JPH083049A - Therapeutic agent for epidermal proliferation disease - Google Patents
Therapeutic agent for epidermal proliferation diseaseInfo
- Publication number
- JPH083049A JPH083049A JP9462095A JP9462095A JPH083049A JP H083049 A JPH083049 A JP H083049A JP 9462095 A JP9462095 A JP 9462095A JP 9462095 A JP9462095 A JP 9462095A JP H083049 A JPH083049 A JP H083049A
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- Japan
- Prior art keywords
- therapeutic agent
- compound
- epidermal
- proliferation disease
- agent
- 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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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Pyrane Compounds (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、有用な表皮増殖疾患治
療剤に関する。さらに詳しくは、本発明はアスコルビン
酸とトコフェロールとのリン酸ジエステル化合物または
その薬理学的に許容できる塩を含有してなる有用な表皮
増殖疾患治療剤に関する。FIELD OF THE INVENTION The present invention relates to a useful therapeutic agent for epidermal proliferation disease. More specifically, the present invention relates to a useful therapeutic agent for epidermal proliferation disease, which comprises a phosphodiester compound of ascorbic acid and tocopherol or a pharmacologically acceptable salt thereof.
【０００２】[0002]
【従来の技術】皮膚の表皮は外界から皮膚の内部環境を
保護する役目を果たしている。この表皮がなんらかの原
因によって損傷を受けると、表皮は強い増殖を引き起こ
し、その結果、乾癬、魚鱗癬、掌蹠膿庖症、掌蹠角化
症、毛孔性紅色粃糠斑などの表皮増殖疾患が生じる。こ
のうち、乾癬は炎症性角化症ともいわれる皮膚疾患の代
表的なものの一つである。その大きさや形はさまざま
で、赤味の強い（紅斑）、正常皮膚面よりわずかに***
し（浸潤）、しばしば厚い鱗屑を伴う（落屑）、単発〜
無数の病巣を形成する。乾癬は一度発症すると難治で、
軽快増悪を繰り返しながら生涯持続する例が殆どであ
る。The epidermis of the skin serves to protect the internal environment of the skin from the outside world. When the epidermis is damaged by any cause, the epidermis causes strong proliferation, resulting in epidermal proliferative diseases such as psoriasis, ichthyosis, palmoplantar purulent disease, palmoplantar keratoses, and erythema erythematosus plaque. Of these, psoriasis is one of the representative skin diseases also called inflammatory keratoses. They vary in size and shape and have a strong reddish color (erythema), slightly elevated from the normal skin surface (infiltration), often accompanied by thick scales (exfoliation), and a single occurrence ~
Form innumerable lesions. Psoriasis is intractable once it occurs,
In most of the cases, lightness and aggravation are repeated and persist for life.
【０００３】従来、乾癬などの表皮増殖疾患治療剤とし
ては、ステロイド系抗炎症剤および免疫抑制剤などが用
いられている。このうち、ステロイド系抗炎症剤は、乾
癬などに対する治療効果は優れているものの、真菌・細
菌の感染やその増悪、紫斑および口囲皮膚炎などの種々
の副作用を引き起こす。このため、ステロイド系抗炎症
剤を多量にまたは長期間に亘って投与する場合には、こ
れら副作用の発現に注意しつつ慎重に行う必要があると
いう欠点がある。また、免疫抑制剤は、腎障害や高血圧
症などの副作用を引き起こすという欠点がある。さら
に、最近では乾癬などの表皮増殖疾患治療のためビタミ
ンＤ製剤も用いられているが、必ずしも満足すべきもの
とは言いがたい。Heretofore, steroidal anti-inflammatory agents, immunosuppressive agents and the like have been used as therapeutic agents for epidermal proliferative diseases such as psoriasis. Of these, steroidal anti-inflammatory agents have excellent therapeutic effects on psoriasis and the like, but cause various side effects such as fungal / bacterial infection and its exacerbation, purpura, and periorbital dermatitis. Therefore, there is a drawback in that when a large amount of a steroidal anti-inflammatory drug is administered or over a long period of time, it is necessary to be careful while paying attention to the occurrence of these side effects. In addition, immunosuppressants have the drawback of causing side effects such as renal damage and hypertension. Furthermore, recently, vitamin D preparations have been used for treating epidermal proliferative diseases such as psoriasis, but it is not always satisfactory.
【０００４】[0004]
【発明が解決しようとする課題】したがって、皮膚科治
療の分野において、さらに優れた表皮増殖疾患治療剤を
求めて、鋭意研究・開発が進められている。このような
状況下、本発明者らは、アスコルビン酸とトコフェロー
ルとのリン酸ジエステル化合物の薬効を鋭意検討するう
ちに、これら化合物が乾癬などの表皮増殖疾患治療剤と
して有用であることを見出した。本発明は、この新知見
に基づき完成されたものである。Therefore, in the field of dermatological treatment, earnest research and development are being pursued in order to find a better therapeutic agent for epidermal proliferation disease. Under such circumstances, the present inventors have found that these compounds are useful as therapeutic agents for epidermal proliferative diseases such as psoriasis, while diligently examining the drug efficacy of phosphodiester compounds of ascorbic acid and tocopherol. . The present invention has been completed based on this new finding.
【０００５】本発明は、リン酸ジエステル化合物を含有
する、優れた表皮増殖疾患治療剤を提供するものであ
る。The present invention provides an excellent therapeutic agent for epidermal proliferation disease containing a phosphodiester compound.
【０００６】[0006]
【課題を解決するための手段】すなわち、本発明は、
（１）次の式That is, the present invention is
(1) The following formula
【０００７】[0007]
【化２】 Embedded image
【０００８】［式中、Ｒ1 およびＲ2 は、同一または異
なって水素原子またはメチル基を示す。］で表されるリ
ン酸ジエステル化合物またはその薬理学的に許容できる
塩（以下「本化合物」という。）を含有してなる表皮増
殖疾患治療剤、（２）局所投与剤である上記（１）記載
の表皮増殖疾患治療剤、（３）局所投与剤の剤型が軟膏
剤、水性液剤またはゲル化剤である上記（２）記載の表
皮増殖疾患治療剤、（４）軟膏剤およびゲル化剤におけ
る上記化合物またはその薬理学的に許容できる塩の濃度
が０．０１〜５（ｗ／ｗ）％である上記（３）記載の表
皮増殖疾患治療剤、および（５）水性液剤における上記
化合物またはその薬理学的に許容できる塩の濃度が０．
０１〜５（ｗ／ｖ）％である上記（３）記載の表皮増殖
疾患治療剤に関する。[In the formula, R 1 and R 2 are the same or different and each represents a hydrogen atom or a methyl group. ] The epidermal proliferation disease therapeutic agent containing the phosphodiester compound represented by these or its pharmacologically acceptable salt (henceforth "this compound"), (2) above-mentioned (1) which is a local administration agent. The therapeutic agent for epidermal proliferation disease according to the above, (3) The therapeutic agent for epidermal proliferation disease according to the above (2), wherein the dosage form of the topical administration agent is an ointment, an aqueous solution or a gelling agent, (4) ointment and gelling agent The therapeutic agent for epidermal proliferation disease according to (3) above, wherein the concentration of the compound or a pharmaceutically acceptable salt thereof is 0.01 to 5 (w / w)%, and (5) the compound in an aqueous solution or The concentration of the pharmacologically acceptable salt is 0.
The present invention relates to the therapeutic agent for epidermal proliferation disease according to the above (3), which is 01 to 5 (w / v)%.
【０００９】本発明の表皮増殖疾患治療剤に用いられる
本化合物は、たとえば特公平２−４４４７８号や特開昭
６２−２０５０９１号公報記載の方法またはこれらに準
じて適宜合成することができる。The present compound used for the therapeutic agent for epidermal hyperplasia of the present invention can be appropriately synthesized, for example, by the methods described in JP-B-2-44478 and JP-A-62-205091, or by modifications thereof.
【００１０】本発明の表皮増殖疾患治療剤に用いられる
本化合物は、抗白内障剤、更年期障害予防・治療剤、美
肌作用を有する化粧品（特公平２−４４４７８号）、抗
炎症剤（特公平１−２７０４４号）、抗潰瘍剤（特開昭
６３−２７０６２６号）、虚血性臓器障害予防・治療剤
（特開平２−１１１７２２号）さらにメイラード反応阻
害剤（特開平３−１６１４４４号）などの種々の用途が
既に知られている。The compound used in the therapeutic agent for epidermal hyperplasia of the present invention is an anti-cataract agent, a prophylactic / therapeutic agent for menopausal disorders, a cosmetic having a skin-skinning effect (Japanese Patent Publication No. 2-44478), an anti-inflammatory agent (Japanese Patent Publication No. -27044), an anti-ulcer agent (JP-A-63-270626), a preventive / therapeutic agent for ischemic organ injury (JP-A-2-111722), and a Maillard reaction inhibitor (JP-A-3-161444). The uses of are already known.
【００１１】本発明の表皮増殖疾患治療剤によって治療
されうる疾患としては、乾癬、魚鱗癬、掌蹠膿庖症、掌
蹠角化症、毛孔性紅色粃糠斑などが挙げられる。Examples of diseases that can be treated by the therapeutic agent for epidermal hyperplasia of the present invention include psoriasis, ichthyosis, palmoplantar pus, keratokeratosis palmaris, and pityriasis erythema pilaris.
【００１２】本発明の表皮増殖疾患治療剤に用いられる
本化合物は、遊離のものであっても、その薬理学的に許
容できる塩であっても、本発明の目的のため適宜に使用
することができる。その薬理学的に許容できる塩として
は、たとえばナトリウム塩、カリウム塩などのアルカリ
金属塩やカルシウム塩、マグネシウム塩などのアルカリ
土類金属塩などが例示されるが、これら以外の塩であっ
ても薬理学的に許容できる塩であればいずれのものであ
っても適宜に使用することができる。The present compound used for the therapeutic agent for epidermal proliferation disease of the present invention, whether it is a free compound or a pharmacologically acceptable salt thereof, is appropriately used for the purpose of the present invention. You can Examples of the pharmacologically acceptable salt include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, and other salts. Any salt can be used as appropriate as long as it is a pharmacologically acceptable salt.
【００１３】本発明の表皮増殖疾患治療剤には、目的と
必要に応じて、本化合物のうち１種または２種以上を適
宜組み合せて含有させることもできる。The therapeutic agent for epidermal proliferative disorders of the present invention may contain one or more of the present compounds in an appropriate combination depending on the purpose and need.
【００１４】本発明の表皮増殖疾患治療剤に活性成分と
して用いられる本化合物は、毒性がきわめて低く安全性
に優れているので、本発明の目的のため有利に用いるこ
とができる［たとえば、Ｌ−アスコルビン酸、ＤＬ−α
−トコフェロールリン酸ジエステルカリウム（略称：Ｅ
ＰＣ−Ｋ）のＬＤ50：経口投与５ｇ／ｋｇ（ラット）、
静脈注射１００ｍｇ／ｋｇ（ラット）以上］。The present compound, which is used as an active ingredient in the therapeutic agent for epidermal hyperplasia of the present invention, has extremely low toxicity and excellent safety, and therefore can be advantageously used for the purpose of the present invention [for example, L- Ascorbic acid, DL-α
-Tocopherol phosphate diester potassium (abbreviation: E
LD of PC-K) 50: Oral administration 5 g / kg (rat),
Intravenous injection 100 mg / kg (rat) or more].
【００１５】本発明の表皮増殖疾患治療剤は、経口的
（たとえば錠剤など）にあるいは非経口的（たとえば軟
膏剤、水性液剤、ゲル化剤などの局所投与）に適宜に使
用される。製剤の形態としては、たとえば軟膏剤、水性
液剤、ゲル化剤、錠剤、顆粒または散剤などが挙げら
れ、いずれも公知の方法により適宜調製することができ
る。これら製剤には通常用いられる賦形剤、結合剤、崩
壊剤、分散剤、再吸収促進剤、緩衝剤、界面活性剤、溶
解補助剤、保存剤、乳化剤、等張化剤、安定化剤やｐＨ
調整剤などの各種添加剤を適宜使用してもよい。The therapeutic agent for epidermal proliferation disease of the present invention is appropriately used orally (for example, tablets) or parenterally (for example, topical administration of ointments, aqueous solutions, gelling agents, etc.). Examples of the form of the preparation include ointments, aqueous liquids, gelling agents, tablets, granules or powders, all of which can be appropriately prepared by known methods. For these preparations, commonly used excipients, binders, disintegrants, dispersants, reabsorption promoters, buffers, surfactants, solubilizers, preservatives, emulsifiers, isotonic agents, stabilizers and pH
Various additives such as a regulator may be appropriately used.
【００１６】本化合物を表皮増殖疾患治療剤として使用
する場合の用量は、使用する化合物の種類、対象疾患の
種類、患者の年齢、体重、適応症状およびその剤型など
によって異なるが、たとえば局所投与用の軟膏剤および
ゲル化剤としては、その濃度が約０．０１〜５（ｗ／
ｗ）％、好ましくは約０．０５〜２（ｗ／ｗ）％程度の
ものを成人１日数回患部に塗布するのがよい。また、局
所投与用の水性液剤としては、濃度が約０．０１〜５
（ｗ／ｖ）％、好ましくは約０．０５〜２（ｗ／ｖ）％
程度のものを成人１日数回患部に塗布するのがよい。さ
らに、内服剤の場合は、成人１日数回、１回量約１０ｍ
ｇ〜１０００ｍｇ程度投与するのがよい。When the compound is used as a therapeutic agent for epidermal proliferation disease, the dose varies depending on the type of compound used, the type of target disease, the patient's age, body weight, indication symptoms and its dosage form. As an ointment and a gelling agent for use, its concentration is about 0.01 to 5 (w /
It is advisable to apply w)%, preferably about 0.05 to 2 (w / w)%, to the affected area several times a day for adults. In addition, the concentration of the aqueous solution for topical administration is about 0.01 to 5
(W / v)%, preferably about 0.05-2 (w / v)%
It is advisable to apply the same amount to the affected area several times a day for adults. Furthermore, in the case of an oral drug, an adult dose is about 10m several times a day.
It is preferable to administer about g to 1000 mg.
【００１７】本発明の表皮増殖疾患治療剤には、本発明
の目的に反しないかぎり、その他の表皮増殖疾患治療成
分および／または別種の薬効を奏する成分を適宜含有さ
せてもよい。The therapeutic agent for epidermal proliferative diseases of the present invention may appropriately contain other therapeutic components for epidermal proliferative diseases and / or components exhibiting other types of medicinal effects, as long as the object of the present invention is not violated.
【００１８】[0018]
【実施例】以下、実施例および製剤実施例を挙げて、本
発明をさらに詳細に説明するが、本発明はこれらに限定
されるものではない。The present invention will be described in more detail with reference to Examples and Formulation Examples, but the present invention is not limited thereto.
【００１９】［実施例１］マウス尋常性乾癬モデルに対
する本化合物の効果 １２−Ｏ−テトラデカノイルフォルボール−１３−アセ
テート(12-O-tetradecanoylphorbol-13-acetate)（略
称：ＴＰＡ）を用いた、マウス尋常性乾癬モデルに対す
る本化合物の効果について試験した。[Example 1] A model for mouse psoriasis vulgaris model
Effect of this compound on 12-O-tetradecanoylphorbol-13-acetate (12-O-tetradecanoylphorbol-13-acetate) (abbreviation: TPA) was used to test the effect of this compound on a mouse psoriasis model did.
【００２０】試験物質: （１）メタノール（対照群） ２０μｌ／耳介 （２）Ｌ−アスコルビン酸、ＤＬ−α−トコフェロール
リン酸ジエステルカリウム（略称：ＥＰＣ−Ｋ）
５００μｇ／２０μｌ／耳介 （３）ＥＰＣ−Ｋ １０００μｇ／２０μｌ
／耳介 （４）吉草酸べタメタゾン ２５μｇ／２０μｌ
／耳介 Test substance : (1) Methanol (control group) 20 μl / auricle (2) L-ascorbic acid, DL-α-tocopherol phosphate diester potassium (abbreviation: EPC-K)
500 μg / 20 μl / Auricle (3) EPC-K 1000 μg / 20 μl
/ Auricle (4) Betamethasone valerate 25 μg / 20 μl
/ Auricle
【００２１】試験方法：日本エスエルシー株式会社（Ｓ
ＬＣ）より購入した６週齢ｄｄＹ系雄性マウスを本試験
に供した。ＴＰＡメタノール溶液２０ｎｍｏｌ／４０μ
ｌをマウス右側耳介外側表面部の全体に塗布し、６、２
４、４８、７２時間後にダイヤルシックネスゲージにて
耳介の厚みを測定し耳介腫脹率（％）を算出した。ま
た、ＴＰＡ塗布７２時間後にマウスを屠殺し、左右の耳
介を直径８ｍｍのパンチャーにて打ち抜き、耳介表皮を
剥離し表皮重量をそれぞれ測定し、さらに左側耳介の表
皮重量に対する右側耳介の表皮重量増加率（％）を算出
した。試験物質は、メタノールによるＴＰＡとの用時混
合溶液として、マウス右側耳介外側表面部に４０μｌ適
用し、その後各試験物質のメタノール溶液を１日１回２
日間にわたって４０μｌずつ適用した。また、試験物質
の薬効評価の検定にはダネット法を用いた。 Test method : Japan SLC, Inc. (S
A 6-week-old male ddY strain mouse purchased from LC) was subjected to this test. TPA methanol solution 20 nmol / 40μ
1 to the entire outer surface of the auricle on the right side of the mouse,
After 4, 48 and 72 hours, the thickness of the auricle was measured with a dial thickness gauge to calculate the ear swelling rate (%). 72 hours after TPA application, the mice were sacrificed, the left and right auricles were punched out with a puncher having a diameter of 8 mm, the auricle epidermis was peeled off, and the epidermis weight was measured. The increase rate of epidermal weight (%) was calculated. The test substance was applied to the outer surface of the right auricle of the mouse in an amount of 40 μl as a mixed solution with TPA in methanol, and then a methanol solution of each test substance was applied twice a day.
40 μl was applied over the days. The Dunnett's method was used to test the efficacy of the test substance.
【００２２】試験結果：マウス尋常性乾癬モデルにおけ
る耳介表皮重量増加率および耳介腫脹率に関する結果を
表１および図１にそれぞれ示す。 Test results : Results relating to the rate of increase in epidermal epidermis weight and the rate of ear swelling in a mouse psoriasis model are shown in Table 1 and FIG. 1, respectively.
【表１】 マウス尋常性乾癬モデルにおける耳介表皮重量増加に対するＥＰＣ−Ｋの抑制効 果 群 対照 ＥＰＣ−Ｋ 吉草酸べタメタゾン 適応量／耳介 − 500μｇ 1000μｇ 25μｇ 表皮重量 110.9±68.6 52.4 ±40.1＊ 21.8±17.4＊＊ 21.0±19.9＊＊ 増加率（％） 表中の各値は、平均±標準偏差を示す（ｎ＝６〜９）。 対照群に対する有意差：＊；ｐ＜０．０５，＊＊；ｐ＜０．０１．[Table 1] Inhibitory effect of EPC-K on an increase in epidermal weight of the ear in a mouse psoriasis vulgaris model Fruit Group Control EPC-K Betamethasone valerate Adaptation amount / Auricle-500 μg 1000 μg 25 μg Skin weight 110.9 ± 68.6 52.4 ± 40.1 * 21.8 ± 17.4 ** 21.0 ± 19.9 ** Rate of increase (%) Each value in the table indicates the mean ± standard deviation (n = 6-9). Significant difference from control group: *; p <0.05, **; p <0.01.
【００２３】表１から明らかなように、本化合物５０
０、１０００μｇ塗布群においては、表皮重量増加率を
それぞれ有意に５２．８％、８０．３％抑制した。これ
に対し、ステロイド系抗炎症剤である吉草酸べタメタゾ
ン２５μｇ塗布群においては、表皮重量増加率を有意に
８１．１％抑制し、本化合物１０００μｇ塗布群と同等
の抑制作用を示したが、副作用としてマウスの体重減少
が見られた。また、耳介腫脹率においても、図１から明
らかなように、本化合物は各時間において用量依存的に
抑制効果を示した。一方、吉草酸べタメタゾン２５μｇ
塗布群は、６時間後ではかなり強い抑制効果を示した
が、２４、４８時間後においては抑制効果が弱まり、本
化合物１０００μｇ塗布群の方が強い抑制効果を示し
た。以上のことから、本発明の製剤は、表皮増殖疾患の
代表的疾患である乾癬の治療に有用であることが判っ
た。As is clear from Table 1, the present compound 50
In the 0 and 1000 μg application groups, the epidermal weight increase rate was significantly suppressed by 52.8% and 80.3%, respectively. On the other hand, in the betamethasone valerate 25 μg application group, which is a steroidal anti-inflammatory agent, the epidermal weight increase rate was significantly suppressed by 81.1%, and the same inhibitory effect as the 1000 μg application group of the present compound was shown. As a side effect, weight loss of mice was observed. As for the ear swelling rate, as is clear from Fig. 1, the present compound exhibited a dose-dependent inhibitory effect at each time. On the other hand, betamethasone valerate 25 μg
The application group showed a considerably strong inhibitory effect after 6 hours, but the inhibitory effect weakened after 24 and 48 hours, and the 1000 μg application group of the present compound showed a stronger inhibitory effect. From the above, it was found that the preparation of the present invention is useful for the treatment of psoriasis, which is a typical epidermal proliferation disease.
【００２４】 ［製剤実施例１］軟膏剤 ＥＰＣ−Ｋ １．０ｇ 親水軟膏 全量１００ｇ 以上の成分を常法により混合し、軟膏剤とする。[Formulation Example 1] Ointment EPC-K 1.0 g Hydrophilic ointment Total amount 100 g The above components are mixed by a conventional method to give an ointment.
【００２５】 ［製剤実施例２］水性液剤 ＥＰＣ−Ｋ ０．５ｇ グリセリン １．０ｇ プロピレングリコール １．５ｇ エタノール ３０ｍｌ 滅菌精製水 全量１００ｍｌ 以上の成分を常法により混合し、水性液剤とする。[Formulation Example 2] Aqueous liquid preparation EPC-K 0.5 g Glycerin 1.0 g Propylene glycol 1.5 g Ethanol 30 ml Sterilized purified water Total amount 100 ml The above components are mixed by a conventional method to prepare an aqueous liquid preparation.
【００２６】 ［製剤実施例３］ゲル化剤 ＥＰＣ−Ｋ ０．５ｇ カルボキシビニルポリマー １．０ｇ トリエタノールアミン 適量 エタノール ３０ｍｌ 滅菌精製水 全量１００ｍｌ ｐＨ７．０ 以上の成分を常法により混合し、ゲル化剤とする。[Formulation Example 3] Gelling agent EPC-K 0.5 g Carboxyvinyl polymer 1.0 g Triethanolamine Appropriate amount ethanol 30 ml Sterilized purified water Total amount 100 ml pH 7.0 The above components are mixed by a conventional method to form a gel. Use as an agent.
【００２７】［製剤実施例４］内服錠 ＥＰＣ−Ｋ １００ｍｇ 乳糖 ７５ｍｇ デンプン ２０ｍｇ ポリエチレングリコール６０００ ５ｍｇ 以上の成分を常法により混合し、１錠分の錠剤とする。
必要に応じて糖衣を付してもよい。[Formulation Example 4] Oral tablet EPC-K 100 mg Lactose 75 mg Starch 20 mg Polyethylene glycol 6000 5 mg The above ingredients are mixed by a conventional method to give a tablet for 1 tablet.
A sugar coating may be added if necessary.
【００２８】[0028]
【発明の効果】本発明の製剤は、乾癬、魚鱗癬、掌蹠膿
庖症、掌蹠角化症、毛孔性紅色粃糠斑などの表皮増殖疾
患治療剤として有用である。INDUSTRIAL APPLICABILITY The preparation of the present invention is useful as a therapeutic agent for epidermal proliferative diseases such as psoriasis, ichthyosis, palmoplantar pustulosis, palmoplantar keratoses, and erythema erythematosus pityrus of the pores.
【図１】マウス尋常性乾癬モデルにおける、経時的な耳
介腫脹率を示すグラフである。横軸は時間（ｈｒｓ）を
示し、縦軸は腫脹率（％）を示す。FIG. 1 is a graph showing the rate of ear swelling over time in a mouse psoriasis model. The horizontal axis represents time (hrs) and the vertical axis represents swelling rate (%).
□：対照（メタノール）群 ●：ＥＰＣ−Ｋ ５００μｇ群 ■：ＥＰＣ−Ｋ １０００μｇ群 △：吉草酸べタメタゾン ２５μｇ群 対照群に対する有意差：＊；ｐ＜０．０１． □: Control (methanol) group ●: EPC-K 500 μg group ■: EPC-K 1000 μg group Δ: Betamethasone valerate 25 μg group Significant difference from the control group: *; p <0.01.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 庁内整理番号 ＦＩ 技術表示箇所 // Ｃ０７Ｄ 311/72 １０２ ─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 6 Identification code Office reference number FI technical display location // C07D 311/72 102
Claims (5)
子またはメチル基を示す。］で表されるリン酸ジエステ
ル化合物またはその薬理学的に許容できる塩を含有して
なる表皮増殖疾患治療剤。1. The following formula: [In the formula, R 1 and R 2 are the same or different and each represents a hydrogen atom or a methyl group. ] The epidermal proliferation disease therapeutic agent containing the phosphodiester compound represented by these, or its pharmacologically acceptable salt.
殖疾患治療剤。2. The therapeutic agent for epidermal proliferation disease according to claim 1, which is a topical agent.
たはゲル化剤である請求項２記載の表皮増殖疾患治療
剤。3. The therapeutic agent for epidermal proliferation disease according to claim 2, wherein the dosage form of the topical administration agent is an ointment, an aqueous solution or a gelling agent.
物またはその薬理学的に許容できる塩の濃度が０．０１
〜５（ｗ／ｗ）％である請求項３記載の表皮増殖疾患治
療剤。4. The concentration of the above compound or a pharmaceutically acceptable salt thereof in the ointment and gelling agent is 0.01.
The therapeutic agent for epidermal hyperplasia according to claim 3, which is -5% (w / w)%.
薬理学的に許容できる塩の濃度が０．０１〜５（ｗ／
ｖ）％である請求項３記載の表皮増殖疾患治療剤。5. The concentration of the compound or a pharmacologically acceptable salt thereof in the aqueous liquid preparation is 0.01 to 5 (w /
v)%, The therapeutic agent for epidermal proliferation disease according to claim 3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9462095A JPH083049A (en) | 1994-04-22 | 1995-04-20 | Therapeutic agent for epidermal proliferation disease |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8424894 | 1994-04-22 | ||
| JP6-84248 | 1994-04-22 | ||
| JP9462095A JPH083049A (en) | 1994-04-22 | 1995-04-20 | Therapeutic agent for epidermal proliferation disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH083049A true JPH083049A (en) | 1996-01-09 |
Family
ID=26425311
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9462095A Pending JPH083049A (en) | 1994-04-22 | 1995-04-20 | Therapeutic agent for epidermal proliferation disease |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH083049A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6083315A (en) * | 1996-12-20 | 2000-07-04 | Seiko Epson Corporation | Agglomerated pigment, process for producing the same, aqueous pigment dispersion, and water-based ink composition |
| JP2005015702A (en) * | 2003-06-27 | 2005-01-20 | Asahi Kasei Chemicals Corp | Emulsion with high durability, and manufacturing method thereof |
| WO2014069510A1 (en) | 2012-10-31 | 2014-05-08 | 富山化学工業株式会社 | Novel amine derivative or salt thereof |
| US10348673B2 (en) | 2016-02-04 | 2019-07-09 | Canon Kabushiki Kaisha | Management server system, system, method of system, and storage medium |
| JP2023084184A (en) * | 2021-12-07 | 2023-06-19 | 栗田工業株式会社 | Water treatment information system |
-
1995
- 1995-04-20 JP JP9462095A patent/JPH083049A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6083315A (en) * | 1996-12-20 | 2000-07-04 | Seiko Epson Corporation | Agglomerated pigment, process for producing the same, aqueous pigment dispersion, and water-based ink composition |
| JP2005015702A (en) * | 2003-06-27 | 2005-01-20 | Asahi Kasei Chemicals Corp | Emulsion with high durability, and manufacturing method thereof |
| WO2014069510A1 (en) | 2012-10-31 | 2014-05-08 | 富山化学工業株式会社 | Novel amine derivative or salt thereof |
| US9624215B2 (en) | 2012-10-31 | 2017-04-18 | Toyama Chemical Co., Ltd. | Amine derivative or salt thereof |
| US10348673B2 (en) | 2016-02-04 | 2019-07-09 | Canon Kabushiki Kaisha | Management server system, system, method of system, and storage medium |
| JP2023084184A (en) * | 2021-12-07 | 2023-06-19 | 栗田工業株式会社 | Water treatment information system |
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