TW201014616A - Miglitol medicine composition - Google Patents
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201014616 九、發明說明: 【發明所屬之技術領域】 本發明係關於一種治瘆 合物及其製造綠,肥^_特醫藥組 格利特醫齡合物。 、種/、有減低腹鋼作用之米 【先前技術】201014616 IX. Description of the Invention: [Technical Field to Which the Invention Is Applicable] The present invention relates to a therapeutic composition and a green medicinal composition thereof. , species /, have the effect of reducing the role of abdominal steel [prior art]
隨著社會文明,生活水平古 > 性病患迅速增加,尤,喊人口比例及慢 煃显、)¾古&厶摟~ 、 里糖尿病最具威脅性。2002年 人;&至%歲的老年人口中,就有百分之十以上罹 患糖尿Ϊ。1998年台灣地區糖尿病患者超過8。萬人,治療糖 尿病的化費為300億以上,佔健保醫療費用的i i 5%。2〇〇1年 在美國ί 一千七百萬人罹患第11型糖尿病,是美國排名第六的 死因’消耗了四百四十億美元的醫療費用,更耗損了五百四十With the social civilization, the living standards of ancient > sexually ill patients have increased rapidly, especially, the proportion of people and slow-moving, 3⁄4 ancient & 厶搂~, diabetes is the most threatening. In 2002, more than 10% of the elderly population aged between the ages of the elderly and the elderly were suffering from diabetes. In 1998, there were more than 8 diabetes patients in Taiwan. Ten thousand people, the cost of treating diabetes is more than 30 billion, accounting for 5% of health care medical expenses. 2〇〇1年 In the United States, 157 million people suffer from type 11 diabetes, which is the sixth leading cause of death in the United States. It consumes $44 billion in medical expenses and consumes 540 dollars.
億美元的經濟生產力。預估在2〇1〇年後成為高危險^^,屆時 將增加至二億二千一百萬人。 米格利特是德國拜耳製藥公司2 〇世紀8 0年代初研究開發 的一種新型降糖尿病之用藥。米格利特化合物之化學名稱為 [2民311,411,58]-1-(2-羥乙基)-2-(羥甲基)-3,4,5-三羥基哌啶三 醇’是去氧野尻霉素衍生物。米格利特是一種新的小腸α葡萄 糖苷酶抑制劑,適用於配合飲食控制治療第II型糖尿病,而主 要的作用機制是通過在小腸内可逆性抑制α葡萄糖苷酶,減少 糖類分解為葡萄糖,並能延遲小腸中葡萄糖的吸收,而來達到 降低飯後血糖升高的幅度。 201014616 米格利特的血漿消除半衰期約為2小時。平均在給藥2 至3小時後,可達到其血漿最大藥物濃度,在口服25]〇^後, 24小時内劑量的95%以上經尿液排出,但少量未吸收的藥由 糞便排出,而米格利特主要之副作用為腸胃漲氣、腹痛。 原廠Glyset®產品已知是由九種成分所組成的,在產品說 明書顯示經由962位病人經臨床試驗發現有u.7%腹痛及 41.5°/。為腸胃脹氣;在 Diabetes Care,V17,N1,1994:20-29 之文獻’說明進行米格利特對於6〇幾位糖尿病患治療,發現 • 50mg之米格利特之副作用胃腸脹氣為佔48%,而100mg之米 格利特之副作用胃腸脹氣為佔6〇%,因此可得知劑量越大副作 用越大’此副作用會容易造成病患的不適。其餘分別在DiabetesBillion dollars of economic productivity. It is estimated that after 2, 1 year, it will become a high risk ^^, which will increase to 221 million. Miglit is a new type of diabetes-reducing drug developed by Bayer Pharmaceuticals in Germany in the early 1980s. The chemical name of the Miglit compound is [2 Min 311,411,58]-1-(2-hydroxyethyl)-2-(hydroxymethyl)-3,4,5-trihydroxypiperidine triol It is a deoxynojirimycin derivative. Miglitide is a new inhibitor of small intestinal α-glucosidase, which is suitable for the treatment of type 2 diabetes with diet control. The main mechanism of action is to reversibly inhibit α-glucosidase in the small intestine and reduce the breakdown of sugar into glucose. And can delay the absorption of glucose in the small intestine, and to reduce the increase in blood glucose after meals. 201014616 Miglit's plasma elimination half-life is approximately 2 hours. On average, after 2 to 3 hours of administration, the maximum plasma concentration of the plasma can be reached. After oral administration, more than 95% of the dose is discharged through the urine within 24 hours, but a small amount of unabsorbed drug is excreted by the feces. The main side effects of Miglit are gastrointestinal qi and abdominal pain. The original Glyset® product is known to be composed of nine components, and the product description shows that 962 patients have been found to have u.7% abdominal pain and 41.5°/ via clinical trials. For flatulence; in Diabetes Care, V17, N1, 1994: 20-29, the literature describes the treatment of MiGlite for 6 diabetes patients and found that • 50 mg of MiGlite has a side effect of flatulence. %, and the side effects of 100 mg of MiGlite are gastrointestinal flatulence, which means that the greater the dose, the greater the side effects. This side effect can easily cause discomfort to the patient. The rest are in Diabetes
Care V24 ’ N5 ’ 2001 . 989-94 ; Diabetes Research and Clinical Practice ’ 52,2001 : 205-213 ; Journal of Clinical Endocrinology andMetabolism V83,N5,1998 : 1515-1522 等文獻中也都提 出數據說明Glyset®產品雖然對血糖能夠有效控制,但是此配 方之副作用反應數據亦有說明。 除了 GLYSET®產品的配方之外,關於米格利特藥劑之發 •明’已有大陸專利公開說明書内容第CN 1615862A號,其揭 不一種治療II型糖尿病的米格利特口腔崩解片,此方法為改變 劑型釋放方式’其主要技術特徵在於主藥和賦型劑組成與製備 方法,其中’配方一:米格利特5至5〇%,每片含量為1〇至 200mg ’並添加辅料配方包括:填充劑5至3〇%、助崩劑$至 30%、崩解劑5至45%和微粉石圭膠(u至3% :混合均句後粉末 直接壓片’壓片間溫度18至26。(:,相對溫度控制45至65% ; 配方二:米格利特5至50〇/〇,每片含量為1〇至2〇〇mg,並先 添加填充劑5至30〇/〇、助崩劑5至3〇%混合均句然後加入黏 合劑5至15〇/〇製成軟材’並進行過_製粒、洪乾、整粒,之後 201014616 再加入崩解劑5至45%和潤滑劑0.1至3%等其他輔料, 混合後壓片,壓片間溫度18至26。(: ’相對溫度控制45至卿;7 並且此兩種配方與製程還可添加甜味劑〇 〇5至1〇%或/和^ 劑0.〇5%至10%,而製成口腔崩解片。此篇發明目的^ 口腔崩解片無触嚼,將藥物置於舌上,遇唾液⑼秒即可= 速解小顆粒,因此有利於老人、吞翻難或特殊環境下取 便之患者服用’可大大提高患者服藥的順應性,並 性抑制心㈣糖_ ’減錄類在胃、腸道降解, = 的吸收從有效騎健尿病人錢血糖濃度峰值,了 ^ 控制血糖。然而’該口腔崩解片的缺點為崩麻 ’ ,胃漲氣之副作用仍趨明顯,造成使用者的不適與/苦= 於 米格利特的腸胃道不良反應並無法改善。 、; 人胃GLYSET@或是祕稱藉自吞鶴作 的㈣糊,兩拉梓_㈣胃道的副作用 因此’吾人期待研發出一種新型之米格利特醫 、降低口服之後短時間内之溶作用' ’ -定時間之後達到與傳統藥劑同等之溶離速率藥1在 【發明内容】 之用ΐίΐ二:缺失’本發明之目的在於開發-種新穎 腸胃=鐘有降低之溶離速率,以= 傳統之藥劑-樣,可達到—溶離6g分鐘後,溶出率與 傳統之藥劑相同,兩:4目:=放之效果,樂物動力學上數據 考相比較在療效上具有生體相等性(BE; 201014616Care V24 'N5 ' 2001 . 989-94 ; Diabetes Research and Clinical Practice ' 52, 2001 : 205-213 ; Journal of Clinical Endocrinology and Metabolism V83, N5, 1998 : 1515-1522 and other documents also present data to illustrate Glyset® products Although blood glucose can be effectively controlled, the side effect response data of this formula is also explained. In addition to the formulation of the GLYSET® product, there is a lactic acid orally disintegrating tablet for the treatment of type 2 diabetes, which is disclosed in the Continental Patent Publication No. CN 1615862A. This method is to change the release form of the dosage form. The main technical features are the composition and preparation method of the main drug and the excipient, wherein 'recipe one: 5 to 5 % of MiGlite, each part is 1 to 200 mg' and added Excipient formulations include: fillers 5 to 3 %, helper disintegrating agents to 30 to 30%, disintegrants 5 to 45%, and micronized gums (u to 3%: mixed after the powder is directly compressed into tablets) Temperature 18 to 26. (:, relative temperature control 45 to 65%; Formula 2: Miglilet 5 to 50 〇 / 〇, each tablet content is 1 〇 to 2 〇〇 mg, and first add filler 5 to 30 〇/〇, aiding disintegrating agent 5 to 3〇% mixed and then adding binder 5 to 15〇/〇 to make soft material 'and granulating, driers, granules, then adding disintegrant after 201014616 5 to 45% and other lubricants such as 0.1 to 3% of the lubricant, after mixing, tableting, the temperature between the tablets is 18 to 26. (: 'Relative temperature control 45 to Qing; 7 And the two formulations and processes can also add a sweetener 〇〇 5 to 1% or / and ^ 0. 〇 5% to 10%, and make an orally disintegrating tablet. The purpose of this invention ^ oral disintegration The tablets are not chewable, and the medicine is placed on the tongue. In the case of saliva (9) seconds, the small particles can be quickly dissolved. Therefore, it is beneficial to the elderly, swallowing difficulties or taking the patient in a special environment to take the patient's medication. , and sexual inhibition of heart (four) sugar _ 'reduction of the class in the stomach, intestinal degradation, = absorption from the effective riding of the urine patient blood sugar concentration peak, ^ control blood sugar. However, the shortcoming of the orally disintegrating tablet is collapse ', the side effects of stomach ups and downs are still obvious, causing discomfort and/or bitterness of the user = the adverse reactions of gastrointestinal tract in Miglitt can not be improved.,; GLYSET@ or the secret of the stomach (4) paste, two pull 梓 _ (four) side effects of the stomach tract therefore 'we look forward to the development of a new type of MiGlite doctor, reduce the dissolution in a short time after oral administration ' ' - after the set time to achieve the same dissolution rate as traditional medicine Medicine 1 in the content of the invention ΐ ΐ 2: missing 'the invention The purpose is to develop - a novel gastrointestinal = bell has a reduced rate of dissolution, to = traditional agent - like, can be achieved - after dissolution of 6g minutes, the dissolution rate is the same as the traditional agent, two: 4 mesh: = put the effect, music Physical dynamics data comparison has bioequivalence in efficacy (BE; 201014616)
Bioequivalence)。 為達上述目的,本發明之米格利特醫藥組合物包含: 重量份之米格利特;〇.〇5至20重量份之黏合劑;15至6〇重量 份之崩散劑;50至200重量份之稀釋劑;及〇.〇5至2〇重量^ 之潤滑劑,其中崩散劑係選自以下群組:微晶纖維素、經^ 纖維素鈉、粉末狀纖維素、澱粉及其混合物。 工土 本發明所稱之黏合劑係用於降低米格利特溶出率 2低副仙。在—實施祕中,前述黏合舰含但不限於 -、糖漿、甲基纖維素、經丙基纖維素、㈣基甲基纖維素、 ^基纖維素、瓜爾膠、雜肋、师、聚乙婦錢聚乙 ^維ί旋騎或其齡物。難地,歧齡_經丙基甲 土發明係之崩散劑之選用,當使用特定崩散 基齡細、粉絲雜素、雜或 散劑也具有黏合劑及稀_之魏,而可達到延緩崩散 型之ΐ發除了舰辦,可魏—條速崩散 之第一朋散劑時(例如:羧,基澱粉鈉),這樣 ί『:後一開始具有降低之溶離速度以降低各種副作;:i 後具有與傳統之藥劑同樣之溶離速度以維持相同之華 重重量份之二 維素納、交鶴甲基纖維細、交聯聚乙締轉_聯== 201014616 t波^克林钾、預膠凝化澱粉、緩曱基殿粉鈉、海藻酸鈉、 =乙@夂’殿粉納或其混合物。較佳地,前述崩散劑為羧曱基澱 粉納。 ,發明所稱之稀侧剌於提供所製得之㈣組合物可 動性、潤滑性、可壓性,其與前述崩散劑的搭配 物的釋放性。在一實施態樣中,前述稀釋劑包含 兹撼社丄i,、澱粉、預膠凝化澱粉、碳酸部、硫酸鈣糖、葡 古σ η糊精、右旋糖、二水合磷酸氫二鈣、磷酸三鈣、 Γ馱鎂、氧化鎂、麥芽糊精、甘露糖醇、聚曱基丙烯 二物2、粉末狀纖維素、氣化鈉、山梨糖醇、滑石或其 作口物。較佳地,前述稀釋劑為甘露糖醇。 如卜所稱之潤滑劑_於在使藥物口服後減少沾黏於 於硬雜。在—實施紐巾,前賴㈣包含但不限 /, 甘油基棕櫚酸硬脂酸酯、氧化鎂、普羅莎姆 聚乙二醇、聚乙稀醇、苯甲酸鈉、月桂基硫酸納、 ❹ 二酸硬賴、触錄油、聽祕油、 較佳地,前述潤滑劑為硬脂酸鎂。 m、此口物 前述醫藥組合物可為錠劑、膠囊或粉末型離。 在-較佳實施態樣中’本發明 含:獅重量份之米格利特;80至物包 微晶纖維素;…。重量份之經 素,至重里伤之叛甲基殿粉鈉;以及410重量份 劑。更佳地,前述淵滑劑為硬脂酸鎮。 1月 在上述較佳實施態樣中,前述 而微晶_可做為_、_及_t == 樣中’别賴晶纖維素之主要作料稀釋劑同時亦具有崩^ 201014616 劑之功能。但是,由於微晶纖維素之崩散速度很慢(3〇分鐘), 其與屬於快速崩散劑之羧甲基澱粉鈉(5 m in即可崩散完)搭配 使用時,這樣的組合可以在口服之後一開始具有降低之溶離速 度以降低各種副作用,但在!小時後具有與傳統之藥劑同樣之 :谷離速度以維持相同之藥效。 本發明之包含米格利特的醫藥組合物,其對需要治療糖尿 病之患者進行口服時可降低腹痛、腸胃脹氣等,同時由於減少 添加賦型劑之成分’因此可節省製造成本及降低販售價格。 【實施方式】 上文所述的本發明之較佳實施態樣並不是意圖來限制本 考X月所屬領域具有通常知識者對其作修飾及細微之改變仍然 在本發明之精神及範圍内。本發明之權利範圍應該由附屬在此 說明書之申請專利範圍來決定。 本發明之用於治療糖尿病與或減肥之醫藥組合物,其包 含:100重量份之米格利特;〇·〇5至20重量份之黏合劑了 15 至60重量份之崩散劑;50至200重量份之稀釋劑;及〇 〇5至 =重量份之潤滑劑,其中該崩散劑係選自以下群組:微晶纖維 ”經甲基纖維素納、粉末狀纖維素、澱粉及其混合物。 、適用於本發明之黏合劑、崩散劑、稀釋劑與潤滑劑已如 所述。較佳地,本發明亦可將米格利特、甘露糖醇、羥丙基甲 基纖維素及其他賦型劑一起濕製造粒,此配方與傳統製程$ Ζ達到與原薇相等之療效。此經丙基甲基纖維素材料, =劑、分散劑、增稠劑、薄膜包衣材料,利用以上的特性; 樂物製備成混合材料缓釋片、緩釋膠囊、親水凝膠緩釋 = 緩釋優點具有控制製劑能降低血漿藥物濃度波動、減少紙藥心 201014616 J:療效、降低不良反應。在 本發明之米格利特醫藥組合物包含:漏 樣中, 8〇至120重量份之稀釋劑;20至50重量份里二之利特; 至1〇重量份之經丙基甲基纖維素;2至8重量;^纖甲維其素;1 納;以及i至10重量份之潤滑劑。更佳地甲基殿粉 露糖醇;前述姆m硬脂酸鎮。 W補釋劑為甘 ❹ ❹ f述較佳實施態樣中’前述甘露糖醇為主要 而微曰曰!維素可做為崩散劑、黏合劑、稀釋劑。二稀H 樣中,前述微晶纖維素之主要作用為 ς =能。奴,_嶋㈣崎散 其與屬於快速崩散劑之缓甲美避. 里) 使用時讀的組合可以在口服之後一 溶離速度以維持=之藥t小時後具有與傳統之藥劑同樣之 產口 施態樣中’本發明之米格利特醫藥組合物可使此 分鐘時將緩慢釋放(釋放速度比原廠慢),可 所產生的腸胃脹氣、腹痛之副作用,但在溶離 6〇刀鐘後,溶㈣與原廠—樣’可達到完全釋放出來之效果, 並且可發現BE數據大致與傳統之藥劑相同,因此具有相等之 療效。該具體實施態樣之錠劑成分種類較少、縮短㈣及製程 上時間’並且製備方關單,無轉殊設備和技術條件。 土發明之技術特徵係透過各種組份間的重量份調配以達 至如則所述之優點’而其製備流程係屬於傳統之製備流程,可 行之方式例如但不限於下列之方式: 製備方法-:將100g之米格利特1G7g之甘露糖醇、5g 之夢!丙基曱基纖維素、30g微晶纖維素,在高切變混合器中混 合上述三種成分形成粉末混合物,然後於粉末中加入水或醇類 11 201014616 it 醇或異稱)之溶形成_粒混合物,並 進行過餘丰ί獅C之溫度下乾燥來獲得乾顆粒’將其用篩網 鎂丘⑽ί i顆粒。將約5§級甲基殿粉納與約%之硬脂酸 加人研磨過雜的顆粒,接著進行混合均勻,續 磨後之顆粒壓縮即可製成錠劑。 、 醇,f 二:將100g之米格利特、85g重量份之甘露糖 著將2(Γ刀變,昆合Μ混合上述二種成分形成粉末混合物。接 ㈣與35g之微晶纖_加入水或醇 "乙醇、n-丙醇或異丙醇)混合溶解均勻,然後於粉末中 丙基甲。基纖維素之溶劑來製備成濕顆粒混合物,並 =在J)C至1GG°C之溫度下乾燥來獲得乾顆粒,將其用筛網 =1$去除大顆粒。將6g之解基殿粉鋪4g之硬脂酸録 磨過篩後的顆粒’接著進行混合均勻,紐將研磨 後之顆粒壓縮即可製成錠劑。 ,備方法三:將100g之米格利特、80g之甘露糖醇、45g ΐίΓ維素,在高切變混合11中混合上述二種成分形成粉末 =物。接著將20g之經丙基甲基纖維素加入水或醇類(諸如 乙轉、η喝醇或異丙醇)混合溶解均勻,紐於粉末中加已含有 趣丙基甲錢維素之_來製備麵齡齡物,並進行在 =至100°C之溫度下乾燥來獲得乾顆粒,將其用篩網進行過 j除☆顆粒。將5g之硬脂酸鎂共同加入研磨過篩後的顆粒, 者進行混合均勻’然後將研磨後之顆粒愿縮即可製成鍵劑。 一製備方法四:將100g之米格利特、89g之甘雜醇,在 南切變混合器中混合上述兩種成分形成粉末混合物。將雌之 經丙基f基纖維素與3Gg之微晶纖維素力^入水或醇類(諸如乙 醇、η-丙醇或異丙醇)混合溶解均勻之料液織關浮液型 恶喷射至粉末中製備成濕顆粒混合物,並進行在5〇。〇至1〇〇它 12 201014616 將之其更用r進行過筛去除大顆 =:接著進行叫然 製備方法五:將100g之米格利 之微晶纖維素,在高切蠻、Ύώ、θ人$心甘路楯知與45g "射料自㈣雜,絲㈣浮液型態喷 度下乾燥紐得乾難,料用_ 接著進行混合均句,紐將研磨後之顆粒壓縮㈡ 劑。 參 製備方法六:係將峋之經丙基曱基纖維素與%之微晶 纖維素=人水或賴(諸如乙醇、n__或異㈣)混合溶解均 勻之懸夺液喷射至lGGg之祕利特粉末。在高切變混合器中 加入90g之甘紐醇與上述之職浮液喷射至綠利特進行混 合均勻製備成濕顆粒,並進行在5(rc至⑽。c之溫度下乾燥來 獲得乾顆粒,將其用篩網進行過篩去除大顆粒。將約3g之羧 甲基殿粉納與約10g之硬脂酸鎂共同加入研磨簡後的顆粒, 接著進行混合均勻,然後將研磨後之顆粒壓縮即可製成錠劑。 製備方法七··係將3g之羥丙基曱基纖維素加入水或醇類 (諸如乙醇、η-丙醇或異丙醇)混合溶解均勻之懸浮液喷射至 100g之米格利特粉末。在高切變混合器中加入13%之甘露糖 醇及15g之微晶纖維素與上述之將懸浮液噴射至米格利特進行 混合均勻製備成濕顆粒,並進行在50°C至l〇〇°C之溫度下乾燥 來獲得乾顆粒’將其用_網進行過筛去除大顆粒。將lg之^ 13 201014616 曱,澱粉鈉與約lg之硬脂酸鎂共同加入研磨過篩後的顆粒, 接著進行混合均勻,然後將研磨後之顆粒壓縮即可製成錠劑。 製備方法八:將100g之米格利特、89g之甘露糖醇、2〇g 之羥丙基曱基纖維素、5g之羧甲基澱粉鈉、3〇g之微晶纖維素, 在尚切變混合器中混合上述五種成分形成粉末混合物,然後於 粉末中加入水或醇類(諸如乙醇、η-丙醇或異丙醇)之溶劑來形 成濕顆粒混合物,並進行在50。(:至1〇〇它之溫度下乾燥來獲得 乾顆粒,將其用篩網進行過篩去除大顆粒。將5g之羧甲基澱 •粉鈉與之硬脂酸鎂共同加入研磨過篩後的顆粒,接著進行 混合均勻,然後將研磨後之顆粒壓縮即可製成錠劑。 製備方法九:將50g之米格利特、i〇〇g之甘露糖醇、i〇g 之羥丙基曱基纖維素、30g之微晶纖維素、5g之羧曱基澱粉鈉、 5g之硬脂酸鎂,在高切變混合器中混合上述六種成分形成一粉 末混合物來製備。將混合物放入乾式造粒機乾燥粒,形成不規 則狀之顆粒物質,最後將顆粒進行壓縮成錠。 製備方法十:將50g之米格利特、54g甘露糖醇、2g之經 丙基甲基纖維素、15g之微晶纖維素,在高切變混合器中混合 上述四種成分形成一粉末混合物來製備。將混合物放入乾式造 粒機乾燥粒,形成不規則狀之顆粒物質,然後再加入2g叛甲 基搬粉納、2g之硬脂酸鎂與不規則狀之顆粒物質混合均勻,最 後將混合好之顆粒物質進行壓縮成錠。 製備方法十一:將25g之米格利特、50g之甘露糖醇、5g 之經丙基甲基纖維素、lg之羧甲基澱粉鈉、15g之微晶纖維素, 在高切變混合器中混合上述五種成分形成一粉末混合物來製 備。將混合物放入乾式造粒機乾燥粒,形成不規則狀之顆粒物 質’然後再加入lg之羧甲基澱粉鈉、2g之硬脂酸鎂與不規則 狀之顆粒物質混合均勻,最後將混合好之顆粒物質進行壓縮成 14 201014616 鍵。 之經素將利特、祝之甘露糖醇、lg lg之硬脂酸鎂,在高切、、3入= 曰、·維素、1g之叛甲基凝粉納、 混合物^贼絲成一粉末 素、ΐ 活性成分、甘露辦、躺基甲基纖維 顆-、二。广、硬脂賴之結合㈣溶麟魏乾燥、濕 可使米粉末充填可形成錠劑或膠囊,該錠劑或膠囊 生物i用性,.並液中’因此對於口服患者具有提高Bioequivalence). To achieve the above object, the MiGlite pharmaceutical composition of the present invention comprises: parts by weight of milaginate; 〇. 〇 5 to 20 parts by weight of a binder; 15 to 6 parts by weight of a disintegrating agent; 50 to 200 a diluent of parts by weight; and a lubricant of 5 to 2 parts by weight, wherein the disintegrating agent is selected from the group consisting of microcrystalline cellulose, sodium cellulose, powdered cellulose, starch, and mixtures thereof. . Work Soil The binder referred to in the present invention is used to reduce the dissolution rate of the MiGlite 2 low. In the implementation secret, the aforementioned bonding ship includes but is not limited to -, syrup, methyl cellulose, propyl cellulose, (tetra) methyl cellulose, ^ based cellulose, guar gum, miscellaneous ribs, division, poly E women's money gathers B ^ Wei 旋 spin ride or its age. Difficult, aging age _ propyl sulphate invention system of the choice of disintegration agent, when the use of specific disintegration of the base age, fan impurities, impurities or powder also has a binder and thin _ Wei, can achieve delay collapse In addition to the ship's office, the type of the bulk type can be used for the first time (such as carboxy, sodium starch), which has a reduced dissolution rate to reduce various side effects; :i has the same dissolution rate as the traditional pharmaceutical agent to maintain the same Huazhong weight fraction of the two-dimensional Suina, Jiaohe methyl fiber fine, cross-linked polyethylene-converted _ joint == 201014616 t wave ^ Kelly potassium , pre-gelatinized starch, slow-drying base powder sodium, sodium alginate, = B @夂' temple powder or a mixture thereof. Preferably, the aforementioned disintegrating agent is carboxymethyl amide. The invention is referred to as a thin side which provides the mobility, lubricity, compressibility of the prepared composition (4), and the release property of the collateral with the aforementioned disintegrating agent. In one embodiment, the diluent comprises: 撼i, starch, pregelatinized starch, carbonic acid, calcium sulphate, glucosinolate, dextrose, dicalcium phosphate dihydrate , tricalcium phosphate, strontium magnesium, magnesium oxide, maltodextrin, mannitol, polydecyl propylene dihydrate 2, powdered cellulose, sodium carbonate, sorbitol, talc or its mouth. Preferably, the aforementioned diluent is mannitol. Lubricants, as they are referred to, reduce the adhesion to hard impurities after oral administration of the drug. In the implementation of the towel, the former (4) contains but not limited to, glyceryl palmitate stearate, magnesium oxide, Prosham polyethylene glycol, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, bismuth Preferably, the aforementioned lubricant is magnesium stearate. m. The oral pharmaceutical composition may be in the form of a tablet, a capsule or a powder. In the preferred embodiment, the invention comprises: lion weight parts of milaglin; 80 to the package of microcrystalline cellulose; The weight of the drug, to the severely wounded methylation powder sodium; and 410 parts by weight. More preferably, the aforementioned slip agent is a town of stearic acid. In the above preferred embodiment, the above-mentioned microcrystals can be used as the main diluent for the _, _, and _t == samples, and also have the function of disintegrating the 201014616 agent. However, since the disintegration rate of microcrystalline cellulose is very slow (3 〇 minutes), when combined with sodium carboxymethyl starch which is a rapid disintegrating agent (5 m in can be disintegrated), such a combination can be After oral administration, there is a reduced rate of dissolution at the beginning to reduce various side effects, but at! After the hour, it has the same effect as the traditional medicine: the speed of the valley to maintain the same effect. The pharmaceutical composition comprising the MiGril in the present invention can reduce abdominal pain, flatulence, etc. when administered orally to a patient in need of treatment for diabetes, and at the same time, can reduce manufacturing cost and reduce sales by reducing the addition of the excipient component. price. [Embodiment] The above-described preferred embodiments of the present invention are not intended to limit the modifications and minor modifications of the present invention in the scope of the present invention. The scope of the invention should be determined by the scope of the appended claims. The pharmaceutical composition for treating diabetes and or losing weight of the present invention comprises: 100 parts by weight of MiGlite; 5 to 20 parts by weight of a binder of 15 to 60 parts by weight of a disintegrating agent; 200 parts by weight of a diluent; and 〇〇5 to = parts by weight of a lubricant, wherein the disintegrating agent is selected from the group consisting of microcrystalline fibers" via methylcellulose, powdered cellulose, starch, and mixtures thereof. The binders, disintegrating agents, diluents and lubricants suitable for use in the present invention are as described. Preferably, the present invention may also be used for Miglitle, mannitol, hydroxypropylmethylcellulose and others. The excipient is wet-made together, and the formulation has the same effect as the original process by the conventional process. The propylmethylcellulose material, the agent, the dispersant, the thickener, and the film coating material are utilized. The characteristics of the preparation of the music into a mixed material sustained release tablets, sustained release capsules, hydrophilic gel sustained release = sustained release advantages of control agents can reduce plasma drug concentration fluctuations, reduce paper drug heart 201014616 J: efficacy, reduce adverse reactions. Miglit Pharmaceutical Group of the present invention The composition comprises: 8 to 120 parts by weight of the diluent in the sample; 20 to 50 parts by weight of the lining; to 1 part by weight of the propylmethylcellulose; 2 to 8 by weight; 1% nanocapsule; and 1 to 10 parts by weight of a lubricant. More preferably, methyl phyllo-oligosaccharide; the aforementioned m-stearic acid town. W replenishing agent is gans ❹ 述In the aspect, 'the aforementioned mannitol is the main and slightly sputum! The vitamin can be used as a disintegrating agent, a binder, and a diluent. In the dilute H sample, the main function of the aforementioned microcrystalline cellulose is ς = energy. _ 嶋 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四 四In the sample, the MiGlite pharmaceutical composition of the present invention can release slowly at this minute (release rate is slower than the original factory), and can produce side effects of flatulence and abdominal pain, but after dissolving 6 knives, Dissolved (four) and the original - like 'can achieve the effect of complete release, and can be found that the BE data is roughly the same as the traditional agent The same effect, therefore, has the same effect. The specific composition of the tablet has fewer types of components, shortens (4) and the time on the process, and prepares the customs, no special equipment and technical conditions. The technical characteristics of the soil invention are through various The parts by weight are formulated to achieve the advantages as described, and the preparation process is a conventional preparation process, such as, but not limited to, the following: Preparation method:: 100 g of Miglit 1G7g of mannitol, 5g dream! Propyl mercapto cellulose, 30g microcrystalline cellulose, mixing the above three components in a high shear mixer to form a powder mixture, and then adding water or alcohol to the powder 11 201014616 it The alcohol or the nickname is dissolved to form a granule mixture, and dried at a temperature of yu lion C to obtain dry granules, which are sieved with magnesium mound (10) ί i particles. The granules of about 5 s grades of methyl sulphate and about 1% of stearic acid are added to the pulverized particles, and then uniformly mixed, and the granules after the pulverization are compressed to prepare a troche. , alcohol, f 2: 100g of MiGlite, 85g parts by weight of mannose, 2 (the trowel, Kunming Μ mixed the above two components to form a powder mixture. Connected (4) and 35g of microcrystalline fiber _ join Mix water or alcohol "ethanol, n-propanol or isopropanol to dissolve evenly, then propyl group in powder. The solvent of the cellulose is prepared to form a wet granule mixture, and dried at a temperature of J) C to 1 GG ° C to obtain dry granules, which are removed by a sieve = 1$. 6 g of the solution base powder was applied to 4 g of stearic acid to record the sieved particles, which were then uniformly mixed, and the pellets after the grinding were compressed to prepare a tablet. Method 3: 100 g of Miglilet, 80 g of mannitol, and 45 g of glutamic acid are mixed in the high shear mixing 11 to form a powder. Then add 20g of propylmethylcellulose to water or alcohol (such as B-trans, η-alcohol or isopropanol) and mix and dissolve evenly. Add the powder containing interesting propyl carbaryl to the powder. The surface-aged material was prepared and dried at a temperature of = to 100 ° C to obtain dry granules which were subjected to a sieve removal by a sieve. 5 g of magnesium stearate was added together to the milled granules, and the mixture was uniformly mixed. Then, the milled granules were allowed to shrink to form a bond. A preparation method 4: 100 g of Miglit, 89 g of glycerol was mixed in the south shear mixer to form a powder mixture. Mixing the propyl f-based cellulose of the female with 3Gg of the microcrystalline cellulose into water or an alcohol (such as ethanol, η-propanol or isopropanol) to dissolve the homogeneous liquid A mixture of wet granules was prepared in the powder and carried out at 5 Torr. 〇到1〇〇 It 12 201014616 It is further sieved with r to remove large particles =: Then proceed with the preparation method five: 100g of Megley microcrystalline cellulose, in high cut, Ύώ, θ people $心甘路楯知与45g "Shipping material from (four) miscellaneous, silk (four) floating liquid type spray drying under the dry button, the material used _ then mixed mixed sentence, New Zealand will be crushed particles after the two (2) agent. Reference preparation method 6 is: mixing the propyl fluorenyl cellulose of hydrazine with % microcrystalline cellulose = human water or lysine (such as ethanol, n__ or iso (tetra)) to dissolve the suspension liquid evenly to the secret of lGGg Lit powder. Add 90g of ganol to the high shear mixer and mix it with the above-mentioned floating liquid spray to the green stalk to prepare the wet granules, and dry at 5 (rc to (10).c to obtain dry granules. And sifting it with a sieve to remove large particles. About 3 g of carboxymethyl phosphatide and about 10 g of magnesium stearate are added together to grind the granules, followed by mixing uniformly, and then grinding the granules The tablet can be prepared by compression. Preparation method VII. 3 g of hydroxypropyl fluorenyl cellulose is added to water or an alcohol (such as ethanol, η-propanol or isopropanol) and the mixture is uniformly sprayed to the suspension. 100g of MiGlite powder. Add 13% mannitol and 15g of microcrystalline cellulose to the high shear mixer and spray the suspension onto the MiGlite to prepare the wet granules. Drying is carried out at a temperature of from 50 ° C to 10 ° C to obtain dry granules. The granules are sieved to remove large granules. lg ^ 13 201014616 曱, sodium starch and about lg of magnesium stearate Co-add the pulverized granules together, then mix them evenly, then grind them The granules can be compressed to form a tablet. Preparation method 8: 100 g of Miglit, 89 g of mannitol, 2 g of hydroxypropyl decyl cellulose, 5 g of sodium carboxymethyl starch, 3 The microcrystalline cellulose of 〇g is mixed with the above five components in a shearing shear mixer to form a powder mixture, and then a solvent of water or an alcohol such as ethanol, η-propanol or isopropanol is added to the powder to form Wet the mixture of particles and carry out drying at 50 ° (: to 1 〇〇 to obtain dry granules, which are sieved to remove large particles. 5 g of carboxymethyl silicate and sodium powder are hardened The magnesium sulphate is added to the pulverized granules together, and then uniformly mixed, and then the pulverized granules are compressed to prepare a troche. Preparation Method 9: 50 g of MiGlite, i 〇〇g of mannose Alcohol, i〇g of hydroxypropyl decyl cellulose, 30 g of microcrystalline cellulose, 5 g of sodium carboxymethyl starch, 5 g of magnesium stearate, mixed with the above six components in a high shear mixer to form a Prepare a powder mixture. Put the mixture into a dry granulator to dry the granules to form irregular shapes. Granular material, and finally the granules are compressed into ingots. Preparation Method 10: 50 g of MiGlite, 54 g of mannitol, 2 g of propylmethylcellulose, 15 g of microcrystalline cellulose, mixed in high shear The mixture is prepared by mixing the above four components to form a powder mixture. The mixture is placed in a dry granulator to dry the granules to form irregular granular materials, and then 2 g of methylidene powder and 2 g of magnesium stearate are added. Mixing with the irregular granular material, and finally compressing the mixed particulate matter into an ingot. Preparation Method 11: 25 g of Miglit, 50 g of mannitol, 5 g of propylmethylcellulose , lg of sodium carboxymethyl starch, 15 g of microcrystalline cellulose, prepared by mixing the above five components in a high shear mixer to form a powder mixture. The mixture is placed in a dry granulator to dry the granules to form an irregular granular material. Then, lg of sodium carboxymethyl starch, 2 g of magnesium stearate and irregular particulate matter are uniformly mixed, and finally mixed. The particulate matter is compressed into 14 201014616 keys. It is a powder of Lit, I wish mannitol, lg lg magnesium stearate, in high cut, 3 into = 曰, · 素素, 1g of renegade methyl condensate, mixture ^ thief into a powder Ingredients, 活性 active ingredients, nectar, lying methyl fiber -, two. Combination of broad and hard fats (4) Drying and wetting of the lyophilized granules can be used to form tablets or capsules. The tablets or capsules are bio-use, and the liquid is in the liquid.
表1中列出四組不同成分之本發明之米格利特醫藥組合 物’其製備方法可使用如前所述之任一流程。 表1 成分 第一組 第二組 第三組 第四組 米格利特 100 100 50 25 甘露糖醇 107 70 100 50 羥丙基甲基織維素 5 20 10 5 微晶織維素 30 45 30 15 羧曱基澱粉鈉 5 8 5 2 1 硬脂酸鎂 3 7 5 2 15 201014616 總計(mg) 一. 250 250 200 99 特醫藥组合物生物利用疳公奸 本發明之米格利特醫藥組合物之生物利用度將與 GLYSET®進行比較。⑽孤⑧為Bayer公司製造已商^化^ 米格利特藥劑,除了活性成分米格利特之外,其包含非活性成 分澱粉、微晶纖維素、硬脂酸鎂、羥丙基甲基纖維素、聚乙二 醇、氧化鈦、聚山梨醇酯8〇等。 .米掩jj特邊_樂組合物之贈内試驗藥物動力學I盤⑽ >實驗試驗方法為’讓16位受試者在口服米格利特刚邮 十小時’服藥後仍須禁食4小時,進行隨機、單劑 董”雙向X叉方式。每:欠給紐之下辦間The MiGlite pharmaceutical composition of the present invention in which four different components are listed in Table 1 can be produced by any of the procedures described above. Table 1 Ingredients Group I Group 2 Group 3 Group IV Millipl 100 100 50 25 Mannitol 107 70 100 50 Hydroxypropyl Methyl Vividin 5 20 10 5 Microcrystalline Weaving 30 45 30 15 Carboxymethyl starch sodium 5 8 5 2 1 Magnesium stearate 3 7 5 2 15 201014616 Total (mg) I. 250 250 200 99 Special pharmaceutical composition Bio-use 疳 疳 本 本 本 本 本 本 本 本Bioavailability will be compared to GLYSET®. (10) Solitary 8 is manufactured by Bayer Co., Ltd., which has been invented by the company. In addition to the active ingredient, Miglit, it contains inactive starch, microcrystalline cellulose, magnesium stearate, and hydroxypropylmethyl. Cellulose, polyethylene glycol, titanium oxide, polysorbate 8 oxime, and the like. .米遮jj特边_乐 composition of the internal test pharmacokinetics I disk (10) > experimental test method for 'let 16 subjects in the oral administration of MiGlite just ten hours after taking the drug still need to fast 4 hours, carry out a random, single-agent Dong" two-way X-fork method.
e^l.〇^e,w.5^e,.2.〇^,2.5,^.3.〇lt35I 、5.〇小時、6 0小時、8 〇小時、ιο小時、i2小 3於表舖血漿樣品胳藥物動力學分析。所得到之結 表2 項目 Tmax (hr) 1—---- Tl/2 (hr) -------—__ c 、max (ng/ml) ------ AUC〇-+j (hr · ng/ml) 1 1.— AUC〇—〇〇 (hr · ng/ml) GLYSET® 2.8+0.7 2.1±0.3 1797+418 —-------— 9875±2311 10070+2335 實施例1 2.8±l.〇 2.0+0.2 Π54±464 ··— — 965612205 9827+2244 . .1 由上表中可吾Φ *Jr «fc ua a --- ——___1 之藥物動力學參數τ …小叫|跟製品GLYSET® 之數據差驗魏計彳錢 ί G—1、撕“ ’所得 旻並未有顯者的差異,故評估兩者具有生 16 201014616 體相等性。 實施例3·米格利特罄籌鎰合物之浓龜率屮押 由第一圖 0.1Ν Ηα、第二圖 pH 4.5 Acetate Buffer、第三 圖pH 6.8 Phosphate Buffer之不同溶離液所得的溶離比對圖^ 現’本發明實施例1之米格利特醫藥組合物與GLYSET®相較, 在10至30分鐘之間具有較低溶離率,但在6〇分鐘後與 # GLYSET®的溶離率則可達到一致。根據上述藥物動力學數據顯 示,兩者不僅在生物利用度上效果相當,在體外溶離之溶離率 數,顯示,本發明實施例丨於前3〇分鐘具有較低溶離率,故 萬藥物伙藥劑中釋放到達在胃的部位時,不會因藥物釋放太多 而使得短時間内就產生腹痛、胃腸脹氣之副作用,藉此降低口 服此藥之患者的痛苦。 _ 第四圖顯示不同時間本發明實施例i之米格利特醫藥組 &物與GLYSET之jk清濃度。結果顯*本發明之#格利特醫 藥組合物與GLYSET®具有相同之生物利用性。 » 宜施例4·米格利特旋谢之姿定杻设必 將本發明實施例1之米格利特醫藥組合物保存一年,定期 測量其米格利特之含量,其結果如表3所示。 ' 表3 時間 〇月 1月 2月 3月 4月 6月 9月 12月 含 量 (mg) 101.2 101.1 100.9 100.6 100.1 100.9 100.6 100.2 一 _ 17 201014616 表中可看出本發明之米格利特醫藥組合物所製備成之 4丰执女丨姓、子仃安疋性试驗,結果顯示發現經過保存一年 \ :二,的含置並沒有顯著減退,故本發明之米格利特醫筚 組合物之配方在藥敝成幼當敎。 特醫樂 合物臨床試蜂e^l.〇^e,w.5^e,.2.〇^,2.5,^.3.〇lt35I, 5.〇 hours, 60 hours, 8 hours, ιο hours, i2 small 3 Plasma samples were analyzed for pharmacokinetic analysis. The resulting table 2 items Tmax (hr) 1—T-/2 (hr) -------___ c , max (ng/ml) ------ AUC〇-+ j (hr · ng/ml) 1 1.— AUC〇—〇〇 (hr · ng/ml) GLYSET® 2.8+0.7 2.1±0.3 1797+418 —-------— 9875±2311 10070+2335 Example 1 2.8±l.〇2.0+0.2 Π54±464 ··— 965612205 9827+2244 . .1 From the above table, the pharmacokinetic parameter τ of Φ *Jr «fc ua a --- ——___1 ...small slogan|data difference with GLYSET® products. Wei 彳 彳 ί ί G—1, tear “There is no significant difference in the income ,, so it is evaluated that the two have the same 16 201014616 body equality. Example 3· The dilution ratio of the different concentrations of the solution from the first plot of 0.1Ν Ηα, the second plot of pH 4.5 Acetate Buffer, and the third plot of pH 6.8 Phosphate Buffer is shown in Figure 1. 'The MiGlite pharmaceutical composition of Example 1 of the present invention has a lower elution rate between 10 and 30 minutes compared to GLYSET®, but the dissolution rate of #GLYSET® is consistent after 6 minutes. According to the above pharmacokinetic data, the two are not only in the raw The effect of the degree of utilization is comparable, and the number of elution rates in vitro dissolution shows that the embodiment of the present invention has a lower elution rate in the first 3 minutes, so that when the drug is released into the stomach, it will not be caused by the drug. Excessive release causes side effects of abdominal pain and flatulence in a short period of time, thereby reducing the suffering of patients who take this medicine. _ The fourth figure shows the MiGlite medical group & The concentration of jk with GLYSET is clear. The results show that the #格lite pharmaceutical composition of the present invention has the same bioavailability as GLYSET®. » The application of the example 4·Miglit is to be implemented in accordance with the present invention. The MiGlite pharmaceutical composition of Example 1 was stored for one year, and its content of Miglilet was measured periodically. The results are shown in Table 3. 'Table 3 Time January January February March April June September December content (mg) 101.2 101.1 100.9 100.6 100.1 100.9 100.6 100.2 a _ 17 201014616 The table can be seen that the MiGlite pharmaceutical composition of the present invention is prepared as a 4 fulfilment of female surname, 仃 仃 仃 test Test, the results show that the save was saved One year \ : two, the inclusion of the composition did not significantly decrease, so the formulation of the MiGlite medical composition of the present invention is young in the medicine. Special medical test
將本發明之米格利特醫藥組合物進行臨床試驗觀 胃道的副伽改善情形,本臨床試驗將本發明之米特= =與】,類的另一成分Acarb〇se進行療效及安= 的如纣,其中安全性差異如表4、表5所示。In the clinical trial of the MiGlite pharmaceutical composition of the present invention, the side gamma improvement of the gastric tract is observed. In this clinical trial, the mites of the present invention == and 】, another component of the class Acarb〇se is used for efficacy and safety. For example, the security differences are shown in Table 4 and Table 5.
Acarbose與祕利特關於小腸α葡萄糖鶴抑制劑, 適用於配合飲食控繼療第π麵尿病,主㈣_機制是通 過在、】腸内可逆性抑制α葡萄糖;^酶,減少糖類分解為葡萄 糖’並能延遲小腸巾葡萄㈣吸收,而來達崎低飯後血糖升 南的幅度。兩者皆為治療糖病患者之用藥,依據與 GLYSET®產品賴書巾得知’兩項成分在腸胃道的副作用發 生率皆甚高,腸胃脹氣Acarbose高於miglitol的178倍,腹痛 Acrobose 高於 1.62 倍。Acarbose and Mirius are related to small intestine alpha glucose crane inhibitor, which is suitable for the treatment of π-face urinary disease with diet control. The main (four) _ mechanism is to reversibly inhibit α-glucose in the intestinal tract; Glucose' can delay the absorption of small intestines (four), and the rate of blood sugar rises to the south after the meal. Both of them are used for the treatment of patients with diabetes. According to GLYSET® products, the incidence of side effects in the gastrointestinal tract is very high. The Acarbose of the flatulence is higher than 178 times of the miglitol, and the abdominal pain is higher than the Acrobose. 1.62 times.
*4 -Acarbose ^ GLYSEI\|^B^ 書之依據 腹痛 腸胃脹氣 Acarbose 19% 74% Migliol 11.7% 41.5% 將本發明實施例1之米格利特醫藥組合物所進行之臨床試 驗,此試驗採用47位病患者進行雙盲、單一試驗中心、有效 201014616 藥對照、隨機平行試驗,共治療14週,實驗方法為每日隨餐 一起服用1顆50mg acarbose膠囊及一顆50mg miglitol安慰 劑’服用4星期後增加劑量至每日三餐隨餐一起服用1顆5〇11^ acrabose膠囊及一顆l〇〇mg miglitol安慰劑,服用10星期,其 結果如表5所示。根據數據發現,腸胃脹氣acrob〇se高於 miglitol 2.87倍’腹痛acrab〇se高於4.2倍,且其他副作用如上 腹疾病、腎臟與泌尿疾病、膀胱結石、輸尿管結石、排尿困難、 腎絞痛’此些副作用都相對比acarbose來的低。 表5· Acarbose與本發明實施例1之米格利特醫藥組合物臨床試 驗之數據*4 -Acarbose ^ GLYSEI\|^B^ The basis of the book is abdominal pain, flatulence, Acarbose 19%, 74% Migliol, 11.7%, 41.5%. The clinical trial of the MiGlite pharmaceutical composition of Example 1 of the present invention was carried out. Forty-seven patients underwent double-blind, single-center, effective 201014616 drug control, randomized parallel trials for a total of 14 weeks. The test method was to take one 50mg acarbose capsule and one 50mg miglitol placebo together with the meal. After the week, increase the dose to three meals a day with a 5〇11^ acrabose capsule and a l〇〇mg miglitol placebo for 10 weeks. The results are shown in Table 5. According to the data, the flatulence acrob〇se is 2.87 times higher than the miglitol's abdominal pain acrab〇se is more than 4.2 times, and other side effects such as abdominal diseases, kidney and urinary diseases, bladder stones, ureteral stones, dysuria, renal colic ' These side effects are relatively lower than those of acarbose. Table 5 - Data of clinical trials of Acarbose and the MiGlite pharmaceutical composition of Example 1 of the present invention
Miglitol (%) Acarbose (%) 腹痛 0.0 % 4.2 % 上腹疾病 0.0 % 4.2 % 腸胃脹氣 8.7 % 25.0 % 腸運動頻繁 4.3 % 4.2 % 膀胱結石 0.0 % 4.2 % 輸尿管結石 0.0 % 4.2 % 排尿困難 0.0 % 4.2 % 腎絞痛 0.0 % 4.2 % =於本發明賴發的米格利特(mig腕),&於體外溶離結 果,前30分鐘所釋放速度比GLYSET(g^,由表5的m㈤ 比較表4的本發明實關丨之米格婦㈣ 19 201014616 副作用的趨勢使腸胃不適感較不明顯。 綜上所述’本發明之醫藥組合物米格利特錠劑,其體外溶 離數據,第10至30分鐘的溶離速度比GLYSET®緩慢,因此, 當,者^服此藥在胃期間内將緩慢釋放,可使患者減緩腹痛、 ,胃脹氣之副作用;體内試驗則透過生物利用度試驗得知兩者 藥物動力學上達生體相等性,可稱療效上相同,以及47例之 fern床試驗知知剎作用的發生比率趨缓。加上由於本發明錠劑的 •成分種類較少,縮短秤料及製程上的時間,在製備方面方法簡 單,無須特殊設備和技術條件。 其它實施態樣 所有揭露於本發明書之舰係可使肺何方式結合。本說 明書所揭露之特徵可使用相同、相等或相似目的的特徵取代。 因此,除了特別陳述強調處之外,本說明書所揭露之特徵係為 一系列相等或相似特徵中的一個實施例。 癱4-依據本說明書揭露之内容,減本技術領域者係可 r 、發明之基本特徵,在不脫離本發明之精神與範圍 對不同使財法與情況作適當改變與修飾,因此,其它 實施態樣亦包含於申請專利範圍中。 '、 20 201014616 【圖式簡單說明】 第一圖為0.1N鹽酸溶液中100mg本發明之米格利特醫藥 組合物與lOOmgGLYSET®之溶離比對圖。 ” 第二圖為pH 4.5之醋酸緩衝液中i〇〇mg本發明之米格利 特醫藥組合物與lOOmgGLYSET®之溶離比對圖。 第三圖為pH 6.8之鱗酸緩衝液中i〇〇mg本發明之米格利 特醫藥組合物與lOOmgGLYSET®之溶離比對圖。 第四圖為lOOmg本發明之米格利特醫藥組合物與 參 lOOmgGLYSET®之血清濃度比對圖。 21Miglitol (%) Acarbose (%) Abdominal pain 0.0 % 4.2 % Upper abdominal disease 0.0 % 4.2 % Flatulence 8.7% 25.0 % Frequent bowel movements 4.3 % 4.2 % Bladder stones 0.0 % 4.2 % Ureteral stones 0.0 % 4.2 % Urinary dysfunction 0.0 % 4.2 % renal colic 0.0% 4.2% = in the in vitro dissolution of the MiGril (mig) in the present invention, the rate of release in the first 30 minutes is higher than GLYSET (g^, compared with m (f) in Table 5 The invention of the present invention is based on the fourth aspect of the present invention. The trend of side effects makes the stomach discomfort less obvious. In summary, the pharmaceutical composition of the present invention, the MiGlite tablet, has in vitro dissolution data, the 10th. The dissolution rate to 30 minutes is slower than that of GLYSET®. Therefore, when the drug is released slowly during the stomach, the patient can slow down the side effects of abdominal pain and flatulence; the in vivo test is tested by bioavailability. It is known that the pharmacokinetics of the two organisms are equivalent, and the therapeutic effect is the same, and the occurrence rate of the known brake action in the fern bed test of 47 cases is slowed down. Scale and process Time, in terms of preparation, the method is simple, and no special equipment and technical conditions are required. Other implementations All of the ship systems disclosed in the present invention can combine the lungs and the way. The features disclosed in the present specification can use the same, equal or similar purpose. The features disclosed in this specification are one of a series of equal or similar features, except for the particular statement. 瘫4 - According to the disclosure of this specification, the technical field is reduced. r, the basic characteristics of the invention, the financial law and the situation are appropriately changed and modified without departing from the spirit and scope of the invention. Therefore, other implementation aspects are also included in the scope of the patent application. ', 20 201014616 Brief Description of the Invention The first figure is a comparison of the dissolution ratio of 100 mg of the MiGlite pharmaceutical composition of the present invention and 100 mg of GLYSET® in a 0.1 N hydrochloric acid solution. The second figure is i〇〇mg in acetic acid buffer of pH 4.5. The dissolution ratio of the Miglit pharmaceutical composition and 100 mg of GLYSET®. The third figure is the pH of 6.8 in the sulphate buffer. Pharmaceutical composition from the ratio of the dissolution lOOmgGLYSET® FIG. Split serum MIG fourth graph lOOmg pharmaceutical compositions of the present invention with reference to FIG lOOmgGLYSET® concentration ratio of 21
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