CN100521972C - 用于促进骨生长及维持骨健康的组合物 - Google Patents
用于促进骨生长及维持骨健康的组合物 Download PDFInfo
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- CN100521972C CN100521972C CNB028245172A CN02824517A CN100521972C CN 100521972 C CN100521972 C CN 100521972C CN B028245172 A CNB028245172 A CN B028245172A CN 02824517 A CN02824517 A CN 02824517A CN 100521972 C CN100521972 C CN 100521972C
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Abstract
本发明涉及用于维持骨健康或预防、减轻和/或治疗骨病的组合物。本发明也涉及组合物在制造营养物、补充物、治疗剂或药物的用途；并涉及促进骨生长或维持骨健康的方法，所述方法包括施用有效量的该组合物。
Description
本发明涉及用于维持骨健康或预防、减轻和/或治疗骨病的组合物。本发明也涉及该组合物在制造营养物、补充物或药物中的用途；并涉及促进骨生长或维持骨健康的方法，所述方法包括施用有效量的组合物。
发明背景
健康的骨需要包括骨形成和吸收间平衡的有效骨再造。大多数骨病归咎于骨吸收增加，致使主要治疗目的是抑制骨吸收的增加，因此迄今为止研发的大多数药剂是抗吸收的。例如，雌激素抑制可促进破骨细胞产生和分化的细胞因子的产生。正在研发对骨健康有益同时降低对乳腺或子宫内膜组织产生激素副作用危险的SERMs(选择性雌激素反应调节剂)。认为它们通过与雌激素类似的机理在骨中起作用。二膦酸盐化合物(如阿伦膦酸盐、利塞膦酸盐等)集中于骨，是迄今为止最有效的骨吸收抑制剂。它们抑制关键的酶途径，该途径是破骨细胞活性和破骨细胞存活需要的。降钙素是通过抑制破骨细胞活性而抑制骨吸收的多肽激素。新的靶包括阻断TNF受体/配体家族成员及它们的信号途径，特别是阻断RANK/RANKL，抑制骨特异的金属蛋白酶如组织蛋白酶K或抑制特异的激酶。
刺激骨形成的治疗剂的研发落后于骨吸收治疗剂的研发。已知一些化学品或药剂促进人的骨生长。例如，WO 9619246描述了通过间歇施用甲状旁腺素、PTH-相关蛋白或激动剂至少一个月促进患者骨生长的方法。在WO 9619501中，来源于胰的因子抑制骨吸收并刺激骨细胞增殖和增加骨形成。
最近的主要突破是证实骨形态发生蛋白2(BMP-2)在刺激骨形成中作为关键因素的作用及他汀类药物(通过抑制胆固醇合成降低胆固醇的有效药)改善骨形成的作用，改善骨形成部分是通过诱导BMP-2而介导。已显示重组BMP-2的递送诱导骨或软骨形成。在US 6150328中，描述了诱导骨和软骨形成的方法，所述方法包括施用通过培养用编码BMP的DNA转化了的细胞产生的经纯化骨形态发生蛋白。并且，WO 9711095涉及骨形态发生蛋白组合物用于治疗神经肿瘤及骨生长和创伤愈合的用途。除了BMPs外，生长因子如胰岛素样GF(IGF-1)、转化GF-β(TGF-β)、成纤维细胞GFs(FGFs)在骨折愈合和骨缺损中的局部治疗法正在研究中。然而由于小肠的代谢及也由于对其它组织可能有作用，全身施用是有问题的。正提议基因治疗作为一种选择。该备选方法是通过饮食或药物调节剂调节成骨细胞的基因或蛋白质表达而靶向对成骨细胞产生的调节。
虽然证明了这些化学品和药物化合物用于骨病的治疗，但通过提供安全、有效的营养方式来促进骨生长并预防、减轻或治疗哺乳动物的骨/关节病仍然是令人感兴趣的。
发明概述
因此，第一方面，本发明提供了用于预防、减轻和/或治疗骨病或维持哺乳动物骨健康的组合物，所述组合物包含经筛选的诱导骨形态发生蛋白表达的至少一种植物或植物提取物的有效量作为活性成分。
值得注意，现在发现一些植物或植物提取物通过调节骨或软骨组织中内源性生长因子具有促进骨生长的能力。它们具有诱导体内及骨局部环境中骨形态发生蛋白表达的能力，这种能力对骨形成和修复、骨健康的维持或预防、减轻和/或治疗骨病有积极效果。
根据本发明的组合物可用于人或宠物的营养物、补充物、治疗剂或药物的生产。
向个体施用本发明的食物组合物导致在骨折愈合期间改善骨再生。本组合物进一步有助于抑制骨吸收。它有助于在生长期间增加骨形成及骨矿物质密度，并优化骨量峰值。并且，本食物组合物有助于降低骨丢失，特别是哺乳动物中与年龄相关的骨丢失。因此它有助于维持与年龄有关的骨量并降低骨质疏松症的危险。
此外，它有助于构建哺乳动物的软骨，预防宠物或人的骨关节炎，从而使个体的活动或移动性更好。
另一方面，本发明涉及根据其刺激骨形态发生蛋白和/或抑制骨吸收的能力而筛选的植物或植物提取物的用途，用于制备维持哺乳动物骨健康并预防、减轻和/或治疗骨病的组合物。
另外，本发明提供了预防、减轻和/或治疗骨病或维持骨健康的方法，其包括施用有效量的上述组合物。
本发明进一步提供了在生长期间增加骨形成、骨矿物质密度并优化骨量峰值、治疗或预防骨质疏松症、在骨折愈合期间刺激骨再生的方法，其包括施用有效量的上述组合物。
本发明进一步涉及治疗、减轻和/或预防宠物和人骨关节炎的方法，其包括个体食用上述组合物的步骤。
进一步提供了对人或宠物降低骨丢失，特别是与年龄相关的骨丢失的方法，其包括个体食用上述组合物的步骤。
发明详述
关于本发明的第一个目的，根据本发明的植物或植物提取物包含通过诱导骨形态发生蛋白表达而具有合成代谢潜力并可进一步为抗吸收剂的植物化学品。
在一个优选的实施方案中，植物或植物提取物来自植物源的任何部分，如叶、块茎、果实、种子、根、颖果、胚或细胞培养物。植物或植物提取物取决于植物源，可为叶、根和/或果实的干的、冷冻干燥提取物形式，或为新鲜植物，或为通过本领域公知的无机溶剂或有机溶剂提取方法获得的浓缩级分。
选择具有抑制骨吸收和/或诱导骨形成能力的植物或植物提取物，特别是它可选自山胡椒属(Lindera)、蒿属(Artemisia)、菖蒲属(Acorus)、红蓝花属(Carthamus)、葛缕子属(Carum)、蛇床子(Cnidium)、唐棣属(Amelanchier)、姜黄属(Curcuma)、蒲公英属(Taraxacum)、莎草属(Cyperus)、刺柏属(Juniperus)、李属(Prunus)、鸢尾属(Iris)、菊苣属(Cichorium)、车桑子属(Dodonaea)、淫羊藿属(Epimedium)、Eriogonum、大豆(Soya)、薄荷属(Mentha)、罗勒属(Ocimum)、百里香属(thymus)、艾菊属(Tanacetum)、车前草属(Plantago)、绿薄荷(Spearmint)、红木属(Bixa)、葡萄属(Vitis)、迷迭香属(Rosemarinus)、艾菊属(Tanacetum)、盐肤木属(Rhus)和莳萝属(Anethum)。它也可为蘑菇。
在一个最优选的实施方案中，它可例如为美国山胡椒(Linderabenzoin)的地上部分，艾蒿(Artemisia vulgaris)的地上部分，菖蒲(Acoruscalamus)的根状茎，红花(Carthamus tinctorius)的种子或花，卵圆形唐棣(Amelanchier ovalis)的果实，桤叶唐棣(Amelanchier alnifolia)的果实，菊苣(Cichorium intybus)的根，姜黄(Curcuma longa)的根状茎，短角淫羊藿(Epimedium brevicornum)的地上部分，Eriogonum giganteum的地上部分，药蒲公英(Taraxacum officinalis)的叶或根，香附子(Cyperusrotondus)的根状茎，车桑子(Dodoneae viscosa)的叶，白鸢尾(Iris pallida)的细胞培养物，德国鸢尾(Iris germanica)、白鸢尾(Iris pallida)或黄鸢尾(Iris pseudacorus)的根状茎，欧洲刺柏(Juniperus communis)的果实，桃(Prunus persica)的种子，大豆细胞培养物，留兰香(Mentha spicata)的地上部分，丁香萝勒(Ocimum gratissimum)的地上部分，百里香种(Thymus sp.)的地上部分，光叶漆(Rhus glabra)的地上部分，茴香(aneth)，红木属，葡萄(Vitis vinifera)的果实，迷迭香(Rosmarinusofficinalis)的地上部分，普通菊蒿(Tanacetum vulgare)的地上部分，葛缕子(Carum carvi)，车前草(Plantago maior)，Oxydendron arboreum的地上部分。
植物化学品可为染料木黄酮、大豆黄素、莴苣苦素、山莴苣苦素(lactucopicrin)、3-脱氧-莴苣苦素、香叶醇或香芹酮。
本发明的植物或植物提取物可用于制备食物组合物。所述组合物可为营养均衡的食物或宠物食物、膳食补充物、治疗剂或药物组合物的形式。
植物或植物提取物可单独应用或与其它植物如菊苣、茶树、可可树联合应用，或与其它生物活性分子如抗氧化剂、脂肪酸、益生素纤维、葡糖胺、硫酸软骨素联合应用。
在一个实施方案中，制备了用于人消费的食物组合物。该组合物可为营养完全配方、乳制品、冷的或常温稳定的饮料、汤、膳食补充物、膳食替代品和营养棒或甜食。
除了根据本发明的植物提取物外，营养配方可包含蛋白质源。优选应用膳食蛋白质作为蛋白质源。膳食蛋白质可为任何合适的膳食蛋白质；例如动物蛋白(如乳蛋白、肉蛋白和卵蛋白)；植物蛋白(如大豆蛋白、小麦蛋白、大米蛋白和豌豆蛋白)；游离氨基酸的混合物；或为它们的组合物。特别优选乳蛋白如酪蛋白、乳清蛋白和大豆蛋白。组合物也可包含碳水化合物源和脂肪源。
如果营养配方包括脂肪源，该脂肪源优选地提供营养配方中的约5％至约55％的能量；如提供约20％至50％的能量。组成脂肪源的脂类可为任何合适的脂肪或脂肪混合物。植物脂肪特别适用；如大豆油、棕榈油、椰子油、红花油、葵花子油、玉米油、芸苔油、卵磷脂等。如果需要，也可加入动物性脂肪如乳脂。
营养配方中可加入碳水化合物源。所述碳水化合物源优选地提供占该营养组合物约40％至约80％的能量。可应用任何合适的碳水化合物，如蔗糖、乳糖、葡萄糖、果糖、玉米糖浆固体和麦芽糖糊精及它们的混合物。如果需要也可加入膳食纤维。如果应用碳水化合物，则其优选地包含占营养配方约5％的能量。膳食纤维可来自任何适当来源，包括如大豆、豌豆、燕麦、果胶、瓜尔胶、阿拉伯胶和果糖寡糖。营养配方中也可包括合适的符合适当指标的维生素和矿物质。
如果需要，可在营养配方中掺入一种或多种食物级乳化剂；如单甘油酯和双甘油酯的二乙酰酒石酸酯、卵磷脂及单甘油酯和双甘油酯。同样地可包括合适的盐和稳定剂。植物提取物也可与维生素和矿物质组合。
优选可经肠施用的营养组合物；如以粉剂、片剂、胶囊剂、液态浓缩剂、固体产品或及喝饮料的形式。如果想生产粉剂营养配方，可将经过匀化加工处理的混合物转移到合适的干燥器如喷雾干燥器或冷冻干燥器并转化为粉剂。
在另一实施方案中，营养组合物包含基于乳的谷类并包含益生素的配方。优选地，基于乳的谷类是作为益生素配方的载体的未成熟谷类。
在另一实施方案中，可用至少一种本发明的植物或植物提取物强化普通食品。如发酵乳、酸奶、新鲜乳酪、凝乳、甜食如糖果或甜饮料、甜条、早餐谷片或条、饮料、奶粉、豆制品、非乳发酵品或用于临床营养的营养补充物。
组合物中植物或植物提取物的量可根据植物源和它的用途而改变。在一个优选的实施方案中，其有效日剂量至少为约1mg活性分子/天，更优选地为从1毫克至200毫克活性分子/天。
在一个实施方案中，可制备包含至少一种上述提取物或植物化学品的药物组合物，该药物组合物的量足可使个体达到预期效应。该组合物可为片剂、液体、胶囊剂、软胶囊剂、糊剂、锭剂、胶剂或可饮用溶液或乳剂、干的经口补充物、湿的经口补充物。药物组合物进一步包含适于向靶组织递送不同性质的各活性分子的载体和赋形剂。载体/赋形剂的种类和其量取决于物质的性质和药物递送和/或施用方式。可以理解熟练人员基于他自己的知识可选择适当的组分和植物剂型。
本发明的植物或植物提取物可用于制备宠物食物组合物。所述组合物可作为宠物正常饮食的补充物或作为营养完全的宠物食物组分施用，并且更优选地在低热量宠物食物中。它也可为药物组合物。
植物或植物提取物可单独应用或与其它植物如菊苣、茶树、可可树联合应用，或与其它生物活性分子如抗氧化剂、脂肪酸、益生素纤维、葡糖胺、硫酸软骨素联合应用。
优选地，宠物食物组合物对于15千克的犬，每克干宠物食物包含约0.01至0.5克干植物；对于15千克的犬，每克湿宠物食物包含约0.001至0.1克干植物。
根据本发明的营养完全的宠物食物可为粉状、干燥形式、治疗剂或为湿的、冷的或常温稳定的宠物食物产品。它可冷冻或作为常温稳定产品提供。这些宠物食物可以本领域公知的方式生产。
宠物食物也可任选包含益生素、益生微生物或其它活性剂，如长链脂肪酸。宠物食物中益生素的量优选占低于10％的重量。例如，所包含的益生素可占宠物食物重量的约0.1％至约5％。对于用菊苣作为益生素来源的宠物食物，所包括的菊苣可占食物混合物重量的约0.5％至10％；更优选地占重量的约1％至约5％。
如果应用益生微生物，宠物食物优选每克宠物食物包含约104至约1010个细胞的益生微生物；更优选每克约106至约108个细胞的益生微生物。宠物食物可包含占约0.5％至约20％重量的益生微生物混合物；优选地占重量的约1％至约6％；例如占重量的约3％至约6％。
如果需要，可向宠物食物添加矿物质和维生素以使它们营养完全。此外，根据需要，也可将多种其它成分如糖、盐、香料、调料、调味剂等掺入到宠物食物中。
在另一实施方案中，可制备膳食添加剂以改善宠物食物的质量。作为膳食添加剂，它们无论是湿的还是干的均可被封入胶囊内或可以粉剂形式提供并与正餐一起包装或单独包装。通过举例的方式，含有本发明提取物的粉末可以粉末形式包装入小袋中或包装到凝胶或脂或其它合适的载体中。根据使用者的要求，这些单独的包装单位可与正餐一起提供或为与正餐或治疗剂一同应用的多单位包装。
为达到有益效果，宠物消费的宠物食物的量取决于宠物的大小、宠物的类型和宠物的年龄。但是，每天提供每千克体重约0.5至5克干植物的宠物食物的量对犬和猫一般是足够的。
对人或动物施用上述食物或宠物食物组合物，导致在骨折愈合期间可改善骨再生。它有助于在生长期间刺激骨形成和骨矿物质密度，并优化骨量峰值。特别是它可在儿童期提供最佳骨生长。该食物组合物有助于预防骨丢失，特别是哺乳动物中与年龄相关的骨丢失或长期住院相关的骨丢失。它降低了骨质疏松症的危险并在骨折后改善恢复。此外，它有助于构建哺乳动物软骨，预防宠物和人的骨关节炎，其导致个体活动或移动性更好。
下列实施例仅以阐述的形式给出，不用于限制本发明的主题。除非另有说明，所有百分数均为重量百分数。实施例之前是对附图的简述。
图1：来自美国山胡椒(P.E.740，50μg/ml))或香附子(P.E.205，10μg/ml)的提取物处理48小时后通过RT-PCR测定hPOB-tert细胞中内源性BMP-2mRNA的表达，并显示它们对BMP-2的刺激分别为对照的3.8倍和2.8倍。本测定法以洛伐他汀(0.5μg/ml)作为阳性对照，洛伐他汀显示了诱导BMP-2为对照的2.5倍。
图2：来自丁香罗勒(738)、桤叶唐棣(734)、大豆(Glycine max)(768)、香附子(205)、红花(746)提取物用颅盖测定法(A)和凹陷测定法(pit assay)(B)所测定的抑制值的比较。
实施例
实施例1：骨形成和骨吸收鉴定法
1.骨形成
对91种提取物进行了筛选，其中通过BMP-2(骨形态发生蛋白)基因报道测定法筛选用于骨形成的提取物，通过颅盖测定法筛选用于骨吸收的提取物。这91种提取物对应于30种不同的植物。
材料与方法
●用于筛选测定法的提取物的制备：
磨碎的植物材料用己烷脱脂，然后用醇和水混合物进行提取，不同的水百分比为从10至90％，优选地用50％的水。醇可用甲醇或乙醇，获得提取物1a。
对该第一提取物的残余部分，用α和β糖苷酶进行酶促水解作用。酶可用酸性条件替代。此操作可在温和条件下(室温)进行或用不同酸浓度通过回流进行。含水的水解相用不互溶的溶剂提取，优选用乙酸乙酯提取获得提取物2a。
提取物可干燥、冷冻干燥或以液体形式提供。
在一些情况下，多酚可通过聚乙烯聚吡咯烷酮(PVPP)处理后丢弃，避免筛选测定的假象。
制备提取物之后，每种提取物进行称重，用二甲基亚砜(DMSO)再溶解至终浓度20mg/ml并分装置于-20℃保存。这作为母液应用并随后用各测定法所使用的培养基进行稀释。测定法系统中对一系列的剂量进行检测。
●骨形成测定法
BMP-2萤光素酶测定法—用包含与萤光素酶基因可操作地连接的BMP-2启动子的2T3细胞测定提取物的活性。细胞裂解物中萤光素酶活性增加反映BMP-2启动子活性的增加。提取物最初稀释成100μg/ml，然后进行1/2稀释至0.2μg/ml，进行测定。BMP-2启动子活性通过测定细胞提取物中萤光素酶活性进行测定。
表1 13种植物在刺激BMP-2表达中得到明显的阳性结果
| 拉丁名 | 英文名 | 部分 | 浓度μg/ml | 活性提取物/n<sup>o</sup> |
| Acorus calamus | 菖蒲 | 根状茎 | 5 | MeOH/水/731 |
| Amelanchier ovalis | 卵圆形唐棣 | 果实 | 10 | MeOH/水/219 |
| Artemisia vulgaris | 艾蒿 | 地上部分 | 10 | 乙酸乙酯/225 |
| Cyperus rotundus | 香附子 | 根状茎 | 10 | 乙酸乙酯/205 |
| Taraxacum officinalis | 药蒲公英 | 叶 | 50 | 乙酸乙酯/750 |
| Lindera benzoin | 美国山胡椒 | 地上部分 | 50 | 乙酸乙酯/740 |
| Prunus persica | 桃 | 种子 | 25 | 乙酸乙酯/772 |
| Glycine max | 大豆 | 细胞培养物 | 50 | 乙酸乙酯/768 |
| Iris pallida | 白鸢尾 | 块茎 | 100 | MeOH/水/239 |
| Rosmarinus officianlis | 迷迭香 | 叶 | 50 | MeOH/水/2004乙酸乙酯/2005 |
| Carvi | 葛缕子 | 种子 | 25 | 乙酸乙酯/2074 |
| Thyme | 百里香 | 叶 | 25 | 乙酸乙酯/2067 |
| Mentha spicata | 薄荷 | 叶 | 100 | 乙酸乙酯/2072 |
| Vitis vinifera | 葡萄 | 果实 | 100 | 乙酸乙酯/2069 |
刺激BMP-2的来自同一植物的新制备物和其亚级分的例子是：美国山胡椒、活性提取物/nO乙酸乙酯/740/2059；活性亚级分/nO2060药蒲公英，活性提取物/nO乙酸乙酯/750/2034；活性亚级分/nO2035香附子，活性提取物/nO乙酸乙酯/205/2011；活性亚级分/nO2012、2013白鸢尾，活性提取物/nOMeOH/水/239；活性亚级分/nO760/762/2021、2022
通过在反相硅胶柱上用极性不同的溶剂洗脱而分级分离制备亚级分。纯大豆异黄酮类中的染料木黄酮和大豆黄素(10-6M)刺激BMP-2而雌二醇不刺激BMP-2。
对BMP-2的诱导作用似乎不限于雌激素样活性，因为它是通过植物雌激素进行刺激而不是通过雌激素本身刺激。这表明植物雌激素(如染料木黄酮和大豆黄素)的活性可通过非雌激素机理介导。BMP-2启动子活性不是通过雌二醇进行刺激的，因此植物化合物的动情作用不是本试验需要的活性。
| 植物 | 活性提取物编号 | 浓度(μg/ml) |
| 大豆 | 乙酸乙酯/2001 | 10、50 |
| 迷迭香 | MeOH/水/2004 | 10、50 |
| 迷迭香 | 乙酸乙酯/2005 | 10 |
| 香附子 | 亚级分/2012 | 10、50 |
| 白鸢尾 | 亚级分/2022 | 10 |
| 百里香 | 乙酸乙酯/2067 | 10 |
| 葛缕子 | 乙酸乙酯/2074 | 10 |
在颅盖器官培养物中骨形成的例子
在科学(Science)286：1946-1949(1999)描述了应用的方法。用体外新生鼠颅盖测定法进行4天试验评估了提取物。骨与提取物孵育了整4天。骨形成通过组织学进行评估。
2.骨吸收，颅盖测定法
在新生骨吸收测定法中评估了提取物抑制IL-1(10-10M)刺激的骨吸收的能力。评估了每种提取物在10μg/ml时抑制骨吸收的能力。在新生骨吸收测定法中评估了实施例1制备的提取物抑制IL-1(10-10M)刺激的骨吸收的能力。评估了每种提取物在10μg/ml时抑制骨吸收的能力。
表2 列出了阳性的植物提取物：
| 拉丁名 | 英文名 | 部分 | 活性提取物/n<sup>o</sup> |
| Amelanchier alnifolia | 唐棣 | 果实 | 乙酸乙酯/734 |
| Ocimum gratissimum | 罗勒种 | 叶 | MeOH/H<sub>2</sub>O/737 |
| Ocimum gratissimum | 罗勒种 | 叶 | 乙酸乙酯/738 |
| Carthamus tinctorius | 红花 | 种子 | 乙酸乙酯/746 |
| Cyperus rotundus | 香附子 | 根状茎 | 乙酸乙酯/205 |
| Glycine max | 大豆 | 细胞培养物 | 768 |
下列植物在骨吸收测定法中有活性：桤叶唐棣、丁香罗勒、红花及大豆。香附子抑制骨吸收并诱导BMP-2。
实施例2：植物提取物对人成骨细胞中内源性BMP-2表达的作用
进一步检测了实施例1中BMP-2诱导阳性的植物在人骨膜/前成骨细胞细胞系hPOB-tert中诱导内源性BMP-2表达的能力。这个在成骨细胞的检测证实了实施例1中显示的结果。
例如，用美国山胡椒(提取物740，50μg/ml)和香附子(提取物205，10μg/ml)的提取物处理hPOB-tert细胞48小时，刺激BMP-2表达为对照的3.8和2.8倍(见图1)。用洛伐他汀(0.5μg/ml)作为阳性对照显示其诱导BMP-2为对照的2.5倍，从而验证了本测定法。
细胞长成单层后，细胞与0.05μg/ml的洛伐他汀孵育或与植物提取物孵育。用TRIzol试剂(Gibco)提取总RNA。用第一链cDNA合成试剂盒(Boehringer)对10μg RNA进行反转录。BMP-2cDNA序列用特异寡核苷酸引物(5′：TTGCGGCTGCTCAGCATGTT；3′：CATCTTGCATCTGTTCTCGGAA)在退火温度为55℃的条件下进行35个循环进行扩增。PCR产物通过琼脂糖凝胶电泳进行分离并用溴化乙锭染色进行检测。用NIH图象软件进行定量并用肌动蛋白作为管家基因对结果进行校正。
结果在图1显示。
骨吸收
在颅盖测定法中阳性的植物提取物在骨吸收的第二种测定法中再进行检测，第二种测定法即用在牛骨切片上培养的兔骨混合细胞的凹陷测定法(Tezuka K等人，1992，Biochem.Biophys.Res.Commun.186(2)：911-7和Lorget F.等人，2000，Biochem.Biophys.Res.Commun.268(3)：899-903)。吸收凹陷通过TRAP(酒石酸抗性的酸性磷酸酶)染色进行观察。观察阳性细胞并计数。
图2显示了两种测定系统对10μg/ml提取物测得的活性的比较
实施例3：干宠物食物
饲料混合物由占约58％重量的玉米、占约5.5％重量的玉米麸、占约22％重量的鸡食、2.5％干菊苣、约10％香附子块茎组成，盐、维生素和矿物质组成其余部分。
饲料混合物装入预调节器中并弄湿。然后将湿饲料装入挤压机-炊具中并弄成胶状。离开挤压机的胶状基质通过模具挤压并压出。压出物切成合适的饲喂犬的小块，110℃干燥约20分钟，并冷却形成小块。
该干燥物食对骨和软骨健康有积极效果并增加犬的活动性。
实施例4：有补充物的湿罐装宠物食物
由73％禽尸体、猪肺和牛肝(磨碎)、16％小麦面粉、2％染料、维生素和无机盐制备混合物。混合物在12℃乳化并压挤成布丁形式，然后在90℃烹熟。冷却至30℃并切成大块。45％的这些大块与55％调味料混合，所述调味料由98％水、1％染料和1％瓜尔胶制成。装入马口铁罐中并125℃消毒40分钟。
作为饲养前与该宠物食物混合的补充物，其所在的额外包装(小袋)中包含25克粉状香附子地上部分，用于添加至日常食物中。对于宠物的对应量为约25克/天，并且这可作为罐头的补充物(如在罐头上面)供应。
Claims (12)
1.用于人和宠物预防、减轻和/或治疗骨病和维持骨健康的食物组合物，所述组合物包含作为活性成分的有效量的至少一种植物或植物提取物，植物或植物提取物选自美国山胡椒(Lindera benzoin)的地上部分，艾蒿(Artemisia vulgaris)的地上部分，菖蒲(Acorus calamus)的根状茎，红花(Carthamus tinctorius)的种子或花，卵圆形唐棣(Amelanchier ovalis)的果实，桤叶唐棣(Amelanchier alnifolia)的果实，菊苣(Cichoriumintybus)的根，姜黄(Curcuma longa)的根状茎，短角淫羊藿(Epimediumbrevicornum)的地上部分，Eriogonum giganteum的地上部分，药蒲公英(Taraxacum officinalis)的叶或根，香附子(Cyperus rotondus)的根状茎，车桑子(Dodoneae viscosa)的叶，白鸢尾(Iris pallida)的细胞培养物，德国鸢尾(Iris germanica)、白鸢尾(Iris pallida)或黄鸢尾(Irispseudacorus)的根状茎，欧洲刺柏(Juniperus communis)的果实，桃(Prunus persica)的种子，留兰香(Mentha spicata)的地上部分，丁香萝勒(Ocimum gratissimum)的地上部分，百里香种(Thymus sp.)的地上部分，光叶漆(Rhus glabra)的地上部分，茴香(aneth)，红木属，葡萄(Vitis vinifera)的果实，迷迭香(Rosmarinus officinalis)的地上部分，普通菊蒿(Tanacetum vulgare)的地上部分，葛缕子(Carum carvi)，车前草(Plantago major)，Oxydendron arboreum的地上部分，所述植物或植物提取物含有植物化学品莴苣苦素、山莴苣苦素、3-脱氧-莴苣苦素、香叶醇或香芹酮。
2.根据权利要求1的组合物，其中所述植物或植物提取物还抑制骨吸收。
3.根据权利要求1或2所述的组合物，所述组合物为营养均衡的食物或宠物食物、膳食补充物、治疗剂或药物组合物的形式。
4.根据权利要求1或2所述的组合物在制备食品中的用途，所述食品对人或宠物在骨折愈合期间有助于骨再生，在生长期间有助于增加骨形成及骨矿物质密度，并优化骨量峰值或减少骨丢失。
5.根据权利要求4中所述的用途，其中所述骨丢失是与年龄相关的骨丢失。
6.根据权利要求4或5中所述的用途，其中所制备的食品有助于构建人或宠物的软骨。
7.根据权利要求4或5中所述的用途，其中所制备的食品有助于预防人或宠物的骨关节炎。
8.包含具有刺激骨形态发生蛋白和/或抑制骨吸收能力的植物化学品的植物或植物提取物在制备对人或宠物预防、减轻和/或治疗骨病或维持骨健康的食物或宠物食物组合物中的用途，其中所述植物和植物提取物选自美国山胡椒(Lindera benzoin)的地上部分，艾蒿(Artemisia vulgaris)的地上部分，菖蒲(Acorus calamus)的根状茎，红花(Carthamus tinctorius)的种子或花，卵圆形唐棣(Amelanchier ovalis)的果实，桤叶唐棣(Amelanchier alnifolia)的果实，菊苣(Cichorium intybus)的根，姜黄(Curcuma longa)的根状茎，短角淫羊藿(Epimedium brevicornum)的地上部分，Eriogonum giganteum的地上部分，药蒲公英(Taraxacumofficinalis)的叶或根，香附子(Cyperus rotondus)的根状茎，车桑子(I)odoneae viscosa)的叶，白鸢尾(Iris pallida)的细胞培养物，德国鸢尾(Iris germanica)、白鸢尾(Iris pallida)或黄鸢尾(Iris pseudacorus)的根状茎，欧洲刺柏(Juniperus eommunis)的果实，桃(Prunus persica)的种子，留兰香(Mentha spicata)的地上部分，丁香萝勒(Ocimumgratissimum)的地上部分，百里香种(Thymus sp.)的地上部分，光叶漆(Rhus glabra)的地上部分，茴香(aneth)，红木属，葡萄(Vitis vinifera)的果实，迷迭香(Rosmarinus officinalis)的地上部分，普通菊蒿(Tanacetumvulgare)的地上部分，葛缕子(Carum carvi)，车前草(Plantago major)，Oxydendron arboreum的地上部分，所述植物化学品选自莴苣苦素、山莴苣苦素、3-脱氧-莴苣苦素、香叶醇或香芹酮。
9.根据权利要求8的用途，其中组合物为如权利要求1至3中任一项所述。
10.根据权利要求8或9的用途，其中植物或植物提取物单独应用或与其它植物联合应用，或与其它生物活性分子联合应用。
11.根据权利要求10的用途，其中所述其它生物活性分子为抗氧化剂、脂肪酸、益生素纤维、葡糖胺、硫酸软骨素。
12.根据权利要求10的用途，其中所述其它植物为菊苣、茶树、可可树。
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