JP6477005B2 - Reducing inhibitor of stratum corneum moisture content - Google Patents
Reducing inhibitor of stratum corneum moisture content Download PDFInfo
- Publication number
- JP6477005B2 JP6477005B2 JP2015036220A JP2015036220A JP6477005B2 JP 6477005 B2 JP6477005 B2 JP 6477005B2 JP 2015036220 A JP2015036220 A JP 2015036220A JP 2015036220 A JP2015036220 A JP 2015036220A JP 6477005 B2 JP6477005 B2 JP 6477005B2
- Authority
- JP
- Japan
- Prior art keywords
- stratum corneum
- moisture content
- present
- minoxidil
- improving
- 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.)
- Active
Links
- 210000000434 stratum corneum Anatomy 0.000 title claims description 38
- 239000003112 inhibitor Substances 0.000 title description 12
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- 229960003632 minoxidil Drugs 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 230000007423 decrease Effects 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- 230000007613 environmental effect Effects 0.000 description 10
- 210000003491 skin Anatomy 0.000 description 9
- 230000009471 action Effects 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000003779 hair growth Effects 0.000 description 6
- 210000004761 scalp Anatomy 0.000 description 6
- 239000002537 cosmetic Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- 201000004384 Alopecia Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 230000037336 dry skin Effects 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 210000004209 hair Anatomy 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
Images
Landscapes
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、外的環境要因により誘発される、角層の水分量低下に有効な抑制剤及び／又は改善剤に関する。詳しくは、頭皮を含む皮膚の紫外線照射によって誘発される、角層の水分量低下の抑制剤及び／又は改善剤に関する。さらに詳しくは、ミノキシジルの新規用途に関する。 The present invention relates to an inhibitor and / or an improving agent effective in reducing the water content of the stratum corneum induced by external environmental factors. More specifically, the present invention relates to an inhibitor and / or an improver for reducing water content in the stratum corneum induced by ultraviolet irradiation of the skin including the scalp. More specifically, it relates to a novel use of minoxidil.
皮膚は紫外線や低湿度などの外的環境要因から、内部環境を守るための防御機構を担っているが、そのほとんどの役割を最外殻に位置する角層が果たしている。外的環境要因としての紫外線の影響は大きく、紫外線が照射されると、皮膚の防御反応を担う角層に異常がおこり、角層水分量が低下する（非特許文献１）。
頭部は顔面の約２倍紫外線の害をうける部位である。長期間にわたる紫外線暴露は、脱毛を引き起こす一因となり得るため、男性型脱毛症においても、光悪化する皮膚疾患としての頭皮異常が注目されてきている（非特許文献２）。紫外線の害を防ぐためには、従来、紫外線吸収剤や紫外線散乱剤といった紫外線防御剤が用いられてきた。しかし、これらは皮膚に対する刺激性も高い。
The skin plays a defense mechanism to protect the internal environment from external environmental factors such as ultraviolet rays and low humidity, and the stratum corneum located in the outermost shell plays most of its role. The influence of ultraviolet rays as an external environmental factor is great, and when ultraviolet rays are irradiated, abnormalities occur in the stratum corneum responsible for the defense reaction of the skin, and the moisture content of the stratum corneum decreases (Non-patent Document 1).
The head is a part that is damaged by ultraviolet rays about twice as much as the face. Since exposure to ultraviolet rays over a long period of time can contribute to hair loss, scalp abnormalities have been attracting attention as a skin disease that worsens light even in male pattern alopecia (Non-patent Document 2). In order to prevent damage from ultraviolet rays, conventionally, ultraviolet protective agents such as ultraviolet absorbers and ultraviolet scattering agents have been used. However, they are also highly irritating to the skin.
一方、ミノキシジルは、外用塗布により優れた育毛・発毛効果を発揮する薬剤であり、これを配合した外用剤が国内外で市販されている。ミノキシジルは毛包に作用し、様々な成長因子を産生することで、優れた成長期延長作用、成長期誘導作用を持つことが報告されている（非特許文献３）。ミノキシジルを頭皮に塗布することで、発毛・育毛作用が発揮されるが、頭皮を含む皮膚の角層水分量に対して如何なる効果を有するのかは、これまでに全く知られていない。 Minoxidil, on the other hand, is a drug that exhibits an excellent hair-growth / hair-growth effect when applied externally, and external preparations containing this are marketed in Japan and overseas. It has been reported that minoxidil acts on hair follicles and produces various growth factors, thereby having an excellent growth period extending action and growth period inducing action (Non-patent Document 3). By applying minoxidil to the scalp, hair growth / hair growth action is exhibited, but it has not been known at all what effect it has on the stratum corneum moisture content of the skin including the scalp.
本発明の目的は、外的環境によって誘発される角層水分量の低下を抑制及び／又は改善する手段を提供することである。 An object of the present invention is to provide a means for suppressing and / or improving the decrease in stratum corneum water content induced by the external environment.
本発明者らは、上記目的を達成するために鋭意検討した結果、ミノキシジルが、外的環境、特に紫外線照射によって誘発される角層の水分量低下を抑制及び／又は改善する作用を有することを見出し、本発明を完成するに至った。
すなわち、本発明は、
（１）ミノキシジルを有効成分とする、外的環境要因に起因する角層水分量低下の抑制及び／又は改善剤、
（２）外的環境要因が紫外線である、（１）に記載の角層水分量低下の抑制及び／又は改善剤、
（３）剤形が外用剤である、（１）又は（２）のいずれかに記載の角層水分量低下の抑制及び／又は改善剤、
である。
As a result of intensive studies to achieve the above object, the present inventors have found that minoxidil has an action of suppressing and / or improving a decrease in water content of the stratum corneum induced by an external environment, particularly ultraviolet irradiation. The headline and the present invention were completed.
That is, the present invention
(1) An agent for suppressing and / or improving stratum corneum moisture content caused by external environmental factors, comprising minoxidil as an active ingredient,
(2) The suppression and / or improving agent of stratum corneum moisture content according to (1), wherein the external environmental factor is ultraviolet rays,
(3) Suppression and / or improving agent of stratum corneum moisture content according to either (1) or (2), wherein the dosage form is an external preparation,
It is.
本発明の角層水分量の低下抑制剤及び／又は改善剤は、外的環境要因、特に紫外線により誘発される角層の水分量低下を抑制又は改善することができる。 The stratum corneum water content lowering inhibitor and / or the improving agent of the present invention can suppress or improve a decrease in water content of the stratum corneum induced by external environmental factors, particularly ultraviolet rays.
本発明の角層水分量の低下抑制剤及び／又は改善剤は、有効成分としてミノキシジルからなるものである。本発明の角層水分量の低下抑制剤及び／又は改善剤は、特定の要因すなわち外的環境要因により誘発される角層水分量の低下を抑制及び／又は改善する作用を有する。したがって、本発明のミノキシジルは、外的環境要因により低下する角層水分量を増加させる目的のために使用すればよい。 The stratum corneum moisture content reduction inhibitor and / or improver of the present invention comprises minoxidil as an active ingredient. The stratum corneum water content lowering inhibitor and / or improving agent of the present invention has an action of suppressing and / or improving the stratum corneum water content lowering induced by a specific factor, that is, an external environmental factor. Therefore, the minoxidil of the present invention may be used for the purpose of increasing the amount of stratum corneum moisture that decreases due to external environmental factors.
本発明において、外的環境要因とは、外的環境由来の角層の水分量を低下させる因子であり、例えば低湿度、低温、紫外線等が挙げられる。 In the present invention, the external environmental factor is a factor that reduces the moisture content of the stratum corneum derived from the external environment, and examples thereof include low humidity, low temperature, and ultraviolet rays.
本発明の角層水分量の低下抑制剤及び／又は改善剤は、化粧品、医薬部外品又は医薬品等として提供することができる。本発明の角層水分量の低下抑制剤及び／又は改善剤は、外用塗布により、外的環境由来の角層水分量の低下を抑制及び／又は改善することができる。本発明の角層水分量の低下抑制剤及び／又は改善剤の剤形は、特に限定されるものではないが、頭皮を含む皮膚に適用可能な製剤として使用することができる。例えば、ローション剤、液剤、クリーム剤、軟膏剤、ゲル剤、スプレー剤、フォーム剤等の外用剤が挙げられる。これらは公知の方法で製造することができる。製造に際しては、本発明の効果を損なわない範囲で、化粧品、医薬部外品又は医薬品に含有可能な種々の添加物を配合することができる。また、本発明においては、さらにプロピレングリコールまたは１，３−ブチレングリコールを配合すると、ミノキシジルの溶解性向上の点でより好ましい。 The stratum corneum moisture content reduction inhibitor and / or improver of the present invention can be provided as cosmetics, quasi-drugs, pharmaceuticals, and the like. The decrease inhibitor and / or improver of the stratum corneum moisture amount of the present invention can suppress and / or improve a decrease in stratum corneum moisture amount derived from the external environment by external application. The dosage form of the stratum corneum moisture content lowering inhibitor and / or improving agent of the present invention is not particularly limited, but can be used as a preparation applicable to skin including scalp. Examples include external preparations such as lotions, liquids, creams, ointments, gels, sprays, foams and the like. These can be produced by known methods. In the production, various additives that can be contained in cosmetics, quasi-drugs, or pharmaceuticals can be blended within a range that does not impair the effects of the present invention. In the present invention, it is more preferable to further add propylene glycol or 1,3-butylene glycol in terms of improving the solubility of minoxidil.
ミノキシジルの配合量は、作用効果或いは当該角層水分量の低下抑制剤及び／又は改善剤の剤型等により適宜調整されるものであるが、通常角層水分量の低下抑制剤及び／又は改善剤の総量を基準として、固形分換算で０．１〜１０ｗ／ｗ％が好ましく、さらに好ましくは１〜５ｗ／ｗ％である。 The compounding amount of minoxidil is appropriately adjusted depending on the action effect or the dosage form of the stratum corneum water content lowering inhibitor and / or improving agent, but usually the stratum corneum water content lowering inhibitor and / or improvement. Based on the total amount of the agent, it is preferably 0.1 to 10 w / w%, more preferably 1 to 5 w / w% in terms of solid content.
さらに、本発明の角層水分量の低下抑制剤及び／又は改善剤においては、本発明の効果を損なわない範囲で、通常外用に用いられる種々の成分を配合することができる。 Furthermore, in the stratum corneum moisture content lowering inhibitor and / or improving agent of the present invention, various components that are usually used for external use can be blended within a range not impairing the effects of the present invention.
以下に実施例および試験例をあげ、本発明をさらに具体的に説明するが、本発明は実施例に限定されない。 EXAMPLES The present invention will be described more specifically with reference to examples and test examples below, but the present invention is not limited to the examples.
（試験例１）紫外線を照射した角層水分低下に対する作用
＜試験方法＞
以下表１の処方１〜２、及び対照処方１を調製した。
へアレスマウス（Ｈｏｓ：ＨＲ−１、雄）は６週齢で入荷し、以下の飼育環境で入荷日を含めて５日間馴化させた。温度２３±３℃、湿度５０±２０％、照明時間約１２時間、換気回数１０回以上／時間、固型飼料（ＭＦ、オリエンタル酵母工業株式会社）および飲料水（殺菌水）は自由摂取とした。馴化終了後、以下表２に記載の群分けを行った。
群分け後、Ｂ〜Ｅ群については、紫外線照射を行った。紫外線照射は、ＵＶＢランプ（Ｍ−ＤＭＲ−８０形、ＦＬ２０Ｓ・Ｅ−３０／ＤＭＲ ＦＧ−１Ｐ、テルモ・クリニカルサプライ株式会社）を用いて、マウス背部に最小紅斑量以下の条件であるＵＶＢ７０ｍＪ／ｃｍ2を１日１回、１日置きに計３回照射した。処方１〜２、及び対照処方１の投与は、１００μＬ／個体を紫外線照射開始日より１日１回５日間連続でマウス背部皮膚に塗布した。なお、紫外線照射実施日は照射後に塗布を行った。角層水分量の測定は、コルネオメーター（ＣＭ８２５、Ｃｏｕｇｒａｇｅ＋Ｋｈａｚａｋａ ｅｌｅｃｔｒｏｎｉｃ ＧｍｂＨ社）を用いて、最終塗布の翌日に行った。
(Test Example 1) Action on moisture reduction in stratum corneum irradiated with ultraviolet rays <Test method>
Formulations 1 and 2 in Table 1 below and Control Formulation 1 were prepared.
Hairless mice (Hos: HR-1, male) were received at the age of 6 weeks and acclimated for 5 days including the arrival date in the following breeding environment. Temperature 23 ± 3 ° C., humidity 50 ± 20%, lighting time about 12 hours, ventilation rate 10 times / hour, solid feed (MF, Oriental Yeast Co., Ltd.) and drinking water (sterilized water) were freely ingested . After the acclimatization, the grouping described in Table 2 was performed.
After grouping, UV irradiation was performed for the groups B to E. UVB irradiation is performed using a UVB lamp (M-DMR-80, FL20S • E-30 / DMR FG-1P, Terumo Clinical Supply Co., Ltd.), UVB 70 mJ / cm, which is a condition below the minimum erythema amount on the back of the mouse. 2 was irradiated once a day for a total of 3 times every other day. For the administration of Formulations 1 and 2 and Control Formulation 1, 100 μL / individual was applied to the back skin of mice once a day for 5 consecutive days from the date of starting ultraviolet irradiation. In addition, application | coating was performed after irradiation on the ultraviolet irradiation implementation day. The stratum corneum moisture content was measured using a Corneometer (CM825, Cougrage + Khazaka electronic GmbH) on the day after the final application.
＜試験結果＞
図１に、試験例１における角層水分量を示す。紫外線の照射により、角層水分量は有意に低下したが（投与群ＡとＢとの比較）、ミノキシジルを塗布した投与群Ｄ、Ｅでは、角層水分量が有意に高まった（投与群Ｃと、投与群Ｄ、Ｅとの比較）。ミノキシジルを投与しなかった投与群Ｃでは、改善作用は認められなかった。
すなわち、ミノキシジルには、紫外線照射により誘発される角層水分量低下を抑制及び／又は改善する効果があることが示された。
<Test results>
FIG. 1 shows the stratum corneum moisture content in Test Example 1. The stratum corneum water content decreased significantly by irradiation with ultraviolet rays (comparison between administration groups A and B), but in administration groups D and E coated with minoxidil, the stratum corneum water content increased significantly (administration group C). And comparison with administration groups D and E). In the administration group C in which minoxidil was not administered, no improving action was observed.
That is, it was shown that minoxidil has an effect of suppressing and / or improving the decrease in stratum corneum water content induced by ultraviolet irradiation.
本発明の角層水分量低下の抑制及び／又は改善剤は、外的環境要因、特に紫外線により誘発される角層の水分量低下を抑制及び／又は改善するために用いられる。本発明の角層水分量低下の抑制及び／又は改善剤は、化粧品、医薬部外品又は医薬品の分野に利用可能である。本発明により、紫外線により誘発されるダメージ肌、肌荒れ、乾燥肌、シミ、シワの改善・緩和が期待できる。 The agent for suppressing and / or improving the stratum corneum moisture content of the present invention is used to suppress and / or improve the stratum corneum moisture content induced by external environmental factors, particularly ultraviolet rays. The agent for suppressing and / or improving the stratum corneum moisture content of the present invention can be used in the field of cosmetics, quasi drugs or pharmaceuticals. According to the present invention, improvement / reduction of damaged skin, rough skin, dry skin, spots and wrinkles induced by ultraviolet rays can be expected.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2015036220A JP6477005B2 (en) | 2014-03-25 | 2015-02-26 | Reducing inhibitor of stratum corneum moisture content |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2014061257 | 2014-03-25 | ||
| JP2014061257 | 2014-03-25 | ||
| JP2015036220A JP6477005B2 (en) | 2014-03-25 | 2015-02-26 | Reducing inhibitor of stratum corneum moisture content |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2015193591A JP2015193591A (en) | 2015-11-05 |
| JP6477005B2 true JP6477005B2 (en) | 2019-03-06 |
Family
ID=54432992
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015036220A Active JP6477005B2 (en) | 2014-03-25 | 2015-02-26 | Reducing inhibitor of stratum corneum moisture content |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP6477005B2 (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070270336A1 (en) * | 2006-05-12 | 2007-11-22 | Shiseido Company, Ltd. | Method for accelerating cutaneous barrier recovery |
-
2015
- 2015-02-26 JP JP2015036220A patent/JP6477005B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2015193591A (en) | 2015-11-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2002309036B2 (en) | Preparation for hair and/or scalp | |
| AR047513A1 (en) | METHODS AND COMPOSITIONS FOR THE TREATMENT OF CHANGES IN THE SKIN RELATED TO AGING AND DAMAGES CAUSED BY THE ENVIRONMENT | |
| JPH05320028A (en) | Hair-growing agent | |
| JP5824739B2 (en) | Topical fungicides for the treatment of nail disorders | |
| JP7450324B2 (en) | Composition containing D-chiro-inositol | |
| US20070154432A1 (en) | Compositions and methods for hair growth | |
| RU2012149868A (en) | SEED POLYSACCHARIDE FOR APPLICATION IN TREATMENT OF INFLAMMATORY DISEASES | |
| KR20150066811A (en) | Cosmetics compositions for hair growth promoter | |
| WO2018000060A1 (en) | Anti-acne sunscreen composition | |
| JP6477005B2 (en) | Reducing inhibitor of stratum corneum moisture content | |
| JP6382668B2 (en) | Hair restoration cosmetics | |
| JP2002332240A (en) | Hair grower composition | |
| KR20110138709A (en) | Composition for improving acne comprising 5-aminolevulinic acid or ester thereof | |
| CN1738591A (en) | Method of stimulating hair growth using benzopyrans | |
| JP6903411B2 (en) | Topical composition | |
| JP4032246B2 (en) | White hair prevention and improvement agent | |
| JP5876103B2 (en) | Skin preparation | |
| KR101321045B1 (en) | Composition of preventing hair loss and promoting hair growth | |
| JP2008094784A (en) | Hair growing or restoring agent | |
| JP2004231630A (en) | Hair-growing composition | |
| KR20170134109A (en) | Composition for promoting the hair growth comprising Tabersonine | |
| CN104306168A (en) | Application of N-(4-chloro-2,5-dimethoxyphenyl)-5-isopropyl-2-methoxybenzenesulfonamide in promotion of hair growth | |
| JP2010105932A (en) | Hair-nourishing cosmetic | |
| WO2014092007A1 (en) | Hair growing agent | |
| KR20150051075A (en) | A body hair growth inhibition composition comprising palmatine as an effective ingredient |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180216 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20181002 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181129 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20190108 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190121 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6477005 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |