JPS5885819A

JPS5885819A - Bronchodilator

Info

Publication number: JPS5885819A
Application number: JP18304481A
Authority: JP
Inventors: Yuzaburo Inaba; 稲葉　雄三郎
Original assignee: Chugai Pharmaceutical Co Ltd
Current assignee: Chugai Pharmaceutical Co Ltd
Priority date: 1981-11-17
Filing date: 1981-11-17
Publication date: 1983-05-23
Also published as: JPH0141126B2

Abstract

PURPOSE:A bronchodilator containing nitric ester of N-(2-hydroxyethyl)nicotinic acid amide as an active constituent. CONSTITUTION:A bronchodilator containing nitric ester of N-(2-hydroxyethyl) nicotinic acid or a salt thereof found to be useful as a remedy for not only angina pectoris but also an asthmatic symptom. The bronchodilator is formulated into dosage forms of a tablet, capsule, granule, injection, inhalant or troche and administered in a dose of 5-200mg per day for an adult. The compound has very low toxicity and exhibits improved activity, and 25% remarkable effect is recognized by the administration of the compound at one time. The improvement of the asthmatic symptom is found in about 60% patients as a whole. 5mg compound is fully mixed with lactose, mannitol, and magnesium stearate, and the resultant mixture is used as a sublingual tablet.

Description

【発明の詳細な説明】本発明は、Ｎ−（２−ハイドルオキシエチル）ニコチン
酸アミド硝酸エステル又はその＃１（以下ｒ本化合物」
と称する）ｔ−有効成分とする気管支拡張剤の発明であ
る。Detailed Description of the Invention The present invention relates to N-(2-hydroxyethyl)nicotinamide nitrate or #1 thereof (hereinafter referred to as "the present compound").
This is an invention of a bronchodilator having a t-active ingredient.

本化合物が、循環器系疾患、殊に狭心症の予防。This compound is effective in preventing cardiovascular diseases, especially angina pectoris.

及び治療効果を有することはａＫ知られている（特開昭
５３−９３２３号公報）。It is known that aK has a therapeutic effect (Japanese Unexamined Patent Publication No. 53-9323).

本発＾、本化合物の臨床試験の過楊で、気管支喘息を併
発している狭心叱患者の本化合物投与群で、狭心症の改
善のみならず喘息症状の軽減又呟消失が見られるという
意外な事実を見出し、この新知見に基づき更に検討して
、本発明を完成した。In a recent clinical trial of this compound, in a group of angina patients with concurrent bronchial asthma treated with this compound, not only an improvement in angina but also a reduction in asthma symptoms and disappearance of asthma symptoms was observed. After discovering this unexpected fact, we conducted further studies based on this new knowledge and completed the present invention.

本発明を実施するに当って、本化合物は、慣用される製
剤技術によって、錠剤・カプセル剤・顆粒剤・注射剤・
吸入剤・ト′ローチなどに製剤化されて用いられる。In carrying out the present invention, the present compound can be prepared in tablets, capsules, granules, injections, etc. by conventional formulation techniques.
It is formulated into inhalants, lozenges, etc.

投与量は、患者の年齢・症状等に応じ、又投与経路によ
って適宜定められるが、通常、成人に対して、１日当り
５〜２００１１９程度の投与量で充分な効果をあげるこ
とができる。The dosage is appropriately determined depending on the patient's age, symptoms, etc., and the route of administration, but usually, a sufficient effect can be achieved for adults at a dosage of about 5 to 200,119 doses per day.

本化合物は極めて低毒性で、８Ｄ系雌雄ラツト（４週齢
）を用いて経口投与及び静脈内投与時の気性毒性を調べ
た結果、軽口投与によるＬＤｇ・値は峻雄と４１２００
１１９／＃以上１３０Ｇ！／岬以下であり、静脈内投与
で遣雌雄とも８００ｙ／Ａｙ以−ｈｌＧｏ０１１Ｆ／Ｈ
以下であった。＜実施例１（製剤例）（１）本化合物５〜、乳９１９．７岬、マンニトール２
５キ及びステアリン噴マグネシウＡ　Ｏ，３ｍ９　（ｈ
ずれも１錠当！７）？よく混合し、直径５■、重量５Ｑ
ａｖに直接打錠し、舌下錠として用いる。This compound has extremely low toxicity, and as a result of investigating the temperamental toxicity during oral and intravenous administration using 8D male and female rats (4 weeks old), the LDg value after light administration was 41,200, which was the same as that of male and female 8D rats (4 weeks old).
119/# or more 130G! / cape and below, and intravenous administration for both males and females is 800y/Ay or less - hlGo011F/H
It was below. <Example 1 (Formulation Example) (1) Compound 5~, Milk 919.7 Misaki, Mannitol 2
5ki and stearin injection magnesium A O, 3m9 (h
Get 1 tablet for each difference! 7)? Mix well, diameter 5■, weight 5Q
Compress the tablet directly into the AV and use it as a sublingual tablet.

（ｂ１本化合物（堪噴塩）１０１９．乳糖４４．５１９
、トウモロコシテＡ、５ン２０　ｑ、結４セルロース２
ｓａｐ及びステアリン暖マグネシウム０．５ＮＩＩ（−
ずれも１゛錠当り）をよく混合し死後、Ｉ［接打錠し、
直径７−１重量１００ｑの内服用錠剤として用いる。(b1 Compound (tanpan salt) 1019. Lactose 44.519
, Corn Tee A, 5 N 20 q, Knot 4 Cellulose 2
sap and stearin warm magnesium 0.5NII(-
Mix well (per tablet) and after death, press I
It is used as an internal tablet with a diameter of 7-1 and a weight of 100q.

（ｃ１本化合物ｓ’ｖ＋びマンニトール５０ｑの混合物
をアンプルに充填し、凍結乾燥後密閉して、長期保存用
注射剤とする。このものは用時１ＩＩｊの蒸留水會加え
て溶解して使用する。(c1 A mixture of this compound s'v + mannitol 50q is filled into an ampoule, lyophilized and sealed to make an injection for long-term storage. When used, this product is dissolved in 1IIj of distilled water before use. .

実施例２（臨床例）気臂支鳴患と給断された２２〜７１歳の患者（男１０名
９女２名）に、前記実施例１１ｂ）で得られ九錠剤ｔ−
２錠（有効成分２０ｑ）ずつ投与し、１時間後の肺機能
所見を調べたところ下表の成績が得られた。Example 2 (clinical case) Patients aged 22 to 71 years old (10 males, 9 females) who were diagnosed with arthronchitis were given 9 tablets of t-
Two tablets (20q of active ingredient) were administered, and lung function findings were examined 1 hour later, with the results shown in the table below.

農上表のように、本化合物の１回投与でｒ著効」が２５Ｘ
ＫＩＩめられ、全体で約６ＯＮの患者に喘息症状の改善
が見られ九。As shown in the agricultural table, one dose of this compound has a ``remarkable effect'' of 25X.
Overall, approximately 6 patients with asthma showed improvement in their asthma symptoms.

出願人　　中外製薬株式会社手続補正書（方式）％式％１、事件の表示、昭和５６年特許ｊｌ［８１８３０４４号２　発明の名
称気管支・拡張剤 λ　補正をする者事件との関係　特許出願人東京都北区浮間五丁目５番１号（３３１）中外製薬株式会社代表者　　上　野　公　夫東京都豊島区高田三丁目４１番８号６、補正の対象願書および明細書７、補正の内容別紙のとおり明細書の浄書（内容に変更なし）Applicant Chugai Pharmaceutical Co., Ltd. Procedural amendment (method) % formula % 1. Indication of the case, 1983 patent jl [No. 8183044 2 Name of the invention Bronchodilator λ Person making the amendment Relationship with the case Patent applicant Tokyo 5-5-1 (331) Ukima, Kita-ku, Tokyo Representative Kimio Ueno Ueno 3-41-8-6, Takada, Toshima-ku, Tokyo Application to be amended and specification 7, details of the amendment attached Engraving of the detailed statement (no changes to the contents)

Claims

[Claims]

A bronchodilator containing N-(2-hi)'o#xyethyl)nicotinamide nitrate or a salt thereof as an active ingredient.