200900057 九、發明說明： 【發明所屬之技術領域】 本發明係關於一種含雷米普利(Ramipril)安定化醫藥組成物。 【先前技術】200900057 IX. DESCRIPTION OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention relates to a medicinal composition containing ramipril. [Prior Art]
Ramipril之結構由美國專利(US 5061722)所揭露；雷米普利 (Ramipril)在肝臟被代謝形成活性代謝物一雷米普拉特(Ramipriiat)二為 一血管張力素轉換酶抑制劑(ACEI)，其藉由抑制血管張力素轉換酶的 活性，進而降低血管張力素Π的產生，使得如血管收縮…等作用減少 Γ 以達到降壓之目的，可用於各種病因所起之高血壓之控制。 已發現在藥物製備的過程，由於輔助劑的選擇，製造過程與保存 狀態的不同，而使Ramipril具有不安定的傾向。根據美國專利(us 5403856)以及中華民國專利(TW 149449)揭露，利用流動床的方式在活 性物質外覆蓋一層醫藥上可接受之聚合物，如經丙基纖維素、乙基纖 維素、聚乙烯吡咯烷酮或醋酸纖維素等，可以增加Ramipril的安定性。 此外亦可將緩衝劑混以活性物質或是具保護層的活性物質，藉由如穩 定pH值達到安定性的效果，合適的緩衝劑如磷酸二氫鈉二水合物，^ 檬酸三鈉二水合物，碳酸鈉，碳酸氫鈉與三羥甲基胺基甲烷。利用緩 , 衝劑配合具聚合物保護層之活性物質的混合安定效果是較為有利的。 【發明内容】 本發明係關於一種雷米普利速效醫藥組成物，該醫藥組成物未利 用聚合物在藥物主成分上形成薄膜，但可以幫助醫藥組成物之安定性。 本發明係關於一種雷米普利安定化醫藥組成物，包含藥物主成分 雷米普利(Ramipril)及一種醫藥上可接受的聚合物，其中醫藥上可接受 的聚合物包含羥丙基曱基纖維素、聚乙烯吡咯烷酮或K〇Uid〇n 。 該醫藥組合物，可視需要添加其他醫藥上可接受之賦型劑， 包含界面活性劑、潤滑劑、稀釋劑或崩散劑。 本發明亦關於一種製造雷米普利安定化醫藥組成物之方法，該方法 5 200900057 包含下列步驟： (1) 將雷米普利與至少一種醫藥上可接受的聚合物及賦型劑混合； (2) 將潤滑劑加入前述混合粉末中； (3) 混合均勻後打成錠劑。 本發明又關於—種製造f米普利安定化醫藥組成物之方法 ，該方法 包含下列步驟： ⑴將雷米普利與K〇Uid〇n K30，乳糖及Primojel在V-blender中 混合均勻； (2) 將滑石粉及丁烯二酸硬脂酸納加入前述混合粉末中；及 (3) 混合均勻後打成錠劑。 【實施方式】 本發明係關於-種雷米普利安定化醫齡成物，包含藥物主成分 雷米普利(Ramipril)及-種醫藥上可接受的聚合物，其中醫藥上可接受 的聚合物包含經丙基甲基纖維素、聚乙稀轉細或K〇Uid〇n 。 該醫藥組合物’可視需要添加其他醫藥上可接受之賦型劑， 包含界面活性劑、潤滑劑、稀釋劑或崩散劑。 下述實施例係用於說明本發明，並非用於限制本發明。 實施例一 組成 毫克/錠劑 雷米普利(Ramipril) 2.50 Kollidon K30 5.00 乳糖 83.50 Primojel 5.00 滑石粉 2.00 丁烯二酸硬脂酸鈉 2.00 總和 100.00 200900057 製備方法： 將雷米普利與Kollidon K30，乳糖及Primojel在V-blender中混合均 勻，再將滑石粉及丁烯二酸硬脂酸納加入前述混合粉末中，最後將上 述粉末混合均勻後打成錠劑。 實施例二 組成 毫克/鍵劑 雷米普利(Ramipril) 2.50 Kollicoat IR 5.00 乳糖 91.50 丁烯二酸硬脂酸鈉 1.00 總和 1 ⑻.00 製備方法： 將雷米普利與Kollicoat IR，及乳糖在V-blender中混合均勻，再將 丁烯二酸硬脂酸納加入前述混合粉末中，最後將上述粉末混合均勻後 打成旋劑。 實施例三 組成 毫克/筑劑 雷米普利(Ramipril) 2.50 Kollicoat IR 3.00 乳糖 88.50 Primojel 5.00 滑石粉 1.00 總和 100.00 7 200900057 製備方法： 將雷米普利與Kollidon IR，乳糖及Primojel在V-blender中混合均 勻，再將滑石粉加入前述混合粉末中，最後將上述粉末混合均勻後打 成鍵劑。 本發明中所揭露的實施例僅為本發明的數個較佳實施 例，任何熟悉本技術領域之人士皆可根據說明書之内容及實 施例瞭解本發明，並視需要選擇改變賦型劑及其比例來實施 本發明，因此本發明之申請專利範圍並不限於實施例。 【圖式簡單說明】 無 【主要元件符號說明】 無The structure of Ramipril is disclosed in US Patent (US 5,061, 722); Ramipril is metabolized in the liver to form an active metabolite, Ramipriat, which is an angiotensin converting enzyme inhibitor (ACEI). By inhibiting the activity of angiotensin-converting enzyme, thereby reducing the production of angiotensin, such as reducing the vasoconstriction, etc., to achieve the purpose of blood pressure reduction, it can be used for the control of hypertension caused by various causes. It has been found that during the preparation of the drug, Ramipril has a tendency to be unstable due to the choice of the adjuvant, the manufacturing process and the state of preservation. According to the U.S. Patent (us 5, 403, 856) and the Republic of China Patent (TW 149 449), a fluidized bed is used to coat the active material with a layer of pharmaceutically acceptable polymer, such as propyl cellulose, ethyl cellulose, polyethylene. Pyrrolidone or cellulose acetate can increase the stability of Ramipril. In addition, the buffering agent may be mixed with the active material or the active material with a protective layer. By stabilizing the pH to achieve stability, a suitable buffering agent such as sodium dihydrogen phosphate dihydrate, trisodium citrate Hydrate, sodium carbonate, sodium bicarbonate and trishydroxymethylaminomethane. It is advantageous to use a mixing effect of a slowing agent and an active material having a polymer protective layer. SUMMARY OF THE INVENTION The present invention relates to a ramipril quick-acting pharmaceutical composition which does not utilize a polymer to form a film on a main component of a drug, but which can contribute to the stability of a pharmaceutical composition. The present invention relates to a ramipril tranquilization pharmaceutical composition comprising a pharmaceutical main component Ramipril and a pharmaceutically acceptable polymer, wherein the pharmaceutically acceptable polymer comprises hydroxypropyl sulfhydryl Cellulose, polyvinylpyrrolidone or K〇Uid〇n. The pharmaceutical composition may optionally contain other pharmaceutically acceptable excipients, including surfactants, lubricants, diluents or disintegrating agents. The invention also relates to a method of making a ramipril stabilized pharmaceutical composition, the method 5 200900057 comprising the steps of: (1) mixing ramipril with at least one pharmaceutically acceptable polymer and excipient; (2) Adding a lubricant to the above mixed powder; (3) Mixing uniformly and then forming a tablet. The invention further relates to a method for producing a fmuritanized pharmaceutical composition, the method comprising the steps of: (1) mixing ramipril with K〇Uid〇n K30, lactose and Primojel in a V-blender; (2) adding talc and sodium butyrate stearate to the above mixed powder; and (3) mixing and forming into a tablet. [Embodiment] The present invention relates to a ramipril angiostatin, comprising a pharmaceutical main component Ramipril and a pharmaceutically acceptable polymer, wherein the pharmaceutically acceptable polymerization The substance comprises propylmethylcellulose, polyethylene slip or K〇Uid〇n. The pharmaceutical composition 'additionally other pharmaceutically acceptable excipients, including surfactants, lubricants, diluents or disintegrating agents, may be added as needed. The following examples are intended to illustrate the invention and are not intended to limit the invention. Example 1 Composition mg/tablet Ramipril 2.50 Kollidon K30 5.00 Lactose 83.50 Primojel 5.00 Talc 2.00 Sodium succinate Sodium 2.00 Total 100.00 200900057 Preparation: Ramipril and Kollidon K30, Lactose and Primojel are uniformly mixed in V-blender, and then talc powder and sodium butyrate stearate are added to the above mixed powder, and finally the above powder is uniformly mixed and then tableted. Example 2 Composition of mg/bond ramipril (Ramipril) 2.50 Kollicoat IR 5.00 Lactose 91.50 Sodium succinate stearate 1.00 Total 1 (8).00 Preparation: Ramipril and Kollicoat IR, and lactose The mixture was uniformly mixed in V-blender, and then sodium butyrate stearate was added to the above mixed powder, and finally the above powder was uniformly mixed and then turned into a spinning agent. Example 3 Composition mg/Builder Ramipril 2.50 Kollicoat IR 3.00 Lactose 88.50 Primojel 5.00 Talc 1.00 Total 100.00 7 200900057 Preparation: Ramipril with Kollidon IR, lactose and Primojel in V-blender The mixture is uniformly mixed, and talc powder is added to the above mixed powder, and finally the above powder is uniformly mixed and then used as a bonding agent. The embodiments disclosed in the present invention are only a few preferred embodiments of the present invention, and anyone skilled in the art can understand the present invention according to the contents and embodiments of the specification, and optionally change the excipient and its The present invention is embodied in proportions, and thus the scope of the invention is not limited to the embodiments. [Simple diagram description] None [Main component symbol description] None