CN101573127B - 硬组织再生促进剂 - Google Patents
硬组织再生促进剂 Download PDFInfo
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- CN101573127B CN101573127B CN200780040020XA CN200780040020A CN101573127B CN 101573127 B CN101573127 B CN 101573127B CN 200780040020X A CN200780040020X A CN 200780040020XA CN 200780040020 A CN200780040020 A CN 200780040020A CN 101573127 B CN101573127 B CN 101573127B
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Abstract
本发明的目的是提供不论是在费用方面还是在劳力方面均能以低成本制备的含有对缺陷或缺损的硬组织的再生有用的物质的硬组织再生促进剂、医药组合物、食品组合物、食品等。即,通过使所述药剂或组合物含有硅藻土,并在缺陷或缺损的硬组织附近的骨膜下给药或口服给药,可促进缺陷或缺损的部分的硬组织的再生。
Description
对相关申请的引用
本申请主张基于2006年9月21日提出申请的日本专利申请第2006-256374号的优先权,通过引用该基础申请将其包括到本说明书中。
技术领域
本发明涉及对硬组织再生有用的药剂、医药组合物、食品组合物、食品、动物用饲料等。
背景技术
为了修复硬组织的缺陷部或缺损部,以往开发了将含有人造羟基磷灰石、牛骨干燥粉末、硅酸盐玻璃粉末、硅酸盐水泥的填充材料填充于硬组织的缺陷部或缺损部的方法(美国专利第5769638号说明书);将300~360μm的粒状材料插入缺陷部或缺损部内,从而形成骨组织的方法,该粒状材料通过将由SiO2(45重量%)、CaO(24.5重量%)、Na2O(24.5重量%)及P2O5(6重量%)混合而成的混合物熔化后粉碎而得(日本专利特开平3-136664号公报);以及促进骨再生的药剂(日本专利特开2003-55237号公报)等。
发明的揭示
本发明的目的是提供不论是在费用方面还是在劳力方面均能以低成本制备的含有对缺陷或缺损的硬组织的再生有用的物质的硬组织再生促进剂、医药组合物、食品组合物、食品、动物用饲料等。
本发明人发现,如实施例所示,通过在硬组织发生缺损的部分附近的骨膜下给予硅藻土或是口服给予硅藻土,缺损的硬组织的再生得到促进,从而完成了本发明。
即,本发明的硬组织再生促进剂含有硅藻土作为有效成分。所述硬组织例如为硬骨、修复性牙本质等。所述硬骨例如为牙槽骨等。本发明的硬组织再生促进剂例如可以是在骨膜下给药(填充)的促进剂,也可以是在因拔牙等而导致缺损的骨髓腔内或骨折部位附近的骨髓腔内给药的促进剂,或者是口服给药的促进剂。
此外,本发明的医药组合物含有硅藻土作为有效成分。本发明的药物组合物可以是在骨膜下给药的制剂,也可以是在因拔牙等而导致缺损的骨髓腔内或骨折部位附近的骨髓腔内给药的制剂,或者是口服给药的制剂。
另外,本发明的食品组合物含有硅藻土。
本发明的食品含有硅藻土。
此外,本发明的动物用饲料含有硅藻土。
另外,本说明书中的“硅藻土”是指由硅藻的遗骸形成的堆积物,包括由海洋性硅藻类堆积而成的海洋性硅藻土(包括硅藻软泥)、由淡水性硅藻类堆积而成的淡水性硅藻土等。本发明的药剂、医药组合物、食品组合物、食品、动物用饲料等所含的硅藻土可以是在高温下烧成而得的烧成物,也可以是自然干燥而成的干燥物。
附图的简单说明
图1是表示作为本发明的一种实施方式进行说明的牙的结构的图。
图2是表示作为本发明的一种实施方式进行说明的骨的结构的图。
图3是表示本发明的一个实施例中,在硅藻土的骨膜下给药后,用微焦点X射线放大观察装置对拔牙部分附近及硅藻土给予部分附近进行观察的结果的图。
图4是表示本发明的一个实施例中,在硅藻土的骨膜下给药后,用微焦点X射线放大观察装置对拔牙部分附近及下牙槽部进行观察的结果的图。
图5是表示本发明的一个实施例中,用基于EPMA的钙和来源于硅藻土的硅的元素分布像(element mapping)法来验证通过硅藻土的口服给药可促进拔牙后或植入牙床骨穿孔后的骨再生和治愈的事实的结果的图。
图6是表示本发明的一个实施例中,用微焦点X射线显微观察系统来观察对于人为穿孔的下肢骨,通过口服给予硅藻土可促进骨再生的事实的结果的照片。
图7是表示本发明的一个实施例中,用微型CT系统对于人为穿孔的下肢骨,通过口服给予硅藻土可促进骨再生的事实进行X射线显微立体观察的结果的照片。另外,在这些图像中,在骨附近、骨髓腔内观察到的直线的高反差阴影(用白色箭头表示)均为因血管造影而产生的阴影,与骨再生的观察结果无关。
图8是表示本发明的一个实施例中,根据图7所示的X射线显微图像信息对骨盐量进行定量分析的结果的照片。
实施发明的最佳方式
下面,例举实施例对基于上述发现而完成的本发明的实施方式进行详细说明。另外,使用市售的测定装置时,只要没有特别说明,就使用该装置附带的试验方案。
此外,通过本说明书的记载,本发明的目的、特征、优点及其技术思想对于从业人员来说是显而易见的,根据本说明书的记载,只要是本领域的技术人员,即可容易地再现本发明。下面记载的发明的实施方式及具体的实施例等是揭示本发明的优选实施方式的例子,是为了举例或说明而揭示的,本发明并不局限于此。对本领域的技术人员来说显而易见的是,在本说明书所揭示的本发明的意图和范围内,可基于本说明书的记载进行各种改变和修改。
==硅藻土的药理作用==
如图1所示,牙100由牙釉质10、牙本质20、牙骨质80、牙髓30等构成,由牙龈(牙床)40、牙根膜60以及由骨皮质(骨密质)71、骨松质72等构成的作为硬组织的牙槽骨等牙周组织所支承。
如实施例1所示,在狗中,在拔牙后,将附着于牙槽骨的牙龈40和骨膜50一起剥离,在覆盖牙槽骨表面的骨膜50下埋入硅藻土,结果发现在硅藻土的给药部位附近的骨皮质71上、牙100的缺损部(牙槽骨)附近的骨髓腔73的底部以及骨髓腔73的上部,缺损的骨松质72的新生骨的再生得到促进。此外,如实施例2所示,可知对于在拔牙后用钻头将牙槽骨内部打磨光滑的狗,通过口服给予硅藻土,骨皮质71上和牙100的缺损部(牙槽部骨松质72)的新生骨的再生同样得到促进。因此,可知硅藻土有助于促进由拔牙、植入体的埋入和固定、牙内及牙周疾病的病原菌的毒素、感染、为了手术的方便而进行的骨凿除等引起的骨损坏、吸收、骨折等所导致的缺陷或缺损的部分的硬组织的再生。
此外,作为硬组织的硬骨、例如图2所示的肱骨或股骨等长骨200的干部由骨膜110、骨皮质120、骨髓130等构成,骨200的端部由骨膜140、骨皮质150、骨松质160、骨髓等构成,对于上述硬骨,在由骨折、植入体的埋入、细菌的毒素、化脓等导致部分发生缺陷或缺损时,通过在其附近的骨膜110、140下给予硅藻土,或在骨髓腔内给予硅藻土,或口服给予硅藻土,也可使缺陷或缺损的部分的硬组织再生(实施例3中揭示通过口服给药使下肢骨再生的例子)。因此,硅藻土有助于促进由骨折、植入体的埋入、细菌的毒素、化脓等导致的缺陷或缺损的部分的硬组织的再生。
这里,作为可利用硅藻土促进再生的硬组织,可例举例如硬骨(牙槽骨、颌骨、股骨、肱骨、胫骨、桡骨、尺骨、椎骨等)、牙100的修复性牙本质等。此外,作为所使用的硅藻土,只要是例如海洋性硅藻土、淡水性硅藻土等由硅藻化石化而成的硅藻土,或者是硅藻土的烧成物或干燥物等即可,无特别限制。
==本发明的药剂、医药组合物、食品组合物及食品等==
如上所述,由于硅藻土可促进缺陷或缺损的硬组织的再生,因此硅藻土作为对需要缺陷或缺损的硬组织的再生的患者提供的医药或食品的组合物以及对需要缺陷或缺损的硬组织的再生的忠畜提供的饲料组合物有用,含有硅藻土作为有效成分的药剂作为促进缺陷或缺损的硬组织的再生的药剂有用,而且含有硅藻土的食品作为功能性食品、特定保健用食品等对需要缺陷或缺损的硬组织的再生的患者有用,含有硅藻土的动物用饲料对需要缺陷或缺损的硬组织的再生的患畜有用。此外,硅藻土是天然材料,能以低廉的价格大量获得,因此不论是在费用方面还是在劳力方面均能以低成本提供本发明的药剂、医药组合物、食品组合物及食品等。
作为本发明的药剂,只要是含有硅藻土作为有效成分的药剂即可,无特别限制,根据使用部位或目的、给药方式等,可进一步含有药理学上可接受的制剂添加物(例如赋形剂、pH调整剂、粘合剂、润滑剂、崩解剂、矫味剂、溶剂、稳定剂、糖衣剂、防腐剂、缓冲剂、悬浮剂、乳化剂、芳香剂、助溶剂、着色剂、增稠剂等)。此外,用于促进牙周组织的修复和再生、预防细菌感染或抑制炎症的药剂中还可含有例如多磷酸钠等多磷酸盐、作为创伤覆盖剂的褐藻酸等。
另外,本发明的药剂可以对人或人以外的脊椎动物进行例如口服给药,也可以在骨髓腔或骨膜50、110、140下等位置给药。口服给予本发明的药剂时,可制成片剂、胶囊剂、颗粒剂、散剂、糖浆剂、丸剂等制剂,在骨膜50、110、140下给药时,可制成注射剂等制剂。另外,这些制剂可以用上述制剂添加物通过常规方法制造。
此外,本发明的食品只要是含有硅藻土的食品即可,可以是任意食品,除硅藻土外,还可含有维生素A、C、E、K或多酚等抗氧化物质、阿斯巴甜或木糖醇等甜味剂、山梨酸钾或苯甲酸钠等防腐剂、亚硫酸钠或L-抗坏血酸钠等抗氧化剂、姜黄色素或辣椒红色素等着色剂、氨基酸或畜肉提取物等调味剂、柠檬酸或苹果酸等酸味剂等现有的食品添加物。
作为本发明的食品,可制成例如胶囊、片剂、颗粒等形状的营养补充剂、面类(例如乌冬面等)、酸乳酪、糖(糖果、水果糖等)、粉末状调味食品(ふりかけ)等形态来使用,但不限定于这些形态。另外,本发明的食品最终可以是固态物、粉末、液状、液体状、膏状、凝胶状等任何形状。此外,本发明的食品基本上以给予健康人群为目的,但需要缺陷或缺损的硬组织的再生的患者也可摄取。
作为本发明的动物用饲料,只要是含有硅藻土的动物用饲料即可,可以是任意动物用饲料,除硅藻土外,还可含有抗氧化剂、防霉剂、粘结剂、乳化剂、调整剂、氨基酸、维生素、矿物质、色素、合成抗菌剂、抗生素、香料、调味剂、酶、活菌剂等现有的饲料添加物。
==本发明的药剂、医药组合物及食品等的使用方法==
含有硅藻土作为有效成分的硬组织再生促进剂可以不通过口服在具有缺陷或缺损的硬组织的患者的任何部位给药,但优选在硬组织的缺陷或缺损的部分直接给药,或者是在需要硬组织的再生的部分的附近给药。例如,如果在与需要再生的硬骨距离最近的骨膜50、110、140下、或者在牙100的牙髓腔穿孔部AA、根尖31或根管32处给药,则硬骨的再生得到促进。此外,牙100发生缺陷或缺损时,如果在缺陷或缺损的牙100的牙本质20等处填充本发明的硬组织再生促进剂,则修复性牙本质的再生得到促进。特别是在牙100的缺陷或缺损深入至牙髓30的情况下,在缺陷或缺损的牙100的牙本质20等处填充本发明的硬组织再生促进剂,使牙髓30不暴露即可。另外,给药方法有注入、涂布、填充等,无特别限制。或者,也可对具有缺陷或缺损的硬组织的患者口服给予硬组织再生促进剂。
此外,为了迅速地发挥硬组织再生促进作用,可以在硬组织发生缺陷或缺损前以含有硅藻土作为有效成分的医药组合物或食品的形式摄取硅藻土。
实施例
下面,通过实施例对本发明进行具体说明。另外,这些实施例用于对本发明进行说明,并不对本发明的范围进行限定。
[实施例1]
对于牙槽骨缺损的狗,为了促进缺损部位处的新生骨的再生,在骨膜下给予硅藻土。
拔牙时,用骨膜刮骨刀同时将狗的牙龈和骨膜一起剥离,在骨膜下埋入0.2g溶于蒸馏水而制成糊状的硅藻土(干燥品;中央化成株式会社、中央二氧化硅(中央シリカ)株式会社)。1个月后,对于注入硅藻土的部位的附近,使用宝尼工业(PONY industry)株式会社制的微焦点X射线检查装置P70 II(焦点尺寸10μm×10μm),将内置有柯达公司制的胶片或富士胶片医疗器材(Fujifilm medical)株式会社制的成像板(imaging plate)HR的暗盒以几何学放大倍数为3倍的方式配置,在摄影条件(30KV 90μA胶片为15分钟,成像板为30秒)下对胶片(图3)或成像板(图4)进行放大X射线摄影。另外,成像板用FCR 50000MA(FCR(Fuji Computed Radiography:数字X射线图像诊断系统);富士照片胶卷株式会社制)来进行图像信息的读取和观察(观察部分:参照图1)。此外,作为对照,也用微焦点X射线放大观察装置对未给予硅藻土的狗进行观察。其结果示于图3及图4。另外,图3中的尖头表示硅藻土给药部位。
在未给予硅藻土的狗中,拔牙窝下部的骨髓腔内壁(图4)及骨膜下骨皮质(密质)上仅观察到少量的新生骨的形成,与此相对,如图3及图4所示,在骨膜下给予了硅藻土的狗中,在拔牙窝的骨髓腔底部(图3中的方框所包围的部分及图4中的圆圈所包围的部分)、骨髓腔侧壁(参照图3中的圆圈所包围的部分)、硅藻土给药部位附近的骨膜下骨皮质上(图3中的箭头)及下牙槽部(图4中的箭头)处观察到幼弱的新生骨的形成,在拔牙窝的骨髓腔内观察到骨松质(图3中的V字)的形成,长时间观察这些部分,结果按照骨膜下骨皮质上→骨髓腔底部、侧壁→骨髓腔内的骨松质的顺序形成新生骨。由此可知,硅藻土通过骨膜下给药促进骨新生。此外,即使在骨膜下给予硅藻土,在骨髓腔内也有新生骨形成,由此可知直接在骨髓腔内给药时骨新生也可得到促进。
[实施例2]
接着,对于牙槽骨缺损的狗,为了促进缺损部位处的新生骨的再生,口服给予硅藻土。
对于在拔牙后用钻头将牙槽骨内部打磨光滑的狗,每天和饵料一起口服给予相当于一天的饲料量的2~5%的8~20g的硅藻土。1个月后制作切片,对于缺损的牙槽骨附近的骨新生组织,用EPMA(电子探针显微分析仪(Electron Probe Micro Analyzer);岛津EPMA8705,加速电压20kV,试样吸收电流15nA,MAP 512×512点)进行钙和硅的元素分布像测定(观察部分:参照图1)。其结果示于图5。
如图5所示,来源于硅藻土的硅(图5中的白色粉状的信号)分布于骨的内部,其周围(牙槽骨内的骨松质的缺损部位)有新生骨(图5中的缺损骨的灰色部分)形成。此外,在骨皮质71上也观察到新生骨的形成(图5中的框所包围的部分)。由此可知,即使口服给予硅藻土,硅也可到达骨缺损部位,形成新生骨。因此可以得出结论,除了骨膜下给药、骨髓腔给药之外,硅藻土在口服给药时也是有效的。
[实施例3]
另外,人为地将大鼠的下肢骨穿孔,为了促进孔部处的新生骨的再生,口服给予硅藻土。
<标本的处理>
作为实验用大鼠,使用BrlHan:WISTJcl(GALAS)(日本柯力亚(CLEA)株式会社:9周龄♀),驯化后,在处置预定日的2天前进行分组。
处置当日,在尽可能不损伤骨膜的情况下将大鼠的下肢骨(胫骨)暴露,用牙科种植用钻头(圆钢(roundbar))在生理盐水注水下开出直径约2mm、深度约3mm多的孔。关于深度,确认圆钢头部将骨皮质完全穿孔、连通至骨髓侧。然后,口服给予相对于标准饲料CE-2添加混合以重量比计为2%、5%、10%的硅藻土并进行过电子射线灭菌而得的饲料进行饲养。
在穿孔手术后2周、4周、5周,从各个体上切除左右侧下肢,将各侧下肢分别用福尔马林固定后冷却保存,直至进行处理为止。另外,为进行比较,作为对照,在同样地进行穿孔手术后,口服给予对仅有标准饲料CE-2、未添加硅藻土的饲料进行电子射线灭菌而得的饲料,进行个体的饲养、处理和观察。
<试样的制作及观察方法>
(1)利用微焦点X射线显微观察系统的X射线显微观察
首先,为了非破坏性地观察穿孔创伤部,在一概不从骨上除去软组织的情况下,使用宝尼工业株式会社制的微焦点X射线检查装置P70 II(焦点尺寸10μm×10μm),将内置有富士胶片医疗器材株式会社制的成像板HR的暗盒以几何学放大倍数为3倍的方式配置,在摄影条件(30KV 90μA10秒)下对整块骨进行X射线放大投影。然后,用富士胶片医疗器材株式会社制的数字X射线诊断装置:FCR 7000MA进行成像板的图像信息的读取,得到各试样的X射线显微图像。下面,参照图6对观察结果进行详细描述。
(2)利用微型CT系统的X射线显微立体观察
对于穿孔手术后第2周和第4周的穿孔创伤治愈部位,用日立医疗(Hitachi medical)株式会社制的MCT-CB100MF进行同部位的三维结构精查。试样用透明胶带固定在将聚丙烯制离心沉降管沿长轴方向割断而成的半圆柱状管上,固定于装置试样台。摄影条件为(60KV 100μA 2分钟)。下面参照图7对观察结果进行详细描述。
(3)根据利用微型CT系统获得的X射线显微图像信息的骨盐量定量分析
对于(2)的微型CT图像信息,用拉托克系统工程(Ratoc systemengineering)株式会社制的软件TRI/3D-BON-BMD来进行骨盐量的随时间的相对变化比较。骨盐量的校正中,作为骨盐量模型(phantom)的代用品,参照与试样台聚丙烯制离心沉降管的截面比穿孔创伤部相距更远的位置的骨皮质部。下面参照图8对分析结果进行详细描述。另外,图8中,与色带左侧的红色对应部分描绘出的是骨盐量最高的部位,越靠近色带右侧的绿色对应部分,所描绘出的位置的骨盐量相对越低。
<结果>
(1)利用微焦点X射线显微观察系统的X射线显微观察
穿孔手术后第2周(图6A~D):在对照个体(图6A)中,可以明显地观察到与穿孔用的钻头直径相近的半圆形凹陷,而在硅藻土给药组(图6B:2%,C:5%,D:10%)中,在半圆形凹陷部均观察到骨痂样的不透射部,其面积随着给予的硅藻土的浓度的增加而与硅藻土的浓度相关地增加。在硅藻土给药组中,还在半圆形凹陷部的下底部的骨髓侧观察到骨皮质的显著的修复性肥厚。
穿孔手术后第4周(图6E~H):在对照个体(图6E)中,半圆形凹陷部变浅,恢复至盘状的凹陷。另一方面,在硅藻土给药组(图6F:2%,G:5%,H:10%)中,已几乎观察不到上述盘状凹陷,已治愈的骨皮质的厚度随着给予的硅藻土的浓度的增加而与硅藻土的浓度相关地恢复。另外,在硅藻土给药组中,填满手术后第2周观察到的半圆形凹陷的对应部位的骨再生所导致的不透射性恢复到与周围同等的水平,并且在凹陷部位下底的对应部位附近的骨髓侧观察到骨皮质的少量的修复性肥厚。
穿孔手术后第5周(图6I~L):在对照(图6I)和硅藻土给药组(图6J:2%,K:5%,L:10%)的所有个体中,半圆形凹陷部均消失,基本恢复到正常的骨皮质形态。另外,在给药组中,在手术后第4周观察到的骨皮质的骨髓侧处的修复性肥厚还残存有痕迹。
由此可以确认,通过对下肢骨穿孔的大鼠口服给予硅藻土,穿孔部处的骨再生得到促进。
(2)利用微型CT系统的X射线显微立体观察
穿孔手术后第2周:
体绘制(volume rendering)图像(图7A):在对照个体中,仍明显地观察到与穿孔用的钻头直径相近的半球形穿孔。另一方面,在硅藻土10%给药组中可观察到明显的半球形穿孔部的直径缩小,穿孔创伤的闭合治愈正在进行中。另一方面,在硅藻土10%给药组中,周边的骨皮质的X射线透射性亢进。
矢状截面图像(图7B):在对照个体中,明确地观察到与穿孔用的钻头直径相近的半圆形凹陷。此外,该凹陷下底部仍与骨髓腔存在大的连通,几乎未观察到穿孔创伤的闭合治愈和骨皮质的再生。另一方面,在硅藻土10%给药组中,观察到明显的半圆形凹陷部的深度缩小,凹陷下底部与骨髓腔的连通变得狭小,观察到穿孔创伤的闭合治愈和骨皮质的再生的征兆。另一方面,在附近的骨皮质内部,在板层骨间观察到空隙,这与在体绘制图像中观察到的透射性亢进的观察结果一致。认为其原因在于,硅藻土给药组中,在该时期,由创伤部位的硅藻土引起的矿化和随后进行的钙化置换较早地旺盛起来,因此附近的骨钙成分的吸收、溶出和向创伤部位的添加协调地活跃起来。
穿孔手术后第4周:
体绘制图像(图7C):在对照和给药组中,半球形凹陷均变浅,恢复至盘状,但在对照个体中,在中央可明显地观察到较大的穿孔部的残存。在给药组中,在中央仅观察到极小的穿孔部残存。
矢状截面图像(图7D):在对照个体中,虽然半圆形凹陷变浅,但骨皮质的骨膜侧的肥厚不充分,整个层的厚度也薄。另一方面,在给药组中观察到半月形的骨再生部,该骨再生部与半圆形凹陷下底部间有一层边界,整个骨皮质层的厚度也恢复到与周边基本同等的水平。
(3)根据利用微型CT系统获得的X射线显微图像信息的骨盐量定量分析
穿孔手术后第2周:
体绘制图像(图8A):在对照和给药组中,均观察到将半圆形凹陷堵塞、X射线透射性高于周边、即密度相当低的栓塞物质。
矢状截面图像(图8B):在对照个体中,虽然凹陷部的一半被低密度的栓塞物质填满,但下底部的密度疏,与骨髓腔的穿孔部未闭合,未观察到基于致密的再生骨的下底部的修复。另一方面,在硅藻土给药组中,在下底部观察到基于坚固的致密的再生骨的修复。凹陷部的栓塞物质的容积小于对照,认为这是因为骨皮质的再生已经比对照更早地进行,基于栓塞物质的从初期的矿化到钙化的置换先于对照进行。在硅藻土给药组中,在穿孔部附近的骨皮质的板层骨间观察到低密度部的存在,认为这是因为:如上所述,在该时期,由于给予了硅藻土,因此早期的创伤部位的矿化和随后进行的钙化置换得到促进,所以附近的骨钙成分的吸收、溶出和向创伤部位的添加协调地活跃起来。
穿孔手术后第4周(图8C):
体绘制图像:未观察到大的差异,但从整体来看,硅藻土给药组的骨密度较高。
矢状截面图像(图8D):在对照个体中,虽然半圆形凹陷变浅,但整个骨皮质层的厚度仍较薄。下底部的再生骨的骨密度处于与周边部基本同等的水平。另一方面,在硅藻土给药组中,观察到半月形的骨再生部,该骨再生部与半圆形凹陷下底部间有一层边界,骨皮质的厚度也恢复到与周边基本同等的水平,骨密度也处于与周边同等的水平。因此认为,硅藻土给药组的骨的治愈在结构强度方面也恢复到了能承受负荷的水平。
产业上利用的可能性
本发明可以提供不论是在费用方面还是在劳力方面均能以低成本制备的含有对缺陷或缺损的硬组织的再生有用的物质的硬组织再生促进剂、医药组合物、食品组合物、食品、动物用饲料等。
Claims (12)
1.硅藻土在制备硬组织再生促进剂中的应用,所述硬组织为硬骨或者缺陷或缺损深入至牙髓的牙的修复性牙本质。
2.如权利要求1所述的应用,其特征在于,所述硬骨为牙槽骨。
3.如权利要求1或2所述的应用,其特征在于,制备在骨膜下给药的硬组织再生促进剂。
4.如权利要求1或2所述的应用,其特征在于,制备在骨髓腔内给药的硬组织再生促进剂。
5.如权利要求1或2所述的应用,其特征在于,制备口服给药的硬组织再生促进剂。
6.硅藻土在制备治疗硬骨的缺陷或缺损,或者再生缺陷或缺损深入至牙髓的牙的修复性牙本质的药物中的应用。
7.如权利要求6所述的应用,其特征在于,所述药物是骨膜下给药制剂。
8.如权利要求6所述的应用,其特征在于,所述药物是骨髓腔给药制剂。
9.如权利要求7所述的应用,其特征在于,所述药物是口服给药制剂。
10.如权利要求6所述的应用,所述硬骨为牙槽骨。
11.如权利要求6~10中任一项所述的应用,所述硬骨的缺陷或缺损是由拔牙、植入体的埋入和固定、牙内及牙周疾病的病原菌的毒素、感染、骨损坏、吸收或骨折所引起的。
12.如权利要求6~10中任一项所述的应用,所述硬骨的缺陷或缺损是由骨折、植入体的埋入、细菌的毒素或化脓所引起的。
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- 2007-09-21 JP JP2008535422A patent/JP5557448B2/ja not_active Expired - Fee Related
- 2007-09-21 WO PCT/JP2007/069118 patent/WO2008035816A1/ja active Application Filing
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Also Published As
Publication number | Publication date |
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WO2008035816A1 (fr) | 2008-03-27 |
EP2070541A4 (en) | 2011-04-13 |
EP2070541A1 (en) | 2009-06-17 |
JP2012116844A (ja) | 2012-06-21 |
US20100143488A1 (en) | 2010-06-10 |
CN101573127A (zh) | 2009-11-04 |
JPWO2008035816A1 (ja) | 2010-01-28 |
JP5557448B2 (ja) | 2014-07-23 |
KR20090098783A (ko) | 2009-09-17 |
JP5898500B2 (ja) | 2016-04-06 |
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