JP3629283B2 - Skin preparation - Google Patents
Skin preparation Download PDFInfo
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- JP3629283B2 JP3629283B2 JP01800294A JP1800294A JP3629283B2 JP 3629283 B2 JP3629283 B2 JP 3629283B2 JP 01800294 A JP01800294 A JP 01800294A JP 1800294 A JP1800294 A JP 1800294A JP 3629283 B2 JP3629283 B2 JP 3629283B2
- Authority
- JP
- Japan
- Prior art keywords
- skin
- external preparation
- weight
- plasticizer
- inflammatory
- 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.)
- Expired - Lifetime
Links
Description
【0001】
【産業上の利用分野】
本発明は皮膚外用剤に関し、更に詳しくは皮膚真菌症治療用の皮膚外用剤に関する。
【0002】
【従来の技術】
水虫に代表される皮膚真菌症は、罹患者数が多く、しかも治癒しにくいので隠れた大きな社会問題であるといわれている。更にこれらの疾病は、ひどい痒みを罹患者に与えるため、その患者の集中力を低下せしめ、社会生活に於ける生産性を著しく阻害し、人間社会に大きな悪影響を及ぼしていることは、想像に難くない。即ち、「隔靴掻痒」と言う言葉が生まれるほど、古くから皮膚真菌症は人間を悩ませ、その作業効率を低下せしめてきたものである。
【0003】
従って、皮膚真菌症を治療するにあたり、抗真菌剤により真菌の生育を阻止したり、真菌を死滅させると同時に真菌症に起因する掻痒感を和らげることは、社会生活でのクォリティーを考えると大変重要なことである。
【0004】
かかる視点より、現在まで各種の抗真菌剤と抗炎症性化合物を組み合わせた皮膚外用剤が開発されてきたが、抗真菌剤により抗炎症性化合物の経皮吸収が阻害され、更に真菌症による皮膚の糜爛等のために抗炎症性化合物の吸収が阻害されるため、期待した程の効果が得られなかった。
【0005】
【発明が解決しようとする課題】
従って本発明の目的は、抗炎症性化合物を効率よく経皮吸収せしめる真菌症治療用の皮膚外用剤を提供することにある。
【0006】
【課題を解決するための手段】
かかる実状に鑑み、本発明者らは抗真菌剤の存在下で抗炎症性化合物を効率よく経皮吸収させ得る製剤について鋭意研究を重ねた結果、エチルセルロースの含水アルコールゲルが経皮吸収作用に優れることを見出し、従ってこれを皮膚外用剤に配合することにより抗炎症性化合物が効率的に経皮吸収され得ることを見出し、発明を完成させた。
【0007】
即ち、本発明はエチルセルロース1〜5重量%、水1〜10重量%、可塑剤2.2〜25重量%、抗真菌剤0.1〜5重量%、抗炎症性化合物0.1〜5重量%及びアルコール50〜95重量%を含有し、且つ可塑剤のエチルセルロースに対する割合が重量比で2.2〜5であることを特徴とする皮膚外用剤を提供するものである。
【0008】
ここで、本発明で用いるエチルセルロースは非水溶性の被膜形成剤として、例えば錠剤や顆粒をコーティングする目的で使用されるなど、特に医薬品の分野で広く用いられてきたものであり、エチルセルロースでコーティングされた顆粒は腸溶性或いは徐放性を有することが知られている。本発明の皮膚外用剤に於いて、エチルセルロースは後述する水及びアルコールと共に、経皮吸収性のよいエチルセルロースの含水アルコールゲルを形成し、このゲルによって抗炎症性化合物の皮膚に対する吸収が促進される。
エチルセルロースの配合量は皮膚外用剤全量の1〜5重量%(以下、単に%で示す)、特に3〜4%とすることが好ましい。配合量が1%未満及び10%を超えると抗炎症剤に対する経皮吸収促進効果が得られない。
【0009】
本発明の皮膚外用剤に於いて、水は溶媒として作用する必須成分である。水の配合量は皮膚外用剤全量に対して1〜10%、特に3〜6%とすることが好ましい。水の配合量が少なすぎると抗炎症剤の経皮吸収が促進されず、多すぎるとエチルセルロースを可溶化できない。
【0010】
本発明に於いて、可塑剤は必須成分である。これは、可塑剤と水分とエチルセルロースとで形成される塗布被膜によって、抗炎症性化合物の経皮吸収が促進されるからである。このような可塑剤としては、一般的に用いられているものであれば特に限定されないが、例えば、アジピン酸ジイソプロピル、セバシン酸ジエチル、フタル酸ジエチル、グリセリルモノオレート、クエン酸トリエチル等が例示できる。このうちの点から、特にアジピン酸ジイソプロピルを用いることが好ましい。
これらの可塑剤の配合量は、エチルセルロースに対して重量比で2.2〜5、特に2.3〜3、従って、皮膚外用剤全量に対しては2.2〜25%、特に7〜12%であることが好適である。可塑剤がエチルセルロースの2.2倍量より少なくとも5倍量より多くとも抗炎症性化合物の吸収が促進されず、また、系そのものが不安定になる原因となる。
【0011】
本発明の皮膚外用剤に用いる抗真菌剤としては、クロトリマゾール、硝酸ミコナゾール、硝酸エコナゾール、硝酸イソコナゾール、ピロールニトリン、トルナフテート、ビフマシン、トリコマイシン、シクロピロクスオクラミン、エキサラミド、ハロプロジンなどが好適に使用され、このうち、抗炎症剤との相性からクロトリマゾールが最も好ましい。これらは1種を単独て用いても2種以上を組み合わせて用いてもよい。
この抗真菌剤の配合量は通常皮膚外用剤に配合される量とすることができ、即ち抗真菌作用が発現するのに充分な量である0.1〜5%、特に0.8〜1.5%とすることが好ましい。
【0012】
本発明の皮膚外用剤に配合する抗炎症性化合物としては、グリチルレチン酸、グリチルリチン、ブフェキサマック等の抗炎症剤;クロタミトン等の鎮痒剤;ジフェンヒドラミン等の抗ヒスタミン剤などが挙げられ、これらは1種を単独で又は2種以上を組み合わせて用いることができるが、ジフェンヒドラミンとグリチルレチン酸とを等量用いることが痒みと炎症の両者を緩和する点から最も好ましい。
これらの本発明の皮膚外用剤に於ける配合量は通常通りで良く、即ち、抗炎症作用が発現するのに充分な量である0.1〜5%、特に0.8〜1.5%とすることが好ましい。
【0013】
本発明の皮膚外用剤に配合するアルコールとは、低鎖長のアルキル基を有するアルコールであり、具体的にはメタノール、エタノール、ノルマルプロパノール、イソプロパノール、ノルマルブタノール、t−ブチルアルコール等の炭素数1〜4のアルコールが例示できる。これらは1種を単独でも2種以上を混合して用いることもできるが、安全性及び皮膚浸透性の観点から、特にエタノール及び/又はイソプロパノールを用いることが好ましく、最も好適なのはエタノールを単独で用いることである。
アルコールの配合量は皮膚外用剤全量の50〜95%、特に60〜85%とすることが好ましい。配合量が50%未満では被膜形成剤が十分に溶解しないため、薬物の角質層への浸透性が悪くなるなどの不都合があり、また配合量が90%を超えると他の成分の自由度が制限され過ぎることとなる。
【0014】
本発明の皮膚外用剤として特に好ましい成分及びその含有割合は、エチルセルロース1〜5%、特に3〜4%、水1〜10%、特に3〜6%、可塑剤としてアジピン酸ジイソプロピル2.2〜25%、特に7〜12%、抗炎症性化合物としてジフェンヒドラミン及び/又はグリチルレチン酸0.1〜5%、特に0.8〜1.5%、エタノール50〜90%、特に60〜85%である。
【0015】
本発明の皮膚外用剤には、これらの必須成分以外に通常の皮膚外用剤で用いられる任意成分を本発明の効果を損なわない範囲に於いて配合することができる。任意成分としては、例えばpH調整剤、界面活性剤、増粘剤、メチルパラベン、ブチルパラベン等の防腐剤、ベンゾフェノン誘導体、アミノ安息香酸誘導体等の紫外線吸収剤、γ−トコフェロール、BHT等の抗酸化剤、香料などが挙げられる。
【0016】
これらの必須成分及び任意成分より本発明の皮膚外用剤を製造するには、通常の方法を用いて行えばよく、例えば、これら成分を秤量し、加熱撹拌して溶解させた後、冷却するなどの方法を採用することができる。
【0017】
【実施例】
以下に実施例を挙げて、更に詳しく本発明について説明するが、本発明がこれら実施例に限定されないことはいうまでもない。
【0018】
実施例1〜3及び比較例1〜5
表1に示す成分を秤量し、80℃に加熱撹拌して溶解させ、撹拌冷却することにより、実施例1〜3及び比較例1〜5の皮膚外用剤を得た。
得られた皮膚外用剤について、シンクタイプの拡散セルを用いて薬物の経皮吸収について検討した。即ち、ハートレイ系白色種モルモット(雄性、350〜400g)の背部皮膚を剃毛した後摘出し、これをシンクタイプの拡散セルに装着した。ドナー側には皮膚外用剤を塗布し、アクセプター側には燐酸緩衝生理食塩水溶液を入れ、37℃で24時間放置後アクセプター側の薬物の濃度を高速液体クロマトグラフィーで定量した。この定量は、抗真菌剤であるクロトリマゾール、抗炎症性化合物であるジフェンヒドラミンについて行った。アクセプター側への薬物移行率を表1に併記する。
表1から、本発明の皮膚外用剤は抗真菌剤のみならず抗炎症性化合物に対しても経皮吸収を促進していることが明らかであるが、可塑剤のエチルセルロースに対する重量比が2.2〜5を満たしていない場合は薬物の経皮吸収性が悪いことが分かる。従って、本発明の皮膚外用剤によれば皮膚真菌症の治療と抗炎症性化合物による掻痒感の抑制が期待できることが分かる。
【0019】
【表1】
【0020】
【発明の効果】
本発明の皮膚外用剤は、抗真菌剤及び抗炎症性化合物に対して優れた経皮吸収促進作用を有するので、皮膚真菌症の治療に大変有益なものである。[0001]
[Industrial application fields]
The present invention relates to an external preparation for skin, and more particularly to an external preparation for skin for treating dermatomycosis.
[0002]
[Prior art]
Dermatomycosis, represented by athlete's foot, is said to be a hidden social problem because it has many affected people and is difficult to cure. Furthermore, these illnesses give severe itch to the affected people, which reduces the concentration of the patient, significantly impedes productivity in social life, and has a great negative impact on human society. Not difficult. In other words, dermatomycosis has long plagued humans and reduced its work efficiency as the term “seed itch” was born.
[0003]
Therefore, when treating dermatomycosis, it is very important to prevent the growth of fungi with antifungal agents and to kill the fungus while at the same time relieving itching feeling caused by mycosis. It is a thing.
[0004]
From this point of view, skin external preparations combining various antifungal agents and anti-inflammatory compounds have been developed so far. However, percutaneous absorption of anti-inflammatory compounds is inhibited by antifungal agents, and skin caused by mycosis Since the absorption of the anti-inflammatory compound is hindered due to wrinkles, etc., the expected effect could not be obtained.
[0005]
[Problems to be solved by the invention]
Accordingly, an object of the present invention is to provide a skin external preparation for the treatment of mycosis that allows an anti-inflammatory compound to be efficiently transdermally absorbed.
[0006]
[Means for Solving the Problems]
In view of this situation, the present inventors have conducted extensive research on a preparation capable of efficiently transdermally absorbing an anti-inflammatory compound in the presence of an antifungal agent. As a result, the hydrous alcohol gel of ethyl cellulose has an excellent transdermal absorption action. Thus, the present inventors have found that an anti-inflammatory compound can be efficiently transdermally absorbed by blending it into an external preparation for skin, thereby completing the invention.
[0007]
That is, the present invention is 1-5 wt% ethyl cellulose, 1-10 wt% water, 2.2-25 wt% plasticizer, 0.1-5 wt% antifungal agent, 0.1-5 wt% anti-inflammatory compound. And 50 to 95% by weight of alcohol, and the ratio of plasticizer to ethylcellulose is 2.2 to 5 by weight ratio.
[0008]
Here, ethylcellulose used in the present invention has been widely used in the field of pharmaceuticals as a water-insoluble film-forming agent, for example, for the purpose of coating tablets and granules, and is coated with ethylcellulose. The granules are known to have enteric or sustained release properties. In the external preparation for skin of the present invention, ethyl cellulose forms a hydrous alcohol gel of ethyl cellulose with good transdermal absorbability together with water and alcohol described later, and this gel promotes absorption of the anti-inflammatory compound into the skin.
The blending amount of ethyl cellulose is preferably 1 to 5% by weight (hereinafter simply referred to as%), particularly 3 to 4% of the total amount of the external preparation for skin. When the blending amount is less than 1% and exceeds 10%, the effect of promoting percutaneous absorption for an anti-inflammatory agent cannot be obtained.
[0009]
In the external preparation for skin of the present invention, water is an essential component that acts as a solvent. The blending amount of water is preferably 1 to 10%, particularly 3 to 6%, based on the total amount of the external preparation for skin. If the amount of water is too small, transdermal absorption of the anti-inflammatory agent is not promoted, and if it is too large, ethylcellulose cannot be solubilized.
[0010]
In the present invention, the plasticizer is an essential component. This is because percutaneous absorption of the anti-inflammatory compound is promoted by a coating film formed of a plasticizer, moisture and ethyl cellulose. Such a plasticizer is not particularly limited as long as it is generally used, and examples thereof include diisopropyl adipate, diethyl sebacate, diethyl phthalate, glyceryl monooleate, and triethyl citrate. From these points, it is particularly preferable to use diisopropyl adipate.
The blending amount of these plasticizers is 2.2 to 5, particularly 2.3 to 3 in terms of weight ratio with respect to ethylcellulose, and therefore 2.2 to 25%, particularly 7 to 12 with respect to the total amount of the external preparation for skin. % Is preferred. If the plasticizer is at least 5 times more than 2.2 times the amount of ethyl cellulose, the absorption of the anti-inflammatory compound is not promoted, and the system itself becomes unstable.
[0011]
As the antifungal agent used in the external preparation for skin of the present invention, clotrimazole, miconazole nitrate, econazole nitrate, isoconazole nitrate, pyrrolnitrin, tolnaftate, bifmachine, tricomycin, ciclopirox oclamamine, exeramide, haloprozine and the like are suitable Of these, clotrimazole is most preferred because of its compatibility with anti-inflammatory agents. These may be used alone or in combination of two or more.
The compounding amount of the antifungal agent can be set to an amount usually blended with an external preparation for skin, that is, 0.1 to 5%, particularly 0.8 to 1 which is an amount sufficient to exhibit an antifungal action. 0.5% is preferable.
[0012]
Examples of the anti-inflammatory compound to be blended in the external preparation for skin of the present invention include anti-inflammatory agents such as glycyrrhetic acid, glycyrrhizin, and bufexamac; antipruritic agents such as crotamiton; antihistamines such as diphenhydramine, and the like. Although it can be used alone or in combination of two or more, it is most preferable to use equal amounts of diphenhydramine and glycyrrhetinic acid from the viewpoint of alleviating both itching and inflammation.
The blending amount in these external preparations for skin of the present invention may be as usual, that is, 0.1 to 5%, particularly 0.8 to 1.5%, which is a sufficient amount to develop an anti-inflammatory action. It is preferable that
[0013]
The alcohol blended in the external preparation for skin of the present invention is an alcohol having a low chain length alkyl group, specifically, carbon number 1 such as methanol, ethanol, normal propanol, isopropanol, normal butanol, t-butyl alcohol and the like. -4 alcohols can be exemplified. These may be used singly or in combination of two or more. However, from the viewpoint of safety and skin permeability, it is particularly preferable to use ethanol and / or isopropanol, most preferably ethanol is used alone. That is.
The blending amount of the alcohol is preferably 50 to 95%, particularly 60 to 85% of the total amount of the external preparation for skin. If the blending amount is less than 50%, the film-forming agent is not sufficiently dissolved, resulting in inconveniences such as poor penetration of the drug into the stratum corneum, and if the blending amount exceeds 90%, the degree of freedom of other components is increased. It will be too limited.
[0014]
Ingredients particularly preferred as an external preparation for skin of the present invention and the content thereof are ethyl cellulose 1 to 5%, particularly 3 to 4%, water 1 to 10%, particularly 3 to 6%, and diisopropyl adipate 2.2 to 25%, especially 7-12%, diphenhydramine and / or glycyrrhetinic acid 0.1-5%, especially 0.8-1.5%, ethanol 50-90%, especially 60-85% as anti-inflammatory compounds .
[0015]
In addition to these essential components, the external preparation for skin of the present invention can be blended with optional components used in normal external preparations for skin within a range that does not impair the effects of the present invention. Optional components include, for example, pH adjusters, surfactants, thickeners, preservatives such as methylparaben and butylparaben, UV absorbers such as benzophenone derivatives and aminobenzoic acid derivatives, and antioxidants such as γ-tocopherol and BHT And fragrances.
[0016]
In order to produce the skin external preparation of the present invention from these essential components and optional components, it may be carried out using ordinary methods. For example, these components are weighed, heated and stirred to be dissolved, and then cooled. This method can be adopted.
[0017]
【Example】
Hereinafter, the present invention will be described in more detail with reference to examples, but it goes without saying that the present invention is not limited to these examples.
[0018]
Examples 1-3 and Comparative Examples 1-5
The components shown in Table 1 were weighed and dissolved by heating and stirring at 80 ° C., followed by stirring and cooling to obtain external preparations for Examples 1 to 3 and Comparative Examples 1 to 5.
About the obtained skin external preparation, the percutaneous absorption of the drug was examined using a sink type diffusion cell. That is, the back skin of a Hartley white guinea pig (male, 350-400 g) was shaved and extracted, and this was attached to a sink type diffusion cell. An external skin preparation was applied to the donor side, a phosphate buffered saline solution was added to the acceptor side, and allowed to stand at 37 ° C. for 24 hours. This quantification was performed for clotrimazole, an antifungal agent, and diphenhydramine, an anti-inflammatory compound. The drug transfer rate to the acceptor side is also shown in Table 1.
From Table 1, it is clear that the external preparation for skin of the present invention promotes percutaneous absorption not only for antifungal agents but also for anti-inflammatory compounds, but the weight ratio of plasticizer to ethylcellulose is 2. When 2-5 is not satisfy | filled, it turns out that the transdermal absorbability of a drug is bad. Therefore, it can be seen that according to the external preparation for skin of the present invention, treatment of dermatomycosis and suppression of pruritus caused by an anti-inflammatory compound can be expected.
[0019]
[Table 1]
[0020]
【The invention's effect】
Since the external preparation for skin of the present invention has an excellent percutaneous absorption promoting action for antifungal agents and anti-inflammatory compounds, it is very useful for the treatment of dermatomycosis.
Claims (5)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP01800294A JP3629283B2 (en) | 1994-02-15 | 1994-02-15 | Skin preparation |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP01800294A JP3629283B2 (en) | 1994-02-15 | 1994-02-15 | Skin preparation |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH07223971A JPH07223971A (en) | 1995-08-22 |
JP3629283B2 true JP3629283B2 (en) | 2005-03-16 |
Family
ID=11959500
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP01800294A Expired - Lifetime JP3629283B2 (en) | 1994-02-15 | 1994-02-15 | Skin preparation |
Country Status (1)
Country | Link |
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JP (1) | JP3629283B2 (en) |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH09169637A (en) * | 1995-10-18 | 1997-06-30 | Sekisui Chem Co Ltd | External preparation for treating dermatosis |
DE19639816A1 (en) * | 1996-09-27 | 1998-04-02 | Hoechst Ag | Antifungal agents with high drug release |
DE19954421A1 (en) * | 1999-11-12 | 2001-05-31 | Lohmann Therapie Syst Lts | Film-like preparation for the biphase release of pharmacologically active or other substances |
US8039452B2 (en) | 2002-06-18 | 2011-10-18 | Pola Pharma Inc. | Antifungal medicinal compositions |
AU2003242346A1 (en) * | 2002-06-27 | 2004-01-19 | Pola Chemical Industries Inc. | Drug composition |
JPWO2005000287A1 (en) * | 2003-06-25 | 2006-10-05 | 久光製薬株式会社 | External preparation for athlete's foot treatment |
JP5062995B2 (en) * | 2004-12-20 | 2012-10-31 | ロート製薬株式会社 | Preventive and therapeutic agent for vaginal candidiasis or vulvar candidiasis |
JP2010279384A (en) * | 2005-08-31 | 2010-12-16 | Pola Pharma Inc | Method for evaluating antifungal agent |
JP4974526B2 (en) * | 2005-12-29 | 2012-07-11 | ロート製薬株式会社 | Composition for preventing or treating candidiasis |
US8349882B2 (en) | 2006-03-08 | 2013-01-08 | Nihon Nohyaku Co., Ltd. | Pharmaceutical composition for external use |
RU2419429C2 (en) | 2006-03-08 | 2011-05-27 | Нихон Нохияку Ко.,Лтд. | Pharmaceutical composition for external application |
WO2007102243A1 (en) | 2006-03-08 | 2007-09-13 | Nihon Nohyaku Co., Ltd. | External pharmaceutical composition |
CN101808637B (en) | 2007-09-05 | 2013-07-24 | 宝丽制药股份有限公司 | Pharmaceutical composition |
JP5345937B2 (en) | 2007-09-05 | 2013-11-20 | 株式会社ポーラファルマ | Antifungal composition |
JP5453093B2 (en) | 2007-09-05 | 2014-03-26 | 株式会社ポーラファルマ | Antifungal pharmaceutical composition |
EP2416758B8 (en) | 2009-04-09 | 2017-10-18 | Pola Pharma Inc. | Antimycotic pharmaceutical composition |
US10130610B2 (en) | 2009-04-09 | 2018-11-20 | Pola Pharma Inc. | Antimycotic pharmaceutical composition |
CN102481286B (en) | 2009-08-25 | 2014-02-26 | 宝丽制药股份有限公司 | Antimycotic pharmaceutical composition |
-
1994
- 1994-02-15 JP JP01800294A patent/JP3629283B2/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
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JPH07223971A (en) | 1995-08-22 |
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