JP2003128536A - Percutaneous absorption formulation used together with hyperthermic treatment - Google Patents
Percutaneous absorption formulation used together with hyperthermic treatmentInfo
- Publication number
- JP2003128536A JP2003128536A JP2001328428A JP2001328428A JP2003128536A JP 2003128536 A JP2003128536 A JP 2003128536A JP 2001328428 A JP2001328428 A JP 2001328428A JP 2001328428 A JP2001328428 A JP 2001328428A JP 2003128536 A JP2003128536 A JP 2003128536A
- Authority
- JP
- Japan
- Prior art keywords
- percutaneous absorption
- skin
- moxibustion
- heat treatment
- treatment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- Medicinal Preparation (AREA)
- Finger-Pressure Massage (AREA)
Abstract
Description
【０００１】本発明は経皮吸収製剤を投与するに当た
り、温熱処理により、皮膚角質層に小孔を生成せしめる
事によって、薬物の経皮吸収を増進させて治療効果を促
進することのできる経皮吸収剤に関する。In the present invention, upon administration of a percutaneous absorption preparation, a heat treatment is performed to form small pores in the stratum corneum of the skin, whereby percutaneous absorption of a drug can be enhanced and the therapeutic effect can be promoted. Regarding absorbent.
【０００２】[0002]
【従来の技術】従来、貼付剤などについて薬物吸収を増
進させるために色々工夫がなされており、例えば温感付
与物質（例えばカプサイシン、カプサイシノイド、トウ
ガラシエキス、トウガラシチンキなど）を配合した多く
の発明があり（例えば特開平３−１８４９１５号）、す
でに市販されているものもある。市販されてはいない
が、発熱体（金属粉末などを使ったいわゆるインスタン
トカイロ）などを組合わせた貼付剤に関する多くの発明
が知られている。2. Description of the Related Art Conventionally, various efforts have been made to enhance drug absorption in patches and the like. For example, many inventions containing a warming substance (eg capsaicin, capsaicinoid, capsicum extract, capsicum tincture) have been proposed. There are some (for example, JP-A-3-184915) and some are already on the market. Although not commercially available, many inventions relating to a patch combining a heating element (so-called instant body warmer using a metal powder) and the like are known.
【０００３】[0003]
【発明が解決すべき課題】しかしながら、温感付与物質
を配合した貼付剤は、それなりの効果はあるが、通常の
ものと比較して、それほど吸収が高くなるわけではな
い。発熱体を組合わせたものは、無論効果は認められる
が、加熱時間が長く、その温度制御が困難であったり、
場合によっては低温やけどが発生する恐れがある。又皮
膚刺激が発生したり、薬物が吸収開始後直線的に上昇
し、吸収過度になる恐れもある。このような欠点を防ぐ
ため、種々工夫がなされている（例えば特開平５−１７
０６４４号、特開平７−２８４５０６号など）が、これ
らもまだ充分その欠点が解決されているとはいえないも
のである。更には、これら発明の製剤は、構成が複雑で
あったり、又それ故に生産工程も長くなったりして費用
がかさみ、経済的にも不利である。又発熱体は気密性の
袋などに保存されているが、経年変化を完全に防ぐこと
は出来ない（発熱体としての用をしなくなる）。However, the patch containing the warming sensation-imparting substance has a certain effect, but the absorption is not so high as compared with a normal patch. The combination of heating elements is of course effective, but the heating time is long and it is difficult to control the temperature.
In some cases, low temperature burns may occur. In addition, skin irritation may occur, or the drug may increase linearly after absorption starts, resulting in excessive absorption. Various measures have been taken to prevent such defects (for example, Japanese Patent Laid-Open No. 5-17).
No. 0644, JP-A-7-284506, etc.), but these cannot be said to have sufficiently solved their drawbacks. Furthermore, the formulations of these inventions are complicated in structure and, therefore, the production process is long, which is costly and economically disadvantageous. Although the heating element is stored in an airtight bag, etc., it cannot completely prevent aging (it is no longer used as a heating element).
【０００４】[0004]
【課題を解決するための手段】このような状況のもと、
本発明者らは、種々検討した結果、経皮吸収製剤を投与
するに当たり、温熱処理（上記の如き発熱体による方法
を除く）により、皮膚角質層に微小孔を生成せしめる
（厳密には、細胞間隔を広げる）ことによって、薬物の
吸収が理想的な形で増進されることを見出し、本発明を
完成した。即ち、本発明は（１）皮膚角質層に小孔を生
成せしめる温熱処理と併用する経皮吸収製剤、（２）温
熱処理が灸処理である（１）記載の経皮吸収製剤、
（３）温熱処理が電気灸処理である（１）記載の経皮吸
収製剤、（４）経皮吸収製剤がパップ剤である（１）、
（２）又は（３）記載の経皮吸収製剤、（５）経皮吸収
製剤がプラスター剤、テープ剤又はパッチ剤である
（１）、（２）又は（３）記載の経皮吸収製剤、（６）
経皮吸収製剤がゲル剤、クリーム剤又は軟膏剤である
（１）、（２）又は（３）記載の経皮吸収製剤、（７）
経皮吸収製剤が液剤又は皮膜形成性溶液剤である
（１）、（２）又は（３）記載の経皮吸収製剤、（８）
温熱処理後、適用するものである（１）、（２）、
（３）、（４）、（５）、（６）又は（７）記載の経皮
吸収製剤、（９）その適用中に温熱処理を併用する
（１）、（２）、（３）、（４）、（５）、（６）又は
（７）記載の経皮吸収製剤、（１０）１個以上の小孔を
設けた灸処理用台座及びもぐさと経皮吸収製剤とを組合
わせた経皮吸収剤キット、（１１）経皮吸収製剤を投与
するに当たり、温熱処理により皮膚角質層に微小孔を生
成せしめることを特徴とする薬物の皮膚中及び筋肉内濃
度野増進方法並びに皮膚透過促進方法、に関する。そし
て薬物の皮膚中及び筋肉内濃度の増進方法並びに皮膚透
過促進法法として、次の方法が行なわれる。
（１）経皮吸収製剤を投与するに当たり、温熱処理によ
り皮膚角質層に微小孔を生成せしめることを特徴とする
薬物の皮膚中及び筋肉内濃度野増進並びに皮膚透過促進
方法。
（２）温熱処理が灸処理である（１）の薬物の皮膚中及
び筋肉内濃度の増進方法並びに皮膚透過促進方法。
（３）温熱処理が電気灸処理である（１）の薬物の皮膚
中及び筋肉内濃度の増進方法並びに皮膚透過促進方法。
（４）経皮吸収製剤がプラスター剤、テープ剤或いはパ
ッチ剤である（１）〜（３）いずれかの薬物の皮膚中及
び筋肉内濃度の増進方法並びに皮膚透過促進方法。
（５）経皮吸収製剤がパップ剤である（１）〜（３）い
ずれかの薬物の皮膚中及び筋肉内濃度の増進方法並びに
皮膚透過促進方法。
（６）経皮吸収製剤がゲル剤、クリーム剤或いは軟膏剤
である（１）〜（３）いずれかの薬物の皮膚中及び筋肉
内濃度の増進方法並びに皮膚透過促進方法。
（７）経皮吸収製剤が液剤或いは皮膜形成性溶剤である
（１）〜（３）いずれかの薬物の皮膚中及び筋肉内濃度
の増進方法並びに皮膚透過促進方法。
（８）予め、皮膚に温熱処理をした後、経皮吸収剤を投
与する（１）〜（７）いずれかの薬物の皮膚中及び筋肉
内濃度の増進方法並びに皮膚透過促進方法。
（９）経皮吸収剤を皮膚投与中に温熱処理をする（１）
〜（７）いずれかの薬物の皮膚中及び筋肉内濃度の増進
方法並びに皮膚透過促進方法。[Means for Solving the Problems] Under these circumstances,
As a result of various studies, the inventors of the present invention produced micropores in the stratum corneum of the skin by heat treatment (excluding the above-mentioned method using a heating element) when administering a transdermal absorption preparation (strictly speaking, cells). The present invention has been completed by finding that the absorption of a drug is enhanced in an ideal manner by increasing the interval). That is, the present invention provides (1) a percutaneous absorption preparation which is used in combination with a heat treatment for producing small pores in the stratum corneum of the skin, (2) a heat treatment is a moxibustion treatment, (1) the percutaneous absorption preparation,
(3) The percutaneous absorption preparation according to (1), wherein the heat treatment is electric moxibustion treatment, (4) the percutaneous absorption preparation is a poultice (1),
(2) or (3) The percutaneous absorption preparation, (5) The percutaneous absorption preparation is a plaster, tape or patch, (1), (2) or (3) The percutaneous absorption preparation, (6)
The transdermal preparation according to (1), (2) or (3), wherein the transdermal preparation is a gel, a cream or an ointment, (7)
The transdermal preparation according to (1), (2) or (3), wherein the transdermal preparation is a liquid preparation or a film-forming solution preparation, (8)
It is applied after heat treatment (1), (2),
(3), (4), (5), (6) or (7) described in the percutaneous absorption preparation, (9) during its application together with heat treatment (1), (2), (3), (4), (5), (6) or (7) described percutaneous absorption preparation, (10) a moxibustion treatment pedestal provided with one or more small holes and a moxa and percutaneous absorption preparation Transdermal absorption kit, (11) A method for enhancing skin and intramuscular concentration field of skin and promoting permeation of skin, characterized in that upon administration of a transdermal absorption preparation, micropores are formed in the stratum corneum of the skin by heat treatment. About the method. Then, the following method is carried out as a method for increasing the concentration of the drug in the skin and in the muscle and a method for promoting skin permeation. (1) A method for increasing the concentration of drug in the skin and in the muscle and promoting skin permeation, characterized in that upon administration of a percutaneously absorbable preparation, micropores are generated in the stratum corneum of the skin by heat treatment. (2) The method of increasing the concentration of the drug in the skin and the muscle and the method of promoting skin permeation according to (1), wherein the heat treatment is moxibustion treatment. (3) The method of increasing the concentration of the drug in the skin and the muscle and the method of promoting skin permeation as described in (1), wherein the heat treatment is electric moxibustion. (4) The percutaneous absorption preparation is a plaster agent, a tape agent, or a patch agent. (1) to (3) A method for increasing the concentration of the drug in the skin and in the muscle and a method for promoting skin permeation. (5) A method for enhancing skin and intramuscular concentration of the drug of any one of (1) to (3), wherein the transdermal preparation is a poultice, and a method for promoting skin permeation. (6) A method for increasing skin and intramuscular concentration of the drug of any one of (1) to (3) and a method for promoting skin permeation, wherein the transdermal preparation is a gel, cream or ointment. (7) A method for enhancing the concentration of the drug of any one of (1) to (3) in the skin and in the muscle and a method for promoting skin permeation, wherein the percutaneously absorbable preparation is a solution or a film-forming solvent. (8) A method for increasing the concentration of the drug in the skin or in the muscle and a method for promoting skin permeation, wherein the transdermal absorbent is administered after heat-treating the skin in advance. (9) Heat treatment of transdermal absorbent during skin administration (1)
(7) A method for enhancing the concentration of any drug in the skin and muscle and a method for promoting skin permeation.
【０００５】本発明では以下に述べるように経皮吸収製
剤の投与前又は投与中、皮膚を例えば灸処理することに
より、薬物の経皮吸収を理想的な形で増進させることが
可能であり、それによって皮膚中及び筋肉内の薬物濃度
を予想外に高めることが出来る。これは灸処理すること
により、皮膚角質層に微小孔が生成し、それにより薬物
の吸収が増進されるものである。この場合、薬物の単な
る経皮吸収増進ではなく、皮膚のより深部への薬物移
行、又経皮吸収製剤投与直後の薬物の吸収促進（投与後
速やかに吸収が始まる）がなされる。従来の発熱体を組
合わせたものと異なり、本発明においては、灸処理と例
えばパップ剤等とを組合わせるものであって、安全性が
高く、それによって予測を越える治療効果が発揮される
ものである。又本発明においては、最近行われている治
療法である電気灸も問題なく使用できる。本発明で用い
られる経皮吸収製剤については、特に制限はなく、例え
ば、上記のパップ剤の他、プラスター剤、テープ剤、パ
ッチ剤、クリーム剤、ゲル剤、軟膏剤、液剤、皮膜形成
溶液剤などを挙げることが出来る。このうち特に好まし
いのはパップ剤である。又薬物については、経皮吸収さ
れるものであれば、いずれのものでも使用できる。In the present invention, as described below, it is possible to enhance the transdermal absorption of a drug in an ideal form by treating the skin with moxibustion before or during the administration of the transdermal preparation, This can result in unexpectedly high drug concentrations in the skin and muscle. This is because moxibustion treatment produces micropores in the stratum corneum of the skin, thereby enhancing drug absorption. In this case, not only the percutaneous absorption of the drug is promoted, but the drug is transferred to a deeper part of the skin, and the absorption of the drug is promoted immediately after administration of the transdermal absorption preparation (absorption starts immediately after administration). Unlike the conventional combination of heating elements, in the present invention, the moxibustion treatment is combined with, for example, a poultice, etc., and the safety is high, and thereby a therapeutic effect exceeding the prediction is exerted. Is. In the present invention, electric moxibustion, which is a recent treatment method, can be used without any problem. The percutaneous absorption preparation used in the present invention is not particularly limited, and examples thereof include plasters, tapes, patches, creams, gels, ointments, liquids, and film-forming solutions other than the poultices described above. And so on. Of these, particularly preferred are poultices. Any drug can be used as long as it is percutaneously absorbed.
【０００６】温熱処理は灸処理、電気灸処理が用いられ
る。灸処理について述べるならば、通常行われる方法、
即ち、皮膚の一点にもぐさを置いて着火する方法で差し
支えないが、好ましくは出来るだけ広い範囲（例えば貼
付剤の大きさに近い範囲）に灸処理をした方が薬物の吸
収が良好である。但し無論貼付剤と同じ範囲一面にもぐ
さを置いてやることは常識的にも行なえない（熱すぎて
やけどを負ってしまう）ので、ある範囲の中で何箇所か
にもぐさを置いて行なうのが良い。電気灸についても、
もぐさの時と同様一ヶ所のみでなく、ある範囲内で何箇
所かに行なうことが好ましい。この灸処理のために１個
以上の小孔を設けた灸処理用台座が用いられる。この灸
処理台座は図１に示すものであり、例えば直径２５ｍ
ｍ、高さ１〜３ｍｍの台座であり、例えばその中央に直
径４ｍｍの円形の孔を設けたものからなる。この台座の
大きさ、高さは適宜に選択され、又孔の数は１以上適宜
に選択設けることができる。直径４ｍｍの円形の孔を有
する台座にあってはそのもぐさは例えば直径５ｍｍ、高
さ９ｍｍのものを用いると好適である。経皮吸収製剤の
投与は、温熱処理、例えば灸処理或いは電気灸処理の直
後が最も効果的であるが、処理後３０〜４０分以内に投
与すれば十分効果は発揮される。又可能であれば経皮吸
収製剤を投与してから温熱処理をしても良い。例えば、
パップ剤やプラスター剤の場合は、それらを皮膚に貼っ
た後、その上から例えば灸処理をすればよい。As the hot heat treatment, moxibustion treatment and electric moxibustion treatment are used. If we talk about moxibustion, the usual method,
In other words, the method of igniting by putting a limbs on a point on the skin may be used, but preferably the moxibustion treatment is carried out in a range as wide as possible (for example, a range close to the size of the patch) so that the absorption of the drug is good. However, as a matter of course, it is not possible to put the gusset on the same side as the patch, because it is too common to get burns, so it is best to put the gusset on several points within a certain range. good. For electric moxibustion,
As in the case of moxa, it is preferable to carry out not only in one place but in several places within a certain range. For this moxibustion treatment, a moxibustion treatment pedestal provided with one or more small holes is used. This moxibustion processing pedestal is shown in FIG. 1, and has a diameter of 25 m, for example.
The pedestal has a height of 1 to 3 mm and a height of 1 to 3 mm, and has, for example, a circular hole with a diameter of 4 mm provided in the center thereof. The size and height of this pedestal can be appropriately selected, and the number of holes can be appropriately selected as one or more. In the case of a pedestal having a circular hole with a diameter of 4 mm, it is preferable to use a mast with a diameter of 5 mm and a height of 9 mm. The administration of the transdermal preparation is most effective immediately after the heat treatment such as moxibustion treatment or electric moxibustion treatment, but the effect is sufficiently exerted if it is administered within 30 to 40 minutes after the treatment. If possible, the transdermal preparation may be administered before the heat treatment. For example,
In the case of poultices and plasters, after applying them to the skin, for example, moxibustion treatment may be performed thereon.
【０００７】前記の如き従来の発熱体を組合わせた貼付
剤などの場合、通常の場合より１０℃くらい高くした場
合で吸収は２倍程度になるが、本発明の温熱処理との併
用処理する場合は、通常の貼付剤を、ただ貼付しただけ
の場合に比し、約３倍の吸収が得られる。又本発明の場
合には、単に経皮吸収製剤を投与した場合に比し、例え
ば可塑剤などの効果をより高めることが出来る。又発熱
体を用いた場合は単に活性化エネルギーを高めるだけで
あるが、本発明では適用部位皮膚温が完全に灸処理前に
戻った後に投与したにもかかわらず、薬剤の経皮吸収が
促進し、治療効果が上がるのである。さらに本発明にお
いては、温熱処理と貼付剤とがお互いに補助的役割を果
たすことにより効果がより高められる。In the case of a patch or the like combining the conventional heating element as described above, the absorption is about doubled when the temperature is raised by about 10 ° C. compared with the usual case, but it is treated together with the heat treatment of the present invention. In this case, about 3 times as much absorption can be obtained as compared with the case where a normal patch is simply applied. Further, in the case of the present invention, the effect of, for example, a plasticizer can be further enhanced as compared with the case of simply administering a transdermal preparation. Further, when a heating element is used, the activation energy is simply increased.However, in the present invention, the transdermal absorption of the drug is promoted despite administration after the application site skin temperature completely returns to before moxibustion treatment. However, the therapeutic effect is improved. Furthermore, in the present invention, the effect is further enhanced by the heat treatment and the patch acting as auxiliary roles for each other.
【０００８】[0008]
【実施例】以下本発明を実施例について説明するが、本
発明はこれに限定されるものではない。実施例１
実験で使用した灸は、図１に示されているように、市販
されている「せんねん灸オフレギュラー灸伊吹」で、台
座部分を取り外し、代わりに中央に直径４ｍｍの孔を１
個或いは３個設けた直径２５ｍｍ、高さ１ｍｍ、２ｍ
ｍ、３ｍｍの台座を作成し使用した。対象動物としては
雄のヘアレスラットを用いた。灸による皮膚処理は、麻
酔下雄性ヘアレスラットの腹部皮膚に台座を装着し、中
央の孔の上に灸（直径５ｍｍ、高さ９ｍｍのもぐさを１
個或いは３個）を置き点火後５分間そのままで放置し
た。煙は点火後約１分半後に消えた。EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited thereto. Example 1 As shown in FIG. 1, the moxibustion used in the experiment was a commercially available “Senen moxibustion off-regular moxibustion Ibuki”, and the pedestal part was removed, and instead a hole having a diameter of 4 mm was formed in the center.
25 mm in diameter, 1 mm in height, 2 m in height
A pedestal of m and 3 mm was prepared and used. Male hairless rats were used as target animals. For skin treatment with moxibustion, a pedestal was attached to the abdominal skin of anesthetized male hairless rats, and a moxibustion (diameter 5 mm, height 9 mm 1
(Or 3 pieces) were placed and left for 5 minutes after ignition. The smoke went out about one and a half minutes after ignition.
【０００９】（１）インビトロ皮膚透過実験
ラットにつき灸処理〔灸処理面積（灸の数）の比較につ
いては、灸１個、距離２ｍｍと灸３個、距離２ｍｍで、
灸皮膚間距離の比較については灸３個で距離３ｍｍ、２
ｍｍ、１ｍｍで実施〕後直ちに腹部皮膚を切り取り、２
−チャンバー横型拡散セルに装着し、灸処理後３０分経
過した時点で、角質層側（ドナー側）にサリチル酸ナト
リウム溶液又はインドメタシン含有の経皮吸収製剤を適
用し（サリチル酸ナトリウム溶液をドナー側のチャンバ
ーに入れる、或いは経皮吸収剤の場合は皮膚に貼り付け
る）、真皮側（レシーバー側）に７．４等張リン酸緩衝
液を適用した（緩衝液をレシーバー側のチャンバーに入
れる）。セルの温度は３２℃に保った。この装置につい
ては図２に示す。この灸処理後３０分経過したときを０
時間とし、その後１時間毎に緩衝液をサンプリングし、
サリチル酸ナトリウム或いはインドメタシンの定量をＨ
ＰＬＣを用いて行なった。なお、コントロールとしては
灸処理を行なわない他は上記と全く同じ操作を行なっ
た。実験結果を図３に示す。図３から明らかなように、
灸処理面積が広くなるほど（灸の本数が多い程）、又皮
膚と灸の距離が短いほど薬物の透過性は増加した。(1) In vitro skin permeation experiment Moxibustion treatment for rats [For the comparison of moxibustion treated area (number of moxibustion), one moxibustion, 2 mm distance and 3 moxibustion, 2 mm distance,
For comparison of moxibustion skin distance, 3 moxibustion distances 3 mm, 2
mm, 1 mm] Immediately after cutting off the abdominal skin, 2
-When attached to a chamber horizontal diffusion cell, and 30 minutes after the moxibustion treatment, a sodium salicylate solution or a percutaneous absorption preparation containing indomethacin is applied to the stratum corneum side (donor side) (sodium salicylate solution is applied to the donor side chamber). , Or in the case of a transdermal absorbent, it is attached to the skin), and a 7.4 isotonic phosphate buffer solution is applied to the dermis side (receiver side) (the buffer solution is put into the chamber on the receiver side). The cell temperature was maintained at 32 ° C. This device is shown in FIG. 0 when 30 minutes have passed after this moxibustion treatment
Time, then sample the buffer every hour,
H for the determination of sodium salicylate or indomethacin
Performed using PLC. As a control, the same operation as above was performed except that moxibustion treatment was not performed. The experimental results are shown in FIG. As is clear from FIG.
The larger the area treated with moxibustion (the greater the number of moxibustion) and the shorter the distance between the skin and moxibustion, the higher the drug permeability.
【００１０】（２）インビボ皮膚適用実験
図４に示すように、ラットにつきウレタン麻酔下、灸処
理を行ない（もぐさ３本、距離１ｍｍ）、３０分後頚静
脈にサリチル酸ナトリウム溶液を充填し、その適用時を
０時間とし、その後１時間毎に採血した。実験終了時に
断頭脱血し、腹部皮膚と筋肉を直径２．５ｃｍの円状に
摘出した。血中濃度・皮膚／筋肉中薬物量はＨＰＬＣを
用いて測定した。なお、コントロールとしては、灸処理
を行なわない他は上記と全く同じ操作を行なった。実験
結果を図５に示す。この実験では、図５から明らかなよ
うに薬物の皮膚透過性はコントロールに比し７〜８倍
（血漿中濃度の比）に増加した。(2) In vivo skin application experiment As shown in FIG. 4, rats were subjected to moxibustion treatment under urethane anesthesia (3 moxas, distance 1 mm), and after 30 minutes, the jugular vein was filled with sodium salicylate solution. The time of application was set to 0 hour, and blood was collected every hour thereafter. At the end of the experiment, the blood was decapitated and the abdominal skin and muscle were excised into a circle with a diameter of 2.5 cm. The blood concentration and the amount of drug in skin / muscle were measured using HPLC. As a control, the same operation as above was performed except that moxibustion treatment was not performed. The experimental results are shown in FIG. In this experiment, as is apparent from FIG. 5, the skin permeability of the drug was increased 7 to 8 times (ratio of plasma concentration) as compared with the control.
【００１１】以上の結果から灸処理によりインビトロ、
インビボのどちらの状態でも皮膚透過量が増加すること
が判った。From the above results, moxibustion treatment was performed in vitro,
It was found that skin permeation increased in both in vivo conditions.
【００１２】（３）次に、適用部位の皮膚筋肉中の濃度
について調べた。静脈内注射又は局所適用の場合におけ
る灸処理の影響について図６に示す。図６から分かるよ
うに、灸処理後の静脈内注射の場合、コントロールに比
べて２〜３倍の皮膚／血漿中濃度比を示した。このこと
から全身循環系から皮膚への薬剤分布も灸処理により皮
膚透過の場合と同じように増加することが判る。一方灸
処理後の局所適用の場合においても、上記同様コントロ
ールに比べて２〜３倍の皮膚／血漿中濃度比を示した。
この場合灸処理によって先に述べたように７〜８倍の血
漿中濃度を得られているので、結果として皮膚中の量は
２０倍にも増加したことになる。(3) Next, the concentration in the skin muscle of the application site was examined. The effect of moxibustion treatment in the case of intravenous injection or topical application is shown in FIG. As can be seen from FIG. 6, the intravenous injection after the moxibustion treatment showed a skin / plasma concentration ratio that was 2-3 times that of the control. From this, it is understood that the distribution of the drug from the systemic circulation system to the skin is increased by the moxibustion treatment as in the case of the skin penetration. On the other hand, in the case of topical application after moxibustion treatment, the skin / plasma concentration ratio was 2-3 times higher than that of the control as in the above.
In this case, the moxibustion treatment obtained a plasma concentration of 7 to 8 times as described above, and as a result, the amount in the skin increased to 20 times.
【００１３】灸処理後の静脈内注射の場合、図７に示す
ように筋肉中の量についてコントロールに比べて２倍の
筋肉／血漿中濃度になっている。それに対して局所適用
ではコントロールに比べて筋肉／血漿中濃度比は１０倍
になっている。血漿中濃度が増加したことからすると、
筋肉中の量は約７０〜８０倍にも増加したことになる。In the case of intravenous injection after moxibustion treatment, as shown in FIG. 7, the muscle / plasma concentration is twice as high as that of the control in terms of the amount in muscle. On the other hand, in the topical application, the muscle / plasma concentration ratio was 10 times that of the control. The increase in plasma concentration indicates that
This means that the amount in muscle has increased about 70 to 80 times.
【００１４】（４）次に実際市販されているインドメタ
シン含有パップ剤の皮膚透過試験を行なった。結果を図
８及び図９に示す。図８及び図９から明らかなようにサ
リチル酸ナトリウムと同様に灸処理により薬物の透過性
が増加した。(4) Next, a skin permeation test was conducted on a commercially available indomethacin-containing poultice. The results are shown in FIGS. 8 and 9. As is clear from FIGS. 8 and 9, the permeation of the drug was increased by the moxibustion treatment as in the case of sodium salicylate.
【００１５】[0015]
【発明の効果】経皮吸収製剤と温熱処理との併用によ
り、薬物の経皮吸収が増進される。EFFECTS OF THE INVENTION The percutaneous absorption of a drug is enhanced by the combined use of a percutaneous absorption preparation and a heat treatment.
【００１６】[0016]
【図１】本発明の熱処理に用いる灸の構造の一例を示す
図である。FIG. 1 is a diagram showing an example of the structure of moxibustion used for heat treatment of the present invention.
【図２】本発明の経皮吸収製剤の in vitro の効果をみ
るための方法を示す図である。FIG. 2 is a diagram showing a method for examining the in vitro effect of the transdermal preparation of the present invention.
【図３】本発明の in vitro の効果を示すグラフであ
る。FIG. 3 is a graph showing the in vitro effect of the present invention.
【図４】本発明の経皮吸収製剤の in vitro の効果をみ
るための方法を示す図である。FIG. 4 is a view showing a method for examining the in vitro effect of the transdermal preparation of the present invention.
【図５】本発明の in vitro の効果を示すグラフであ
る。FIG. 5 is a graph showing the in vitro effect of the present invention.
【図６】本発明の in vitro の効果を示すグラフであ
る。FIG. 6 is a graph showing the in vitro effect of the present invention.
【図７】本発明の in vitro の効果を示すグラフであ
る。FIG. 7 is a graph showing the in vitro effect of the present invention.
【図８】本発明の in vitro の効果を示すグラフであ
る。FIG. 8 is a graph showing the in vitro effect of the present invention.
【図９】本発明の in vitro の効果を示すグラフであ
る。FIG. 9 is a graph showing the in vitro effect of the present invention.
フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ テーマコート゛(参考） Ａ６１Ｍ 35/00 Ａ６１Ｐ 21/00 Ａ６１Ｐ 21/00 Ａ６１Ｍ 35/00 (72)発明者 長谷川 哲也 埼玉県坂戸市関間４丁目４番39号ライオン ズガーデン若葉409 Ｆターム(参考） 4C076 AA87 AA88 BB31 CC01 CC38 4C101 CA01 CA11 4C167 AA71 AA72 BB42 CC01 GG16Front page continuation (51) Int.Cl. 7 Identification code FI theme code (reference) A61M 35/00 A61P 21/00 A61P 21/00 A61M 35/00 (72) Inventor Tetsuya Hasegawa 4 Sekima, Sakado City, Saitama Prefecture 4-39 Lions Garden Wakaba 409 F term (reference) 4C076 AA87 AA88 BB31 CC01 CC38 4C101 CA01 CA11 4C167 AA71 AA72 BB42 CC01 GG16
Claims (11)
と併用する経皮吸収製剤。1. A percutaneous absorption preparation which is used in combination with a heat treatment for forming pores in the stratum corneum of the skin.
皮吸収製剤。2. The percutaneous absorption preparation according to claim 1, wherein the heat treatment is moxibustion treatment.
の経皮吸収製剤。3. The percutaneous absorption preparation according to claim 1, wherein the heat treatment is electric moxibustion treatment.
２又は３記載の経皮吸収製剤。4. The percutaneous absorption preparation is a poultice,
The percutaneous absorption preparation according to 2 or 3.
はパッチ剤である請求項１、２又は３記載の経皮吸収製
剤。5. The transdermal preparation according to claim 1, 2 or 3, which is a plaster, a tape or a patch.
膏剤である請求項１、２又は３記載の経皮吸収製剤。6. The transdermal preparation according to claim 1, 2 or 3, which is a gel, a cream or an ointment.
である請求項１、２又は３記載の経皮吸収製剤。7. The percutaneous absorption preparation according to claim 1, 2 or 3, which is a liquid preparation or a film-forming solution preparation.
１、２、３、４、５、６又は７記載の経皮吸収製剤。8. The percutaneous absorption preparation according to claim 1, which is applied after heat treatment.
１、２、３、４、５、６又は７記載の経皮吸収製剤。9. The percutaneous absorption preparation according to claim 1, 2, 3, 4, 5, 6, or 7, which is combined with a heat treatment during its application.
びもぐさと経皮吸収製剤とを組合わせた経皮吸収剤キッ
ト。10. A percutaneous absorption kit in which a moxibustion treatment pedestal having one or more small holes and a moxa and a percutaneous absorption preparation are combined.
処理により皮膚角質層に微小孔を生成せしめることを特
徴とする薬物の皮膚中及び筋肉内濃度野増進方法並びに
皮膚透過促進方法。11. A method for increasing the concentration of drug in the skin and in the muscle and a method for promoting skin permeation, which comprises producing micropores in the stratum corneum of the skin by heat treatment upon administration of a transdermal preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001328428A JP2003128536A (en) | 2001-10-25 | 2001-10-25 | Percutaneous absorption formulation used together with hyperthermic treatment |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001328428A JP2003128536A (en) | 2001-10-25 | 2001-10-25 | Percutaneous absorption formulation used together with hyperthermic treatment |
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| Publication Number | Publication Date |
|---|---|
| JP2003128536A true JP2003128536A (en) | 2003-05-08 |
Family
ID=19144491
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015128599A (en) * | 2005-06-17 | 2015-07-16 | 日東電工株式会社 | Permeant delivery system and methods for use thereof |
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| JPS5739844A (en) * | 1980-08-22 | 1982-03-05 | Nitsushin Yakuhin Kogyo Kk | Garlic tablet for moxa cautery treatment |
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| JP2015128599A (en) * | 2005-06-17 | 2015-07-16 | 日東電工株式会社 | Permeant delivery system and methods for use thereof |
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