200401643 玖、發明說明： 【發明所屬之技術領域】 、 本發明有關於一種偏頭痛之預防或治療劑。 【先前技術】 偏頭痛是頭前側部—陣陣跳動之頭痛，其4成不僅僅單側 而是兩側皆疼痛。其發作頻率為每月丨〜2次多為每周i次， 反设發作’持續4〜7 2小時。立徒p左产山 才其伴症狀除σ惡心、。區吐外， 亦有對光或聲音敏感者。偏鹿 . b 侷頭痛發作珂，亦有出現閃輝暗 點專刖兆現象者。 據說日本人約有8%有偏頭痛，有百分之幾的病人到醫療 機構就診，其餘半數人服用大㈣（〇TC)，此兩者皆不採用 之其他人則可說是在忍耐，強忍疼痛中過活。 偏頭痛的發病機制和原因有①血管說、②神經說、③三叉 神經血官說等’雖然至今沒有定論，但各學說均認爲有顱 内血流的變化。因此，纟日本現有的對「偏頭痛」有功效 的藥物有，具有收縮顱内血管作用的佐米曲普坦 (zolmitriptan)製劑、舒馬曲普坦（Sumatriptan)琥珀酸鹽製劑 或酒石酸麥角胺及無水咖啡因的混合製劑。 在美國市售的對”偏頭痛，，有功效的非處方藥物有以乙醯 氨基苯盼、阿司匹林及咖啡因爲有效成分的”Exced比200401643 (1) Description of the invention: [Technical field to which the invention belongs] The present invention relates to a preventive or therapeutic agent for migraine. [Previous technique] Migraine is a headache with front-side and throbbing beats. Its 40% pain is not only on one side but on both sides. The frequency of attacks is from 丨 to 2 times per month, i times per week, and the counter-attacks last 4 to 72 hours. Lituo p Zuo Shanshan, with its symptoms in addition to σ nausea. Outside the area, there are also people sensitive to light or sound. Partial deer. B Local headache attack Ke, there is also a phenomenon of flashing dark spots special signs. It is said that about 8% of Japanese people have migraines, and a few percent of patients go to medical institutions for treatment, and the other half take Daigo (〇TC). Others who do not use either can be said to be patient. Live in pain. The pathogenesis and causes of migraine include ① the theory of blood vessels, ② the theory of nerves, ③ the theory of trigeminal nerves, and so on. 'Although no conclusion has been made, all theories believe that there is a change in intracranial blood flow. Therefore, the drugs that are effective for "migraine" in Japan include zolmitriptan preparations, Sumatriptan succinate preparations, or ergot tartrate, which have the effect of contracting intracranial blood vessels. A mixture of amine and anhydrous caffeine. For the "migraine" marketed in the United States, the effective over-the-counter drugs are "Exced ratio" based on the effective ingredients of acetaminophen, aspirin, and caffeine.
Migraine”（Bristol-Myers公司）、以布洛芬（Ibuprofen)爲有 效成分的”Advil Migraine" (Whitehall-Robins 公司）和 Mortrin Migraine Pain Caplets’’（NcNeil Consumer公司）， 在曰本，作爲大眾藥銷售的布洛芬或者乙醯氨基苯酚等雖 84266 200401643 然沒有治症，I — 原^偏頭痛，，i 以亦被用於偏頭痛。、功效’但有治療”頭痛”的功效，所 然而，佐半 ^ m Μ 、曰垣製劑等存在的問題為對循产糸姑古Μ 作用，例如有可处处 Θ野循¥系統有副 用布洛芬或者乙Γ 痛或心肌梗塞惡化，另外單獨使 達到充分的治療效果。 、偏碩痛患者無法 Χ月之目的為提供一種對偏頭痛的預防$、厶&古 效果，並且忠人^ ^用W頂防或治療有優良 卫且文全性高的藥劑。 【發明内容】 本發明人等根據實際情 藥布洛落盘Λ , 衣所九的結果，將解熱鎮痛 啡因類組合使用時，比單獨使用布洛芬具有 果二！！頭痛效果’對偏頭痛的預防或治療有優良效 禾因而完成本發明。 亦即’本發明提供—插冬# 成八 ，、 3有布洛分與咖啡因類作爲有效 刀的偏頭痛之預防或治療劑。 實施發明之最佳態樣 布亦即2_(4_異丁基苯基)丙酸係爲對①慢性關節風 ^關郎痛及關節炎、神經痛及神經炎、腰背痛、頸腕综 =子呂附件炎、月經不調症、紅斑（結節性紅斑、多形 /多出性紅斑、離心性環狀紅 )寺的肩火鎮痛、②手術及外 傷後的消炎鎮痛、③急性上 * 〜上吁及道炎（包括伴隨急性支氣管 -之心、性上呼吸道炎)的解熱鎮痛有效之市售荜劑。 本發明的布洛芬亦可為2_(4·異丁基苯基)丙酸之鹽類，例 如鈉、m敍、甲基葡糖胺，甚至賴氨酸等氨基 84266 200401643 酸之鹽。 本發明的咖啡因類’除咖啡因、無水 列舉女息香酸納咖_因、咖啡因鹽可以 ，其中以無水咖啡因為佳。 “一因等 本心月之藥劑爲上述布洛芬和咖啡因 述實施例所述，與單獨投予布洛芬相比，= 如後 抑制偏頭痛之力文果。因奸, n以叙揮顯著的 偏頭痛有^ 本發明的藥劑對爲預防或治療 本t明偏頭痛之預防或治療财，布洛芬和咖啡因之使 用形您沒有特殊限制。 稀’ Γ各芬和咖啡因類可以與其他藥劑學上可容許之 稀釋W丨、賦形劍裳^ ^|) JL' va 別製成Μ 製劑’亦可將兩種藥劑分 成製劑時，劑型外，兩種藥物分別製 痛之預防或治療劑，可根據用法製成各種劑型的醫 樂：囊:丨’劑型可以列舉如散劑、顆粒劑、細粒劑、片劑 =、液體製劑、糖麵。再者，亦可製成可以控 制成刀釋放的緩釋性製劑型態。 山此等製劑可以根據其劑型，與製劑學上容許之賦形劑、 ^粘D劑、潤滑劑、稀釋劑、緩衝劑、穩定劑、溶 解助劑等醫藥品添加物進行適當的混合、稀釋或者溶解， 按照常規的方法製備。 命例如，政劑亦可將有效成分（布洛芬及咖啡因類）與根據 而要適當添加的賦形劑、潤滑劑等充分混合配製，片劑及 84266 200401643 顆粒劑則根據需要添加乳糖、白糖、葡萄糖等、甘露糖等 糖類、結晶纖維素等之賦形劑；明膠、海藻酸鈉、羥丙基 曱基纖維素、聚乙烯啦咯烷酮、羧曱基纖維素等粘合劑； 羧甲基纖維素鈣、低取代度羥丙基纖維素、碳酸鈣等崩解 劑；硬脂酸鎂、硬化蓖麻油等加氫植物油、滑石等潤滑劑 等’按照常規方法製備。另夕卜’片劑可以根據需要進行包 衣，可以製成薄膜衣片、糖衣片等。 本發明偏頭痛之預防或治療劑中，在不影響偏頭痛的治 療預防效果之限度下’亦可摻合其他藥效成分，尤其是從 保護胃枯膜及速效性的觀點出發，以掺合氫氧化鎂、氧化 鎮、甲基矽酸鋁酸鎂、碳酸鎂等抑酸劑為佳。 t發明偏頭痛之預防或治療劑中，布洛芬和咖啡因類之 含量可以根據製劑進行適當選擇，以布洛芬爲20〜50重量 =’，咖啡因類爲1G〜3G重量％為佳，相對於賴量份布洛 力以摻合20〜7〇重量份咖啡因類為佳。 本發明偏頭痼夕π t i # g ^防或治療劑之給藥量，根據偏頭痛的 種類及症狀進行適當 100〜、，布洛芬每日爲50〜600 mg，以 mg為佳，以 啡因類每曰爲2。〜—以一。 【實施方式】 次到分數次給藥為佳。 實施例 實施例1 1所示之薄膜包衣片 製備下述表^ 84266 200401643 表1 本發明藥物 比較藥物 (Α)布洛芬 150 mg 150 mg (Β)無水♦啡因 —^—_____— 80 mg —— 載體(結晶纖維素以外） (Α)/(Β)重量比 100/53.3 — 使每月2次左右的輕度偏頭痛自願者5名，每次偏頭痛時 服用表1之2種製劑1次’在！小時内疼痛消失者視爲有效。' 其結果為：服用本發明產品之自願者在i小時内疼痛均、、肖 失’比較㈣只有4名在H、時内疼痛消失。另外，服用本 發明藥物的5人中有4人認為本發明的藥物可使疼痛消失的 時間略為縮短。 產業上之利用性 根據本發明偏頭痛之早§ P六十、 一 屌之預防或治療劑，可以使偏頭痛及其 伴隨之°惡心、η區吐、斜土斗、1 匕土、對先或聲音敏感得以緩和。"Migraine" (Bristol-Myers), "Advil Migraine" (Whitehall-Robins) and Mortrin Migraine Pain Caplets (NcNeil Consumer) with Ibuprofen as active ingredients. Although ibuprofen or acetaminophen is sold, although 84266 200401643 does not cure the disease, I is the original migraine, and i is also used for migraine. "Effectiveness", but has the effect of treating "headache". However, the existing problems such as Zuo Ban ^ m Μ, Yue Yuan preparations, etc., have effects on Xun Gong Gu M. For example, there is a side effect. Ibuprofen or acetonitrile pain or myocardial infarction worsens, and alone achieves sufficient therapeutic effect. Patients with partial pain can not use the purpose of the month to provide a preventive effect on migraine, and to be loyal ^ ^ use W to prevent or treat drugs with excellent health and high integrity. [Summary of the invention] According to the actual situation of the drug ibuprofen Λ and Yisuojiu, the inventors have a combination of antipyretic analgesic and phageine than ibuprofen alone! !! The headache effect is excellent in the prevention or treatment of migraine, and the present invention has been completed. In other words, the present invention provides-insert winter # 成 八, 3, has bulofen and caffeine as a preventive or therapeutic agent for migraine which is an effective knife. The best form of implementation of the invention, that is, 2_ (4-isobutylphenyl) propionic acid is ① chronic arthritis ^ Guanlang pain and arthritis, neuralgia and neuritis, low back pain, neck and wrist complex = Zilu appendicitis, irregular menstruation, erythema (nodular erythema, polymorphous / multiple erythema, centrifugal ring-shaped red) temple fire analgesia, ② anti-inflammatory analgesia after surgery and trauma, ③ acute on * ~ on Call for effective antipyretic and analgesic elixirs for Daoitis (including acute bronchial-heart, upper respiratory tract inflammation). The ibuprofen of the present invention may also be a salt of 2- (4-isobutylphenyl) propionic acid, such as sodium, methyl, methylglucosamine, and even amino 84266 200401643 acid such as lysine. The caffeine type of the present invention is decaffeinated and anhydrous. It is possible to use narcotic acid narcotic acid and caffeine salt. Among them, anhydrous caffeine is preferred. "Yin Yin's medicament is described in the above-mentioned examples of ibuprofen and caffeine, compared with ibuprofen alone, = as a result of migraine suppression. As a result, n to Syria There are significant migraine headaches. The agent of the present invention has no special restrictions on the use of ibuprofen and caffeine for the prevention or treatment of migraine in this invention. Rare 'ΓGefen and caffeine Can be diluted with other pharmacologically tolerable W 丨, shaped sword clothes ^ ^ |) JL 'va Do not make M preparations' When two kinds of medicines are divided into preparations, the two medicines make pain separately Prophylactic or therapeutic agents can be made into various types of medical music according to usage: capsules: 丨 'Formulations can be listed as powder, granules, fine granules, tablets =, liquid preparations, sugar noodles. Furthermore, it can also be made into The type of sustained-release preparations that can be controlled to release into a knife can be controlled. These preparations can be formulated with excipients, adhesives, lubricants, diluents, buffers, stabilizers, dissolving agents, etc., which are acceptable in formulation according to their dosage forms. Proper mixing, dilution or dissolution of pharmaceutical additives such as auxiliaries, Prepared according to conventional methods. For example, government agents can also be prepared by mixing the active ingredients (ibuprofen and caffeine) with excipients and lubricants to be appropriately added according to the requirements. Tablets and 84266 200401643 granules Then add excipients such as lactose, sugar, glucose, mannose and other sugars, crystalline cellulose, etc .; gelatin, sodium alginate, hydroxypropyl fluorenyl cellulose, polyvinyl pyrrolidone, and carboxyfluorinated fiber Disintegrating agents such as calcium carboxymethyl cellulose, low-substitution hydroxypropyl cellulose, calcium carbonate; hydrogenated vegetable oils such as magnesium stearate, hardened castor oil, lubricants such as talc, etc. Preparation method. In addition, tablets can be coated as required, and can be made into film-coated tablets, sugar-coated tablets, etc. In the preventive or therapeutic agent for migraine of the present invention, the effect of preventing and preventing migraine is not affected. 'It can also be blended with other medicinal ingredients, especially from the viewpoint of protecting the gastric dry film and fast-acting properties, it is better to blend with acid inhibitors such as magnesium hydroxide, oxidized town, magnesium aluminosilicate, magnesium carbonate and the like. T hair The content of ibuprofen and caffeine in the preventive or therapeutic agent for migraine can be appropriately selected according to the preparation, preferably 20 ~ 50 weight = for ibuprofen, and 1G ~ 3G weight% for caffeine. It is better to blend 20 ~ 70 parts by weight of caffeine with respect to the amount of Brilliant. According to the present invention, the dosage of the anti-or therapeutic agent mirti π ti # g ^ is based on the type and symptoms of migraine Appropriate 100 ~, daily ibuprofen is 50 ~ 600 mg, preferably mg, and morphine per day is 2. ~-by one. [Embodiment] It is better to administer to several times. Implementation EXAMPLES Example 11 The film-coated tablets shown in Table 1 were prepared as shown in the following Table ^ 84266 200401643 Table 1 Comparative drug of the present invention (A) Ibuprofen 150 mg 150 mg (B) Anhydrophine — ^ — ____ — 80 mg —— Carrier (other than crystalline cellulose) (Α) / (Β) weight ratio 100 / 53.3 — 5 volunteers with mild migraine about 2 times a month, taking 2 preparations of Table 1 each time for migraine 1 time 'in! Those who have disappeared within an hour are considered effective. 'As a result, the volunteers who took the product of the present invention all had pain within one hour, and they lost each other.' Compared with only four, the pain disappeared within hours. In addition, 4 out of 5 people taking the medicine of the present invention thought that the time for which the medicine of the present invention could make the pain disappear was slightly shortened. Industrial applicability According to the early migraine of the present invention, § P 60, a preventive or therapeutic agent for migraine, can make migraine and its accompanying ° nausea, η-zone vomiting, oblique soil bucket, 1 dagger, right First or sound sensitive to ease.
8426684266