JP3567350B2 - Anti-alopecia - Google Patents
Anti-alopecia Download PDFInfo
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- JP3567350B2 JP3567350B2 JP08466796A JP8466796A JP3567350B2 JP 3567350 B2 JP3567350 B2 JP 3567350B2 JP 08466796 A JP08466796 A JP 08466796A JP 8466796 A JP8466796 A JP 8466796A JP 3567350 B2 JP3567350 B2 JP 3567350B2
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- Prior art keywords
- ile
- thr
- leu
- met
- pro
- 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
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- Cosmetics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Description
【0001】
【発明の属する技術分野】
本発明は抗癌剤の副作用による脱毛症の予防及び改善に有効な抗脱毛症剤に関し、更に詳しくは、大豆蛋白質由来ペプチド(以下、Soymetide と称する)を有効成分として含有することを特徴とする抗脱毛剤に関するものである。
【0002】
【従来の技術】
癌の治療のために、抗癌剤が単独で、或は外科的除去法及び放射線療法と共に広く使用されている。しかしながら、適切な抗癌剤の使用は癌の治療あるいは延命の上で有効とされる一方で、ある程度の副作用をもたらすことは避けられないのが現状である。
脱毛症もその副作用の一つとして、かなり高い頻度で発生する。脱毛症は生命に直接関わらず又身体的苦痛を与えないとはいえ、患者の心理状態に及ぼす影響は極めて大きく、臨床の場においてその軽減が強く望まれている。
【0003】
本発明の抗脱毛症剤の有効成分であるSoymetide は既に知られている物質で、免疫系賦活作用等の、幾つかの有用な生理作用を有することが知られている。例えば、ファゴサイトーシス促進作用(特開平7−224093号公報)等が知られている。
しかしながら、Soymetide が抗脱毛症剤としての作用を有することは全く知られていない。
【0004】
【発明が解決しようとする課題】
従って、本発明の目的は、新しいタイプの副作用の少ない、優れた抗脱毛症作用を有する抗脱毛症剤を提供することにある。
【0005】
【課題を解決するための手段】
本発明者らは脱毛症、特に抗癌剤の投与に伴う脱毛症の軽減について鋭意検討を重ねた結果、Soymetide の投与が脱毛を抑制するという新たな知見に基づき、本発明を完成した。
すなわち、本発明は、次式で示される配列番号1ないし10の大豆蛋白質由来ペプチド(Soymetide )を有効成分として含有することを特徴とする抗脱毛剤である。
【0006】
【発明の実施の形態】
本発明に使用する大豆蛋白質由来ペプチドは、大豆蛋白質を酵素加水分解し、得られた消化物を、DEAE−セルロースカラムによるクロマトグラフィー、さらにオクタドデシル(ODS)カラム及びフェネチルカラムによる高速液体クロマトグラフィー(HPLC)によって分画することにより得ることができる。
【0007】
本発明の抗脱毛症剤は経口的あるいは非経口的に投与することができる。経口投与剤としては散剤、顆粒剤、カプセル剤、錠剤などの固形製剤あるいはシロップ剤、エリキシル剤などの液状製剤とすることができる。また、非経口投与剤として注射剤あるいは座薬等とすることができる。
これらの製剤は活性成分に薬理学的、製剤学的に認容される製造助剤を加えることにより常法に従って製造される。更に公知の技術により持続性製剤とすることも可能である。当該製造助剤を用いる場合は、本発明の抗脱毛症剤中の大豆蛋白質由来ペプチドの配合量は、通常1〜100重量%、好ましくは10〜100重量%である。
【0008】
経口投与用の固形製剤を製造するには、有効成分と賦形剤例えば乳糖、デンプン、結晶セルロース、乳糖カルシウム、無水ケイ酸などと混合して散剤とするか、さらに必要に応じて白糖、ヒドロキシプロピルセルロース、ポリビニルピロリドンなどの結合剤、カルボキシメチルセルロース、カルボキシメチルセルロースカルシウムなどの崩壊剤などを加えて湿式又は乾式造粒して顆粒剤とする。錠剤を製造するには、これらの散剤及び顆粒剤をそのまま或はステアリン酸マグネシウム、タルクなどの滑沢剤を加えて打錠すればよい。これらの顆粒又は錠剤はヒドロキシプロピルメチルセルロースフタレート、メタクリル酸−メタクリル酸メチルコポリマーなどの腸溶性基剤で被覆して腸溶性製剤、あるいはエチルセルロース、カルナウバロウ、硬化油などで被覆して持続性製剤とすることもできる。また、カプセル剤を製造するには、散剤又は顆粒剤を硬カプセルに充填するか、有効成分をそのまま或はグリセリン、ポリエチレングリコール、ゴマ油、オリーブ油などに溶解したのちゼラチン膜で被覆し軟カプセル剤とすることができる。
【0009】
経口投与用の液状製剤を製造するには、有効成分と白糖、ソルビトール、グリセリンなどの甘味剤とを水に溶解して透明なシロップ剤、更に精油、エタノールなどを加えてエリキシル剤とするか、アラビアゴム、トラガント、ポリソルベート80、カルボキシメチルセルロースナトリウムなどを加えて乳剤又は懸濁剤としてもよい。これらの液状製剤には所望により矯味剤、着色剤、保存剤などを加えてもよい。
【0010】
注射剤を製造するには、有効成分を必要に応じて塩酸、水酸化ナトリウム、乳糖、乳酸、ナトリウム、リン酸−水素ナトリウム、リン酸二水素ナトリウムなどのpH調整剤、塩化ナトリウム、ブドウ糖などの等張化剤とともに注射用蒸留水に溶解し、無菌濾過してアンプルに充填するか、更にマンニトール、デキストリン、シクロデキストリン、ゼラチンなどを加えて真空凍結乾燥し、用時溶解型の注射剤としてもよい。また、有効成分にレシチン、ポリソルベート80、ポリオキシエチレン硬化ヒマシ油などを加えて水中で乳化せしめ注射用乳剤とすることもできる。
【0011】
直腸投与剤を製造するには、有効成分をカカオ脂、脂肪酸のトリ、ジ及びモノグリセリド、ポリエチレングリコールなどの坐剤用基剤と共に加湿して溶解し型に流し込んで冷却するか、有効成分をポリエチレングリコール、大豆油などに溶解したのち、ゼラチン膜で被覆すればよい。
【0012】
皮膚用外用剤を製造するには、有効成分を白色ワセリン、ミツロウ、流動パラフィン、ポリエチレングリコールなどに加えて必要ならば加湿して練合し軟膏剤とするか、ロジン、アクリル酸アルキルエステル重合体などの粘着剤と練合したのちポリエチレンなどの不織布に展延してテープ剤とする。
【0013】
上記構成を有する本発明の抗脱毛症剤は、公知の製造法、例えば日本薬局方第10版製剤総則記載の方法ないし適当な改良を加えた方法によって製造することができる。
投与量は、対象疾患の種類、患者の性別、年齢、体重、症状或は投与形態により異なるが、一般には、Soymetide の量として、1日あたり約0.3〜1g/人であり1回あるいは数回に分けて使用される。
以下、本発明を実施例により詳細に説明する。
【0014】
【実施例】
[実施例1]
検体として6日齢のSD雄性ラットを用いた。この検体を以下のA〜Cの3群に分けた。各群には母親を一匹つけ、自由に哺乳させた。母親には日本クレア製の固形食CE2を自由に摂取させ、飲水も自由にさせた。薬剤の投与は1日1回、朝10時より11時の間に行った。
なお、本発明の大豆蛋白質由来ペプチドとして配列番号4のもの(Soymetide 4)を用いた。
【0015】
A)エトポシド(日本化薬製 ラステット:抗ガン剤) 単独投与群 5匹
エトポシドは、20mg/mlの注射液を0.9%生理食塩水にて2mg/mlに希釈し、1.5mg/kg体重の用量で、腹腔内に生後11日目から3日間連続投与した。
B)エトポシドと Soymetide4 併用投与群 4匹
同じく生後11日から3日間連続して、エトポシドを上記と同用量で腹腔内に投与し、Soymetide 4は、生後6日目から8日間、乳児用に特殊加工した経口ゾンデを用いて10mg/kgを経口投与した。
C)コントロール群 2匹
生理食塩水のみを腹腔内投与した。
【0016】
上記3群の投与検体について、20日齢に、肉眼的観察により脱毛度を判定した。脱毛度の判定は下記の基準に従って行った。試験結果を表1に示す。
脱毛度判定基準
スコア
0: 0〜25%脱毛
1:26〜50%脱毛
2:51〜75%脱毛
3:76〜100%脱毛
【0017】
【表1】
上記の結果より、 Soymetide4併用投与群において、脱毛の抑制が認められた。
【0018】
【発明の効果】
本発明の大豆蛋白質由来のペプチドを有効成分とする抗脱毛症剤は、脱毛症、特に抗癌剤の使用に伴う脱毛症の進行を顕著に抑制する。有効成分であるペプチドは毒性の極めて低い物質であり、本発明の抗脱毛症剤の有用性は高い。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to an anti-alopecia agent effective for preventing and improving alopecia due to the side effect of an anticancer agent, and more particularly, to an anti-alopecia agent comprising a soy protein-derived peptide (hereinafter referred to as Soymetide) as an active ingredient. It relates to the agent.
[0002]
[Prior art]
For the treatment of cancer, anticancer drugs are widely used alone or in conjunction with surgical removal and radiation therapy. However, while the use of appropriate anticancer agents is effective in treating cancer or prolonging life, it is presently inevitable to cause some side effects.
Alopecia is one of its side effects that occurs quite frequently. Although alopecia is not life-threatening and does not cause physical distress, its effect on the patient's psychological state is extremely large, and its reduction is strongly desired in clinical settings.
[0003]
Soymetide, which is an active ingredient of the anti-alopecia agent of the present invention, is a known substance, and is known to have some useful physiological actions such as an immune system activating action. For example, a phagocytosis promoting action (Japanese Patent Application Laid-Open No. Hei 7-224093) is known.
However, it is not known at all that Soymetide has an action as an anti-alopecia agent.
[0004]
[Problems to be solved by the invention]
Accordingly, an object of the present invention is to provide a new type of anti-alopecia agent having an excellent anti-alopecia effect with few side effects.
[0005]
[Means for Solving the Problems]
The present inventors have conducted intensive studies on the reduction of alopecia, particularly alopecia associated with the administration of anticancer agents, and as a result, completed the present invention based on a new finding that administration of Soymetide suppresses alopecia.
That is, the present invention is an anti-hair loss agent characterized by containing a soybean protein-derived peptide (Soymetide) represented by the following formulas of SEQ ID NOS: 1 to 10 as an active ingredient.
[0006]
BEST MODE FOR CARRYING OUT THE INVENTION
The soybean protein-derived peptide used in the present invention is obtained by subjecting soybean protein to enzymatic hydrolysis and subjecting the obtained digest to chromatography on a DEAE-cellulose column, and high-performance liquid chromatography on an octadodecyl (ODS) column and a phenethyl column ( (HPLC).
[0007]
The anti-alopecia agent of the present invention can be administered orally or parenterally. Oral preparations can be solid preparations such as powders, granules, capsules and tablets, or liquid preparations such as syrups and elixirs. In addition, injections or suppositories can be prepared as parenteral administration agents.
These preparations are produced in a conventional manner by adding a pharmacologically and pharmaceutically acceptable production aid to the active ingredient. Furthermore, it is also possible to prepare a sustained-release preparation by a known technique. When the production aid is used, the amount of the peptide derived from soy protein in the anti-alopecia agent of the present invention is usually 1 to 100% by weight, preferably 10 to 100% by weight.
[0008]
To prepare a solid preparation for oral administration, the active ingredient and excipients such as lactose, starch, microcrystalline cellulose, lactose calcium, silicic acid anhydride and the like are mixed into powders or, if necessary, sucrose, hydroxy A binder such as propylcellulose and polyvinylpyrrolidone and a disintegrating agent such as carboxymethylcellulose and calcium carboxymethylcellulose are added, and wet or dry granulation is performed to obtain granules. In order to produce tablets, these powders and granules may be compressed as they are or by adding a lubricant such as magnesium stearate or talc. These granules or tablets should be coated with an enteric base such as hydroxypropylmethylcellulose phthalate, methacrylic acid-methyl methacrylate copolymer and enteric coated, or coated with ethylcellulose, carnauba wax, hardened oil, etc. to form a sustained release formulation. Can also. To produce capsules, powders or granules are filled in hard capsules, or the active ingredient is dissolved as it is or dissolved in glycerin, polyethylene glycol, sesame oil, olive oil, etc., and then coated with a gelatin film to form soft capsules. can do.
[0009]
To produce a liquid preparation for oral administration, the active ingredient and a sweetener such as sucrose, sorbitol and glycerin are dissolved in water to give a clear syrup, essential oil, ethanol and the like to add an elixir, Emulsions or suspensions may be prepared by adding gum arabic, tragacanth, polysorbate 80, sodium carboxymethylcellulose and the like. If desired, flavoring agents, coloring agents, preservatives, and the like may be added to these liquid preparations.
[0010]
In order to manufacture an injection, the active ingredient is adjusted to a pH adjuster such as hydrochloric acid, sodium hydroxide, lactose, lactic acid, sodium, sodium phosphate-hydrogen phosphate, sodium dihydrogen phosphate as needed, sodium chloride, glucose and the like. Dissolve in distilled water for injection together with an isotonic agent, filter aseptically and fill into ampoules, or add mannitol, dextrin, cyclodextrin, gelatin, etc., and freeze-dry in vacuo to obtain a ready-to-use dissolvable injection. Good. Also, lecithin, polysorbate 80, polyoxyethylene hydrogenated castor oil and the like can be added to the active ingredient and emulsified in water to prepare an injection emulsion.
[0011]
To prepare a rectal preparation, the active ingredient is moistened with a suppository base such as cocoa butter, fatty acid tri-, di- and monoglycerides, and polyethylene glycol, dissolved and poured into a mold, and cooled, or the active ingredient is polyethylene. After dissolving in glycol, soybean oil or the like, it may be coated with a gelatin film.
[0012]
To produce an external preparation for the skin, the active ingredient is added to white petrolatum, beeswax, liquid paraffin, polyethylene glycol, etc. and, if necessary, humidified and kneaded to form an ointment, or rosin, an alkyl acrylate polymer After kneading with an adhesive such as polyethylene, it is spread on a nonwoven fabric such as polyethylene to form a tape.
[0013]
The anti-alopecia agent of the present invention having the above constitution can be produced by a known production method, for example, a method described in the Japanese Pharmacopoeia 10th Edition General Rules for Preparations or a method with appropriate improvements.
The dosage varies depending on the type of the target disease, the sex, age, weight, symptoms or the administration form of the patient, but generally, the amount of Soymetide is about 0.3 to 1 g / person per day, which is once or once. Used several times.
Hereinafter, the present invention will be described in detail with reference to examples.
[0014]
【Example】
[Example 1]
Six-day-old SD male rats were used as specimens. This sample was divided into the following three groups A to C. Each group had one mother and was allowed to feed freely. The mothers were allowed to freely take CLEA Japan's solid food CE2 and drink water freely. The drug was administered once a day between 10 am and 11 am.
In addition, the peptide of SEQ ID NO: 4 (Soymetide 4) was used as the soybean protein-derived peptide of the present invention.
[0015]
A) Etoposide (Nippon Kayaku Rastet: anticancer agent) Single administration group 5 animals Etoposide was prepared by diluting a 20 mg / ml injection solution to 2 mg / ml with 0.9% physiological saline and 1.5 mg / kg. It was administered intraperitoneally at the dose of body weight for 3 consecutive days from the 11th day after birth.
B) Etoposide and Soymetide4 combined administration group Four animals were also intraperitoneally administered with etoposide at the same dose as above for 3 consecutive days from 11 days after birth. 10 mg / kg was orally administered using a processed oral sonde.
C) Control group Two animals received only saline intraperitoneally.
[0016]
At the age of 20 days, the degree of hair loss was determined by visual observation at the age of 20 days for the three groups of administration samples. The degree of hair removal was determined according to the following criteria. Table 1 shows the test results.
Degree of hair loss evaluation criterion score: 0 to 25% hair loss 1: 26 to 50% hair loss 2: 51 to 75% hair loss 3: 76 to 100% hair loss
[Table 1]
From the above results, suppression of hair loss was observed in the Soymetide4 combination administration group.
[0018]
【The invention's effect】
The anti-alopecia agent comprising the soy protein-derived peptide of the present invention as an active ingredient remarkably suppresses the progression of alopecia, especially alopecia associated with the use of anticancer agents. The peptide which is an active ingredient is a substance having extremely low toxicity, and the anti-alopecia agent of the present invention is highly useful.
Claims (1)
配列番号1:Met-Ile-Thr-Leu-Ala-Ile-Pro-Val-Asn-Lys-Pro-Gly-Arg
配列番号2:Met-Ile-Thr-Leu-Ala-Ile-Pro-Val-Asn-Lys-Pro-Gly
配列番号3:Met-Ile-Thr-Leu-Ala-Ile-Pro-Val-Asn-Lys-Pro
配列番号4:Met-Ile-Thr-Leu-Ala-Ile-Pro-Val-Asn-Lys
配列番号5:Met-Ile-Thr-Leu-Ala-Ile-Pro-Val-Asn
配列番号6:Met-Ile-Thr-Leu-Ala-Ile-Pro-Val
配列番号7:Met-Ile-Thr-Leu-Ala-Ile-Pro
配列番号8:Met-Ile-Thr-Leu-Ala-Ile
配列番号9:Met-Ile-Thr-Leu-Ala
配列番号10:Met-Ile-Thr-Leu An anti-alopecia agent for alopecia due to side effects of an anti-cancer agent, which comprises, as an active ingredient, one or more of the soybean protein-derived peptides represented by SEQ ID NOS: 1 to 10 represented by the following formulas.
Sequence number 1: Met-Ile-Thr-Leu-Ala-Ile-Pro-Val-Asn-Lys-Pro-Gly-Arg
Sequence number 2: Met-Ile-Thr-Leu-Ala-Ile-Pro-Val-Asn-Lys-Pro-Gly
Sequence number 3: Met-Ile-Thr-Leu-Ala-Ile-Pro-Val-Asn-Lys-Pro
Sequence number 4: Met-Ile-Thr-Leu-Ala-Ile-Pro-Val-Asn-Lys
Sequence number 5: Met-Ile-Thr-Leu-Ala-Ile-Pro-Val-Asn
SEQ ID NO: 6: Met-Ile-Thr-Leu-Ala-Ile-Pro-Val
Sequence number 7: Met-Ile-Thr-Leu-Ala-Ile-Pro
Sequence number 8: Met-Ile-Thr-Leu-Ala-Ile
SEQ ID NO: 9: Met-Ile-Thr-Leu-Ala
SEQ ID NO: 10: Met-Ile-Thr-Leu
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP08466796A JP3567350B2 (en) | 1996-03-13 | 1996-03-13 | Anti-alopecia |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP08466796A JP3567350B2 (en) | 1996-03-13 | 1996-03-13 | Anti-alopecia |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH09249535A JPH09249535A (en) | 1997-09-22 |
JP3567350B2 true JP3567350B2 (en) | 2004-09-22 |
Family
ID=13837072
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP08466796A Expired - Lifetime JP3567350B2 (en) | 1996-03-13 | 1996-03-13 | Anti-alopecia |
Country Status (1)
Country | Link |
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JP (1) | JP3567350B2 (en) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1132396A4 (en) * | 1998-11-13 | 2002-05-08 | Kyowa Hakko Kogyo Kk | Physiologically active peptides |
AU2001218024A1 (en) * | 2000-06-19 | 2002-01-02 | University Of Southern California | Methods for treating and preventing alopecia |
US6747008B1 (en) | 2000-06-19 | 2004-06-08 | University Of Southern California | Methods for treating and preventing alopecia |
DE10106852A1 (en) * | 2001-02-14 | 2002-09-05 | T Luger | Anti-inflammatory compounds |
ATE551048T1 (en) * | 2004-06-28 | 2012-04-15 | Dsm Ip Assets Bv | COSMETIC COMPOSITIONS CONTAINING PROTEIN HYDROLYSATES |
JP5048372B2 (en) * | 2007-03-30 | 2012-10-17 | 日本サプリメント株式会社 | Hair growth promoter |
JP5216414B2 (en) * | 2007-10-11 | 2013-06-19 | ロート製薬株式会社 | Hair restorer |
JP5166116B2 (en) * | 2007-10-16 | 2013-03-21 | ロート製薬株式会社 | Hair restorer |
-
1996
- 1996-03-13 JP JP08466796A patent/JP3567350B2/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
JPH09249535A (en) | 1997-09-22 |
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