TW200946142A

TW200946142A - Tablet

Info

Publication number: TW200946142A
Application number: TW98110516A
Authority: TW
Inventors: Yuichiro Kano
Original assignee: Kowa Co
Priority date: 2008-03-28
Filing date: 2009-03-30
Publication date: 2009-11-16
Also published as: CN101543480A; JP2009256349A

Abstract

The invention provides a preparation method of tablets with good disintegrative and excellent mechanical strength. The method is a preparation method of tablets with (A) active ingredients, wherein the tablets contain (B) carboxymethyl cellulose or salt thereof, and (C) silicon dioxide.

Description

200946142 六、發明說明：【發明所屬之技術領域】本發明係關於一種兼顧崩解性及機械強度之錠劑及其製造方法。【先前技術】在醫藥品之經口投予製劑中’錠劑具有製備簡便、劑型中之成分含量準破、易於掩蓋苦味等、可大量生產等優點’因此應用範圍最為廣泛。另一方面，由於生物體可用 ® 率容易因製劑技術之微妙差異而有所改變，故而需要較其他製劑更為慎重地對錠劑進行製劑評價及品質管理。於進行錠劑之製劑設計時，除了對原料粉體之流動性、結合性、潤滑性等有要求以外，壓縮後之錠劑必需具有適度之機械強度與崩解性。即，若機械強度提高，則崩解性有降低之傾向；若崩解性良好，則機械強度有降低之傾向。 φ 羧甲基纖維素或其鹽、及二氧化矽係眾所周知之製劑添加物。作為將該等兩種添加物組合調配而成之錠劑，於專利文獻1〜10中已得知，然而該等專利文獻中，關於將兩者 * 組合時所得之錠劑的機械強度會如何變化完全無記載。， [專利文獻丨]曰本專利特開平6-183964號公報 [專利文獻2]曰本專利特開2〇〇3119134號公報 [專利文獻3]日本專利特開2〇〇5_154281號公報 [專利文獻4]日本專利特開2〇〇7 332〇63號公報 [專利文獻5]曰本專利特開2〇〇7_191419號公報 139389.doc 200946142 [專利文獻6]曰本專利再表2〇〇4/〇〇6945號公報 [專利文獻7]日本專利特開2〇〇5_1942〇3號公報 [專利文獻8]日本專利特開20054 62619號公報 [專利文獻9]曰本專利特開平ι〇_298〇61號公報 [專利文獻10]日本專利特開2007-169195號公報【發明内容】 [發明所欲解決之問題] 本發明之課題係提供一種崩解性良好且機械強度優異之錠劑及其製造方法者。 [解決問題之技術方法] 本發明者在製造錠劑時，發現藉由將作為製劑添加物而眾所周知之羧甲基纖維素或其鹽與二氧化矽組合調配，可獲得具有顯示良好之生物體可用率的崩解性，並且機械強度優異’尤其是於流通階段或作業時、進而於包衣時會成為之問題之磨損幾乎不存在之錠劑（素錠），從而完成了本發明。即’本發明係提供一種具有耐磨損性之錠劑之製造方法者’其特徵在於：其係製造含有（A)藥效成分之錠劑者，且使該鍵劑含有（B)羧曱基纖維素或其鹽、及（c)二氧化石夕。又’本發明係提供一種具有良好之崩解性且具有耐磨損性之錠劑之製造方法者，其特徵在於：其係製造含有（A) 藥效成分之錠劑者，且使該錠劑含有羧甲基纖維素或其鹽、及（C)二氧化石夕。 139389.doc 200946142 進而，本發明係提供一種錠劑者，其含有：（A)選自消化性潰瘍用劑、健胃劑、消化劑、抗酸劑、胃黏膜修復劑及整腸藥中之藥效成分；（B)羧甲基纖維素或其鹽；及（c) -氧化梦。 [發明之效果] 藉由本發明之方法而獲得之錠劑具有良好之崩解性且幾 . 乎不產生磨損，因此於流通階段或作業時、進而於包衣時錢損且可獲得良好之生物體可用率。尤其是，藉由本發明之方法而獲得之錠劑，藉由依據第十五改正日本藥典「崩解試驗法」之速釋製劑之方法，即藉由使崩解試驗裝置在如下條件（試驗液：水，液量：1〇〇〇 mL，試驗溫度： 37±2°C )下運作之方法而測得之崩解時間為3〇分鐘以内，且藉由依據第十五改正日本藥典中說明書之參考資訊「旋劑之磨損度試驗法」之方法，即藉由將規定量之鍵劑放入轉筒並使其旋轉100轉，再於試驗後以目測計算有缺損之 ❹ 冑的數量之方法而測得之磨損度為0,因此藉由本發明而獲得之錠劑特別有用。又，根據本發明，可容易地製造保持顯示良好之生物體可用态通j用率的朋解性並且改善磨損度之錠 . 劑。【實施方式】本發明之具有耐磨損性之錠劑係藉由含有⑷藥效成分、（Bm甲基纖維素或其鹽、及（c)二氧化石夕而製造。更具體而言，係藉由對冬古γ 3有（A)樂效成为、（B)羧甲基纖維素BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a tablet which combines disintegration and mechanical strength and a method for producing the same. [Prior Art] In the oral administration of pharmaceutical preparations, the tablet has the advantages of simple preparation, quasi-breaking of the components in the dosage form, easy masking of bitterness, and the like, and mass production. On the other hand, since the bioavailable ® rate is subject to change due to subtle differences in formulation techniques, it is necessary to more carefully evaluate the formulation and quality of the tablet than other formulations. In the preparation of the formulation of the tablet, the compressed tablet must have moderate mechanical strength and disintegration in addition to the fluidity, bonding, lubricity and the like of the raw material powder. That is, when the mechanical strength is increased, the disintegration property tends to be lowered, and when the disintegration property is good, the mechanical strength is lowered. φ Carboxymethylcellulose or a salt thereof, and cerium oxide are well-known preparation additives. A tablet prepared by combining these two additives is known from Patent Documents 1 to 10. However, in the patent documents, what is the mechanical strength of the tablet obtained when the two are combined? The change is completely undocumented. [Patent Document 丨] 专利专利 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 6-1 专利专利[Patent Document 5] Japanese Patent Laid-Open Publication No. Hei. No. Hei. No. 2, No. Hei. No. Hei. No. Hei. [Patent Document 7] Japanese Patent Laid-Open Publication No. Hei. No. Hei. No. Hei. No. Hei. No. Hei. [Problem to be Solved by the Invention] The object of the present invention is to provide a tablet having excellent disintegration properties and excellent mechanical strength and its manufacture. Method. [Technical method for solving the problem] When the present inventors produced a tablet, it was found that a well-displayed organism can be obtained by combining carboxymethylcellulose or a salt thereof which is well known as a formulation additive with cerium oxide. The disintegration of the usability and the excellent mechanical strength are particularly in the form of a tablet (primary ingot) which is hardly present in the circulation stage or during the operation, and which is a problem which may become a problem at the time of coating, thereby completing the present invention. That is, the present invention provides a method for producing a tablet having abrasion resistance, which is characterized in that it is a tablet containing (A) a medicinal ingredient, and the bond contains (B) carboxy hydrazine. a cellulose or a salt thereof, and (c) a dioxide dioxide. Further, the present invention provides a method for producing a tablet having good disintegration and abrasion resistance, which is characterized in that a tablet containing (A) a medicinal ingredient is produced and the ingot is made The agent contains carboxymethylcellulose or a salt thereof, and (C) a dioxide dioxide. Further, the present invention provides a tablet comprising: (A) selected from the group consisting of a peptic ulcer agent, a stomachic agent, a digestive agent, an antacid, a gastric mucosa repairing agent, and an intestine drug. a medicinal ingredient; (B) carboxymethylcellulose or a salt thereof; and (c) - an oxidative dream. [Effects of the Invention] The tablet obtained by the method of the present invention has good disintegration property and hardly causes abrasion, so that it is profitable in the circulation stage or work, and further in the coating, and a good living body can be obtained. Body availability. In particular, the tablet obtained by the method of the present invention is subjected to the method of correcting the immediate release preparation of the Japanese Pharmacopoeia "disintegration test method" according to the fifteenth, that is, by disintegrating the test device under the following conditions (test liquid : water, liquid volume: 1 〇〇〇 mL, test temperature: 37 ± 2 ° C) The method of operation is measured and the disintegration time is within 3 〇 minutes, and the instructions in the Japanese Pharmacopoeia are corrected according to the fifteenth The reference information "method of the abrasive wear test" is to calculate the amount of defect 目 by visually measuring the amount of the key into the drum and rotating it for 100 revolutions. The degree of wear measured by the method is 0, and thus the tablet obtained by the present invention is particularly useful. Further, according to the present invention, it is possible to easily manufacture an ingot which maintains the usability of the usable state of the living body and improves the degree of wear. [Embodiment] The tablet having abrasion resistance of the present invention is produced by containing (4) a medicinal ingredient, (Bm methylcellulose or a salt thereof, and (c) a silica dioxide. More specifically, By (A) music effect, (B) carboxymethyl cellulose

或其鹽、及（C)二惫外rA 夕之混合物或顆粒進行打鍵而製 139389.doc 200946142 造。本發明之錠劑含有（A)藥效成分。作為該藥效成分，若為藉由經口投予而發揮藥效之成分，則無特別限定，但是本發明之錠劑所含有之藥效成分不包括如下成分：中藥劑、鹽酸葡萄糖胺、軟骨素硫酸鈉、辛伐他汀（simvastatin)、普威隆碘（povidone iodine)、匹莫苯（pimobendan)、泛雙硫醇、半胱胺酸、抗壞血酸、鹽酸》比哆醇、核黃素、布洛芬、鱗酸二氫可待因、dl-鹽酸甲基麻黃驗、異丙破胺、那可汀、馬來酸氣菲安明、硝酸硫胺、去水性咖啡因、西洋甘菊、熊葡萄、那普洛仙（naproxen)(再者，中藥劑為當歸芍藥散萃取物、加味逍遙散萃取物、桂枝茯苓丸萃取物、大黃甘草湯萃取物、葛根湯萃取物、柴胡桂枝湯萃取物、薏仁湯萃取物、桂枝加苓術附湯萃取物、防己黃耆湯萃取物）。作為藥效成分，例如可列舉：催眠/鎮靜劑、抗癲痛藥、解熱鎮痛消炎藥、興奮/清醒劑、抗暈劑、精神神經用劑、骨絡肌鬆弛劑、自主神經用劑、鎮痙劑、抗帕金森症劑、抗組織胺劑、抗過敏劑、強心劑、抗心律不整劑、降壓劑、丘管收縮劑、冠企管擴張藥、末梢血管擴張劑、南脂血症用藥、鎮咳祛痰劑、抗消化性潰瘍劑、健胃劑、消化劑、抗酸劑、整腸藥、止瀉劑、鎮痛鎮痙劑、胃黏膜修復劑、抗菌劑、止血劑、維生素劑、抗凝血劑、肝病用劑、痛風治療劑、酵素製劑、糖尿病用劑、抗惡性腫瘤藥、抗流感病毒藥等。更具體而言，作為催眠/鎮靜劑，可列舉：二氮平、艾 139389.doc 200946142 泮、阿普女疋：三唑侖、硝西泮、氣二氮平、勞拉西曰网、奥沙唑侖、氣氟革乙酯、溴西泮、氟一平、托非旁沭笪# _ 亂一氮、术一鼠平系藥劑，氯西泮、依替嗤余尊读鈉、卡本妥奂、本巴比女、撲米酮、丙戊酸、、、乙琥胺、甲酮氮平、唑尼沙胺、加巴潘把nts旨等。作為解熱鎮痛消炎劑，可列舉：乙酿胺笨 ❹ 參 t那西/j·、曱芬那酸、雙氣芬酸、阿司匹胺、柳醯胺、枷舱 # % 口比唾1吟美Γ 洛芬、嗣基布洛芬、芬特明、嗔舉· :美辛、洛索洛芬等。作為興奮/清醒劑，可列 .甲基安非他命、麵胺酸、γ_胺基丁酸等。劑，可列I .思工败 q机車、腎上腺素、地芬尼多等。作為精神神經 151，可列舉：氣丙喷等酚噻。井系藥劑、氟哌啶醇酮系藥劑、三環系抗抑繫藥等。作為自主神經用劑，可列舉.乙醯膽鹼等膽鹼能藥、抗膽鹼酯酶劑等。藥作：鎮痙劑’可列舉：阿托品、讓等膽驗能阻斷二為抗組織胺劑，可列舉：鹽酸塞浦希他啶水合物、苯海抵明、富馬酸氣馬斯汀、鹽酸氮卓斯汀、奥沙：特、過敏美奎錠、鹽酸依匹斯汀、依巴斯汀、鹽酸西替利坪、 :酸非索那、鹽酸奥洛他定、氯雷他定等。作為抗過敏可列舉：色甘酸納、曲尼司特、0比响司特卸、特水合物、孟魯司特、雷馬曲班（ram b 2 (s叫aUsttosUate)等。甲％司特作為強心劑，可列舉：毛地黃、洋地黃等。作為抗心律 I39389.doc 200946142 不整劑，可列舉：鹽酸普魯卡因胺、丙。比胺、琥拍酸西唾琳、鹽酸〇比美諾、鹽酸阿普林定、鹽酸美西律、酷卡尼、鹽酸吡西卡尼、鹽酸普羅帕酮等鈉離子通道阻劑’鹽酸胺蛾網、鹽酸索他洛爾等卸離子通道阻斷劑、賤酸普萘洛爾、酒石酸美托洛爾、阿替洛爾 '卡維地襞受體阻斷劑等。作為降壓劑，可列舉：三氣嗟啡、氫氣嘆呼、曲帕胺"引塔帕胺、螺内醋、利尿績胺等利尿劑，= 酸哌唑畊、鹽酸布那唑喷、甲磺酸多沙唑畊、鹽酸特拉二畊水合物、烏拉地爾等α受體阻斷劑，鹽酸普萘洛爾、^ 哚洛爾、鹽酸卡替洛爾 '阿替洛爾、酒石酸美托洛爾、二丨二酸波吲洛爾 '富馬酸比索洛爾、鹽酸塞利洛爾、鹽酸= 索洛爾等Ρ受體阻斷劑，鹽酸氨磺洛爾、卡維地洛、鹽酸阿羅洛爾等αβ受體阻斷劑，硝苯地平、鹽酸尼卡地平、睡酸地爾硫革、尼伐地平、鹽酸巴尼地平、尼索地平、尼群地平、苯磺酸胺氯地平、鹽酸馬尼地平、鹽酸貝尼地平、非洛地平、鹽酸依福地平、阿折地平等鈣拮抗劑，卡托普利、馬來酸依那普利、鹽酸地拉普利、鹽酸咪達普利、鹽酸喹那普利、鹽酸替莫普利、賴諾普利等血管緊縮素轉化酶（ACE，angi〇tensin-converting enzyme)抑制劑，坎地沙坦酯、氯沙坦鉀、纈沙坦、奥美沙坦酯、替米沙坦等血管緊縮素II受體拮抗劑等。作為高脂血症用藥，可列舉：普伐他丁鈉、阿托伐他汀鈣、氟伐他汀鈉、匹伐他、;丁舞、瑞素伐他汀鈣、依折麥布、安妥明、苯紮貝特、非諾貝特、克利貝特、生育酚煙酸酯、戊四醇煙酸酯、尼可莫耳、普 139389.doc 200946142 羅布考等。作為鎮咳祛痰劑，可列舉：磷酸可待因、氫溴酸右美沙茹磷酸二甲啡烷、替培啶、鹽酸甲氧那明、鹽酸特美奎諾、綾曱司坦、乙醯半胱胺酸、乙基半胱胺酸、鹽酸溴己 . 新、、沙雷肽酶、鹽酸溶菌酶、安布索、茶鹼、胺茶鹼等。作為消化性潰瘍用劑，可列舉：麩醯胺、吉法酯、鹽酸西曲酸酯（cetraxate hydrochloride)、西咪替丁、鹽酸雷尼替 φ 丁、法莫替丁、羅沙替丁醋酸酯鹽酸鹽、尼紮替丁、拉呋替丁奥美拉唑、蘭索拉唑、雷貝拉唑鈉、奥諾前列素、恩前列素、米索前列醇、鹽酸哌侖西平、丙榖胺等。薑莪紅山作為健胃劑，例如可列舉：大茴香籽、蘆薈、茴香黃、烏帛、延命草、黃答、黃柏、黃連、加工大蒜術、霍香、菖蒲根、乾薑、枸橘、枳實、桂皮、龍膽蔘厚檁、吳茱笑、胡椒、非洲防己根、治癌蔓皮椒、山柰、紫蘇子、砂仁、生薑、小豆寇、青皮、石富 ❹ 根W金才匕、當藥、蒼術、蘇葉、大菌香、大黃、竹節人丁香陳皮、辣椒、燈皮、動物膽（包括熊膽）、苦樹二肉丑蔻、人蔘、薄荷(包括洋薄荷)、蓽茇、白術、啤 • 酒花二馬錢子萃取物、睡菜葉、木香、益智、龍膽、良口香油桂皮油、生薑油、小豆寇油、丁香油、橙皮油、薄荷油、擦檬油、L-薄荷腦、DL-薄荷腦、鹽酸甜菜驗、麵胺酸鹽酸鹽、氣化肉驗、腺醋膽驗、乾酵母等。作為/肖化劑，例如可列舉m肖化酵素、蛋白消化酵 ”月曰肪消化酵素、纖維素消化酵素、熊去氧膽酸、去氧 139389.doc 200946142 膽酸鹽類'膽酸、膽汁粉末、膽汁萃取物（粉末）、去氧膽酸、動物膽（包括熊膽）等。作為整腸藥，例如可列舉：整腸生菌成分、野桐、兒茶、烏梅、決明子、桅牛兒苗等。作為止满劑，例如可列舉：阿克利諾兒、氣化黃連素、癒創木紛、木餾油、柳酸苯酯、碳酸癒創木酚、單寧酸黃連驗、次柳酸鉍、次硝酸鉍、次碳酸鉍、次沒食子酸絲、鞣酸、鞣酸蛋白、鞣酸甲基瑞香草酚、高嶺土、天然矽酸鋁、羥萘酸鋁、果膠、藥用碳、乳酸鈣、兒茶、烏梅、黃柏、黃連、苦蔘、槐牛兒苗、五倍子、山楂、當藥、楊梅皮等。作為鎮痛鎮痙劑，例如可列舉：鹽酸歐範來明 (Oxyphencyclimine Hydrochloride)、鹽酸雙環維林、鹽酸美噻噸（Metixene Hydrochloride)、氫溴酸莨菪鹼、甲溴化阿托〇口、曱 /臭化辛托品（Anis〇tr〇pine Methylbromide)、甲溴化東良菪鹼、甲溴化_L_茛菪鹼、溴曱貝那替秦 (methylbenactyzium bromide)、顛茄萃取物、碘化二苯基哌啶基甲基二氧戊環、東莨菪萃取物、檸檬酸東莨菪根植物鹼、鹽酸罌粟鹼、胺基苯甲酸乙酯、延胡索、甘草、厚檁、芍藥等。作為胃黏膜修復劑，例如可列舉：奠磺酸鈉、尿囊素鋁、甘草酸及其鹽類以及甘草萃取物、L_麵醯胺、銅葉綠素鉀、銅葉綠素鈉、鹽酸組胺酸 '豬胃壁之胃蛋白酶分解物、豬胃壁之酸水解物、氣化曱硫胺基酸、野桐、延胡 139389.doc •10· 200946142 索、甘草、琉糖銘、瑞巴派特、麥滋林、聚普瑞辞、海藻酸納、吉法醋、替普瑞酮、曲昔匹特、鹽酸貝奈克醋p環糊精包合物、普勞諾托、馬來酸伊索拉咬、索法嗣等。作為維生素類’例如可列舉：視黃醇醋酸酯、視黃醇棕搁酸酉曰、視H酵/由、肝油、強肝油、麥角約化固醇、膽妈化醇、d-α-生育酚琥珀酸酯、仏心生育酚琥珀酸酯、仏心生育酚琥珀酸鈣、d-a-生育酚醋酸酯、dl_a_生育酚醋酸 ❿ Sa d-a-生月酚、dl_a-生育酚、鹽酸噻胺、硝酸雙硫胺素一硫化硫胺、一錄蝶基硫酸硫胺素酯鹽、鹽酸基世甲命鹽酸呋喃硫胺、奥托硫胺、賽可硫胺、雙異丁硫胺、雙苯醯硫胺、呋喃硫胺、丙舒硫胺、苯磷硫胺、磷酸核黃素鈉、丁酸核汽素、鱗酸D比哆醛、經始銨、鹽酸羥姑敍、醋酸羥鈷銨、氰鈷銨、抗壞血酸鈣、抗壞血酸鈉、菸鹼酸、菸鹼醯胺、泛醇、泛酸鈣、泛酸鈉、生物素等。作為抗酸劑，可列舉：合成矽酸鋁、天然矽酸鋁、氫氧參化鋁、鋁矽酸鎂、偏鋁矽酸鎂、鋁碳酸鎂、矽酸鋁酸鎂鉍、碳酸氫鈉、氧化鎂、氫氧化鎂、碳酸鎂、沈澱碳酸鈣、矽酸鎂、氫氧化鋁鎂、磷酸氫鈣、無水磷酸氫鈣、胺，基醋酸、二羥基胺基乙酸鋁、甘胺酸、烏賊骨、石決明、 .牡蠣、東莨菪萃取物等。作為肝疾患用劑，可列舉：三氮唑核苷、拉米夫定、恩替卡韋水合物、乾適能（Adefovir dipivoxil)、丙帕鍺、熊去氧膽酸等。作為抗菌劑’可列舉：各種抗生素、左氧氟沙星水合物、氧氟沙星、鹽酸環丙沙星、甲苯磺酸托氟沙 I39389.doc 200946142 星諾版沙星、西他沙星水合物、鹽酸洛美沙星、加替沙星普利沙星、鹽酸莫西沙星、依諾沙星、司帕沙星等喧諾_系抗菌劑等。作為糖尿病用劑，可列舉：格列吼腺、格列齊特、格列美脲、那格列奈、米格列奈約水合物、鹽酸-甲雙胍、鹽酸丁雙胍、鹽酸吨格列綱、阿卡波糖、伏格列波糖、米格列醇等。作為抗惡性腫瘤藥物，可列舉：氟尿嘧啶η夫氟啶、去氧氟尿苷、卡培他濱、鹽酸法倔坐阿那曲唾、依西美坦、來曲嗤、環峨酿胺、甲確酸伊馬替尼等。作為抗流感病毒藥，可列舉：磷酸奥司他韋、鹽酸金剛烷胺等。該等藥效成分中，較好的是調配消化性潰瘍用劑、健胃劑、消化劑、抗酸劑、胃黏膜修復劑、整腸藥、維生素類等。進而，當採用抗酸劑、健胃劑、消化劑、胃黏膜修復劑等作用於胃之藥劑時，由於較理想的是崩解性良好，故而較好的是應用於含有該等藥效成分之錠劑。尤其是採用含有選自碳酸氫鈉' 氧化鎂、氫氧化鎂、碳酸鎂、碳酸鈣、沈澱碳酸鈣、矽酸鎂、磷酸氫鈣、無水磷酸氫鈣中之一種或兩種以上之錠劑之情形時，可顯著表現出本發明之效果。其中更好的是含有兩種以上之錠劑。進而’本發明尤其好的是應用於調配有含有氬氧化鎂、碳酸氫鈉及碳酸鈣之抗酸劑的錠劑。氫氧化鎂之調配量相對於製劑總量較好的是0_01〜20質量％，更好的是〇m質量％，尤其好的是1〜7質量％。碳酸氫鈉之調配量相對於疑 139389.doc -12- 200946142 劑總量較好的是1〜50質量％，更好的是5〜4〇質量％，尤其好的疋10〜30質量％。作為碳酸鈣，例如可列舉碳酸鈣、以沈澱碳酸鈣或碳酸鈣為主成分之牡蠣、牡蠣粉末、石決明或者烏賊骨等》碳酸鈣之調配量相對於錠劑總量較好的是10〜80質量。/。，更好的是15〜7〇質量％，尤其好的是2〇〜6〇質量％。氫氧化鎂與碳酸氫鈉之質量比較好的是1 : 〇1〜15，更好的疋1 . 1〜12，尤其好的是丨：3〜9。氫氡化鎂與碳酸鈣之質量比較好的是1 ··卜如，更好的是！： 3〜3〇,尤其好的是1 : 5〜20。碳酸氫鈉與碳酸鈣之質量比較好的是 0^5:卜40,更好的是卜12: 3〜3〇,尤其好的是3〜9: 5〜20 ° 該含抗酸劑之錠劑中，可視需要而使用上述以外之抗酸劑、健胃劑、消化劑、整腸藥、止填劑、鎮痛鎮痙劑、胃黏膜修復劑、維生素類、消泡劑等藥物。 ❹ 該等含有抗酸劑之藥效成分於本發明之錠劑中較好的β 含有Μ0質量。/。，更好的是含有質量％，尤其好= 是含有2〜80質量％。作為（B)羧甲基纖維素或其鹽，可列舉：羧甲基纖維素、羧甲基纖維素鈉、羧甲基纖維素姜 ’寻其中尤其好的是叛甲基纖維㈣。緩甲基纖維素㈣由與成分合，可獲得尤其顯著之崩解性與機械強度之改善效 1 獲得良好之崩解性與機械強度之提昇。就双果方面而言，（B) 羧甲基纖維素或其鹽在本發明之錠劑中較好的是含有1 Μ 139389.doc 200946142 質量。/。，更好的是含有i.5〜18質量％，尤其好的是含有 2〜16質量％。作為（C)二氧化矽，可列舉：含水二氧化矽輕質無水矽酸，就崩解性及機械強度提昇效果之方面而言，尤其好的是含水二氧切。就獲得良好之崩解性與機械強度之提昇效果方面而言’ (B)二氧化石夕在本發明之錠劑中較好的是含有o.wo質量％，更好的是含有0.2〜9質量％，尤直好的是含有〇·3〜8質量％。又’本發明之旋劑中，就媒值自削甲就獲传良好之崩解性與機械強度之提昇效果之方面而言’⑻叛曱基纖維素或其鹽與（c)二氧化石夕之含有質量比（(B)/(c))較好是的q」〜細更 0.5〜100，尤其好的是丨〜75。疋本發明之錠劑中，進而可視 J优而要而調配賦形劑、崩劑、黏合劑、潤滑劑、助泠為丨# & 鮮爪劑、者色劑、矯味劑等製劑添加物。作為賦形劑，可列舉： ” * ώ ^ 孔糖灰粉類、結晶纖維素、庶糖、甘露糖醇等。作基镞堆音mg 劑’可列舉：經丙基甲基纖維素、羥丙基纖維素芦京明膠、α_化澱粉、聚乙嬌< & 啶酮、聚乙烯醇、支鏈澱敬乙烯比咯鮮祕，又鏈㈣4。作為崩解劑’可列舉：交聯聚維酮、玉米澱粉、彳乂劑，可列舉：硬脂酸鎂矛作為潤滑 ^月石、硬化油等。作*莫备办丨可列舉：f、油色素、：备乍為著色劑’ 舉.甜益一氧化二鐵等。作為矯味劑，可列舉·甜菊、阿斯巴甜糖、香料等。 » 本發明之錠劑，其崩魅 Μ ,α 解性良好，且機械強度，尤J:县科磨知性優異。更具體及尤其疋耐 5 ’藉由依據第十五改正曰本藥典 I39389.doc 200946142 「崩解試驗法」之速釋製劑之方法，即藉由使崩解試驗裝置在如下條件（試驗液：水’液量：1000 mL，試驗溫产. 37±2°C)下運作而測得之崩解時間為3〇分鐘以内。又，藉由依據第十五改正日本藥典中說明書之參考資訊「錠劑之磨損度武驗法」之方法’即藉由將規定量之錠劑放入轉筒而使其旋轉100轉，並在試驗後以目測計算有缺損者之數量而測得之磨損度為0。如此，由於崩解性良好且磨損度低，故而在製造階段及流通階段之中，錠劑無缺損且可於服用後獲得較高之生物體可用率。作為本發明之錠劑之實施例，可列舉裸錠（素錠）、多層錠、有核錠、口含錠、口腔内崩解片、咀嚼錠等。本發明之錠劑中，亦可藉由適當之方法而形成衣膜，作為形成有衣膜之錠劑，可列舉膜衣錠、糖衣錠。本發明之錠劑，由於磨損度極低，故而在形成衣膜時幾乎無問題，且可容易地形成適合於藥效成分之衣媒。〇本發明之錠劑之製造方法並無特別限定，為使錠劑（在錠劑上形成衣膜之情形時，係指形成衣膜前之錠劑）中含有（A)藥效成分、（3)羧子基纖維素或其鹽、及（c)二氧化矽， <方式而製造的方法即可。即’本發明之錠劑可藉由直接錢片法而製造，亦可如乾式顆粒壓片法、半乾式顆粒 I片法、濕式顆粒壓片法等般，在造粒後進行塵縮成形而製造’較好的是在造粒後進行廢縮成形。造粒法並無特別限制，可採用擠出造粒、流動層造粒、授拌造粒、喷霧乾燥造粒、粉碎造粒等。本發明之錠劑之製造方法，可依據 I39389.doc 15 200946142 ，常法對（A)藥效成分、（B)羧甲基纖維素或其鹽、及（c)二氧化矽之混合物進行打錠，亦可製造含有（A)藥效成分、（B) 羧f基纖維素或其鹽、及（C)二氧化矽之顆粒，再進行打錠，藉此製造錠劑。尤其好的是將（A)藥效成分及（B)羧甲基纖維素或其鹽混合造粒，其後添加（c)二氧化矽再進行造粒。所獲得之顆粒可依據常法進行打錠而製成錠劑。又，所獲得之錠劑可視需要依據常法形成衣膜，而製成膜衣錠或糖衣鍵；。 [實施例] 以下列舉實施例對本發明進行詳細地說明，但本發明並不限定於此。 1.錠劑之製造製造例核錠將150質量份氯化s_甲基蛋胺酸、90質量份東莨菪萃取物三倍散、30質量份啤酒花乾燥萃取物、15質量份脂肪酶 AP、24質量份生物澱粉酶（2〇〇〇)、24質量份羥丙基纖維素、110質量份硬化油、70質量份羧甲基纖維素鈣、38質量伤玉米澱粉、10質量份甘油單硬酯酸酯、5質量份硬脂酸聚烴氧（40)酯、及20質量份滑石依據常法製成顆粒。將 591質量份該顆粒與9質量份硬脂酸鎂混合而製成打錠用顆粒。使用具有φ為7 mm之沖模的打錠機來對該打錠用顆粒進行打錠，而製造1錠為1〇〇 mg之核錠。實施例1 將900質量份碳酸氫鈉、1〇〇質量份氫氧化鎂、12〇〇質量 139389.doc •16- 200946142 份沈澱碳酸鈣、120質量份聚乙浠醇、15〇質量份羧甲基纖維素鈣、375質量份結晶纖維素、i2〇質量份硬化油、及2〇質量份硬脂酸鎂依據常法製成顆粒。將497 5質量份該顆粒與2.5質量份含水二氧化矽混合而製成外層顆粒。使用具有4為11 mm之沖模的打錠機，將製造例中所製造之1錠為100 mg之核錠與500 mg本外層顆粒製成}錠為 600 mg之有核錢。實施例2 將900質量份碳酸氫鈉、1〇〇質量份氫氧化鎂、12〇〇質量份沈澱碳酸鈣、120質量份聚乙烯醇、15〇質量份羧甲基纖維素鈣、360質量份結晶纖維素、12〇質量份硬化油、及2〇質量份硬脂酸鎂依據常法製成顆粒。將495質量份該顆粒與5質量份含水二氧化矽混合而製成外層顆粒。使用具有$ 為11 mm之沖模的打錠機，將製造例中所製造錠為1〇〇 mg之核錠與500 mg本外層顆粒製成1錠為6〇() mg之有核錠。比較例1 將900質量份碳酸氫鈉、ι〇〇質量份氩氧化鎂、12〇〇質量份沈澱碳酸鈣、120質量份聚乙烯醇、i 5〇質量份羧甲基纖維素鈣、390質量份結晶纖維素、12〇質量份硬化油、及2〇質量伤硬月曰酸鎮依據常法製成顆粒而作為外層顆粒。使用具有Φ為11 mm之沖模的打錠機，將製造例中所製造之1錠為100 mg之核錠與500 mg本外層顆粒製成}錠為6〇〇 mg2 有核錢。 139389.doc •17· 200946142 比較例2 將900質量份碳酸氫鈉、1〇〇質量份氫氧化鎂、i2〇〇質量份沈殿碳酸妈、12〇質量份聚乙稀醇、15Gf量份低取代經丙基纖維素、375質量份結晶纖維素、12〇質量份硬化油、及20質量份硬脂酸鎂依據常法製成顆粒。將495質量份該顆粒與5質量份含水二氧化矽混合而製成外層顆粒◊使用具有Φ為11 mm之沖模的打錠機，將製造例中所製造之1錠為100 mg之核錠與500 mg本外層顆粒製成1錠為6〇〇 mg之有核鍵。試驗例1 (崩解試驗）使用朋解试驗裝置（NT-40H ’富山產業製造），測定實施例1、2及比較例1、2所獲得之各有核錠之崩解時間。以水 (1000 mL、37°C )作為試驗液，每例測定6錠，算出平均值作為崩解時間（依據第十五改正日本藥典「崩解試驗法」速釋製劑）。 (結果）調配有羧甲基纖維素約與含水二氧化碎之實施例1、2，與未調配含水二氧化矽之比較例1或未調配羧甲基纖維素鈣之比較例2相比，崩解時間極度縮短且崩解性良好。因此，推測胃酸之中和等可迅速顯現而提高治療效果（表1)。試驗例2 (硬度）使用錠劑硬度計（PHARMA TEST PTB-311，日本機械公 139389.doc -18- 200946142 司製造），測定實施例1、2及比較例1、2所獲得之各有核錠之錠劑硬度。每例測定20錠，算出平均值作為硬度。 (結果）調配有含水二氧化矽之實施例1、2，與未調配含水二氧化矽之比較例1相比，可判明硬度之提高。因此，推測其有助於在製造、包裝時之操作性或流通下之品質維持方面佔據極大優勢（表1)。試驗例3139389.doc 200946142 Manufactured by a mixture or a particle of (C) a mixture of ruthenium or ruthenium. The tablet of the present invention contains (A) a medicinal ingredient. The medicinal ingredient is not particularly limited as long as it is a component that exerts medicinal effects by oral administration, but the medicinal component contained in the tablet of the present invention does not include the following components: a medicinal agent, glucosamine hydrochloride, Sodium chondroitin, simvastatin, povidone iodine, pimobendan, panthenol, cysteine, ascorbic acid, hydrochloric acid, sterol, riboflavin, Ibuprofen, dihydrocodeine citrate, dl-methyl methacrylate hydrochloride, isopropylamine, narcotine, maleic acid phenanthrene, thiamine nitrate, dehydrated caffeine, western chamomile, Bear grape, naproxen (again, the Chinese medicine is Danggui Shaoyao San extract, Jiawei Xiaoyao San extract, Guizhi Fuling Pill extract, rhubarb licorice soup extract, Pueraria extract, Chaihu Guizhi Soup extract, lotus root extract, cassia twig plus soup extract, anti-Huangqi soup extract). Examples of the medicinal ingredient include hypnotic/sedative, anti-epileptic, antipyretic, analgesic and anti-inflammatory drugs, excitatory/awake agents, anti-corona agents, psychotropic agents, skeletal muscle relaxants, autonomic nerve agents, and antispasmodic agents. , anti-Parkinson's agent, antihistamine, anti-allergic agent, cardiotonic agent, anti-arrhythmia, antihypertensive agent, tube contraction agent, coronary tube expansion drug, peripheral vasodilator, serotonin medication, antitussive phlegm Tincture, anti-peptic ulcer, stomachic, digestive, antacid, intestine, antidiarrheal, analgesic, sputum, gastric mucosal repair, antibacterial, hemostatic, vitamin, anticoagulant , liver disease agents, gout therapeutic agents, enzyme preparations, diabetes agents, anti-neoplastic drugs, anti-influenza drugs, and the like. More specifically, as a hypnotic/sedative, there may be mentioned: diazapine, Ai 139389.doc 200946142 泮, Apu virgin: triazolam, nitrazepam, nitrodiazepine, lorazepam, oxa Oxazolam, fluoroethyl ester, bromozinidine, fluoroyiping, 托非旁沭笪# _ 乱一氮, 一一一平平药, 氯西泮,依替嗤余尊读,卡本妥奂, Babbi female, primidone, valproic acid, ethosylamine, ketoprofen, zonisamide, and gabapan nts. As an antipyretic and analgesic anti-inflammatory agent, it can be exemplified: Ethylamine, astringent, ginseng, t-naxi, j, fentanic acid, difenfen, aspirin, salicylamine, cockroach cabin Γ 洛洛嗣嗣嗣洛洛洛洛洛洛洛 : : : : : : : : : : : : : : : : As an excitatory/awake agent, methyl amphetamine, amygic acid, γ-aminobutyric acid, and the like can be listed. Agent, can be listed I. Thinking lost q locomotive, adrenaline, difenidol and so on. As the mental nerve 151, a phenol thiophene such as a gas spray can be cited. Well-formed drugs, haloperidol ketone-based drugs, tricyclic anti-repressive drugs, and the like. Examples of the autonomic nerve agent include a cholinergic agent such as acetylcholine and an anticholinesterase agent. Drugs: antispasmodic agent can be enumerated: atropine, let the biliary test can block the two antihistamines, which can be listed as: cape citrate hydrochloride hydrate, benzodiazepine, fumarate gas mastin, Azelastine hydrochloride, Oxa: special, allergic mecoside, epilisine hydrochloride, ebastine, cetirizine hydrochloride, acid fifenofol, olopatadine hydrochloride, loratadine, etc. . As anti-allergic, there are mentioned: sodium cromoglycate, tranilast, 0 to squirrel unloading, special hydrate, montelukast, remaquban (ram b 2 (s called aUsttos Uate), etc. Examples of the cardiotonic agent include foxglove, digitalis, and the like. As an anti-heart rhythm I39389.doc 200946142, the agent may be exemplified by procainamide hydrochloride, propylamine, specific amine, samarium citrate, and guanidine hydrochloride. Sodium, apalidine hydrochloride, mexiletine hydrochloride, cocayne, pyridoxine hydrochloride, propafenone hydrochloride and other sodium ion channel blockers 'hydrochloric acid amine moth net, sotalol hydrochloride and other unloading ion channel block Agent, propranolol citrate, metoprolol tartrate, atenolol 'carvedidin receptor blocker, etc. As a hypotensive agent, can be cited as: three gas morphine, hydrogen sigh, 曲帕Amines, such as dipamide, snail vinegar, diuretic amine, diuretics, = piperazine, bunazole hydrochloride, doxazole sulfonate, travertine hydrochloride, urapidil Such as α receptor blockers, propranolol hydrochloride, 哚哚 ol, carteolol hydrochloride ' atenolol, metoprolol tartrate, Bismuthic acid dipolocycline bisoprolol fumarate, celiolol hydrochloride, hydrochloric acid = sorolol and other sputum receptor blockers, amlsulfolol hydrochloride, carvedilol, aloilo hydrochloride And other αβ receptor blockers, nifedipine, nicardipine hydrochloride, sleeping acid diltiazem, nilvadipine, barnidipine hydrochloride, nisoldipine, nitrendipine, amlodipine besylate, hydrochloric acid Manidipine, benidipine hydrochloride, felodipine, eflodipine hydrochloride, adipine equal calcium antagonist, captopril, enalapril maleate, delaipril hydrochloride, midazolam hydrochloride , quinapril hydrochloride, temocapril hydrochloride, lisinopril and other inhibitors of angiotensin-converting enzyme (ACE, angi〇tensin-converting enzyme), candesartan cilexetil, losartan potassium, valsartan Angiotensin II receptor antagonists such as olmesartan and telmisartan, etc. As a drug for hyperlipemia, pravastatin sodium, atorvastatin calcium, fluvastatin sodium, and pit He, Ding Wu, rosuvastatin calcium, ezetimibe, clofibrate, bezafibrate, fenofibrate, clebate, Tocopheryl nicotinate, pentaerythritol nicotinate, nicomole, 139389.doc 200946142 Robbock, etc. As an antitussive expectorant, exemplified by codeine phosphate, dextromethorphan hydrobromide Bromidine, tibepine, methoxyphenamine hydrochloride, temequinol hydrochloride, strobantan, acetaminos, ethylcysteine, bromohexidine hydrochloride, new, sarapeptidase, Hydrochloric acid lysozyme, ambroxol, theophylline, amine theophylline, etc. Examples of the peptic ulcer agent include branamide, geminyl ester, cetraxate hydrochloride, cimetidine, and hydrochloric acid. Ranitidine φ, famotidine, roxatidine acetate hydrochloride, nizatidine, lafutidine omeprazole, lansoprazole, rabeprazole sodium, ornoprost , esprost, misoprostol, pirenzepine hydrochloride, acetaminophen and the like. As a stomachic agent, Jiangyan Hongshan can be exemplified by: aniseed seeds, aloe vera, fennel yellow, black mulberry, marigold, yellow answer, yellow cypress, berberine, processed garlic, fragrant fragrant, calamus root, dried ginger, medlar orange, medlar Real, cinnamon, gentian, thick 檩, Wu Xiaoxiao, pepper, African anti-root, cancer vine pepper, hawthorn, perilla, Amomum, ginger, cardamom, green skin, Shi Fuzhen root W gold Hemorrhoids, medicine, atractylodes, sage, large scent, rhubarb, bamboo cloves, pepper, lamp skin, animal gallbladder (including bear bile), bitter tree ugly, mandarin, mint (including peppermint ), 荜茇, Atractylodes, beer • hops two horses money extract, sleeping vegetables, woody, puzzle, gentian, good fragrant oil cinnamon oil, ginger oil, cardamom oil, clove oil, orange peel oil , peppermint oil, lemon oil, L-menthol, DL-menthol, hydrochloric acid beet test, face amine hydrochloride, gasified meat test, gland vinegar test, dry yeast, etc. Examples of the/smoulding agent include m-synthesis enzyme, protein digested yeast, "digestive enzyme", cellulose digestive enzyme, ursodeoxycholic acid, and deoxygenation 139389.doc 200946142 cholate "cholic acid, bile" Powder, bile extract (powder), deoxycholic acid, animal bile (including bear bile), etc. As an intestine medicine, for example, whole intestinal bacteria, wild tong, catechu, ebony, cassia seed, yak As a stop-up agent, for example, Achillos, gasified berberine, guaiac, creosote, phenyl ruthenium carbonate, guaiacol carbonate, tannic acid yellow test, times Barium strontium sulphate, bismuth subnitrate, bismuth subcarbonate, bismuth citrate, citric acid, citrate protein, methyl thymol, potassium kaolin, natural aluminum citrate, aluminum hydroxynaphate, pectin, medicine Use carbon, calcium lactate, catechu, ebony, Phellodendron, berberine, tartary buckwheat, yak seedling, gallnut, hawthorn, medicine, bayberry, etc. As an analgesic tincture, for example, Oxyphencycline Hydrochloride), bicyclovirin hydrochloride, methiopyrene hydrochloride (Metix) Ene Hydrochloride), hydrazine hydrobromide, atropine methyl bromide, Anis 〇tr〇pine Methylbromide, formazan bromide, methyl bromide _L_茛菪Alkali, methylbenactyzium bromide, belladonna extract, diphenylpiperidinylmethyldioxol iodide, sorghum extract, citric acid root plant alkali, papaverine hydrochloride, Ethyl benzoate, eucalyptus, licorice, sorghum, peony, etc. As a gastric mucosa repairing agent, for example, sodium sulfonate, allantoin aluminum, glycyrrhizic acid and its salts, and licorice extract, L_ Facial amine, copper chlorophyll potassium, copper chlorophyll sodium, histidine acid 'pepsin decomposition of pig stomach wall, acid hydrolyzate of pig stomach wall, gasified sulfamethic acid, wild paulownia, Yanhu 139389.doc •10 · 200946142 Cord, licorice, sucrose, rebamipide, zizilin, polypred, sodium alginate, vinegar vinegar, teprenone, tripipeptide, benez vine hydrochloride p cyclodextrin Inclusion complex, Pronoto, maleic acid isola bite, sofafa, etc. as a vitamin 'for example Can be enumerated: retinol acetate, retinol palmoate, sputum / yeast, liver oil, strong liver oil, ergot steroid, bile alcohol, d-α-tocopherol succinate , heart toxin phenol succinate, heart tocopherol calcium succinate, da-tocopheryl acetate, dl_a_tocopherol acetate da Sa da-shengyol, dl_a-tocopherol, thiamine hydrochloride, dithiamine nitrate Thiamine sulfide, thiamine sulfate sulfate, chlorhexidine hydrochloride, olston thiamine, seletonamide, bis-isobutyl thiamine, stilbene thiamine, furan thiamine , propyl sulphide, phenylphosphine thiamine, riboflavin sodium phosphate, butyric acid nucleus, squaric acid D than furfural, transaluminum, hydroxy hydroxy citrate, hydroxycobalt sulphate, cyanocobalam, calcium ascorbate , sodium ascorbate, nicotinic acid, nicotinamide, panthenol, calcium pantothenate, sodium pantothenate, biotin, and the like. Examples of the antacid include synthetic aluminum niobate, natural aluminum niobate, aluminum hydroxide, aluminum aluminosilicate, magnesium metasilicate, aluminum magnesium carbonate, magnesium niobate aluminate, and sodium hydrogencarbonate. Magnesium oxide, magnesium hydroxide, magnesium carbonate, precipitated calcium carbonate, magnesium citrate, magnesium aluminum hydroxide, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, amine, acetic acid, aluminum dihydroxy Aminoacetate, glycine, squid bone , stone cassia, . oysters, sorghum extracts, etc. Examples of the agent for liver diseases include ribavirin, lamivudine, entecavir hydrate, adefovir dipivoxil, propylparaben, ursodeoxycholic acid and the like. As an antibacterial agent, various antibiotics, levofloxacin hydrate, ofloxacin, ciprofloxacin hydrochloride, toloxasulfonate I39389.doc 200946142 Xingnuo sand star, statabofloxacin hydrate, hydrochloric acid hydrochloride Methadone, gatifloxacin, prisafloxacin, moxifloxacin hydrochloride, enoxacin, sparfloxacin, etc. Examples of the agent for diabetes include gadolinium gland, gliclazide, glimepiride, nateglinide, mitiglinide hydrate, hydrochloride-methylene guanidine, butyl guanidine hydrochloride, and ton glibenclamide hydrochloride. , acarbose, voglibose, miglitol and the like. As an anti-malignant tumor drug, fluorouracil, flavonolidine, deoxyfluorouridine, capecitabine, hydrochloric acid, arson, saliva, exemestane, quercetin, cyclamate, and Acid imatinib and the like. Examples of the anti-influenza virus include oseltamivir phosphate and amantadine hydrochloride. Among these medicinal ingredients, it is preferred to formulate a peptic ulcer agent, a stomachic agent, a digestive agent, an antacid, a gastric mucosa repairing agent, a colon drug, a vitamin, and the like. Further, when an antacid, a stomachic agent, a digestive agent, a gastric mucosa repairing agent or the like is used as an agent for the stomach, since it is preferable that the disintegration property is good, it is preferably applied to the drug-containing component. Lozenges. In particular, a tablet containing one or more selected from the group consisting of sodium hydrogencarbonate magnesium oxide, magnesium hydroxide, magnesium carbonate, calcium carbonate, precipitated calcium carbonate, magnesium citrate, calcium hydrogen phosphate, and anhydrous calcium hydrogen phosphate is used. In the case, the effects of the present invention can be remarkably exhibited. More preferably, it contains two or more kinds of tablets. Further, the present invention is particularly preferably applied to a tablet containing an antacid containing argon magnesium oxide, sodium hydrogencarbonate and calcium carbonate. The amount of the magnesium hydroxide is preferably from 0 to 01% by mass to 20% by mass based on the total amount of the preparation, more preferably 〇m by mass%, particularly preferably from 1 to 7% by mass. The amount of sodium hydrogencarbonate is preferably from 1 to 50% by mass, more preferably from 5 to 4% by mass, particularly preferably from 10 to 30% by mass, based on the total amount of the 139389.doc -12-200946142 agent. Examples of the calcium carbonate include calcium carbonate, oysters which are mainly composed of precipitated calcium carbonate or calcium carbonate, oyster powder, stone cassia or squid bone, etc. The amount of calcium carbonate is preferably 10 with respect to the total amount of the tablet. ~80 quality. /. More preferably, it is 15 to 7 〇 mass%, and particularly preferably 2 〇 to 6 〇 mass%. The quality of magnesium hydroxide and sodium hydrogencarbonate is preferably 1: 〇1~15, more preferably 疋1. 1~12, especially preferably 丨: 3~9. The quality of magnesium hydride and calcium carbonate is better. 1 · · Bu Ru, better! : 3~3〇, especially good is 1: 5~20. The quality of sodium bicarbonate and calcium carbonate is preferably 0^5: Bu 40, more preferably Bu 12: 3~3〇, especially preferably 3~9: 5~20 ° The ingot containing antacid In the agent, an antacid, a stomachic agent, a digestive agent, an intestine drug, an antistaling agent, an analgesic analgesic agent, a gastric mucosa repairing agent, a vitamin, an antifoaming agent and the like may be used as needed. ❹ The pharmaceutically effective ingredients containing the antacids preferably have a Μ0 mass in the β of the tablet of the present invention. /. It is better to contain % by mass, especially good = is contained in 2 to 80% by mass. The (B) carboxymethylcellulose or a salt thereof may, for example, be carboxymethylcellulose, sodium carboxymethylcellulose or carboxymethylcellulose ginger. The slow-methyl cellulose (IV) is combined with the composition to obtain particularly remarkable disintegration and mechanical strength improvement. 1 Good disintegration and mechanical strength are obtained. In terms of the double fruit, (B) carboxymethylcellulose or a salt thereof preferably contains 1 Μ 139389.doc 200946142 mass in the tablet of the present invention. /. More preferably, it contains i. 5 to 18% by mass, particularly preferably 2 to 16% by mass. As the (C) cerium oxide, an aqueous cerium oxide light anhydrous citric acid is exemplified, and in terms of disintegratability and mechanical strength-improving effect, a water-containing dioxotomy is particularly preferable. In terms of obtaining a good disintegratability and an improvement in mechanical strength, '(B) sulphur dioxide is preferably contained in the tablet of the present invention in an amount of o.wo mass%, more preferably 0.2 to 9 The mass %, especially straight, contains 〇·3 to 8 mass%. Further, in the spinning agent of the present invention, in terms of the good disintegration property and the mechanical strength enhancement effect of the media value self-shaving, '(8) renegade-based cellulose or its salt and (c) dioxide The mass ratio ((B)/(c)) of the evening is preferably q"~ finer 0.5~100, especially preferably 丨~75. In the tablet of the present invention, an excipient, a disintegrating agent, a binder, a lubricant, and a formulation of a fresh claw, a coloring agent, a flavoring agent, and the like may be formulated in accordance with J. . Examples of the excipient include: ** ώ ^ pore sugar ash powder, crystalline cellulose, sucrose, mannitol, etc. As a base 镞 mg mg agent, exemplified by: propylmethylcellulose, hydroxypropyl Cellulose rujing gelatin, α-starch, polythene <& pyridine ketone, polyvinyl alcohol, branched chain deuterated ethylene ratio, and chain (4) 4. As a disintegrant' can be cited: cross-linking Povidone, corn starch, tincture, can be cited as: Magnesium stearate spears as lubricated ^moon stone, hardened oil, etc. For the preparation of 莫莫丨丨油油油油油油油油油油油油油油油油油油油油油油油油油Sweetener, iron oxide, etc. As the flavoring agent, stevia, aspartame, flavor, etc. are listed. » The tablet of the present invention has a disintegration, good α-solution, and mechanical strength, especially : County Branch has excellent knowledge of know-how. More specifically and especially 疋5' by means of the fifteenth correction method of the immediate release preparation of the Pharmacopoeia I39389.doc 200946142 "disintegration test method", that is, by disintegrating the test device Measured under the following conditions (test liquid: water 'liquid volume: 1000 mL, test temperature production. 37 ± 2 ° C) 3〇 disintegration time of within minutes. Further, by the method of correcting the reference information of the specification of the Japanese Pharmacopoeia in the fifteenth revision "the method of the abrasiveness of the tablet", that is, by rotating a predetermined amount of the tablet into the drum, it is rotated by 100 turns, and The degree of wear measured by visually calculating the number of defects after the test was zero. Thus, since the disintegration property is good and the degree of wear is low, the tablet is not deficient in the production stage and the circulation stage, and a high bioavailability can be obtained after administration. Examples of the tablet of the present invention include a bare ingot (primary ingot), a multilayer ingot, a cored ingot, a buccal ingot, an orally disintegrating tablet, a chewable ingot, and the like. In the tablet of the present invention, a film can be formed by an appropriate method. Examples of the tablet forming the film include a film ingot and a sugar-coated tablet. Since the tablet of the present invention has extremely low abrasion degree, it has almost no problem in forming a film, and a clothes medium suitable for a medicinal ingredient can be easily formed. The method for producing the tablet of the present invention is not particularly limited, and the tablet (in the case of forming a film on a tablet, the tablet before forming the film) contains (A) a medicinal ingredient, ( 3) A method of producing a carboxy cellulose or a salt thereof and (c) cerium oxide. That is, the tablet of the present invention can be produced by a direct method, or can be subjected to dust formation after granulation, such as a dry granule tableting method, a semi-dry granule tablet method, a wet granule tableting method, or the like. It is preferable to manufacture the waste shrinkage after granulation. The granulation method is not particularly limited, and extrusion granulation, flow layer granulation, batch granulation, spray drying granulation, pulverization granulation, and the like can be employed. The method for producing the tablet of the present invention can be carried out according to the method of I39389.doc 15 200946142, the common method for the mixture of (A) medicinal ingredient, (B) carboxymethyl cellulose or a salt thereof, and (c) cerium oxide. For the ingot, a tablet containing (A) a medicinal ingredient, (B) carboxyf-based cellulose or a salt thereof, and (C) cerium oxide may be produced, and then tableting may be carried out to produce a tablet. Particularly preferably, the (A) medicinal ingredient and (B) carboxymethylcellulose or a salt thereof are mixed and granulated, and then (c) cerium oxide is added and granulated. The obtained granules can be tableted according to a usual method to prepare a tablet. Further, the obtained tablet can be formed into a film or a sugar-coated key according to a usual method. [Examples] Hereinafter, the present invention will be described in detail by way of examples, but the invention is not limited thereto. 1. Manufacturing Example of Tablets The core tablet has 150 parts by mass of s-methyl methionine, 90 parts by mass of the sorghum extract, three times, 30 parts by mass of hop dried extract, 15 parts by mass of lipase AP, 24 parts by mass of bioamylase (2〇〇〇), 24 parts by mass of hydroxypropylcellulose, 110 parts by mass of hardened oil, 70 parts by mass of calcium carboxymethylcellulose, 38 mass of damaged corn starch, 10 parts by mass of glycerin single hard The ester ester, 5 parts by mass of the polyoxyl (40) stearate, and 20 parts by mass of talc are granulated according to a usual method. 591 parts by mass of the granules and 9 parts by mass of magnesium stearate were mixed to prepare granules for tableting. The tablet for tableting was subjected to tableting using a tableting machine having a die having a diameter of 7 mm, and a pellet of 1 ingot of 1 ingot was produced. Example 1 900 parts by mass of sodium hydrogencarbonate, 1 part by mass of magnesium hydroxide, 12 parts by mass of 139389.doc • 16-200946142 parts of precipitated calcium carbonate, 120 parts by mass of polyethylene glycol, 15 parts by mass of carboxymethyl The base cellulose calcium, 375 parts by mass of crystalline cellulose, i2 parts by mass of the hardened oil, and 2 parts by mass of magnesium stearate were granulated according to a usual method. 509 5 parts by mass of the granules were mixed with 2.5 parts by mass of aqueous cerium oxide to form outer layer granules. Using a tableting machine having a die of 4 to 11 mm, one ingot made of 100 mg of the ingot produced in the production example and 500 mg of the outer layer of the ingot were made into a 600 mg piece of nuclear money. Example 2 900 parts by mass of sodium hydrogencarbonate, 1 part by mass of magnesium hydroxide, 12 parts by mass of precipitated calcium carbonate, 120 parts by mass of polyvinyl alcohol, 15 parts by mass of calcium carboxymethylcellulose, and 360 parts by mass Crystalline cellulose, 12 parts by mass of hardened oil, and 2 parts by mass of magnesium stearate were granulated according to a usual method. 495 parts by mass of the granules were mixed with 5 parts by mass of aqueous cerium oxide to form outer layer granules. Using a tableting machine with a die of 11 mm, a 1 ingot of ingots manufactured in the manufacturing example and 500 mg of the outer layer of pellets were made into a 6 ingot (6 mg) cored ingot. Comparative Example 1 900 parts by mass of sodium hydrogencarbonate, 1 part by mass of argon oxide, 12 parts by mass of precipitated calcium carbonate, 120 parts by mass of polyvinyl alcohol, i 5 parts by mass of calcium carboxymethylcellulose, 390 mass Part of the crystalline cellulose, 12 parts by mass of the hardened oil, and 2 〇 of the mass of the hard sulphuric acid are made into granules according to the usual method as the outer layer granules. Using a tableting machine having a die having a Φ of 11 mm, a spindle of 100 mg manufactured in the production example was prepared with 500 mg of the outer layer of the pellet. The ingot was 6 〇〇 mg2 with a nuclear money. 139389.doc •17· 200946142 Comparative Example 2 900 parts by mass of sodium hydrogencarbonate, 1 part by mass of magnesium hydroxide, i2 part by mass of Shen Dian Methane, 12 parts by mass of polyethylene glycol, 15 Gf parts of low substitution The propylcellulose, 375 parts by mass of crystalline cellulose, 12 parts by mass of the hardened oil, and 20 parts by mass of magnesium stearate were granulated according to a usual method. 495 parts by mass of the granules were mixed with 5 parts by mass of aqueous cerium oxide to form an outer layer granule. Using a tableting machine having a Φ 11 mm die, one ingot produced in the production example was a 100 mg core ingot. 500 mg of the outer layer of the granules is made into a nucleus bond of 6 〇〇mg. Test Example 1 (Disintegration test) The disintegration time of each of the core ingots obtained in Examples 1 and 2 and Comparative Examples 1 and 2 was measured using a Pengji test apparatus (manufactured by NT-40H's Toyama Industries). Water (1000 mL, 37 ° C) was used as a test solution, and 6 spindles were measured for each case, and the average value was calculated as the disintegration time (according to the fifteenth correction Japanese Pharmacopoeia "disintegration test method" immediate release preparation). (Results) Compared with Comparative Example 2 in which carboxymethylcellulose was mixed with aqueous oxidized granules and Examples 1 and 2, which were not formulated with aqueous cerium oxide, or Comparative Example 2 in which carboxymethylcellulose calcium was not formulated, The disintegration time is extremely shortened and the disintegration property is good. Therefore, it is speculated that gastric acid neutralization and the like can be rapidly developed to improve the therapeutic effect (Table 1). Test Example 2 (Hardness) Each of the nucleated cores obtained in Examples 1, 2 and Comparative Examples 1 and 2 was measured using a tablet hardness tester (PHARMA TEST PTB-311, manufactured by Nippon Machinery Co., Ltd. 139389. doc -18-200946142). Ingot tablet hardness. 20 spindles were measured for each case, and the average value was calculated as the hardness. (Results) Examples 1 and 2 in which aqueous cerium oxide was formulated were found to have an improvement in hardness as compared with Comparative Example 1 in which aqueous cerium oxide was not formulated. Therefore, it is speculated that it contributes to the superiority in terms of operability during manufacture and packaging, or quality maintenance under circulation (Table 1). Test Example 3

(磨損度試驗）(wear degree test)

對實施例1、2及比較例丨、2所獲得之各有核錠實施磨損度試驗。將每例15錠置於錠劑磨損度試驗器（FRIABILATOREach of the core ingots obtained in Examples 1 and 2 and Comparative Examples 2 and 2 was subjected to a wear test. Place 15 ingots in a lozenge wear tester (FRIABILATOR)

TFR-l2〇，备士產業製造）中並使其旋轉轉（每分υ轉μ 分）’以目測確認旋轉完畢後之有核錠中有缺損者之數量 (依據第十五改正日本藥典中說明書之參考資訊磨損度試驗法」）。 (結果）「旋劑之調配有含水二氧切之實施例1、2，與未調配含水二氧 :之比較例1相t匕’可判明耐磨損性之提高。又，與羧助於在製造、包裝良好之成績。因此，推測其有據極大優勢（表υ。或流通下之品f維持方面佔 139389.doc •19- 200946142 [表i] 實施例1 實施例2 比較例1 比較例2 核錠 600 600 600 600 碳酸氫鈉 900 900 900 900 氫氧化鎂 100 100 100 100 沈澱碳酸鈣 1200 1200 1200 1200 聚乙烯醇 120 120 120 120 羧甲基纖維素鈣 150 150 150 - 低取代羥丙基纖維素 - _ 150 結晶纖維素 375 360 390 375 硬化油 120 120 120 120 硬脂酸鎂 20 20 20 20 含水二氧化矽 15 30 - 15 合計(mg/6T) 3600 3600 3600 3600 崩解時間(分)(n=6) 20 16 42 47 硬度(N)(n=20) 10 12 7 8 磨損試驗(有缺損之錠的數量） 0 0 5 3 由試驗例1〜3之結果可明確：含有藥效成分、羧甲基纖維素或其鹽、及二氧化矽之錠劑具有良好之崩解性且機械強度優異。實施例3 使用混合機，將9.0 kg碳酸氫鈉、1·0 kg氫氧化鎂、12.0 kg沈澱碳酸鈣、1.2 kg聚乙烯醇、1.5 kg羧甲基纖維素鈣、 3.5 kg結晶纖維素、0.15 kg桂皮粉末、1.2 kg硬化油、及 0.2 kg硬脂酸鎂混合、混練，接著使用乾燥機進行乾燥，進而使用整粒機進行整粒而製成顆粒。將5.95 kg顆粒與 0.05 kg含水二氧化矽混合而獲得6.0 kg外層顆粒。使用具有Φ為11 mm之沖模的有核打錠機，將製造例中所製造之1錠為1〇〇 mg之核錠12000錠與6.0 kg外層顆粒製 139389.doc -20- 200946142 成12000錠之1錠為600 mg的有核錠。所獲得之有核錠之崩解時間為17分鐘，硬度為11N。實施例4 使用混合機，將0.75 kg氣化S-曱基蛋胺酸、0.45 kg東笑君萃取物三倍散' 0.25 kg蒼術乾燥萃取物、0.15 kg當藥粉末、0.075 kg 脂肪酶 AP、0.12 kg 生物澱粉酶（2〇〇〇)、0.12 kg經丙基纖維素、0.3 kg硬化油、0.35 kg緩甲基纖維素妈、及0.09 kg玉米澱粉混合、混練’接著使用乾燥機進行乾燥’進而使用整粒機進行整粒而製成顆粒。將2.655 kg 顆粒與0.045 kg硬脂酸鎂混合而製成打錠用顆粒，使用具有Φ為7 mm之沖模的打錠機進行打錠，而製造30000錠之1 鍵為90 mg之錠劑。將〇.〇3 kg硬化油、0.02 kg甘油單硬_ 酸酯、0_008 kg硬脂酸聚烴氧（40)酯、0_008 kg純化蟲膠、 0.054 kg滑石分散於純乙醇中而成的分散液，以乾燥後每錠達到10 mg之方式另行塗布於12000錠之該錠劑上，而製成1錠為1 00 mg之核鍵。使用混合機’將9.0 kg碳酸氫鈉、1.0 kg氫氧化鎮、12.0 kg沈澱碳酸鈣、1.2 kg聚乙烯醇、1.5 kg羧甲基纖維素鈣、 3.5 kg結晶纖維素、0.15 kg桂皮粉末、1.2 kg硬化油、〇.2 kg 硬脂酸鎮混合、混練，接著使用乾燥機進行乾燥，進而使用整粒機進行整粒而製成顆粒。將595 kg顆粒與〇〇4 kg含水二氧化矽、〇.〇1 kg之L-薄荷腦混合而獲得6.0 kg外層顆粒0 使用具有φ為11 mm之沖模的有核打錠機，對12000錠之 139389.doc •21 - 200946142 上述1錠為100 mg之核錠與6.0 kg外層顆粒進行打錠，而製造12000錠之1錠為600 mg之有核錠。 139389.doc 22-TFR-l2〇, manufactured by the company, and rotated (turning μ minutes per minute)' to visually confirm the number of defects in the core after the rotation is completed (according to the fifteenth correction in the Japanese Pharmacopoeia) Reference Information Wear Degree Test Method"). (Results) "Examples 1 and 2 of the preparation of the hydrocyclone with aqueous dioxo, and the phase 1 of the unprepared aqueous dioxygen: Comparative Example 1 can be found to have an improved wear resistance. Good results in manufacturing and packaging. Therefore, it is speculated that it has great advantages (existence. Or maintenance of goods under maintenance 139389.doc •19- 200946142 [Table i] Example 1 Example 2 Comparison Example 1 Comparison Example 2 Core ingots 600 600 600 600 Sodium bicarbonate 900 900 900 900 Magnesium hydroxide 100 100 100 100 Precipitated calcium carbonate 1200 1200 1200 1200 Polyvinyl alcohol 120 120 120 120 Carboxymethyl cellulose calcium 150 150 150 - Low substituted hydroxypropyl Cellulose- _ 150 Crystalline cellulose 375 360 390 375 Hardened oil 120 120 120 120 Magnesium stearate 20 20 20 20 Aqueous cerium oxide 15 30 - 15 Total (mg/6T) 3600 3600 3600 3600 Disintegration time (minutes ) (n=6) 20 16 42 47 Hardness (N) (n=20) 10 12 7 8 Abrasion test (number of ingots with defects) 0 0 5 3 From the results of Test Examples 1 to 3, it is clear that the drug is contained The active ingredient, carboxymethyl cellulose or a salt thereof, and a cerium oxide lozenge have good disintegration properties Excellent mechanical strength. Example 3 Using a mixer, 9.0 kg of sodium bicarbonate, 1.0 kg of magnesium hydroxide, 12.0 kg of precipitated calcium carbonate, 1.2 kg of polyvinyl alcohol, 1.5 kg of calcium carboxymethylcellulose, 3.5 kg of crystals Cellulose, 0.15 kg cinnamon powder, 1.2 kg hardened oil, and 0.2 kg magnesium stearate were mixed and kneaded, then dried using a dryer, and then granulated by a granulator to form granules. 5.95 kg of granules and 0.05 Kg of aqueous cerium oxide is mixed to obtain 6.0 kg of outer granules. Using a nucleation ingot with a Φ 11 mm die, 1 ingot produced in the manufacturing example is 1 锭 ingot of 1 2,000 ingot and 6.0 kg. The outer layer is made of 139389.doc -20- 200946142. One spindle of 12,000 spindles is a 600 mg cored ingot. The obtained core ingot has a disintegration time of 17 minutes and a hardness of 11 N. Example 4 Using a mixer, 0.75 kg gasified S-mercapto methionine, 0.45 kg Dongxiaojun extract triploid '0.25 kg Atractylodes dry extract, 0.15 kg drug powder, 0.075 kg lipase AP, 0.12 kg bioamylase (2〇〇〇), 0.12 kg of propyl cellulose, 0.3 kg of hardened oil, 0.35 kg Mom cellulose, corn starch are mixed and 0.09 kg, kneading 'followed by drying using a dryer' and further granulated using granulator and sieved. A pellet of 2.555 kg was mixed with 0.045 kg of magnesium stearate to prepare pellets for tableting, and a tableting machine having a die of Φ of 7 mm was used for tableting, and a button of 30,000 spindles was used to prepare a tablet of 90 mg. Dispersion of 〇.〇3 kg hardening oil, 0.02 kg glycerol mono- ate, 0_008 kg stearic acid polyoxyl (40) ester, 0_008 kg purified shellac, 0.054 kg talc dispersed in pure ethanol It was applied to 12,000 tablets of the tablet in a manner of 10 mg per ingot after drying to prepare a core of 100 mg. Using a mixer '9.0 kg of sodium bicarbonate, 1.0 kg of hydrazine, 12.0 kg of precipitated calcium carbonate, 1.2 kg of polyvinyl alcohol, 1.5 kg of calcium carboxymethylcellulose, 3.5 kg of crystalline cellulose, 0.15 kg of cinnamon powder, 1.2 Kg hardening oil, 〇.2 kg stearic acid is mixed and kneaded, then dried using a dryer, and then granulated by a granulator to form granules. Mixing 595 kg of granules with kg4 kg of aqueous cerium oxide, 〇.〇1 kg of L-menthol to obtain 6.0 kg of outer granules 0 using a nuclear ingot machine with a φ 11 mm die, for 12,000 spindles 139389.doc •21 - 200946142 The above 1 spindle is 100 mg core and 6.0 kg outer layer is tableted, and 12,000 spindles are made into 600 mg core ingot. 139389.doc 22-

Claims

200946142 VII. Patent application scope: 1. A method for producing a tablet, the tablet having abrasion resistance, the method characterized in that it is manufactured by using a tablet containing (A) a medicinal ingredient, and The money contains (B) carboxymethylcellulose or a salt thereof, and (C) sulphur dioxide. 2. A method for producing a tablet which has good disintegratability and abrasion resistance, and which is characterized in that it is a tablet containing a (A) medicinal ingredient The tablet contains (B) carboxymethylcellulose or a salt thereof, and (C) cerium oxide. 3. The production method according to claim 1 or 2, wherein (B) carboxymethylcellulose or a salt thereof is about methine cellulose. 4. The method of manufacture of claim 1 or 2, wherein (C) cerium oxide is aqueous hydrated cerium. 5. The production method according to claim 1 or 2, wherein the content of (B) carboxymethylcellulose or a salt thereof is from 1 to 20 mass% per oxime. 6. The production method according to claim 1 or 2, wherein the content of (C) cerium oxide is 0.1 to 10 mass. /〇. 7. The production method according to claim 1 or 2, wherein the mass ratio of (B) carboxymethylcellulose or a salt thereof to (C) cerium oxide ((b)/(c)) is (Mdoo. The manufacturing method of claim 1 or 2, wherein the tablet containing the (A) medicinal ingredient is a method of correcting the immediate release preparation by the Japanese Pharmacopoeia "disintegration test method" according to the fifteenth (test liquid: water, liquid amount) : 10 〇〇 mL, test temperature: 37 ± 2 C ) and the measured disintegration time is within 3 〇 minutes, by reference to the fifteenth correction 曰药中说明书之之锭锭锭锭 139 139 139 139389 .doc 200946142 Method of "method" (putting a specified amount of tablet into a drum and rotating it 100 times, after the test, visually calculating the number of defective ingots), the measured degree of wear is 〇. The manufacturing method of claim 1 or 2, wherein (a) the medicinal ingredient is a drug acting on the stomach. 10. The method of claim 1 or 2, wherein (A) the medicinal ingredient is selected from the group consisting of peptic ulcers One or more of a drug, a stomachic agent, a digestive agent, an antacid, a gastric mucosa repairing agent, and an intestine drug. The method for producing the item 1 or 2, wherein the (A) medicinal ingredient is selected from the group consisting of carbonated nitrocarb, emulsified town, emulsified town, carbonated town, carbonated carbonate, precipitated calcium carbonate, magnesium citrate, calcium hydrogen phosphate and anhydrous Among the calcium hydrogen phosphate. 12. A tablet containing: (A) selected from the group consisting of a peptic ulcer agent, a stomachic agent, a digestive agent, an antacid, a gastric mucosa repairing agent, and an intestine drug- Or two or more medicinal ingredients; (B) carboxymethylcellulose or a salt thereof; and (c) sulphur dioxide. 13. The tablet of claim 12, wherein (B) carboxymethylcellulose Or a salt thereof as a slow methylcellulose. 14. A lozenge according to claim 12 or 13, wherein (C) cerium oxide is an aqueous cerium oxide. 15. The lozenge of claim 12, wherein (B The content of carboxymethylcellulose or a salt thereof is from 1 to 20 mass%. 〇. The lozenge of claim 12, wherein the content of (C) cerium oxide is 0 〇 mass%. The lozenge of item 12, wherein (B) carboxymethylcellulose or a salt thereof and (c) 139389.doc ·τ·200946142 cerium oxide have a mass ratio ((Β)/(〇) is 0. 18. If please The tablet of claim 12, wherein the method according to the fifteenth correction of the Pharmacopoeia "disintegration test" immediate release preparation (test liquid: water, liquid amount: 1000 mL, test temperature: 37 ± 2) The measured disintegration time is within 3 〇 minutes, by the method of “the abrasion test method of the lozenge” according to the reference information in the fifteenth correction of the Japanese Pharmacopoeia (the prescribed amount of tablet is put into the drum) It was rotated 100 times, and after the test, the measured degree of wear was measured by visually calculating the number of defects: 19. The lozenge of claim 12, wherein (A) the medicinal ingredient is selected from the group consisting of sodium hydrogencarbonate, magnesium oxide, magnesium hydroxide, carbonic acid, carbonic acid, precipitated carbonic acid magnesium magnesium citrate, calcium hydrogen citrate and One or more of anhydrous calcium hydrogen phosphate. 20. The tablet of claim 12, wherein the medicinal ingredient is selected from the group consisting of sodium hydrogencarbonate, oxidized town, magnesium hydroxide, magnesium carbonate, calcium carbonate, precipitated calcium carbonate, magnesium citrate, calcium hydrogen phosphate, and anhydrous calcium hydrogen phosphate. Two or more of them. 139389.doc 200946142 IV. Designated representative map: (1) The representative representative of the case is: (none) (2) The symbolic symbol of the representative figure is simple: 5. If there is a chemical formula in this case, please reveal the best indication of the characteristics of the invention. Chemical formula: (none) 139389.doc