粘膜吸収用組成物を表24〜表25に示す。
〔製造方法〕
炭酸塩と酸(有機酸及び/又は無機酸)、増粘剤、マトリックス基剤、精製水を表24〜表25のように組み合わせ、酸性組成物と炭酸塩含有シートをあらかじめ調製する。酸性組成物と炭酸塩含有シートを接触させ、二酸化炭素経皮・経粘膜吸収用組成物を得る。
<酸性組成物の製造>
実施例85〜108に記載の酸性組成物の製造方法に従い製造する。
<炭酸塩含有シートの製造>
ビーカー等の容器中でマトリックス基剤を水又はエタノール等の溶媒で溶解又は分散させ、そこに炭酸塩を溶解又は分散させ、ガラス板上に均一な厚さで必要に応じて適当な大きさに広げ、オーブン等で乾燥させて炭酸塩含有シートを得る。必要に応じてこれに適当な添加剤や薬効物質等を加えてもよい。また、不織布や織布、高分子フィルム等を支持体としてもよく、支持体の周囲に粘着剤を塗布して貼付材とすることも可能である。
〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕
<発泡性>
酸性組成物50gをガラス板上に一辺10cmの均一な厚みの正方形にのばし、その上に炭酸塩1.2gを含有する一辺10cmの正方形の炭酸塩含有シートを乗せる。5分後に該シートと該酸性組成物の界面に気泡の認められたものを発泡性「○」、認められなかったものを発泡性「×」と評価する。
<気泡の持続性>
酸性組成物50gをガラス板上に一辺10cmの均一な厚みの正方形にのばし、その上に炭酸塩1.2gを含有する一辺10cmの正方形の炭酸塩含有シートを乗せる。5分後と2時間後の両方で該シートと該酸性組成物の界面に気泡の認められたものを気泡の持続性「○」、5分後には気泡が認められたが、2時間後には認められなかったものを気泡の持続性「×」と評価する。
Examples 273-294
Tables 24 to 25 show carbon dioxide transdermal / transmucosal absorption compositions comprising a combination of an acidic composition and a carbonate-containing sheet.
〔Production method〕
A carbonate and an acid (organic acid and / or inorganic acid), a thickener, a matrix base, and purified water are combined as shown in Tables 24 to 25, and an acidic composition and a carbonate-containing sheet are prepared in advance. An acidic composition and a carbonate-containing sheet are contacted to obtain a carbon dioxide transdermal / mucosal absorption composition.
<Production of acidic composition>
Manufactured according to the method for producing an acidic composition described in Examples 85-108.
<Manufacture of carbonate-containing sheet>
Dissolve or disperse the matrix base with water or a solvent such as ethanol in a container such as a beaker, dissolve or disperse the carbonate there, and make it an appropriate size with a uniform thickness on the glass plate as necessary. Spread and dry in an oven to obtain a carbonate-containing sheet. If necessary, an appropriate additive or medicinal substance may be added thereto. Further, a nonwoven fabric, a woven fabric, a polymer film, or the like may be used as a support, and an adhesive may be applied around the support to form a patch.
[Evaluation of composition for transdermal and transmucosal absorption of carbon dioxide]
<Foaming properties>
50 g of the acidic composition is spread on a glass plate into a square with a uniform thickness of 10 cm on a side, and a 10 cm side square carbonate-containing sheet containing 1.2 g of carbonate is placed thereon. After 5 minutes, the case where bubbles were observed at the interface between the sheet and the acidic composition was evaluated as foaming “◯”, and the case where bubbles were not observed was evaluated as foaming “X”.
<Bubble persistence>
50 g of the acidic composition is spread on a glass plate into a square with a uniform thickness of 10 cm on a side, and a 10 cm side square carbonate-containing sheet containing 1.2 g of carbonate is placed thereon. In both 5 minutes and 2 hours, bubbles were observed at the interface between the sheet and the acidic composition. Persistence of bubbles was “Good”. After 5 minutes, bubbles were observed, but after 2 hours, What was not recognized is evaluated as a bubble persistence “x”.

Figure 2011088930
Figure 2011088930

Figure 2011088930
Figure 2011088930

実施例295(炭酸塩と酸と含水粘性組成物の組み合わせよりなる閉鎖療法用二酸化炭素経皮・経粘膜吸収用組成物)
〔製造方法〕
炭酸水素ナトリウム0.24gとクエン酸0.2gを混合し、6cm×7cmのフィルムドレッシング材(商品名テガダーム、3M社製)の粘着面の端から2cmの内側に均等に広げ、その上から5cm×6cmの薄い不織布をかぶせ、該炭酸水素ナトリウムと該クエン酸の混合物がこぼれないようにこの不織布を該フィルムドレッシング材の粘着面に接着する。該不織布上に、実施例227〜249の<含水粘性組成物の製造>に記載の製造方法に従い製造したアルギン酸ナトリウム0.3g、カルボキシメチルセルロースナトリウム0.2g、精製水9.5gよりなる含水粘性組成物を不織布の端から1cm内側に均一な厚さに塗布し、閉鎖療法用二酸化炭素経皮・経粘膜吸収用組成物を得る。
実施例296(炭酸塩と酸の複合顆粒剤と含水粘性組成物の組み合わせよりなる閉鎖療法用二酸化炭素経皮・経粘膜吸収用組成物)
〔製造方法〕
セタノール5gを100mlのビーカー中で温浴により溶融し、これに炭酸水素ナトリウム24gとクエン酸20gを加えてよくかき混ぜる。これらが十分混合されたら室温で徐々に冷やしながら更にかき混ぜ、ある程度固まってきたらかき混ぜるのをやめて完全に固まるまで放置する。完全に固まったら粉砕し、炭酸塩と酸の複合顆粒剤を得る。
Example 295 (composition for carbon dioxide transdermal / transmucosal absorption for closure therapy comprising a combination of carbonate, acid and water-containing viscous composition)
〔Production method〕
Mix 0.24g of sodium hydrogen carbonate and 0.2g of citric acid, spread evenly 2cm inside from the edge of the adhesive surface of 6cm x 7cm film dressing material (trade name Tegaderm, 3M), 5cm from above A thin non-woven fabric of 6 cm is covered, and this non-woven fabric is adhered to the adhesive surface of the film dressing so that the mixture of sodium bicarbonate and citric acid does not spill. A hydrous viscous composition comprising 0.3 g of sodium alginate, 0.2 g of sodium carboxymethylcellulose, and 9.5 g of purified water produced according to the production method described in <Manufacture of hydrous viscous composition> of Examples 227 to 249 on the nonwoven fabric. The product is applied to the inside of the nonwoven fabric at a uniform thickness 1 cm inside to obtain a carbon dioxide transdermal / transmucosal absorption composition for closure therapy.
Example 296 (composition for carbon dioxide percutaneous and transmucosal absorption for closure therapy comprising a combination of carbonate and acid composite granule and water-containing viscous composition)
〔Production method〕
Cetanol (5 g) is melted in a 100 ml beaker with a warm bath, and sodium hydrogen carbonate (24 g) and citric acid (20 g) are added thereto and mixed well. When they are mixed well, stir them while gradually cooling them at room temperature. When they are hardened to some extent, stop stirring and leave them until they are completely solidified. When completely hardened, the mixture is pulverized to obtain a composite granule of carbonate and acid.

該複合顆粒剤0.49gを6cm×7cmのフィルムドレッシング材(商品名テガダーム、3M社製)の粘着面の端から2cmの内側に薄く広げ、その上から5cm×6cmの薄い不織布をかぶせ、該複合顆粒剤がこぼれないように、この不織布を該フィルムドレッシング材の粘着面に接着する。該不織布上に、実施例227〜249の<含水粘性組成物の製造>に記載の製造方法に従い製造したアルギン酸ナトリウム0.3g、カルボキシメチルセルロースナトリウム0.2g、精製水9.5gよりなる含水粘性組成物を不織布の端から1cm内側に均一な厚さに塗布し、閉鎖療法用二酸化炭素経皮・経粘膜吸収用組成物を得る。
実施例297(塩基性組成物と酸被覆顆粒剤との組み合わせよりなる二酸化炭素経皮・経粘膜吸収用組成物)
〔製造方法〕
塩基性組成物と酸被覆顆粒剤を混合攪拌し、二酸化炭素経皮・経粘膜吸収用組成物を得る。これらの混合比は任意に設定できるが、炭酸塩1.2重量部相当の塩基性組成物に対し、酸1重量部相当の酸被覆顆粒を試験例では用いる。
〈塩基性組成物の製造〉
メチルパラベン2g、炭酸水素ナトリウム24g、カルボキシメチルスターチナトリウム40g、アルギン酸ナトリウム40g、カルボキシメチルセルロースナトリウム40gを2,000mlの水に溶解又は分散させ、十分攪拌して塩基性組成物を得る。必要に応じてこれに適当な添加剤や薬効物質等を加えてもよい。
〈酸被覆顆粒剤の製造〉
常法に従い、クエン酸1.8kgを7%HPC−Lエタノール溶液722gに溶かした溶液をCFグラニュレーターを用いて精製白糖顆粒(商品名ノンパレル103、フロイント産業株式会社)9kgに吹き付け、乾燥後、酸被覆顆粒剤10.7kgを得た。
実施例298(炭酸塩及び植物精油含有含水粘性組成物と酸の顆粒剤との組み合わせよりなる二酸化炭素経皮・経粘膜吸収用組成物)
〔製造方法〕
メチルパラベン1g、炭酸水素ナトリウム12g、カルボキシメチルスターチナトリウム25g、アルギン酸ナトリウム20g、カルボキシメチルセルロースナトリウム25g、グレープフルーツ油0.5ml、カユプテ油0.1ml、ローズウッド油0.1ml、ゼラニウム油0.1ml、食用緑色色素0.01g、酢酸アルファ・トコフェロール1mlを1,000mlの水に溶解又は分散させ、十分攪拌する。必要に応じてこれに適当な添加剤や薬効物質等を加えてもよい。その25gに実施例297の酸被覆顆粒剤1.2gを加えて攪拌し、二酸化炭素経皮・経粘膜吸収用組成物からなるクリームを得る。
実施例299(含水粘性組成物と二酸化炭素よりなる二酸化炭素経皮・経粘膜吸収用組成物)
〔製造方法〕
炭酸水素ナトリウム12g、カルボキシメチルスターチナトリウム20g、アルギン酸ナトリウム20gを1,000mlの水に溶かし、含水粘性組成物を得る。これに小型二酸化炭素ボンベ(商品名テトラCO2ボンベ、ワーナー・ランバート社製)につないだ外径6.0mm、内径3.5mm、長さ60cmのビニールチューブの先端を入れ、二酸化炭素を吹き込みながらカルボキシメチルセルロースナトリウム20gを加えて攪拌しながら溶かすことにより、二酸化炭素経皮・経粘膜吸収用組成物を得る。
試験例1(足白癬に伴う痒みの治療試験)
41歳男性。強い痒みを伴う右足の足白癬に対し、実施例8の組成物100gを洗面器に満たして足を約20分間浸けさせたところ、本組成物による一度の治療で痒みがとれた。
試験例2(足白癬に伴う痒みの治療試験)
73歳女性。非常に強い痒みを伴う両足の足白癬に対し、実施例18の組成物300gを洗面器に満たして足を約20分間浸けさせた。外用抗真菌剤による2年間の治療が全く効果がなかったが、本組成物による一度の治療で痒みがとれた。
試験例3(口角炎治療試験)
41歳男性。実施例8の組成物1gを10分間口角炎に塗布したところ、痛みが消失し、傷口がふさがって治癒した。
試験例4(褥創治療試験)
78歳男性。肺ガンの進行により寝たきりとなり、腰部から臀部にかけて褥創が発生した。褥創の深さは約4cmで筋膜まで達していた。実施例1の組成物100gを褥創のポケットに満たし、20cm×30cmのフィルムドレッシング材(商品名テガダーム、3M社製)で20分間覆った。該組成物とフィルムドレッシング材は毎日交換した。治療開始11日目で褥創の深さは1cmに改善された。治療開始から1ヶ月後には肉芽はほぼ周囲の正常皮膚と同じ高さにまで盛り上がった。
試験例5(ズック靴皮膚炎治療試験)
8歳男性。ズック靴皮膚炎のために両足底が出血し、ステロイド外用剤(商品名リンデロンV軟膏、塩野義製薬社製)を2ヶ月間塗布したが効果がなかった。実施例20の組成物30gを1日1回10分間、毎日足底に塗布したところ、4日目に傷口が塞がり、1ヶ月で完治した。
試験例6(髪の艶に対する試験)
41歳男性。髪の艶がなくなり、老けた感じに見えるのを気にしていたため、実施例18の組成物20gを1日1回約15分間、毎日髪に塗布したところ、3日目から髪の艶がよくなった。
試験例7(アトピー性皮膚炎治療試験)
4歳女性。両膝裏のアトピー性皮膚炎に対し、実施例20の組成物5gを1日1回5分間、毎日塗布したところ、2週間で皮膚の黒ずみが消え、4週間で皮膚の乾燥が治癒した。
試験例8(顔と腹部の部分痩せ試験)
41歳男性。ふっくらした頬と太いウエストを痩せさせたいと希望し、実施例8の組成物を1日1回15分間、毎日右頬に30g、腹部に100g塗布した。2ヶ月後に右頬が5名の評価者全員により明らかに小さくなったと判断された。腹部はウエストが6cm減少した。
試験例9(肌質改善及び顔痩せ試験)
37歳女性。ふっくらした頬と荒れ肌、肌のくすみに悩み、種々の化粧品を試したが効果が得られなかった。実施例20の組成物50gを1日1回10分間、毎日顔全体に塗布したところ、1回目の塗布で肌のくすみが消えて白くなり、きめ細かい肌になった。2週間後には3名の評価者全員により、顔が小さくなったと判断された。
試験例10(頸肩腕症候群治療試験)
42歳男性。コンピュータ操作の疲れからくる頸肩腕症候群(肩こり)に対し、外用抗炎症剤(商品名タイガーバーム、龍角散社製)を塗布したが全く効果が得られなかった。実施例20の組成物40gを20分間肩に塗布したところ、頸肩腕症候群が治癒した。
試験例11(尋常性乾癬治療試験)
37歳女性。非常に強い痒みを伴う膝の尋常性乾癬に対し、実施例20の組成物3gを1日1回10分間、毎日塗布した。1回の塗布で痒みが消失した。2週間後に患部の黒ずみが改善した。
試験例12(鶏眼治療試験)
37歳女性。痛みを伴う左足小指の右側にできた鶏眼に実施例20の組成物2gを1日1回10分間、5日間塗布したところ、サリチル酸製剤のように鶏眼の周囲の正常皮膚が損傷されることなく治癒した。
試験例13(腕の部分痩せ試験)
36歳女性。二の腕の太さを気にしていたため、実施例18の組成物30gを左の二の腕に塗布し、食品包装用フィルム(商品名サランラップ、旭化成社製)をその上からまいて6時間放置したところ、二の腕の周囲長が2cm減少した。
試験例14(臀部の化膿性湿疹治療試験)
29歳男性。臀部全体にできた化膿性湿疹に対し、実施例18の組成物40gを1日1回20分間、7日間塗布したところ、化膿性湿疹が治癒した。
試験例15(虫さされの痒み治療試験)
51歳女性。ハチに腕と手指の2カ所を刺され、抗ヒスタミン剤(商品名セレスタミン錠、シェリングプラウ社製)の服用とステロイド外用剤(商品名テラコートリル軟膏、ファイザー製薬社製)の塗布により局所の腫脹、発赤は消失したが、徐々に痒みが出現し、2週後にも痒みのため不眠をきたすまでになった。実施例18の組成物5gを15分間塗布したところ、痒みが消失し、安眠を得られた。
試験例16(足白癬に伴う痒みの治療試験)
32歳女性。非常に強い痒みを伴う両足の足白癬に対し、抗真菌剤(商品名メンタックスクリーム、科研製薬社製)を2ヶ月間塗布したが、痒みがまったくおさまらなかった。実施例8の組成物100gを洗面器に満たして足を約20分間浸けさせたところ、一度の治療で痒みがとれた。その4日後に再度実施例8の組成物100mlを洗面器に満たして足を約20分間浸けさせたところ、病変の肉眼的所見も著明に改善した。
試験例17(掌蹠膿疱症治療試験)
22歳女性。強い痒みを伴う両手の掌蹠膿疱症に対し、実施例18の組成物100gを洗面器に満たして手を約15分間浸けさせたところ、直ちに痒みが消失した。
試験例18(アトピー性皮膚炎治療試験)
8歳男性。一部角化、亀裂を伴い疼痛と痒みの非常に強い手指のアトピー性皮膚炎に対し、実施例8の組成物50gをカップに満たして指先を20分間浸けさせたところ、直ちに痒みが消失した。翌日には亀裂部に上皮形成が認められ、疼痛も軽減した。
試験例19(尋常性乾癬治療試験)
37歳女性。非常に強い痒みを伴う膝の尋常性乾癬に対し、実施例296の組成物10.49gを30分間貼付した。痒みは直ちに消失し、患部上皮の角化、乾燥が著明に改善した。
試験例20(顔面の擦過傷治療試験)
10歳男性。右顔面の3cm×4cmの擦過傷に対し、実施例296の組成物10.49gを貼付した。該組成物は毎日貼付し、1日1回交換した。2日目に痂皮形成することなく上皮化が認められ、5日目に瘢痕化することなく治癒した。
試験例21(乾燥性皮膚掻痒症)
69歳男性。両下腿の乾燥性皮膚掻痒症に対し、実施例20の組成物50gを塗布し、20分間食品包装用フィルム(商品名サランラップ、旭化成社製)で覆ったところ、痒みが消失した。
試験例22(褥創治療試験)
65歳男性。脳内出血の血腫除去手術後より植物状態になり、仙骨部に15cm×15cm大の骨膜に達するIV度褥創が生じた。創面には壊死組織が付着し、深いポケットが形成され、滲出液も認められた。生理的食塩水による創面の洗浄およびポビドンヨードシュガー塗布による治療を行ったが、ほとんど効果が得られなかった。実施例297の組成物30gを1日1回、ポケット内に充填し、更に創面に盛り上げるように塗布し、その上に20cm×30cmのフィルムドレッシング材(商品名テガダーム、3M社製)を貼付した。該組成物とフィルムドレッシング材は毎日交換した。該組成物投与5日目で創面より壊死組織、滲出液が消失して急速な治癒傾向を示した。同時に、良性肉芽の増生を認めた。2ヶ月目には褥創の大きさ、深さは著明に縮小し、創面には上皮が形成され、ポケットも消失した。
試験例23(歯槽膿漏治療試験)
28歳女性。歯肉の腫脹と発赤が著しく、歯肉が歯牙の上まで達していた。歯周ポケットのスケーリングを行い、実施例297の組成物30gを2日に1回、歯周ポケット内に注入し、更に歯肉全体を覆うように20分間塗布した。1ヶ月後には歯肉の腫脹と発赤はほとんど解消した。
試験例24(口唇裂傷治療試験)
7歳女性。下口唇を上顎前歯にて咬み、歯牙の跡が残る外傷性の裂傷を受けた。実施例297の組成物5gを20分間塗布したところ、ほぼ傷跡が残らない程度に回復した。
試験例25(義歯性潰瘍治療試験)
67歳女性。義歯装着後、義歯床下粘膜に、義歯不適合による疼痛を伴う潰瘍が発生した。義歯を脱着して辺縁部を削り、義歯の適合をはかるとともに、潰瘍部に実施例297の組成物5gを塗布し、義歯を再装着した。5日後の診察では、潰瘍は消失していた。
試験例26(そばかすについての試験)
38歳女性。長年そばかすに悩み、様々な化粧品を使用するも効果がなかったため、実施例298の組成物26.2gを1日1回20分間、毎日顔全体に塗布したところ、3日目でほくろの方が目立つほどにそばかすが薄くなった。
試験例27(口内炎治療試験)
43歳男性。右口蓋部にできた疼痛を伴う口内炎に対し、実施例170の組成物3gを20分間塗布したところ、直ちに疼痛は消失した。
試験例28(膿痂疹治療試験)
4歳女性。右上腕の膿痂疹に対し、実施例297の組成物10gを1日1回20分間塗布したあと、フシジン酸ナトリウム軟膏(商品名フシジンレオ軟膏、三共株式会社製)適量を塗布する治療を毎日行ったところ、5日目に瘢痕を伴わずに治癒した。
試験例29(尋常性ざ瘡治療試験)
28歳女性。顔面全体の尋常性ざ瘡に対し、各種外用非ステロイド性抗炎症剤や内服抗生物質などを試みるも、全く無効であった。実施例297の組成物30gを1日1回30分間、毎日塗布したところ、2ヶ月で丘疹は平坦になり、わずかに発赤を残すのみとなった。
試験例30(下肢皮膚潰瘍治療試験)
63歳女性。下肢静脈瘤による直径1cmの皮膚潰瘍及び点状のびらんに対し、実施例297の組成物15gを1日1回20分間、毎日塗布したところ、びらんは1回目の塗布で消失、治癒した。10日目には皮膚潰瘍も著明に縮小したため、該組成物の投与を中止したが、翌日には痂皮を形成して治癒した。
試験例31(下肢冷感、掻痒、しびれ感治療試験)
71歳男性。末梢循環障害による両下肢の冷感、掻痒、しびれ感に対し、実施例31の組成物30gを週1回20分間下肢に塗布したところ、7回の塗布でこれらの症状が消失した。
試験例32(歯肉炎治療試験)
42歳男性。強い歯痛を併発した、腫脹と発赤が著しい歯肉炎に対し、実施例297の組成物10gを1回10分間、1日目に3回、2日目に2回塗布した。歯痛は1回目の塗布で消失し、歯肉の腫脹と発赤は著明に改善した。
試験例33(除毛後の再発毛抑制試験)
38歳女性。腋のむだ毛を週2回剃刀で剃っていたが、剃刀で剃る回数を少なくできないかと悩んでいた。実施例135の組成物30gを両腋の下に各15gずつ1日1回15分間、毎日塗布したところ、1ヶ月後以降は腋のむだ毛は1度剃るとその後の再発毛が遅れ、1週間に1回剃刀で剃るだけでよくなった。
実施例300
水200mlにヒドロキシプロピルセルロース4g、CMC−Na10g、炭酸水素ナトリウム2.4gを加え、ハンドミキサーで固形分が完全に分散、もしくは溶けるまで攪拌し、薄黄色の非常に粘稠な塩基性組成物216.4gを得た。その25gを計り取り、クエン酸0.24gを加えて完全に溶けるまで混合攪拌し、多量の気泡を含んだ薄クリーム色の二酸化炭素経皮・経粘膜吸収用組成物25.24gを得た。
実施例301
水200mlにヒドロキシプロピルメチルセルロース4g、CMC−Na6g、炭酸水素ナトリウム2.4g、カルボキシメチルスターチナトリウム5g、メチルパラベン0.2g、酢酸トコフェロール0.5g、ゼラニウム抽出液0.1g、ローズウッド抽出液0.1g、グレープフルーツ抽出液0.1gを加え、ハンドミキサーで固形分が完全に分散、もしくは溶けるまで攪拌し、薄茶色の非常に粘稠な塩基性組成物218.4gを得た。その25gを計り取り、クエン酸0.24gを加えて完全に溶けるまで混合攪拌し、多量の気泡を含んだ薄クリーム色の二酸化炭素経皮・経粘膜吸収用組成物25.24gを得た。
実施例302
水200mlにヒドロキシプロピルメチルセルロース4g、CMC−Na8g、炭酸水素ナトリウム2.4g、メチルパラベン0.2g、酢酸トコフェロール1g、ゼラニウム抽出液0.1g、ローズウッド抽出液0.1g、グレープフルーツ抽出液0.1g、銅クロロフィリンナトリウム微量を加え、ハンドミキサーで固形分が完全に分散、もしくは溶けるまで攪拌し、緑色の非常に粘稠な塩基性組成物215.9gを得た。その25gを計り取り、クエン酸コート白糖顆粒1.2gを加えて顆粒が完全に溶けるまで混合攪拌し、多量の気泡を含んだ薄緑色の二酸化炭素経皮・経粘膜吸収用組成物26.2gを得た。
実施例303
水200mlにカルボキシビニルポリマー4g、CMC−Na10g、炭酸水素ナトリウム2.4g、メチルパラベン0.2g、酢酸トコフェロール0.5g、ゼラニウム抽出液0.1g、ローズウッド抽出液0.1g、グレープフルーツ抽出液0.1g、銅クロロフィリンナトリウム微量を加え、ハンドミキサーで固形分が完全に分散、もしくは溶けるまで攪拌し、緑色の非常に粘稠な塩基性組成物217.4gを得た。その25gを計り取り、乳酸0.2gを加えて結晶が完全に溶けるまで混合攪拌し、多量の気泡を含んだ薄緑色の二酸化炭素経皮・経粘膜吸収用組成物25.2gを得た。
実施例304
水200mlにカルボキシビニルポリマー4g、CMC−Na8g、炭酸水素ナトリウム2.4g、メチルパラベン0.2g、酢酸トコフェロール1g、シコン抽出液0.5g、ローズマリー抽出液0.1g、シソ抽出液0.1g、ソウハクヒ抽出液0.1g、ニンジン抽出液0.1gを加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、紫色の非常に粘稠な塩基性組成物216.5gを得た。その25gを計り取り、乳酸0.2gを加えて結晶が完全に溶けるまで混合攪拌し、多量の気泡を含んだ薄ピンク色の二酸化炭素経皮・経粘膜吸収用組成物25.2gを得た。
実施例305
水200mlにカルボキシビニルポリマー4g、CMC−Na8g、炭酸水素ナトリウム2.4g、メチルパラベン0.2g、酢酸トコフェロール1g、シコン抽出液0.1g、ウコン抽出液0.1g、ローズマリー抽出液0.1g、シソ抽出液0.1g、ソウハクヒ抽出液0.1g、ニンジン抽出液0.1gを加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、オレンジ色の非常に粘稠な塩基性組成物216.5gを得た。その25gを計り取り、乳酸0.2gを加えて結晶が完全に溶けるまで混合攪拌し、多量の気泡を含んだ薄オレンジ色の二酸化炭素経皮・経粘膜吸収用組成物25.2gを得た。
実施例306
水200mlにカルボキシビニルポリマー6g炭酸水素ナトリウム2.4g、メチルパラベン0.2g、月見草油0.1g、シコン抽出液0.1g、ローズマリー抽出液0.1g、シソ抽出液0.1g、ソウハクヒ抽出液0.1g、ニンジン抽出液0.1g、銅クロロフィリンナトリウム微量を加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、ペールグリーンの非常に粘稠な塩基性組成物209.2gを得た。その25gを計り取り、乳酸0.2gを加えて結晶が完全に溶けるまで混合攪拌し、多量の気泡を含んだ金属光沢のあるペールグリーンの二酸化炭素経皮・経粘膜吸収用組成物26.2gを得た。
実施例307
水10kgにヒドロキシプロピルメチルセルロース300g、CMC−Na500g、炭酸水素ナトリウム120g、月見草油5g、シソ抽出液5g、シコン抽出液5g、ニンジン抽出液5g、ローズマリー抽出液5g、ソウハクヒ抽出液5g、0.5%銅クロロフィリンナトリウム水溶液8g、天然ビタミンE油10g、フェノキシエタノール100gを加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、ダークグリーンの非常に粘稠な塩基性組成物11.063kgを得た。その25gを計り取り、クエン酸コート白糖顆粒1.2gを加えて顆粒が完全に溶けるまで混合攪拌し、多量の気泡を含んだライトグリーンの二酸化炭素経皮・経粘膜吸収用組成物26.2gを得た。
実施例308
水10.5kgにヒドロキシプロピルセルロース300g、CMC−Na500g、炭酸水素ナトリウム120g、月見草油5g、シソ抽出液5g、シコン抽出液5g、ニンジン抽出液5g、ローズマリー抽出液5g、ソウハクヒ抽出液5g、0.5%銅クロロフィリンナトリウム水溶液8g、天然ビタミンE油10g、フェノキシエタノール100gを加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、ダークグリーンの非常に粘稠な塩基性組成物11.563kgを得た。その25gを計り取り、クエン酸コート白糖顆粒1.2gを加えて顆粒が完全に溶けるまで混合攪拌し、多量の気泡を含んだライトグリーンの二酸化炭素経皮・経粘膜吸収用組成物26.2gを得た。
実施例309
水200mlに炭酸水素ナトリウム2g、アルギン酸Na6g、CMC−Na8g、1,3−ブチレングリコール2g、銅クロロフィリンナトリウム微量を加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、暗緑色の非常に粘稠な塩基性組成物218gを得た。その25gを計り取り、クエン酸コート白糖顆粒1.2gを加えて顆粒が完全に溶けるまで混合攪拌し、多量の気泡を含んだペールグリーンの二酸化炭素経皮・経粘膜吸収用組成物26.2gを得た。
実施例310
水200mlに炭酸水素ナトリウム2g、カルメロースナトリウム6g、CMC−Na8g、プロピレングリコール2g、dl−α−トコフェロール1g、銅クロロフィリンナトリウム微量を加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、暗緑色の非常に粘稠な塩基性組成物219gを得た。その25gを計り取り、クエン酸コート白糖顆粒1.2gを加えて顆粒が完全に溶けるまで混合攪拌し、多量の気泡を含んだペールグリーンの二酸化炭素経皮・経粘膜吸収用組成物26.2gを得た。
実施例311
水200mlに炭酸水素ナトリウム2g、カルボキシメチルスターチナトリウム8g、CMC−Na8g、1,3−ブチレングリコール2g、フェノキシエタノール2g、ポリオキシエチレンアルキルエーテル硫酸ナトリウム1g、dl−α−トコフェロール1g、銅クロロフィリンナトリウム微量を加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、緑色の非常に粘稠な塩基性組成物224gを得た。その25gを計り取り、乳酸0.2gを加えて結晶が完全に溶けるまで混合攪拌し、多量の気泡を含んだペールグリーンの二酸化炭素経皮・経粘膜吸収用組成物20.2gを得た。
実施例312
水200mlに炭酸水素ナトリウム2g、ポリビニルピロリドン6g、CMC−Na8g、フェノキシエタノール2g、オレイン酸オクチルドデシル4gを加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、クリーム色の非常に粘稠な塩基性組成物222gを得た。その25gを計り取り、クエン酸コート白糖顆粒1.2gを加えて顆粒が完全に溶けるまで混合攪拌し、多量の気泡を含んだホワイトクリーム色の二酸化炭素経皮・経粘膜吸収用組成物26.2gを得た。
実施例313
水200mlに炭酸水素ナトリウム2g、ヒドロキシプロピルメチルセルロース6g、CMC−Na8g、グリセリン3g、フェノキシエタノール2g、月見草油0.1g、シソ抽出液0.1g、シコン抽出液0.1g、ニンジン抽出液0.1g、ローズマリー抽出液0.1g、ソウハクヒ抽出液0.1g、天然ビタミンE油0.5g、銅クロロフィリンナトリウム微量を加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、緑色の非常に粘稠な塩基性組成物222.1gを得た。その25gを計り取り、乳酸0.2gを加えて結晶が完全に溶けるまで混合攪拌し、多量の気泡を含んだペールグリーンの二酸化炭素経皮・経粘膜吸収用組成物25.2gを得た。
実施例314
水399.75gに炭酸水素ナトリウム10gを加えて溶かし、別に40℃で熱溶融しておいたポリオキシエチレンノニルフェニルエーテル2.5gと天然ビタミンE油1.25g、フェノキシエタノール5g、月見草油0.25gの混合物を加え、スターラーで攪拌しながら更にシソ抽出液0.25g、シコン抽出液0.25g、ニンジン抽出液0.25g、ローズマリー抽出液0.25g、ソウハクヒ抽出液0.25gを加えて攪拌した。これにあらかじめ50gの1,3−ブチレングリコールで分散させておいたヒドロキシエチルセルロース15gとCMC−Na15gの混合物を徐々に加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、薄褐色の非常に粘稠な塩基性組成物500gを得た。その25gを計り取り、クエン酸コート白糖顆粒1.2gを加えて顆粒が完全に溶けるまで混合攪拌し、多量の気泡を含んだやや黄色がかった二酸化炭素経皮・経粘膜吸収用組成物26.2gを得た。
実施例315
水78.95gに炭酸水素ナトリウム2gを加えて溶かし、別に40℃で熱溶融しておいたポリオキシエチレンノニルフェニルエーテル0.5gと天然ビタミンE油0.25g、フェノキシエタノール1g、月見草油0.05gの混合物を加え、スターラーで攪拌しながら更にシソ抽出液0.05g、シコン抽出液0.05g、ニンジン抽出液0.05g、ローズマリー抽出液0.05g、ソウハクヒ抽出液0.05gを加えて攪拌した。これにあらかじめ10gの1,3−ブチレングリコールで分散させておいたポリビニルアルコール4gとCMC−Na3gの混合物を徐々に加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、薄褐色の非常に粘稠な塩基性組成物100gを得た。その25gを計り取り、クエン酸コート白糖顆粒1.2gを加えて顆粒が完全に溶けるまで混合攪拌し、多量の気泡を含んだやや黄色がかった二酸化炭素経皮・経粘膜吸収用組成物26.2gを得た。
実施例316
水79.95gに炭酸水素ナトリウム2gを加えて溶かし、別に40℃で熱溶融しておいたポリオキシエチレンノニルフェニルエーテル0.5gと天然ビタミンE油0.25g、フェノキシエタノール1g、月見草油0.05gの混合物を加え、スターラーで攪拌しながら更にシソ抽出液0.05g、シコン抽出液0.05g、ニンジン抽出液0.05g、ローズマリー抽出液0.05g、ソウハクヒ抽出液0.05gを加えて攪拌した。これにあらかじめ10gの1,3−ブチレングリコールで分散させておいたアルギン酸Na4gとCMC−Na2gの混合物を徐々に加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、薄褐色の非常に粘稠な塩基性組成物100gを得た。その25gを計り取り、クエン酸コート白糖顆粒1.2gを加えて顆粒が完全に溶けるまで混合攪拌し、多量の気泡を含んだやや黄色がかった二酸化炭素経皮・経粘膜吸収用組成物26.2gを得た。
実施例317
水79.95gに炭酸水素ナトリウム2gを加えて溶かし、別に40℃で熱溶融しておいたポリオキシエチレンポリオキシプロピレンアルキルエーテル0.5gと天然ビタミンE油0.25g、フェノキシエタノール1g、月見草油0.05gの混合物を加え、スターラーで攪拌しながら更にシソ抽出液0.05g、シコン抽出液0.05g、ニンジン抽出液0.05g、ローズマリー抽出液0.05g、ソウハクヒ抽出液0.05gを加えて攪拌した。これにあらかじめ10gの1,3−ブチレングリコールで分散させておいたアルギン酸Na6gを徐々に加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、薄褐色の非常に粘稠な塩基性組成物100gを得た。その25gを計り取り、乳酸0.2gを加えて結晶が完全に溶けるまで混合攪拌し、多量の気泡を含んだやや黄色がかった二酸化炭素経皮・経粘膜吸収用組成物25.2gを得た。
実施例318
水169.9gに炭酸水素ナトリウム2gを加えて溶かし、別に40℃で熱溶融しておいたポリオキシエチレンポリオキシプロピレンアルキルエーテル2gと天然ビタミンE油0.5g、フェノキシエタノール1g、月見草油0.1gの混合物を加え、スターラーで攪拌しながら更にシソ抽出液0.1g、シコン抽出液0.1g、ニンジン抽出液0.1g、ローズマリー抽出液0.1g、ソウハクヒ抽出液0.1gを加えて攪拌した。これにあらかじめ14gの1,3−ブチレングリコールで分散させておいたヒドロキシプロピルセルロース10gを徐々に加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、薄褐色の非常に粘稠な塩基性組成物200gを得た。その25gを計り取り、乳酸0.2gを加えて結晶が完全に溶けるまで混合攪拌し、多量の気泡を含んだやや黄色がかった二酸化炭素経皮・経粘膜吸収用組成物25.2gを得た。
実施例319
水171.9gに炭酸水素ナトリウム2gを加えて溶かし、これにポリオキシエチレンノニルフェニルエーテル2gと天然ビタミンE油0.5g、フェノキシエタノール1g、月見草油0.1gの混合物を加え、スターラーで攪拌しながら更にシソ抽出液0.1g、シコン抽出液0.1g、ニンジン抽出液0.1g、ローズマリー抽出液0.1g、ソウハクヒ抽出液0.1gを加えて攪拌した。これにあらかじめ14gのプロピレングリコールで分散させておいたヒドロキシエチルセルロース10gを徐々に加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、薄褐色の非常に粘稠な塩基性組成物200gを得た。その25gを計り取り、クエン酸コート白糖顆粒1.2gを加えて顆粒が完全に溶けるまで混合攪拌し、多量の気泡を含んだやや黄色がかった二酸化炭素経皮・経粘膜吸収用組成物26.2gを得た。
実施例320
水167gに炭酸水素ナトリウム4g、1,2−ペンタンジオール6gとフェノキシエタノール1gの混合液7gを加えて溶かした。更にシソ抽出液0.1g、シコン抽出液0.1g、ニンジン抽出液0.1g、ローズマリー抽出液0.1g、ソウハクヒ抽出液0.1gを加えて攪拌した。これにあらかじめ16gのプロピレングリコールで分散させておいたカルボキシビニルポリマー4gとCMC−Na5gの分散液25gを徐々に加え、スターラーで固形分が充分に分散、もしくは溶けるまで攪拌し、オレンジ油0.5gを加えて更に攪拌し、白っぽいオレンジ色の非常に粘稠な塩基性組成物200gを得た。その25gを計り取り、乳酸0.2gを加えて結晶が完全に溶けるまで混合攪拌し、多量の気泡を含んだややオレンジ色がかった二酸化炭素経皮・経粘膜吸収用組成物25.2gを得た。
実施例321
水9165gに炭酸水素ナトリウム200gを溶かし、別に調製しておいた1,2−ペンタンジオール300gとフェノキシエタノール40g、天然ビタミンE油25gの混合液を加え、攪拌混合した。これに別に調製しておいた1,3−ブチレングリコール800gとポリビニルピロリドン200g、CMC−Na250gの分散液を徐々に加え、スターラーで固形分が充分に分散、もしくは溶けるまで攪拌し、シソ抽出液5g、シコン抽出液5g、ソウハクヒ抽出液5g、ローズマリー抽出液5gを加えて更に攪拌混合し、薄茶色の非常に粘稠な塩基性組成物10kgを得た。その25gを計り取り、アスコルビン酸0.2gを加えて結晶が完全に溶けるまで混合攪拌し、多量の気泡を含んだ白っぽい二酸化炭素経皮・経粘膜吸収用組成物25.2gを得た。
実施例322
水163.6gに炭酸水素ナトリウム4gを溶かし、別に調製しておいたポリオキシエチレンラウリルエーテル6gとフェノキシエタノール1gの混合液を加え、攪拌混合した。これにシソ抽出液0.1g、シコン抽出液0.1g、ソウハクヒ抽出液0.1g、ローズマリー抽出液0.1gを加えて更に攪拌混合し、別に調製しておいたグリセリン16gとヒドロキシエチルセルロース4g、CMC−Na5gの分散液を徐々に加え、スターラーで固形分が充分に分散、もしくは溶けるまで攪拌し、オレンジ油0.5gと銅クロロフィリンナトリウム微量を加えて更に攪拌し、ペールグリーンの非常に粘稠な塩基性組成物200gを得た。その25gを計り取り、アスコルビン酸0.2gを加えて顆粒が完全に溶けるまで混合攪拌し、多量の気泡を含んだ白っぽい薄緑色の二酸化炭素経皮・経粘膜吸収用組成物25.2gを得た。
実施例323
500mlのビーカー中で水167.6gを4枚羽式攪拌棒の付いたスターラーで1分間に約120回の早さで回転させながら、別に調製しておいたソルビタンモノステアレート6gとフェノキシエタノール1gの混合液を加え、攪拌混合した。これにシソ抽出液0.1g、シコン抽出液0.1g、ソウハクヒ抽出液0.1g、ローズマリー抽出液0.1gを加えて更に攪拌混合した。スターラーから一旦攪拌棒をはずし、ビーカーに攪拌棒を突き破ってパラフィンフィルムをかぶせてビーカーに密着させ、ビーカーのふたつの端にパラフィンフィルムを突き通して2本のシリコンチューブを挿入し、一方のシリコンチューブに小型二酸化炭素ボンベをつないで二酸化炭素を流した。5分後に、別に調製しておいたプロピレングリコール16gとヒドロキシプロピルセルロース4g、CMC−Na5gの分散液を入れた針のない注射器の先端をビーカーにかぶせたパラフィンフィルムに差し込み、二酸化炭素を流しながら該分散液を徐々に加え、スターラーで固形分が充分に分散、もしくは溶けるまで攪拌し、非常に多くの気泡を含んだ薄黄色の非常に粘稠な二酸化炭素経皮・経粘膜吸収用組成物200gを得た。
実施例324
水171.9gに炭酸水素ナトリウム2gを加えて溶かし、これにアシルグルタメート2gと酢酸dl−α−トコフェロール0.5g、フェノキシエタノール1g、月見草油0.1gの混合物を加え、スターラーで攪拌しながら更にウコン抽出液0.1g、シコン抽出液0.1g、キューカンバ抽出液0.1g、ローズウッド抽出液0.1g、ハマメリス抽出液0.1gを加えて攪拌した。これにあらかじめ14gのプロピレングリコールで分散させておいたヒドロキシプロピルセルロース10gを徐々に加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、薄褐色の非常に粘稠な塩基性組成物200gを得た。その25gを計り取り、クエン酸コート白糖顆粒1.2gを加えて顆粒が完全に溶けるまで混合攪拌し、多量の気泡を含んだやや黄色がかった二酸化炭素経皮・経粘膜吸収用組成物26.2gを得た。
実施例325
水169.9gに乳酸2gを加えて溶かし、別に40℃で熱溶融しておいたポリオキシエチレンポリオキシプロピレンアルキルエーテル2gと天然ビタミンE油0.5g、フェノキシエタノール1g、月見草油0.1gの混合物を加え、スターラーで攪拌しながら更にシソ抽出液0.1g、シコン抽出液0.1g、ニンジン抽出液0.1g、ローズマリー抽出液0.1g、ソウハクヒ抽出液0.1gを加えて攪拌した。これにあらかじめ14gの1,3−ブチレングリコールで分散させておいたヒドロキシプロピルセルロース10gを徐々に加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、薄褐色の非常に粘稠な酸性組成物200gを得た。その25gを計り取り、炭酸水素ナトリウム1gを加えて粉末が完全に溶けるまで混合攪拌し、多量の気泡を含んだやや黄色がかった二酸化炭素経皮・経粘膜吸収用組成物26gを得た。
実施例326
水200mlに炭酸水素ナトリウム2g、アルギン酸Na6g、CMC−Na8gを加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、非常に粘稠な塩基性組成物214gを得た。その25gを計り取り、クエン酸コート白糖顆粒1.2gを加えて顆粒が完全に溶けるまで混合攪拌し、多量の気泡を含んだ黄白色の二酸化炭素経皮・経粘膜吸収用組成物26.2gを得た。
実施例327
水200mlに乳酸2g、アルギン酸Na10gを加え、スターラーで固形分が完全に分散、もしくは溶けるまで攪拌し、非常に粘稠な酸性組成物212gを得た。その25gを計り取り、炭酸水素ナトリウム1gを加えて顆粒が完全に溶けるまで混合攪拌し、多量の気泡を含んだ薄黄色の二酸化炭素経皮・経粘膜吸収用組成物26gを得た。
〈クエン酸コート白糖顆粒の製造〉
常法に従い、クエン酸1.8kgを7%HPC−Lエタノール溶液722gに溶かした溶液をCFグラニュレーターを用いて精製白糖顆粒9kgに吹き付け、乾燥後、クエン酸コート白糖顆粒10.8kgを得た。
試験例34(二酸化炭素経皮・経粘膜吸収用組成物の体積増加率評価試験)
直径5.5cm、高さ7cmの透明カップに塩基性組成物25gとクエン酸コート白糖顆粒1.2g、又は酸性組成物25gと炭酸水素ナトリウム1gを入れて体積Aを測定する。1秒間に1回の早さで60回攪拌し、攪拌終了1時間後の体積Bを測定する。体積Aに対する体積Bの増加率Vを%で表し、以下の基準で組成物の体積増加率を評価する。
V>7 +++
7>V>5 ++
5>V>3 +
3>V 0
結果を以下に示す。
Spread 0.49 g of the composite granule thinly 2 cm inside from the end of the adhesive surface of a 6 cm × 7 cm film dressing material (trade name Tegaderm, manufactured by 3M), and cover with a thin non-woven fabric 5 cm × 6 cm from above, The nonwoven fabric is adhered to the adhesive surface of the film dressing so that the composite granule does not spill. A hydrous viscous composition comprising 0.3 g of sodium alginate, 0.2 g of sodium carboxymethylcellulose, and 9.5 g of purified water produced according to the production method described in <Manufacture of hydrous viscous composition> of Examples 227 to 249 on the nonwoven fabric. The product is applied to the inside of the nonwoven fabric at a uniform thickness 1 cm inside to obtain a carbon dioxide transdermal / transmucosal absorption composition for closure therapy.
Example 297 (carbon dioxide transdermal / mucosal absorption composition comprising a combination of a basic composition and acid-coated granules)
〔Production method〕
The basic composition and the acid-coated granule are mixed and stirred to obtain a carbon dioxide transdermal / mucosal absorption composition. Although these mixing ratios can be set arbitrarily, acid-coated granules equivalent to 1 part by weight of acid are used in the test examples with respect to a basic composition equivalent to 1.2 parts by weight of carbonate.
<Manufacture of basic composition>
2 g of methyl paraben, 24 g of sodium hydrogen carbonate, 40 g of sodium carboxymethyl starch, 40 g of sodium alginate and 40 g of sodium carboxymethyl cellulose are dissolved or dispersed in 2,000 ml of water and sufficiently stirred to obtain a basic composition. If necessary, an appropriate additive or medicinal substance may be added thereto.
<Manufacture of acid-coated granules>
According to a conventional method, a solution obtained by dissolving 1.8 kg of citric acid in 722 g of a 7% HPC-L ethanol solution was sprayed onto 9 kg of purified white sugar granules (trade name Nonparel 103, Freund Sangyo Co., Ltd.) using a CF granulator, and after drying, 10.7 kg of acid-coated granules was obtained.
Example 298 (carbon dioxide transdermal / mucosal absorption composition comprising a combination of a water-containing viscous composition containing carbonate and plant essential oil and an acid granule)
〔Production method〕
1 g of methyl paraben, 12 g of sodium bicarbonate, 25 g of sodium carboxymethyl starch, 20 g of sodium alginate, 25 g of sodium carboxymethyl cellulose, 0.5 ml of grapefruit oil, 0.1 ml of cayupute oil, 0.1 ml of rosewood oil, 0.1 ml of geranium oil, edible green Dissolve or disperse 0.01 g of dye and 1 ml of alpha tocopherol acetate in 1,000 ml of water, and stir well. If necessary, an appropriate additive or medicinal substance may be added thereto. To 25 g of the mixture, 1.2 g of the acid-coated granule of Example 297 is added and stirred to obtain a cream comprising a composition for carbon dioxide transdermal / transmucosal absorption.
Example 299 (carbon dioxide transdermal / mucosal absorption composition comprising a hydrous viscous composition and carbon dioxide)
〔Production method〕
12 g of sodium hydrogen carbonate, 20 g of sodium carboxymethyl starch, and 20 g of sodium alginate are dissolved in 1,000 ml of water to obtain a hydrous viscous composition. Insert the tip of a vinyl tube with an outer diameter of 6.0 mm, an inner diameter of 3.5 mm, and a length of 60 cm connected to a small carbon dioxide cylinder (trade name: Tetra CO2 cylinder, manufactured by Warner Lambert), and carboxy while blowing in carbon dioxide. By adding 20 g of methylcellulose sodium and dissolving it with stirring, a carbon dioxide transdermal / mucosal absorption composition is obtained.
Test Example 1 (Treatment test for itching associated with tinea pedis)
A 41-year-old man. For tinea pedis on the right foot with strong itching, the composition of Example 8 was filled with a basin and the foot was soaked for about 20 minutes, and itching was removed by one treatment with this composition.
Test Example 2 (Treatment test for itching associated with tinea pedis)
A 73-year-old woman. For foot tinea of both feet with very strong itching, the basin was filled with 300 g of the composition of Example 18 and the foot was soaked for about 20 minutes. Two years of treatment with a topical antifungal agent had no effect at all, but a single treatment with the composition gave itching.
Test Example 3 (Stomatitis Treatment Test)
A 41-year-old man. When 1 g of the composition of Example 8 was applied to keratitis for 10 minutes, the pain disappeared and the wound was closed and healed.
Test Example 4 (Wound wound treatment test)
78 years old male. Due to the progress of lung cancer, he became bedridden, and a wound was generated from the lower back to the buttocks. The depth of the wound was about 4 cm and reached the fascia. A pocket of wound wound was filled with 100 g of the composition of Example 1, and covered with a 20 cm × 30 cm film dressing (trade name: Tegaderm, 3M) for 20 minutes. The composition and film dressing were changed daily. On the 11th day from the start of treatment, the depth of the wound was improved to 1 cm. One month after the start of treatment, the granulation rose to almost the same height as the surrounding normal skin.
Test Example 5 (Duck Shoe Dermatitis Treatment Test)
8-year-old man. Both foot soles bleed due to Zuku shoe dermatitis, and a topical steroid preparation (trade name Linderon V ointment, manufactured by Shionogi & Co., Ltd.) was applied for 2 months, but there was no effect. When 30 g of the composition of Example 20 was applied to the sole of the foot once a day for 10 minutes every day, the wound was closed on the fourth day and was completely cured in one month.
Test Example 6 (Test for hair gloss)
A 41-year-old man. I was worried that the gloss of the hair disappeared and looked old, so 20g of the composition of Example 18 was applied to the hair once a day for about 15 minutes, and the gloss of the hair was good from the third day. became.
Test Example 7 (Atopic dermatitis treatment test)
4-year-old woman. When 5 g of the composition of Example 20 was applied once daily for 5 minutes against atopic dermatitis on the backs of both knees, darkening of the skin disappeared in 2 weeks and dryness of the skin was healed in 4 weeks.
Test example 8 (partial thinning test of face and abdomen)
A 41-year-old man. Hoping to make the fluffy cheek and thick waist thin, the composition of Example 8 was applied once a day for 15 minutes, 30 g on the right cheek and 100 g on the abdomen. Two months later, the right cheek was judged to be clearly smaller by all five evaluators. The waist of the abdomen was reduced by 6 cm.
Test example 9 (skin quality improvement and facial thinning test)
37-year-old woman. I suffered from plump cheeks, rough skin, and dull skin, and tried various cosmetics, but no effect was obtained. When 50 g of the composition of Example 20 was applied to the entire face once a day for 10 minutes every day, the dullness of the skin disappeared and whitened with the first application, resulting in fine skin. Two weeks later, all three evaluators judged that the face had become smaller.
Test example 10 (cervical shoulder arm syndrome treatment test)
42 years old male. An external anti-inflammatory agent (trade name Tiger Balm, manufactured by Ryukakusan Co., Ltd.) was applied to the neck-shoulder arm syndrome (stiff shoulder) caused by computer operation fatigue, but no effect was obtained. When 40 g of the composition of Example 20 was applied to the shoulder for 20 minutes, the neck-arm syndrome was cured.
Test Example 11 (Treatment for psoriasis vulgaris)
37-year-old woman. For psoriasis vulgaris with very strong itching, 3 g of the composition of Example 20 was applied daily for 10 minutes once a day. Itching disappeared after one application. After 2 weeks, darkening of the affected area improved.
Test Example 12 (chicken eye treatment test)
37-year-old woman. When 2 g of the composition of Example 20 was applied to the chicken eye formed on the right side of the painful left toe for 10 minutes once a day for 5 days, normal skin around the chicken eye was damaged like a salicylic acid preparation. Healed without any problems.
Test example 13 (partial arm thinning test)
A 36-year-old woman. Since I was worried about the thickness of the second arm, 30 g of the composition of Example 18 was applied to the left second arm, and a film for food packaging (trade name Saran Wrap, manufactured by Asahi Kasei Co., Ltd.) was spread over it and left for 6 hours. The perimeter of the upper arm was reduced by 2 cm.
Test Example 14 (Purulative eczema treatment test on the buttocks)
29 year old male. When purulent eczema formed on the entire buttock was applied 40 g of the composition of Example 18 once a day for 20 minutes for 7 days, the purulent eczema was cured.
Test Example 15 (Insect bites treatment test)
A 51 year old woman. The bees were stabbed in the arms and fingers, and local swelling and redness disappeared by taking an antihistamine (trade name Celestamine Tablets, manufactured by Schering-Plough) and applying a topical steroid (trade name: Terracortyl ointment, manufactured by Pfizer Pharmaceutical). However, itching gradually appeared, and after 2 weeks it became insomnia due to itching. When 5 g of the composition of Example 18 was applied for 15 minutes, itching disappeared and a good night's sleep was obtained.
Test Example 16 (Treatment test for itching associated with tinea pedis)
32-year-old woman. An antifungal agent (trade name Mentax Cream, manufactured by Kaken Pharmaceutical Co., Ltd.) was applied to tinea pedis on both legs with very strong itching for 2 months, but itching did not subside at all. When the basin was filled with 100 g of the composition of Example 8 and the foot was soaked for about 20 minutes, itching was removed with one treatment. Four days later, 100 ml of the composition of Example 8 was again filled in the basin and the foot was immersed for about 20 minutes. The gross findings of the lesions were also significantly improved.
Test Example 17 (palmulosa pustulosis treatment test)
A 22-year-old woman. With respect to palmoplantar pustulosis with strong itching, when 100 g of the composition of Example 18 was filled in the basin and the hands were immersed for about 15 minutes, itching immediately disappeared.
Test Example 18 (Atopic dermatitis treatment test)
8-year-old man. For atopic dermatitis of a finger with partial keratinization and cracking and very strong pain and itching, when 50 g of the composition of Example 8 was filled in a cup and the fingertip was immersed for 20 minutes, itching immediately disappeared. . On the next day, epithelial formation was observed in the cracked part, and pain was reduced.
Test Example 19 (Treatment for psoriasis vulgaris)
37-year-old woman. 10.49 g of the composition of Example 296 was applied for 30 minutes to psoriasis vulgaris with very strong itching. Itching disappeared immediately, and the keratinization and dryness of the affected epithelium were markedly improved.
Test Example 20 (Facial Scratch Treatment Test)
10 year old male. 10.49 g of the composition of Example 296 was applied to the 3 cm × 4 cm scratch on the right face. The composition was applied daily and changed once a day. On the second day, epithelialization was observed without scab formation, and on the fifth day it healed without scarring.
Test Example 21 (Drying pruritus)
69 years old male. When 50 g of the composition of Example 20 was applied to dry skin pruritus of both lower legs and covered with a film for food packaging (trade name Saran Wrap, manufactured by Asahi Kasei Co., Ltd.) for 20 minutes, itching disappeared.
Test Example 22 (Wound wound treatment test)
65 years old male. After surgery to remove the hematoma due to intracerebral hemorrhage, the plant became planted, and an IV degree wound that reached the periosteum 15 cm × 15 cm in size occurred in the sacrum. Necrotic tissue adhered to the wound surface, deep pockets were formed, and exudate was also observed. The wound surface was washed with physiological saline and treated with povidone iodine sugar, but almost no effect was obtained. 30 g of the composition of Example 297 was filled in a pocket once a day, and applied so as to be raised on the wound surface, and a 20 cm × 30 cm film dressing material (trade name Tegaderm, manufactured by 3M Company) was affixed thereon. . The composition and film dressing were changed daily. On day 5 after administration of the composition, necrotic tissue and exudate disappeared from the wound surface and showed a rapid healing tendency. At the same time, an increase in benign granulation was observed. In the second month, the size and depth of the wound were significantly reduced, the epithelium was formed on the wound surface, and the pockets also disappeared.
Test Example 23 (Alveolar pyorrhea treatment test)
A 28-year-old woman. The swelling and redness of the gingiva was remarkable, and the gingiva had reached the top of the tooth. Periodontal pockets were scaled, and 30 g of the composition of Example 297 was injected into the periodontal pocket once every two days and further applied for 20 minutes so as to cover the entire gingiva. After one month, gingival swelling and redness almost disappeared.
Test example 24 (labial laceration treatment test)
7 years old woman. The lower lip was bitten by the maxillary anterior teeth and a traumatic laceration was left, leaving a mark on the teeth. When 5 g of the composition of Example 297 was applied for 20 minutes, it was recovered to the extent that almost no scars remained.
Test Example 25 (Denture ulcer treatment test)
A 67-year-old woman. After wearing the denture, an ulcer with pain due to denture incompatibility occurred in the submucosa of the denture base. The denture was removed and the marginal portion was shaved to match the denture, and 5 g of the composition of Example 297 was applied to the ulcer and the denture was remounted. On examination after 5 days, the ulcer had disappeared.
Test Example 26 (Test on freckle)
A 38-year-old woman. After suffering from freckles for many years and using various cosmetics, there was no effect, so 26.2 g of the composition of Example 298 was applied to the entire face once a day for 20 minutes, and the mole was better on the third day. The freckles became thinner to stand out.
Test Example 27 (Stomatitis treatment test)
43 years old male. When 3 g of the composition of Example 170 was applied for 20 minutes against painful stomatitis formed in the right palate, the pain disappeared immediately.
Test Example 28 (treatment for impetigo)
4-year-old woman. For the impetigo of the upper right arm, 10 g of the composition of Example 297 was applied once a day for 20 minutes, and then a daily treatment for applying an appropriate amount of sodium fusidate ointment (trade name Fusidin Leo Ointment, Sankyo Co., Ltd.) was performed. As a result, healed without scarring on the 5th day.
Test Example 29 (Acne vulgaris treatment test)
A 28-year-old woman. Attempts to use various non-steroidal anti-inflammatory drugs and oral antibiotics for acne vulgaris on the entire face were completely ineffective. When 30 g of the composition of Example 297 was applied once a day for 30 minutes every day, the papules became flat in 2 months, leaving only a slight redness.
Test Example 30 (Lower limb skin ulcer treatment test)
A 63-year-old woman. When 15 g of the composition of Example 297 was applied to a skin ulcer and punctate erosion with a diameter of 1 cm due to varicose veins every day for 20 minutes once a day, the erosion disappeared and healed by the first application. On day 10, since the skin ulcer also remarkably reduced, administration of the composition was discontinued, but the next day healed by forming a scab.
Test Example 31 (Lower limb cold feeling, pruritus, numbness treatment test)
71 years old male. When 30 g of the composition of Example 31 was applied to the lower limb once a week for 20 minutes against cold sensation, pruritus and numbness in both lower limbs due to peripheral circulatory disturbance, these symptoms disappeared after 7 applications.
Test Example 32 (Gingivitis treatment test)
42 years old male. For gingivitis with severe toothache and marked swelling and redness, 10 g of the composition of Example 297 was applied once for 10 minutes, 3 times on the first day, and twice on the second day. Toothache disappeared with the first application, and swelling and redness of the gingiva improved markedly.
Test Example 33 (Recurrent hair suppression test after hair removal)
A 38-year-old woman. I was shaving my vagina twice a week with a razor, but I was worried about how many times I could shave with a razor. 30 g of the composition of Example 135 was applied to both under the eyelids, 15 g once a day for 15 minutes every day, and after 1 month, the unwanted hair of the eyelids was shaved once, and the subsequent recurrent hair was delayed. I only got to shave once with a razor.
Example 300
To 200 ml of water, add 4 g of hydroxypropyl cellulose, 10 g of CMC-Na and 2.4 g of sodium hydrogen carbonate, and stir with a hand mixer until the solid content is completely dispersed or dissolved, and light yellow very viscous basic composition 216 .4 g was obtained. 25 g of the solution was weighed, 0.24 g of citric acid was added and mixed and stirred until completely dissolved, and 25.24 g of a light cream carbon dioxide transdermal / transmucosal absorption composition containing a large amount of bubbles was obtained.
Example 301
200 g water, 4 g hydroxypropylmethylcellulose, 6 g CMC-Na, 2.4 g sodium bicarbonate, 5 g sodium carboxymethyl starch, 0.2 g methylparaben, 0.5 g tocopherol acetate, 0.1 g geranium extract, 0.1 g rosewood extract Then, 0.1 g of grapefruit extract was added and stirred with a hand mixer until the solid content was completely dispersed or dissolved to obtain 218.4 g of a light brown very viscous basic composition. 25 g of the solution was weighed, 0.24 g of citric acid was added and mixed and stirred until completely dissolved, and 25.24 g of a light cream carbon dioxide transdermal / transmucosal absorption composition containing a large amount of bubbles was obtained.
Example 302
200 ml of water, 4 g of hydroxypropylmethylcellulose, 8 g of CMC-Na, 2.4 g of sodium bicarbonate, 0.2 g of methylparaben, 1 g of tocopherol acetate, 0.1 g of geranium extract, 0.1 g of rosewood extract, 0.1 g of grapefruit extract, A small amount of copper chlorophyllin sodium was added and stirred with a hand mixer until the solid content was completely dispersed or dissolved to obtain 215.9 g of a green very viscous basic composition. Weigh 25 g of the mixture, add 1.2 g of citric acid-coated sucrose granules, and mix and stir until the granules are completely dissolved. 26.2 g of light green carbon dioxide transdermal / transmucosal absorption composition containing a large amount of bubbles. Got.
Example 303
200 ml of water, 4 g of carboxyvinyl polymer, 10 g of CMC-Na, 2.4 g of sodium bicarbonate, 0.2 g of methylparaben, 0.5 g of tocopherol acetate, 0.1 g of geranium extract, 0.1 g of rosewood extract, 0.1 g of grapefruit extract. 1 g and a trace amount of copper chlorophyllin sodium were added and stirred with a hand mixer until the solid content was completely dispersed or dissolved to obtain 217.4 g of a green very viscous basic composition. 25 g of the solution was weighed, and 0.2 g of lactic acid was added and mixed and stirred until the crystals were completely dissolved. Thus, 25.2 g of a light green carbon dioxide transdermal / transmucosal absorption composition containing a large amount of bubbles was obtained.
Example 304
200 ml of water, 4 g of carboxyvinyl polymer, 8 g of CMC-Na, 2.4 g of sodium hydrogen carbonate, 0.2 g of methylparaben, 1 g of tocopherol acetate, 0.5 g of sycon extract, 0.1 g of rosemary extract, 0.1 g of perilla extract, 0.1 g of Sakuhakuhi extract and 0.1 g of carrot extract were added and stirred with a stirrer until the solid content was completely dispersed or dissolved to obtain 216.5 g of a purple very viscous basic composition. 25 g of the solution was weighed, and 0.2 g of lactic acid was added and mixed and stirred until the crystals were completely dissolved. Thus, 25.2 g of a light pink carbon dioxide transdermal / mucosal absorption composition containing a large amount of bubbles was obtained. .
Example 305
200 ml of water, 4 g of carboxyvinyl polymer, 8 g of CMC-Na, 2.4 g of sodium hydrogen carbonate, 0.2 g of methylparaben, 1 g of tocopherol acetate, 0.1 g of sykon extract, 0.1 g of turmeric extract, 0.1 g of rosemary extract, Add 0.1 g perilla extract, 0.1 g perilla extract, 0.1 g carrot extract, stir with a stirrer until the solids are completely dispersed or dissolved, and an orange very viscous basic composition 216.5 g was obtained. 25 g of the solution was weighed, 0.2 g of lactic acid was added and mixed and stirred until the crystals were completely dissolved, and 25.2 g of a light orange carbon dioxide transdermal / transmucosal absorption composition containing a large amount of bubbles was obtained. .
Example 306
200 ml of water, 6 g of carboxyvinyl polymer, 2.4 g of sodium hydrogen carbonate, 0.2 g of methyl paraben, 0.1 g of evening primrose oil, 0.1 g of citrus extract, 0.1 g of rosemary extract, 0.1 g of perilla extract, 0.1% of Sakuhaku extract Add 0.1 g, carrot extract 0.1 g, copper chlorophyllin sodium trace amount, and stir until the solid content is completely dispersed or dissolved with a stirrer to obtain 209.2 g of pale green very viscous basic composition It was. 25 g of this was weighed, 0.2 g of lactic acid was added and mixed and stirred until the crystals were completely dissolved, and a metallic luster pale green carbon dioxide transdermal / transmucosal absorption composition 26.2 g containing a large amount of bubbles. Got.
Example 307
10 kg of water, 300 g of hydroxypropyl methylcellulose, 500 g of CMC-Na, 120 g of sodium bicarbonate, 5 g of evening primrose oil, 5 g of perilla extract, 5 g of extract of carrot, 5 g of carrot extract, 5 g of rosemary extract, 5 g of Sakuhaku extract Add 8 g of 10% aqueous copper chlorophyllin solution, 10 g of natural vitamin E oil, and 100 g of phenoxyethanol, and stir until the solid content is completely dispersed or dissolved with a stirrer to obtain 11.063 kg of dark green very viscous basic composition It was. Weigh 25 g, add 1.2 g of citric acid-coated sucrose granules, mix and stir until the granules are completely dissolved, and light green carbon dioxide transdermal / mucosal absorption composition 26.2 g containing a large amount of air bubbles. Got.
Example 308
10.5 kg of water, 300 g of hydroxypropylcellulose, 500 g of CMC-Na, 120 g of sodium hydrogen carbonate, 5 g of evening primrose oil, 5 g of perilla extract, 5 g of extract of carrot, 5 g of carrot extract, 5 g of rosemary extract, 5 g of Sakuhaku extract Add 8 g of 5% aqueous solution of copper chlorophyllin, 10 g of natural vitamin E oil, and 100 g of phenoxyethanol, and stir with a stirrer until the solid content is completely dispersed or dissolved. Dark green very viscous basic composition 11.563 kg Got. Weigh 25 g, add 1.2 g of citric acid-coated sucrose granules, mix and stir until the granules are completely dissolved, and light green carbon dioxide transdermal / mucosal absorption composition 26.2 g containing a large amount of air bubbles. Got.
Example 309
Add 2 g of sodium bicarbonate, 6 g of sodium alginate, 8 g of CMC-Na, 2 g of 1,3-butylene glycol, and a trace amount of sodium copper chlorophyllin to 200 ml of water, and stir until the solid content is completely dispersed or dissolved. 218 g of a viscous basic composition was obtained. Weigh 25 g, add 1.2 g of citric acid-coated sucrose granules, mix and stir until the granules are completely dissolved, 26.2 g of pale green carbon dioxide transdermal / transmucosal absorption composition containing a large amount of air bubbles. Got.
Example 310
To 200 ml of water, add 2 g of sodium bicarbonate, 6 g of carmellose sodium, 8 g of CMC-Na, 2 g of propylene glycol, 1 g of dl-α-tocopherol, and a trace amount of copper chlorophyllin sodium, and stir until the solid content is completely dispersed or dissolved. 219 g of a dark green very viscous basic composition was obtained. Weigh 25 g, add 1.2 g of citric acid-coated sucrose granules, mix and stir until the granules are completely dissolved, 26.2 g of pale green carbon dioxide transdermal / transmucosal absorption composition containing a large amount of air bubbles. Got.
Example 311
In 200 ml of water, 2 g of sodium hydrogen carbonate, 8 g of sodium carboxymethyl starch, 8 g of CMC-Na, 2 g of 1,3-butylene glycol, 2 g of phenoxyethanol, 1 g of sodium polyoxyethylene alkyl ether sulfate, 1 g of dl-α-tocopherol, and a trace amount of sodium copper chlorophyllin In addition, the mixture was stirred with a stirrer until the solid content was completely dispersed or dissolved to obtain 224 g of a green very viscous basic composition. 25 g of the solution was weighed, and 0.2 g of lactic acid was added and mixed and stirred until the crystals were completely dissolved to obtain 20.2 g of a pale green carbon dioxide transdermal / transmucosal absorption composition containing a large amount of bubbles.
Example 312
Add 2 g of sodium bicarbonate, 6 g of polyvinylpyrrolidone, 8 g of CMC-Na, 2 g of phenoxyethanol, and 4 g of octyldodecyl oleate to 200 ml of water, and stir until the solid content is completely dispersed or dissolved, and the cream is very viscous 222 g of a basic composition was obtained. 25 g of the mixture was weighed, 1.2 g of citric acid-coated sucrose granules were added, mixed and stirred until the granules were completely dissolved, and a white cream-colored carbon dioxide transdermal / transmucosal absorption composition containing a large amount of air bubbles. 2 g was obtained.
Example 313
200 g of water, 2 g of sodium bicarbonate, 6 g of hydroxypropylmethylcellulose, 8 g of CMC-Na, 3 g of glycerin, 2 g of phenoxyethanol, 0.1 g of evening primrose oil, 0.1 g of perilla extract, 0.1 g of extract of carrot, 0.1 g of carrot extract, Add 0.1 g of rosemary extract, 0.1 g of Sakuhaku extract, 0.5 g of natural vitamin E oil, and a trace amount of copper chlorophyllin sodium and stir with a stirrer until the solid content is completely dispersed or dissolved. 222.1 g of a thick basic composition was obtained. 25 g of the solution was weighed, 0.2 g of lactic acid was added, and the mixture was stirred until the crystals were completely dissolved, to obtain 25.2 g of a pale green carbon dioxide transdermal / transmucosal absorption composition containing a large amount of bubbles.
Example 314
2.5 g of polyoxyethylene nonylphenyl ether and 1.25 g of natural vitamin E oil, 1.25 g of phenoxyethanol, and 0.25 g of evening primrose oil dissolved in 399.75 g of water by adding 10 g of sodium bicarbonate Then, while stirring with a stirrer, 0.25 g perilla extract, 0.25 g perilla extract, 0.25 g carrot extract, 0.25 g rosemary extract, and 0.25 g perilla extract were added and stirred. did. To this, gradually add a mixture of 15 g of hydroxyethyl cellulose and 15 g of CMC-Na previously dispersed with 50 g of 1,3-butylene glycol, and stir with a stirrer until the solid content is completely dispersed or dissolved. 500 g of a viscous basic composition was obtained. 25 g of the mixture was weighed, 1.2 g of citric acid-coated sucrose granules were added, mixed and stirred until the granules were completely dissolved, and a slightly yellowish carbon dioxide transdermal / transmucosal absorption composition containing a large amount of air bubbles. 2 g was obtained.
Example 315
0.5 g of polyoxyethylene nonylphenyl ether and 0.25 g of natural vitamin E oil, 0.25 g of natural vitamin E oil, 0.05 g of evening primrose oil, dissolved by adding 2 g of sodium hydrogen carbonate to 78.95 g of water In addition, with stirring with a stirrer, 0.05 g of perilla extract, 0.05 g of shikon extract, 0.05 g of carrot extract, 0.05 g of rosemary extract, 0.05 g of Sakuhakuhi extract were added and stirred. did. To this, gradually add a mixture of 4 g of polyvinyl alcohol and 3 g of CMC-Na previously dispersed with 10 g of 1,3-butylene glycol, and stir until the solid content is completely dispersed or dissolved with a stirrer. 100 g of a viscous basic composition was obtained. 25 g of the mixture was weighed, 1.2 g of citric acid-coated sucrose granules were added, mixed and stirred until the granules were completely dissolved, and a slightly yellowish carbon dioxide transdermal / transmucosal absorption composition containing a large amount of air bubbles. 2 g was obtained.
Example 316
2 g of sodium bicarbonate was dissolved in 79.95 g of water, 0.5 g of polyoxyethylene nonylphenyl ether and 0.25 g of natural vitamin E oil, 1 g of phenoxyethanol, 0.05 g of evening primrose oil that had been melted separately at 40 ° C. In addition, with stirring with a stirrer, 0.05 g of perilla extract, 0.05 g of shikon extract, 0.05 g of carrot extract, 0.05 g of rosemary extract, 0.05 g of Sakuhakuhi extract were added and stirred. did. To this, gradually add a mixture of 4 g of alginate Na and 2 g of CMC-Na previously dispersed with 10 g of 1,3-butylene glycol, and stir with a stirrer until the solid content is completely dispersed or dissolved. 100 g of a viscous basic composition was obtained. 25 g of the mixture was weighed, 1.2 g of citric acid-coated sucrose granules were added, mixed and stirred until the granules were completely dissolved, and a slightly yellowish carbon dioxide transdermal / transmucosal absorption composition containing a large amount of air bubbles. 2 g was obtained.
Example 317
2 g of sodium bicarbonate was dissolved in 79.95 g of water, 0.5 g of polyoxyethylene polyoxypropylene alkyl ether and 0.25 g of natural vitamin E oil, 0.25 g of phenoxyethanol, evening primrose oil 0 Add 0.05 g of the mixture and add 0.05 g of perilla extract, 0.05 g of shikon extract, 0.05 g of carrot extract, 0.05 g of rosemary extract, and 0.05 g of Sakuhakuhi extract while stirring with a stirrer. And stirred. To this was gradually added 6 g of Na alginate dispersed in advance with 10 g of 1,3-butylene glycol, and the mixture was stirred with a stirrer until the solid content was completely dispersed or dissolved, and a light brown very viscous basic composition 100 g of product was obtained. 25 g of the solution was weighed, 0.2 g of lactic acid was added and mixed and stirred until the crystals were completely dissolved, and 25.2 g of a slightly yellowish carbon dioxide transdermal / transmucosal absorption composition containing a large amount of bubbles was obtained. .
Example 318
29.9 g of sodium bicarbonate was added to 169.9 g of water and dissolved, and 2 g of polyoxyethylene polyoxypropylene alkyl ether and 0.5 g of natural vitamin E that had been melted by heating at 40 ° C., 1 g of phenoxyethanol, and 0.1 g of evening primrose oil Then, while stirring with a stirrer, 0.1 g perilla extract, 0.1 g perilla extract, 0.1 g carrot extract, 0.1 g rosemary extract, and 0.1 g perilla extract were added and stirred. did. Gradually add 10 g of hydroxypropylcellulose previously dispersed with 14 g of 1,3-butylene glycol and stir with a stirrer until the solid content is completely dispersed or dissolved, and a light brown very viscous base 200 g of a composition was obtained. 25 g of the solution was weighed, 0.2 g of lactic acid was added and mixed and stirred until the crystals were completely dissolved, and 25.2 g of a slightly yellowish carbon dioxide transdermal / transmucosal absorption composition containing a large amount of bubbles was obtained. .
Example 319
Add 2 g of sodium bicarbonate to 171.9 g of water and dissolve it. Add a mixture of 2 g of polyoxyethylene nonylphenyl ether, 0.5 g of natural vitamin E oil, 1 g of phenoxyethanol, and 0.1 g of evening primrose oil and stir with a stirrer. Further, 0.1 g perilla extract, 0.1 g perilla extract, 0.1 g carrot extract, 0.1 g rosemary extract and 0.1 g perilla extract were added and stirred. To this, 10 g of hydroxyethyl cellulose previously dispersed with 14 g of propylene glycol was gradually added, and stirred with a stirrer until the solid content was completely dispersed or dissolved, and 200 g of a light brown very viscous basic composition was added. Obtained. 25 g of the mixture was weighed, 1.2 g of citric acid-coated sucrose granules were added, mixed and stirred until the granules were completely dissolved, and a slightly yellowish carbon dioxide transdermal / transmucosal absorption composition containing a large amount of air bubbles. 2 g was obtained.
Example 320
To 167 g of water, 4 g of sodium hydrogen carbonate, 6 g of 1,2-pentanediol 6 g and 1 g of phenoxyethanol 1 g were added and dissolved. Further, 0.1 g perilla extract, 0.1 g perilla extract, 0.1 g carrot extract, 0.1 g rosemary extract and 0.1 g perilla extract were added and stirred. To this, gradually add 4 g of carboxyvinyl polymer previously dispersed with 16 g of propylene glycol and 25 g of CMC-Na 5 g dispersion, and stir with a stirrer until the solid content is sufficiently dispersed or dissolved. And stirred further to obtain 200 g of a whitish orange very viscous basic composition. 25 g of the solution was weighed, 0.2 g of lactic acid was added, and the mixture was stirred until the crystals were completely dissolved, so that 25.2 g of a slightly orange-colored carbon dioxide transdermal / transmucosal absorption composition containing a large amount of air bubbles was obtained. It was.
Example 321
200 g of sodium bicarbonate was dissolved in 9165 g of water, and a mixed solution of 300 g of 1,2-pentanediol, 40 g of phenoxyethanol, and 25 g of natural vitamin E oil prepared separately was added and mixed by stirring. Separately, 800 g of 1,3-butylene glycol, 200 g of polyvinyl pyrrolidone, and 250 g of CMC-Na, which were separately prepared, were gradually added and stirred with a stirrer until the solid content was sufficiently dispersed or dissolved. Then, 5 g of Sikon extract, 5 g of Sakuhaku extract, and 5 g of rosemary extract were added and further stirred and mixed to obtain 10 kg of a light brown very viscous basic composition. 25 g of the solution was weighed, 0.2 g of ascorbic acid was added and mixed and stirred until the crystals were completely dissolved, to obtain 25.2 g of a whitish carbon dioxide transdermal / transmucosal absorption composition containing a large amount of bubbles.
Example 322
In 163.6 g of water, 4 g of sodium hydrogen carbonate was dissolved, and a separately prepared mixed solution of 6 g of polyoxyethylene lauryl ether and 1 g of phenoxyethanol was added and stirred. To this, 0.1 g perilla extract, 0.1 g perilla extract, 0.1 g perilla extract, 0.1 g rosemary extract and further stirred and mixed, separately prepared 16 g glycerin and 4 g hydroxyethylcellulose Then, gradually add 5 g of CMC-Na dispersion, stir with a stirrer until the solid content is sufficiently dispersed or dissolved, add 0.5 g of orange oil and a trace amount of copper chlorophyllin sodium, and stir further. 200 g of a thick basic composition was obtained. 25 g of the solution was weighed, 0.2 g of ascorbic acid was added and mixed and stirred until the granules were completely dissolved, and 25.2 g of a pale white green carbon dioxide transdermal / transmucosal absorption composition containing a large amount of air bubbles was obtained. It was.
Example 323
While rotating 167.6 g of water in a 500 ml beaker with a stirrer equipped with a four-bladed stir bar at a speed of about 120 times per minute, separately prepared 6 g of sorbitan monostearate and 1 g of phenoxyethanol. The mixture was added and mixed with stirring. To this, 0.1 g perilla extract, 0.1 g perilla extract, 0.1 g perilla extract and 0.1 g rosemary extract were added and further stirred and mixed. Remove the stirrer from the stirrer, break the stirrer into the beaker, cover it with a paraffin film and attach it to the beaker, insert the two silicon tubes through the paraffin film at the two ends of the beaker, and insert one silicon tube A small carbon dioxide cylinder was connected to the flow of carbon dioxide. Five minutes later, the tip of a syringe without a needle containing a dispersion of 16 g of propylene glycol, 4 g of hydroxypropyl cellulose and 5 g of CMC-Na prepared separately was inserted into a paraffin film covered with a beaker, and the carbon dioxide was allowed to flow while flowing carbon dioxide. Gradually add the dispersion, stir with a stirrer until the solid content is sufficiently dispersed or dissolved, and light yellow very viscous carbon dioxide transdermal / mucosal absorption composition 200 g containing very many bubbles Got.
Example 324
Add 2 g of sodium bicarbonate to 171.9 g of water and dissolve it, add a mixture of 2 g of acylglutamate, 0.5 g of dl-α-tocopherol acetate, 1 g of phenoxyethanol, and 0.1 g of evening primrose oil, and further stir with a stirrer. 0.1 g of an extract, 0.1 g of a chicory extract, 0.1 g of a Cucumber extract, 0.1 g of a rosewood extract, and 0.1 g of a Hamelis extract were added and stirred. To this, 10 g of hydroxypropylcellulose previously dispersed with 14 g of propylene glycol was gradually added and stirred with a stirrer until the solid content was completely dispersed or dissolved, and 200 g of a light brown very viscous basic composition Got. 25 g of the mixture was weighed, 1.2 g of citric acid-coated sucrose granules were added, mixed and stirred until the granules were completely dissolved, and a slightly yellowish carbon dioxide transdermal / transmucosal absorption composition containing a large amount of air bubbles. 2 g was obtained.
Example 325
A mixture of 2 g of polyoxyethylene polyoxypropylene alkyl ether, 0.5 g of natural vitamin E oil, 0.5 g of natural vitamin E, 1 g of phenoxyethanol, and 0.1 g of evening primrose oil which was dissolved by adding 2 g of lactic acid to 169.9 g of water. While stirring with a stirrer, 0.1 g perilla extract, 0.1 g perilla extract, 0.1 g carrot extract, 0.1 g rosemary extract, and 0.1 g perilla extract were added and stirred. To this, 10 g of hydroxypropylcellulose previously dispersed with 14 g of 1,3-butylene glycol was gradually added and stirred with a stirrer until the solid content was completely dispersed or dissolved. 200 g of composition was obtained. 25 g of the solution was weighed, 1 g of sodium bicarbonate was added and mixed and stirred until the powder was completely dissolved, and 26 g of a slightly yellowish carbon dioxide transdermal / transmucosal absorption composition containing a large amount of bubbles was obtained.
Example 326
To 200 ml of water, 2 g of sodium hydrogen carbonate, 6 g of sodium alginate, and 8 g of CMC-Na were added and stirred with a stirrer until the solid content was completely dispersed or dissolved to obtain 214 g of a very viscous basic composition. Weigh 25 g, add 1.2 g of citric acid-coated sucrose granules, mix and stir until the granules are completely dissolved, and 26.2 g of yellowish white carbon dioxide transdermal / transmucosal absorption composition containing a large amount of air bubbles. Got.
Example 327
To 200 ml of water, 2 g of lactic acid and 10 g of Na alginate were added and stirred with a stirrer until the solid content was completely dispersed or dissolved to obtain 212 g of a very viscous acidic composition. 25 g of the solution was weighed, 1 g of sodium bicarbonate was added and mixed and stirred until the granules were completely dissolved, and 26 g of a pale yellow carbon dioxide transdermal / transmucosal absorption composition containing a large amount of bubbles was obtained.
<Production of citric acid-coated white sugar granules>
According to a conventional method, a solution obtained by dissolving 1.8 kg of citric acid in 722 g of a 7% HPC-L ethanol solution was sprayed on 9 kg of purified white sugar granules using a CF granulator, and dried to obtain 10.8 kg of citric acid-coated white sugar granules. .
Test Example 34 (Volume increase rate evaluation test of carbon dioxide transdermal / mucosal absorption composition)
In a transparent cup having a diameter of 5.5 cm and a height of 7 cm, 25 g of the basic composition and 1.2 g of citric acid-coated sucrose granules, or 25 g of the acidic composition and 1 g of sodium bicarbonate are measured, and the volume A is measured. Stir 60 times at a rate of once per second, and measure the volume B 1 hour after the end of stirring. The increase rate V of the volume B with respect to the volume A is expressed in%, and the volume increase rate of the composition is evaluated according to the following criteria.
V> 7 +++
7>V> 5 ++
5>V> 3 +
3> V 0
The results are shown below.

組成物 評価
実施例300 +++
実施例301 +++
実施例302 +++
実施例303 +++
実施例304 +++
実施例305 +++
実施例306 +++
実施例307 ++
実施例308 ++
実施例309 +++
実施例310 +++
実施例311 ++
実施例312 +++
実施例313 +++
実施例314 ++
実施例315 ++
実施例316 ++
実施例317 ++
実施例318 ++
実施例319 ++
実施例320 ++
実施例321 +++
実施例322 ++
実施例324 ++
実施例325 ++
実施例326 +++
実施例327 +++
試験例35(組成物の流動性の評価試験)
1)塩基性もしくは酸性組成物の流動性
本発明の二酸化炭素経皮・経粘膜吸収用組成物の製造キットに用いる塩基性もしくは酸性組成物は、表面が滑らかな長さ40cmのガラス板の端に、その1gを直径1cmの円盤状に塗り、その円盤が上に来るように水平面に対して60度の角度で立てたときに、5秒後の該組成物の円盤の移動距離が15cm以内のものは、二酸化炭素発生補助剤と反応させて二酸化炭素経皮・経粘膜吸収組成物としたときにそのまま皮膚粘膜に塗布して使うことができる。この位置が15cm以上30cm未満のものは、二酸化炭素発生補助剤と反応させて二酸化炭素経皮・経粘膜吸収用組成物をなさしめたときにそのまま塗布しては塗布部位から流れ落ちやすいため、布やスポンジなどの吸収体に含浸させ、吸収体が該組成物で濡れた面を皮膚粘膜に当てることで既に述べた医療効果もしくは美容効果が得られる。実施例180〜266、300〜322と324の塩基性組成物及び実施例180〜266、325、327の酸性組成物はすべて本試験において、組成物の移動距離が15cm以内であり、二酸化炭素発生補助剤と反応させて二酸化炭素経皮・経粘膜吸収用組成物としたときにそのまま皮膚粘膜に塗布して使うことができるものであった。
2)二酸化炭素経皮・経粘膜吸収用組成物の流動性
本発明に用いる二酸化炭素経皮・経粘膜吸収組成物は、表面が滑らかな長さ40cmのガラス板の端に、その1gを直径1cmの円盤状に塗り、その円盤が上に来るように水平面に対して60度の角度で立てたときに、5秒後の該組成物の円盤の移動距離が15cm以内のものはそのまま皮膚粘膜に塗布して使うことができる。この位置が15cm以上30cm未満のものは、そのまま塗布しては塗布部位から流れ落ちやすいため、布やスポンジなどの吸収体に含浸させ、吸収体が該組成物で濡れた面を皮膚粘膜に当てることで既に述べた医療効果もしくは美容効果が得られる。
Composition Evaluation Example 300 +++
Example 301 +++
Example 302 ++
Example 303 +++
Example 304 ++
Example 305 +++
Example 306 +++
Example 307 ++
Example 308 ++
Example 309 +++
Example 310 ++
Example 311 ++
Example 312 +++
Example 313 +++
Example 314 ++
Example 315 ++
Example 316 ++
Example 317 ++
Example 318 ++
Example 319 ++
Example 320 ++
Example 321 +++
Example 322 ++
Example 324 ++
Example 325 ++
Example 326 +++
Example 327 +++
Test Example 35 (Evaluation test of fluidity of composition)
1) Fluidity of basic or acidic composition The basic or acidic composition used in the kit for producing a composition for transdermal transdermal / mucosal absorption of the present invention has an edge of a glass plate having a smooth surface and a length of 40 cm. 1 g of the composition was applied in a disk shape with a diameter of 1 cm, and when the disk was placed at an angle of 60 degrees with respect to the horizontal plane so that the disk was on top, the moving distance of the disk of the composition after 15 seconds was within 15 cm. The product can be applied to the skin mucous membrane as it is when reacted with a carbon dioxide generating auxiliary agent to form a carbon dioxide transdermal / mucosal absorption composition. If this position is 15 cm or more and less than 30 cm, it is easy to flow down from the application site when it is applied as it is when it is reacted with a carbon dioxide generating auxiliary agent to form a carbon dioxide transdermal / transmucosal absorption composition. A medical effect or a cosmetic effect as described above can be obtained by impregnating an absorbent body such as a sponge or a sponge and applying the surface of the absorbent body wet with the composition to the skin mucous membrane. The basic compositions of Examples 180 to 266, 300 to 322, and 324 and the acidic compositions of Examples 180 to 266, 325, and 327 all have a moving distance of the composition within 15 cm in this test, and generate carbon dioxide. When a composition for carbon dioxide transdermal / transmucosal absorption was prepared by reacting with an adjuvant, it could be applied directly to the skin mucosa.
2) Fluidity of carbon dioxide transdermal / mucosal absorption composition The carbon dioxide transdermal / mucosal absorption composition used in the present invention has a diameter of 1 g at the end of a 40 cm long glass plate with a smooth surface. When a 1 cm disc is applied and the disc is placed at an angle of 60 degrees with respect to the horizontal plane so that the disc is on top, the composition with a moving distance of the disc within 15 cm after 5 seconds is intact as mucosal mucosa Can be used by applying to. If this position is 15 cm or more and less than 30 cm, it can easily flow down from the application site if it is applied as it is, so impregnate an absorbent body such as cloth or sponge, and apply the surface wetted with the composition to the skin mucous membrane. The medical effect or beauty effect already described in (1) can be obtained.

本試験に供した実施例1〜249、297〜327の組成物はすべて移動距離が15cm以内であり、そのまま皮膚粘膜に塗布して使うことができるものであった。
試験例36(皮膚の若返り試験)
33歳の女性の右頬に実施例302の二酸化炭素経皮・経粘膜吸収用組成物26.2gを1日1回、1回15分間のパックを毎日、1ヶ月間続けた。試験開始から1ヶ月目にビデオスコープに20倍の拡大レンズを装着してこの女性の両頬の拡大写真を撮影した。対照として、4歳女児の右頬の写真を同様に撮影した。皮膚科医がこれらの写真を観察し、33歳女性の右頬の写真は4歳女児の右頬の写真と非常に近い皮溝パターンを示し、かつ肌のくすみが取れて若々しい肌であると評価した。一方左頬の写真は典型的な30代女性のみずみずしさを失った皮膚パターンを示していると判断し、本発明の二酸化炭素経皮・経粘膜吸収用組成物に肌の若返り効果があると評価された。
試験例37(顔の部分痩せ試験)
29歳の女性の右頬に実施例309の二酸化炭素経皮・経粘膜吸収用組成物26.2gを1回20分間、毎日塗布し、これを1ヶ月間続けた。本試験実施前日と終了翌日の2回正面からこの女性の顔写真を撮り、スキャナーでコンピュータに画像を読み込み、写真の縮尺率、撮影時の顔の傾きの補正を行ない、顔の横幅の変化を測定した結果、本発明の二酸化炭素経皮・経粘膜吸収用組成物を塗布した頬が顔の横幅の割合で10.9%減少したことが明らかとなった。また本発明の二酸化炭素経皮・経粘膜吸収用組成物を塗布した頬が美白効果によって白くなったことも確認された。なお、この女性は試験期間中に体重が1kg増えたと申告したが、該組成物非塗布側の頬は顔の横幅の割合で15.2%増加していた。
試験例38(手の美白効果試験)
33歳の女性の右手の甲全体に実施例307の二酸化炭素経皮・経粘膜吸収用組成物26.2gを塗布した。5分後に該組成物をティッシュペーパーで除去した後、水で完全に洗い流し、タオルで手を拭いて左手と比較したところ、明らかに右手が白く透明な感じの肌になった。この美白効果は翌朝も持続した。
試験例39(皮膚潰瘍治療試験)
53歳の男性の右下腿外側にできた長径4cm、短径2.5cm、深さ4mmの皮膚潰瘍に実施例327の二酸化炭素経皮・経粘膜吸収用組成物10gを塗布したところ、翌日には肉芽の形成開始が認められた。同様の治療を週2回実施し、2週間で肉芽形成が終了し、3週間で上皮化が完成して皮膚潰瘍は治癒した。
試験例40(組織中酸素飽和度測定試験)
発泡1時間後に実施例1に記載の本発明組成物中に右手人差し指を入れ、5分間浸した後該組成物を完全に拭き取り、パルスオキシメーターにその人差し指を挿入して組織中酸素飽和度を測定した。
All the compositions of Examples 1 to 249 and 297 to 327 used in this test had a moving distance of 15 cm or less, and could be used by directly applying to the skin mucosa.
Test Example 36 (skin rejuvenation test)
On the right cheek of a 33-year-old woman, 26.2 g of the carbon dioxide transdermal / transmucosal absorption composition of Example 302 was packed once a day for 15 minutes once daily for 1 month. In the first month from the start of the test, a 20x magnification lens was attached to the videoscope, and a magnified picture of both female cheeks was taken. As a control, a picture of the right cheek of a 4-year-old girl was similarly taken. A dermatologist observes these photos, and the photo of the right cheek of a 33-year-old woman shows a crevice pattern very similar to the photo of the right cheek of a 4-year-old girl, and the skin is dull and youthful. Evaluated that there was. On the other hand, it is judged that the photograph on the left cheek shows a skin pattern that has lost the freshness of a typical woman in her 30s, and the composition for carbon dioxide transdermal / transmucosal absorption of the present invention has a skin rejuvenation effect. It was evaluated.
Test Example 37 (Face Partial Fading Test)
26.2 g of the carbon dioxide transdermal / transmucosal absorption composition of Example 309 was applied to the right cheek of a 29 year old woman once daily for 20 minutes, and this was continued for 1 month. Take a photo of this woman's face twice from the front of the day before the test and the day after the end of the test, load the image into the computer with a scanner, correct the scale of the photo, and the inclination of the face at the time of shooting, and change the width of the face. As a result of the measurement, it was revealed that the cheeks to which the carbon dioxide transdermal / mucosal absorption composition of the present invention was applied decreased by 10.9% in terms of the width of the face. It was also confirmed that the cheeks coated with the carbon dioxide transdermal / mucosal absorption composition of the present invention became white due to the whitening effect. The woman declared that her weight had increased by 1 kg during the test period, but the cheek on the non-application side increased by 15.2% in terms of the width of the face.
Test Example 38 (Hand whitening effect test)
The carbon dioxide transdermal / mucosal absorption composition 26.2 g of Example 307 was applied to the entire back of the right hand of a 33-year-old woman. After 5 minutes, the composition was removed with tissue paper, washed thoroughly with water, wiped with a towel, and compared with the left hand. As a result, the right hand clearly became white and transparent skin. This whitening effect lasted the next morning.
Test Example 39 (Skin ulcer treatment test)
When 10 g of the carbon dioxide transdermal / mucosal absorption composition of Example 327 was applied to a skin ulcer formed on the outer side of the right lower leg of a 53-year-old man with a major axis of 4 cm, a minor axis of 2.5 cm and a depth of 4 mm, Showed the onset of granulation. Similar treatment was performed twice a week, granulation was completed in 2 weeks, epithelialization was completed in 3 weeks, and the skin ulcer was healed.
Test Example 40 (Tissue oxygen saturation measurement test)
After 1 hour of foaming, put the right index finger into the composition of the present invention described in Example 1, and after immersing for 5 minutes, wipe the composition completely and insert the index finger into a pulse oximeter to determine the oxygen saturation in the tissue. It was measured.

なお、実施例1の本発明組成物に代えて炭酸飲料(商品名コカコーラ、日本コカコーラ社)で同様の実験を行ったが、組織中酸素飽和度に変化は認められなかった。   In addition, it replaced with this invention composition of Example 1, and the same experiment was conducted with the carbonated drink (brand name Coca-Cola, Nippon Coca-Cola Co., Ltd.), but the change in the oxygen saturation in a structure | tissue was not recognized.

パルスオキシメーターによる組織中酸素飽和度Sp02の変化
31歳男 34歳女 42歳男 57歳男 29歳女 47歳女 43歳男
試験前 97 96 96 95 97 96 98
実施例1の 99 99 99 99 99 99 99
組成物に人
差し指挿入
5分後
試験例41(手の甲の美肌・美白試験)
33歳の女性の右手の甲全体に実施例307の二酸化炭素経皮・経粘膜吸収用組成物26.2gを塗布し、左手の甲全体に月見草油0.1g、シコン抽出液0.1g、ローズマリー抽出液0.1g、シソ抽出液0.1g、ソウハクヒ抽出液0.1g、ニンジン抽出液0.1gの混合液を塗布した。5分後に両手の甲を水で塗布物が完全に取れるまで洗い、タオルで手を拭いて両手を比較したところ、明らかに右手の甲が白く透明な感じの肌になったのに対し、左手の甲はやや肌が滑らかになり、若干の美白効果が感じられたに過ぎず、肌の透明感が認められることはなかった。右手甲の美白効果は翌朝も持続した。この結果から、本発明の組成物はハーブエキスの塗布よりも強い美肌、美白効果を有することが示唆された。
試験例42(手の甲の美肌・美白試験)
33歳の女性の右手の甲全体に実施例307の二酸化炭素経皮・経粘膜吸収用組成物26.2gを、左手の甲全体に実施例326の組成物26.2gを塗布した。5分後に両手の甲を水で塗布物が完全に取れるまで洗い、タオルで手を拭いて両手を比較したところ、両手の甲共に試験前と比較して白く透明な感じになったが、右手の甲がより白く透明な感じの肌になった。両手甲の美白効果は翌朝も持続した。この結果及び試験例41の結果とを考え併せると、本発明の組成物は強い美肌、美白効果を有するとともに、ハーブエキスの経皮吸収効率を高め、ハーブエキスとの相乗効果をも有することが示唆された。
比較例1
水とノニオン系高分子凝集剤であるポリアクリルアミド、グリセリン、ビタミンE、二酸化炭素を含むムース状発泡性組成物(商品名スキンレスゼリー1500・オカモト、オカモト社)を実施例1〜84の〔二酸化炭素経皮・経粘膜吸収用組成物の評価〕の<気泡の持続性>に準じた試験を行った。ただし、該ムース状発泡組成物は体積対重量比が非常に小さいため、試験にはその8gを供した。<評価基準2>に従った該ムース状発泡組成物の評価は0であった。またパルスオキシメーターを用いる組織中酸素飽和度測定試験を試験例40に準じて実施しようとしたが、発泡1時間後には該ムース状発泡組成物の泡はほとんど消失し、試験は実施できなかった。

Changes in tissue oxygen saturation Sp02 by pulse oximeter
31 year old man 34 year old woman 42 year old man 57 year old man 29 year old woman 47 year old woman 43 year old man
Before test 97 96 96 95 97 96 98
99 99 99 99 99 99 99 of Example 1
Insert index finger into the composition
after 5 minutes
Test Example 41 (Beautiful skin / whitening test on back of hand)
Applying 26.2 g of the carbon dioxide transdermal / transmucosal absorption composition of Example 307 to the entire back of the right hand of a 33-year-old woman, 0.1 g of evening primrose oil, 0.1 g of chicory extract, rosemary A mixed solution of 0.1 g of the extract, 0.1 g of the perilla extract, 0.1 g of the persimmon extract, and 0.1 g of the carrot extract was applied. After 5 minutes, wash the back of both hands with water until the applied product is completely removed, wipe the hands with a towel, and compare the hands. When the back of the right hand clearly became white and transparent, the back of the left hand The skin became slightly smoother and only a slight whitening effect was felt, and no skin transparency was observed. The whitening effect on the right back lasted the next morning. From these results, it was suggested that the composition of the present invention has a stronger skin and whitening effect than application of the herb extract.
Test Example 42 (Beautiful skin / whitening test on back of hand)
26.2 g of the carbon dioxide transdermal / transmucosal absorption composition of Example 307 was applied to the entire back of the right hand of a 33 year old woman, and 26.2 g of the composition of Example 326 was applied to the entire back of the left hand. After 5 minutes, wash the back of both hands with water until the applied product is completely removed, wipe the hands with a towel and compare both hands. The back of both hands looked whiter and clearer than before the test. The back of my hand became whiter and more transparent. The whitening effect of both hands lasted the next morning. Considering this result and the result of Test Example 41 together, the composition of the present invention has strong skin and whitening effects, enhances the transdermal absorption efficiency of the herb extract, and has a synergistic effect with the herb extract. It was suggested.
Comparative Example 1
A mousse-like foaming composition (trade name Skinless Jelly 1500, Okamoto, Okamoto Co., Ltd.) containing water and nonionic polymer flocculant polyacrylamide, glycerin, vitamin E, and carbon dioxide was used in Examples 1 to 84. The test according to <Evaluation of composition for carbon transdermal / transmucosal absorption] was performed. However, since the mousse-like foam composition has a very small volume to weight ratio, 8 g of the mousse foam composition was used for the test. The evaluation of the mousse-like foamed composition according to <Evaluation Criteria 2> was 0. Further, a tissue oxygen saturation measurement test using a pulse oximeter was attempted in accordance with Test Example 40, but the foam of the mousse-like foamed composition almost disappeared after 1 hour of foaming, and the test could not be performed. .

Claims (7)

水、ヒドロキシエチルセルロース、及び炭酸塩を含有する塩基性組成物と、
塩基性組成物に含まれる炭酸塩のモル数に対して少なくとも10%以上の酸を含有する顆粒剤である二酸化炭素発生補助剤(I)と
からなる、二酸化炭素経皮・経粘膜吸収用組成物の製造キット。
A basic composition containing water, hydroxyethyl cellulose, and carbonate;
A composition for carbon dioxide transdermal / transmucosal absorption comprising a carbon dioxide generating auxiliary agent (I) which is a granule containing at least 10% or more acid with respect to the number of moles of carbonate contained in the basic composition. Product manufacturing kit.
塩基性組成物が、水、増粘剤及び炭酸塩の合計量に対し、水60〜99.8重量%、増粘剤0.1〜30重量%、炭酸塩0.1〜10重量%を含有する請求項1に記載のキット。 60 to 99.8 wt% water, 0.1 to 30 wt% thickener, 0.1 to 10 wt% carbonate with respect to the total amount of water, thickener and carbonate. The kit according to claim 1, which is contained. 塩基性組成物が、フェノキシエタノールを含む、請求項1又は2に記載のキット。   The kit according to claim 1 or 2, wherein the basic composition comprises phenoxyethanol. 塩基性組成物が、グリセリンを含む、請求項1〜3のいずれかに記載のキット。   The kit according to any one of claims 1 to 3, wherein the basic composition contains glycerin. 二酸化炭素発生補助剤(I)が、酸としてアスコルビン酸を含む、請求項1〜4のいずれかに記載のキット。   The kit in any one of Claims 1-4 in which a carbon dioxide generation adjuvant (I) contains ascorbic acid as an acid. 二酸化炭素発生補助剤(I)が、酸としてクエン酸を含む、請求項1〜6のいずれかに記載のキット。   The kit in any one of Claims 1-6 in which a carbon dioxide generation adjuvant (I) contains a citric acid as an acid. 化粧料として使用される二酸化炭素経皮・経粘膜吸収用組成物を得るためのキットである、請求項1〜6のいずれかに記載のキット。

The kit according to any one of claims 1 to 6, which is a kit for obtaining a composition for carbon dioxide transdermal / transmucosal absorption used as a cosmetic.

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JP2013018719A (en) * 2011-07-08 2013-01-31 Kao Corp Cosmetic for promoting skin blood circulation
JP5380758B1 (en) * 2013-02-19 2014-01-08 株式会社ピカソ美化学研究所 Two-component carbon dioxide generating composition
JP2014088345A (en) * 2012-10-30 2014-05-15 Toyo Shinyaku Co Ltd Foamable external preparation for skin
JP2015010089A (en) * 2014-02-06 2015-01-19 株式会社東洋新薬 Foamable skin external preparation
JPWO2013011935A1 (en) * 2011-07-15 2015-02-23 ネオケミア株式会社 Fracture treatment agent, bone growth promoter or bone disease treatment or prevention agent containing carbon dioxide as an active ingredient
JP2016169190A (en) * 2015-03-13 2016-09-23 株式会社東洋新薬 Foamable skin external preparation
JP2017105864A (en) * 2013-01-22 2017-06-15 株式会社東洋新薬 Foaming external preparation for skin
JP2018012683A (en) * 2016-03-31 2018-01-25 株式会社東洋新薬 Foamable external preparation for skin

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013018719A (en) * 2011-07-08 2013-01-31 Kao Corp Cosmetic for promoting skin blood circulation
JPWO2013011935A1 (en) * 2011-07-15 2015-02-23 ネオケミア株式会社 Fracture treatment agent, bone growth promoter or bone disease treatment or prevention agent containing carbon dioxide as an active ingredient
JP2015107987A (en) * 2011-07-15 2015-06-11 ネオケミア株式会社 Therapeutic agent for bone fracture, bone growth enhancer, or therapeutic or prophylactic agent for bone diseases, each comprising carbon dioxide as active ingredient
JP2014088345A (en) * 2012-10-30 2014-05-15 Toyo Shinyaku Co Ltd Foamable external preparation for skin
JP2017105864A (en) * 2013-01-22 2017-06-15 株式会社東洋新薬 Foaming external preparation for skin
JP5380758B1 (en) * 2013-02-19 2014-01-08 株式会社ピカソ美化学研究所 Two-component carbon dioxide generating composition
JP2015010089A (en) * 2014-02-06 2015-01-19 株式会社東洋新薬 Foamable skin external preparation
JP2016169190A (en) * 2015-03-13 2016-09-23 株式会社東洋新薬 Foamable skin external preparation
JP2018012683A (en) * 2016-03-31 2018-01-25 株式会社東洋新薬 Foamable external preparation for skin

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