部份中文米诺膦酸处方资料（仅供参考）
商品名：Bonoteo Tablets
英文名：Minodronic Acid Hydrate
中文名：米诺膦酸水合物
生产商：安斯泰来制药
药品介绍
米诺膦酸(Minodronic acid) 是一种含氮的 二碳磷酸盐化合物为第三代含氮芳杂环双膦酸盐，可用于治疗骨质疏松症。本品由日本小野药品工业株式会社和日本Astellas制药株式会社共同开发，于2006年7月向日本厚生省提交申请，于2009年1月21日首次获准上市，商品名分别为Recalbon®(小野药品)和Bonoteo®(Astellas制药)。
本品用于骨质疏松症的治疗，通过抑制破骨细胞内焦磷酸法呢酯(FPP)合成酶活性，抑制破骨细胞的骨吸收，降低骨转换，起到防治骨质疏松的效果。是1mg的片剂， 1天1次，1次1片。该药品的比较优势表现在：与目前临床上常用的双膦酸盐比较，其抑制骨吸收的活性强，是英卡膦酸二钠的2倍，阿仑膦酸的钠的10倍，帕米膦酸二钠的100倍，且消化道不良反应发生率较现有的双膦酸类药物少。
ボノテオ錠1mg
药用类别名称
骨质疏松症治疗剂
批准日期：2011年9月
商標名
Bonoteo Tablets
一般名
ミノドロン酸水和物（Minodronic Acid Hydrate）
化学名
［1-Hydroxy-2-（imidazo［1,2-a］pyridin-3-yl）ethylidene］bisphosphonic acid monohydrate
構造式
分子式
C9H12N2O7P2・H2O
分子量
340.16
融点
約250℃（分解）
性状：
盐酸水合物是一种白色-微带红白色晶体或结晶性粉末。 非常溶于水, 几乎不溶于乙醇(99.5)。它融化成氢氧化钠测试溶液。
药用药理学
1. 作用机制
根据以下结果, 明德龙酸水合物抑制破骨细胞中的法尼辛酯焦磷酸盐合成酶, 通过抑制破骨细胞的骨吸收功能, 被认为可以减少骨代谢的旋转。
(1) 给大鼠服用破骨细胞。
(2) 体外抑制法内西西米焦磷酸盐合成酶。
(3) 在兔破骨细胞培养系统中, 减少破骨细胞的数量。
2. 药理作用
(1) 骨吸收的抑制作用
在兔破骨细胞培养系统中, 抑制i型胶原蛋白交联c-恐怖肽从骨(体外)释放。
(2) 骨质疏松症模型动物的作用
1) 在大鼠喷水模型中, 抑制尿脱氧素蛋白浓度的增加, 抑制骨密度和骨强度的降低。
2) 在西莫美耳卵巢切除模型中, 抑制尿I型胶原蛋白交联n-恐怖肽和脱氧吡咯素浓度的增加。 此外, 抑制骨密度和骨强度的下降, 观察到骨密度与骨强度呈正相关。
3) 在大鼠类固醇诱导模型中, 抑制尿脱氧西林浓度的增加, 抑制骨密度和骨强度的降低。
4) 在大鼠固定化模型中, 抑制骨密度的下降。
(3) 对骨钙化的影响
在正常大鼠中, 不观察到高达100倍的剂量来增加骨量, 不观察钙化障碍。 此外, 在大鼠和子卵巢切除模型中, 未观察到同种骨宽度的增加。
(4) 对骨折愈合的影响
在大鼠腓骨骨折模型中, 暂时骨吸收延迟, 骨强度没有下降。
适应症
骨质疏松症
用法与用量
通常情况下, 成人每天一次1mg作为薄荷酸水合物, 口服足够数量的水(约180毫升)在醒来的时候。需要注意的是, 服用后至少30分钟, 不要躺下、吃喝(水除外), 还要避免口服其他药物。
临床结果
1. 骨密度测试
52周 II iii 期试验*1)为退行性骨质疏松症患者, 最终评估的变化率±标准偏差从腰椎平均骨密度开始[2)1时间50毫克给药组6.461±3.67%水水合物4周, 薄荷水合物1毫克给药组6.730±3.98 90%, 每天。在对1MG 给药组的最终评价中, 腰椎平均骨密度(差异的95%置信区间) 的变化率差异为0.269(-1.1093~0.5706), 4周内每天 1次, 按 Dunnett 型调整1mg 给药组1次450mg 给药每周一次被证实是不少于1mg给药一次, 每天5)。
此外, 骨代谢标志物(尿I型胶原交联n-恐怖肽: 尿NTX, 血清骨型碱性磷酸酶), 一次50毫克给药组和氨酸水合物一天1毫克给药组在一个氨酸水合物4周, 5)这被证实几乎保持。(见临床结果表 3)
*1)口服400IU 作为钙6 10mg 和维生素D3在晚餐后, 每天一次作为基本的治疗剂
*2)在管理52周后或停止行政管理时
2. 断裂试验
退行性骨质疏松症*3患者2年的第三阶段双盲试验(骨折试验)、1毫克给药组(1毫克制剂组) 和氨基酸水合物安慰剂组每天一次(累计)分别为10.4, 24.0%(相对风险降低率59%), 对安慰剂有显著的骨折预防作用(对数等级试验: P<0.0001)6)。(见临床结果表4)
此外, 在8.267±5.360%(最终评价*4)中, 腰椎平均骨密度的标准差±标准差在8.26±5.360%(最终评价*4)中, 为2年, 安慰剂的变化率明显较大(t-测试:p<0.001) 6)。
此外, 在已进行的继续试验中, 1毫克制剂组(194例)的椎体骨折发生率为12.4(累计)。每年椎体骨折 (累计)的发生率在第一年为6.7%, 第二年为3.6%, 第三年为3.2%。3年给药后, 1毫克制剂组(56例) 腰椎平均骨密度的变化率为10.271±5.9692%(上一次评价*5)。
* 3) 口服200IU 作为钙600毫克和维生素D3在晚餐后, 每天一次作为基本的治疗剂
* 4) 经过104周的管理或停止行政管理时
* 5) 在管理156周后或在行政停止时
包装
100錠（10錠×10）
140錠（14錠×10）
制造商
安斯泰来制药公司
注：以上中文处方资料不够完整，使用者以原处方资料为准。
完整资料附件：http://www.info.pmda.go.jp/go/pack/3999026F1026_1_16/
Bonoteo Tablets 1mg（Minodronic acid hydrate ボノテオ錠）
Brand name:Bonoteo Tablets 1mg
Active ingredient:Minodronic acid hydrate
Dosage form:white tablet (diameter: approximately 6.6mm, thickness: approximately3.0mm)
Print on wrapping:（Face）1 日 1 回 1 錠, ボノテオ 1mg, （Back）ボノテオ, 1mg,house-mark, 骨粗鬆症治療剤
Effects of this medicine
This medicine inhibits osteoclastic bone resorption and increases bone density and bone strength, thus preventingbone fracture.
It is usually used for the treatment of osteoporosis.
Before using this medicine, be sure to tell your doctor and pharmacist
・If you have previously experienced any allergic reactions (itch, rash, etc.) to any medicines.
If you have a disorder that delays esophageal transit such as esophageal stenosis.
If you are unable to sit upright for more than 30 minutes when taking this medicine.
If you have hypocalcemia.
・If you are pregnant, possibly pregnant or breastfeeding.
・If you are taking any other medicinal products. (Some medicines may interact to enhance or diminish medicinaleffects. Beware of over-the-counter medicines and dietary supplements as well as other prescription medicines.)
Dosing schedule (How to take this medicine)
・Your dosing schedule prescribed by your doctor is<< to be written by a healthcare professional>>
・In general, for adults, take 1 tablet (1 mg of the active ingredient) at a time, once daily, with a cup of water(approximately 180 mL), before the first meal or beverage of the day. At least for the first 30 minutes after takingthe medicine, do not lie down, and refrain from eating, drinking (including mineral water that contains plenty ofcalcium or magnesium) or taking other medicine, except water. Strictly follow the instructions.
・This medicine may irritate the inside of the mouth and throat. Do not crunch or dissolve the medicine in the mouth.
・Do not take the medicine at bedtime or before rising.
・If you miss a dose, and not yet had any foods or beverages, take the missed dose as soon as possible. If you havealready had some foods and beverages, skip the missed dose and continue your regular dosing schedule from nextmorning. You should not take two doses at one time.
・If you accidentally take more than your prescribed dose, consult with your doctor or pharmacist.
・Do not stop taking this medicine unless your doctor instructs you to do so.
Precautions while taking this medicine
・Maintain your oral hygiene while taking this medicine. Otherwise pain or swelling of the jaw, numbness of the jawand loosening of the teeth may occur.
・If you receive dental treatment, report to your dentist or oral surgeon that you are taking this medicine.
・Try to consume calcium and vitamin D from food, etc. However, since intake of food, beverages or vitaminsupplements that contain a considerable amount of calcium may affect the absorption of this medicine, theseproducts should be taken at least 30 minutes apart after taking this medicine.
Possible adverse reactions to this medicine
The most commonly reported adverse reactions include stomach discomfort, abdominal discomfort, abdominal pain,and gastritis. If any of these symptoms occur, consult with your doctor or pharmacist.
The symptoms described below are rarely seen as initial symptoms of the adverse reactions indicatedin brackets. If any of these symptoms occur, stop taking thismedicine and see your doctorimmediately.
・epigastric pain, tenderness, vomiting [upper gastrointestinal disorder]
・pain of the teeth, gingiva or jaw, swelling and pus discharge of the gingiva, looseness of the teeth [osteonecrosis ofthe jaw, osteomyelitis of the jaw]
・otitis externa (itch of the ear, hotness in the ear, discomfort of the ear), ear discharge, ear pain [osteonecrosis ofexternal auditory canal]
・pain in the thighs or inner groin [atypical femoral subtrochanteric fracture and atypical femoral hip and shaftfractures]
・general malaise, loss of appetite, yellowness in the skin and/or whites of the eyes [liver dysfunction, jaundice]
The above symptoms do not describe all the adverse reactions to this medicine. Consult with your
doctor or pharmacist if you notice any symptoms of concern other than those listed above.
Storage conditions and other information
・Keep out of the reach of infants and children. Store away from direct sunlight, heat and moisture.
・Discard the remainder. Do not store them. Consult with your dispensing pharmacy when you discard the medicine.
Internal
Revised: 06/2016
The information on this sheet is based on approvals granted by the Japanese regulatory authority. Approvaldetails may vary by country. Medicines have adverse reactions (risks) as well as efficacies (benefits). It isimportant to minimize adverse reactions and maximize efficacy. To obtain a better therapeutic response,patients should understand their medication and cooperate with the treatment.