CN1278710C - 关节炎的预防剂或治疗剂 - Google Patents
关节炎的预防剂或治疗剂 Download PDFInfo
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- CN1278710C CN1278710C CNB028120256A CN02812025A CN1278710C CN 1278710 C CN1278710 C CN 1278710C CN B028120256 A CNB028120256 A CN B028120256A CN 02812025 A CN02812025 A CN 02812025A CN 1278710 C CN1278710 C CN 1278710C
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Abstract
本发明涉及含有属于虎耳草科植物的植物体或该植物体提取物作为有效成分的关节炎的预防剂或治疗剂,添加属于虎耳草科植物的植物体或该植物体提取物制成的饮食品或饲料,使动物摄取该关节炎的预防剂或治疗剂、或饲料的动物的关节炎的预防方法或治疗方法,以含有属于虎耳草植物的植物体或该植物体提取物作为有效成分的关节炎的预防或治疗用饮食品或饲料。通过摄取本发明的虎耳草提取物可以抑制关节炎的发病。
Description
技术领域
本发明涉及关节炎的预防剂或治疗剂、具有关节炎预防作用或治疗作用的饮食品或饲料、具有关节炎预防作用或治疗作用的饮食品用添加剂或饲料用添加剂以及动物关节炎的预防方法或治疗方法。
背景技术
属于虎耳草科的鸦嘴大叶绣球(
Hydrangea
macrophylla Seringevar.Thunbergii Makino)是绣球花邻域种,据说是在江户时代野绣球花(
Hydrangea
macrophylla SER var.acuminata)培育出来的。甜茶(Hydrangeae Dulcis Folium)是采集鸦嘴大叶绣球叶部、技尖经发酵后干燥处理调制的。
该甜茶或甜茶提取物从前一直作为丸剂等矫味(甜味)剂和口腔清凉剂的原料使用。甜茶水提取物以液体或粉末形态被用作甜味料。甜味成分是甜菜内酯。
已知甜茶具有抗球虫活性、抗霉活性、抗溃疡活性、抗过敏活性、高胆固醇血症抑制作用、抗牙周病菌作用及抗氧化作用等(第二届药物与食物专题讨论会演讲要旨集,85页,1999年)。另外已知甜茶提取物显示利胆作用(药学杂志,114卷6号,401-413页,1994年)。再有,已知甜茶提取物在体外培养显示肝微粒体的脂质过氧化反应的抑制作用(Natural Medicines,49(1),84-87页,1995年)。
虎耳草科虎耳草(
Saxifraga
stolonifera Meerb.)是在山中阴湿的岩石面上等地方群生的多年生草。据说虎耳草的叶自古无论日本和中国作为民间药之一,揉、烤后贴在患处有治疗火伤的效果。另外,叶子也供食用。
虎耳草或其提取物作为美白、防止皮肤老化、预防褐斑及雀斑等化妆品来使用。
已知虎耳草具有美白作用(特许第2749218号)、抗紫外线诱发突变作用(特许第1851704号)、除臭作用(特许第2015731号)、睾酮-5α-还原酶阻碍作用(特开平5-17365号)、抗氧化作用(特开平10-46142号)及抑制组胺游离产生抗炎症作用(特开平4-346911号)等。
但是,甜茶、虎耳草等属于虎耳草科的植物所具有关节炎的预防或治疗作用还未被知晓。
发明内容
本发明的课题是提供关节炎的预防剂或治疗剂、具有关节炎的预防作用或治疗作用的饮食品或饲料、具有关节炎的预防作用或治疗作用的饮食品用添加剂或饲料用添加剂及动物的关节炎预防方法或治疗方法。
本发明涉及以下(1)-(46)。
(1)关节炎的预防剂或治疗剂,其特征在于,把含有属于虎耳草科植物的植物体或该植物体提取物作为有效成分。
(2)前述(1)所述的关节炎的预防剂或治疗剂,其中属于虎耳草科的植物是属于虎耳草属的植物。
(3)前述(2)所述的关节炎的预防剂或治疗剂,其中属于虎耳草属的植物是虎耳草(
Saxifraga
stolonifera Meerb.)。
(4)前述(1)所述的关节炎的预防剂或治疗剂,其中属于虎耳草科的植物是属于绣球花属的植物。
(5)前述(4)所述的关节炎的预防剂或治疗剂,其中属于绣球花属的植物是鸦嘴大叶绣球(
Hydrangea
macrophylla Seringe var.Thunbergii Makino)。
(6)前述(1)-(5)的任何一项所述的关节炎的预防剂或治疗剂,其中属于虎耳草科的植物的植物体提取物是属于虎耳草科的植物的植物体水性介质提取物残渣的醇提取物。
(7)前述(1)-(6)的任何一项所述的关节炎的预防剂或治疗剂,其中,关节炎是指慢性风湿性关节炎。
(8)前述(1)-(7)的任何一项所述的关节炎的预防剂或治疗剂,其是口服给药的。
(9)添加属于虎耳草科植物的植物体或该植物体提取物制成的饮食品。
(10)前述(9)所述的饮食品,其是用于关节炎的预防或治疗的饮食品。
(11)前述(9)或(10)所述的饮食品,其中属于虎耳草科的植物是属于虎耳草属的植物。
(12)前述(11)所述的饮食品,其中属于虎耳草属的植物是虎耳草(
Saxifraga
stolonifera Meerb.)。
(13)前述(9)或(10)所述的饮食品,其中属于虎耳草科的植物是属于绣球花属的植物。
(14)前述(13)所述饮食品,其中属于绣球花属的植物是鸦嘴大叶绣球(
Hydrangea
macrophylla Seringe var.Thunbergii Makino)。
(15)前述(9)-(14)的任何一项所述的饮食品,其中属于虎耳草科植物的植物体提取物是属于虎耳草科植物的植物体的水性介质提取物残渣的醇提取物。
(16)添加属于虎耳草科植物的植物体或该植物体提取物制成的饲料。
(17)前述(16)所述的饲料,其是用于关节炎的预防或治疗的饮食品。
(18)前述(16)或(17)所述的饲料,其中,属于虎耳草科的植物是属于虎耳草属的植物。
(19)前述(18)所述的饲料,其中,属于虎耳草属的植物是虎耳草(
Saxifraga
stolonifera Meerb.)。
(20)上述(16)或(17)所述的饲料,其中,属于虎耳草科的植物是属于绣球花属的植物。
(21)上述(20)所述的饲料,其中,属于绣球花属的植物是鸦嘴大叶绣球(
Hydrangea
macrophylla Seringe var.Thunbergii Makino)。
(22)上述(16)-(21)的任何一项所述的饲料,其中,属于虎耳草科植物的植物体提取物是属于虎耳草科植物的水性介质提取物残渣的醇提取物。
(23)具有关节炎的预防或治疗作用的饮食品用添加剂,其特征在于,含有属于虎耳草科植物的植物体或该植物体提取物。
(24)上述(23)所述的饮食品用添加剂,其中,属于虎耳草科的植物是属于虎耳草属的植物。
(25)上述(24)所述的饮食品用添加剂,其中,属于虎耳草属的植物是虎耳草(
Hydrangea stolonifera Meerb.)。
(26)上述(23)所述的饮食品用添加剂,其中,属于虎耳草科的植物是属于绣球花属的植物。
(27)上述(26)所述的饮食品用添加剂,其中,属于绣球花属的植物是鸦嘴大叶绣球(
Hydrangea
macrophylla Seringe var.ThunbergiiMakino)。
(28)上述(23)-(27)的任何一项所述的饮食品用添加剂,其中属于虎耳草科植物的植物体提取物是属于虎耳草科植物的植物体的水性介质提取物残渣的醇提取物。
(29)具有关节炎的预防或治疗作用的饲料用添加剂,其特征在于,含有属于虎耳草科植物的植物体或该植物体提取物。
(30)上述(29)所述的饲料用添加剂,其中,属于虎耳草科的植物是属于虎耳草属的植物。
(31)上述(30)所述的饲料用添加剂,其中,属于虎耳草属的植物是虎耳草(
Saxifraga
stolonifera Meerb.)。
(32)上述(29)所述的饲料用添加剂,其中,属于虎耳草科的植物是属于绣球花属的植物。
(33)上述(32)所述的饲料用添加剂,其中,属于绣球花属植物是鸦嘴大叶绣球(
Hydrangea
macrophylla Seringe var.ThunbergiiMakino)。
(34)上述(29)-(33)的任何一项所述的饲料用添加剂,其中,属于虎耳草科植物的植物体提取物是属于虎耳草科植物体的水性介质提取物残渣的醇提取物。
(35)动物关节炎的预防方法或治疗方法,其特征在于,把上述(1)-(7)的任何一项所述的关节炎的预防剂或治疗剂给与动物,或者使动物摄取上述(16)-(22)的任何一项所述的饲料。
(36)上述(35)所述方法,其中动物是宠物或家畜。
(37)关节炎的预防或治疗作用的饮食品或饲料,其特征在于,含有属于虎耳草科植物的植物体或该植物体提取物作为有效成分。
(38)上述(37)所述的关节炎的预防或治疗用饮食品或饲料,其中,属于虎耳草科植物体的植物是属于虎耳草属的植物。
(39)上述(38)所述的关节炎的预防或治疗用饮食品或饲料,其中,属于虎耳草科的植物是虎耳草(
Saxifraga
stolonifera Meerb.)。
(40)上述(37)所述的关节炎的预防或治疗用饮食品或饲料,其中,虎耳草科植物体的植物是属于绣球花属的植物。
(41)上述(40)所述的关节炎的预防或治疗用饮食品或饲料,其中,属于绣球花属的植物是鸦嘴大叶绣球(
Hydrangea
macrophyllaSeringe var.Thunbergii Makino)。
(42)上述(37)-(41)的任何一项所述的关节炎的预防或治疗用饮食品或饲料,其中,属于虎耳草科植物体的植物体提取物是属于虎耳草科植物的植物体水性介质提取物残渣的醇提取物。
(43)属于虎耳草科植物的植物体或该植物体提取物在制造关节炎的预防剂或治疗剂中的使用。
(44)属于虎耳草科植物的植物体或该植物体提取物在制造具有关节炎的预防或治疗作用的饮食品或饲料中的使用。
(45)属于虎耳草科植物的植物体或该植物体提取物在制造具有关节炎的预防或治疗作用的饮食品用添加剂或饲料用添加剂中的使用。
(46)关节炎的预防或治疗方法,其特征在于,给与属于虎耳草科植物的植物体或该植物体提取物。
具体实施方式
本发明中所谓属于虎耳草科的植物是意味着属于虎耳草科(Saxifragaceae)的植物[牧野新日本植物图鉴(第40版,昭和59年,北隆馆),原色牧野植物大图鉴续编(初版,昭和58年,北隆馆)]。
属于虎耳草科的植物可举出,例如落新妇(Astilbe)属、鬼灯擎(Rodgersia)属、虎耳草(Saxifraga)属、峨屏草(Tanakaea)属、槭叶草(Aceriphyllum)属、八幡草(Boykinia)属、金腰子(Chrysosplenium)属、黄水枝(Tiarell)属、唢呐草(Mitella)属、梅花草(Parnassia)属、山梅花(Philadelphus)属、溲疏(Deutzia)属、蛛网萼(Platycrater)属、绣球花(Hydrangea)属、钻地风(Schizophragma)属、草绣球(Cardiandra)属、银梅草(Deinanthe)属、老鼠刺(Itea)属、茶藨子(Ribes)属及黄山梅(Kirengeshoma)属植物以及由这些植物育种的植物品种等,优选属于绣球花属、虎耳草属的种和为增强关节炎的预防或治疗作用由这些种育种的植物品种。
属于落新妇属的种可举出,例如小叶落新妇(
Astilbe
microphyllaKnoll)、童氏落新妇(
Astilbe
thunbergii Miq.)、牙叶落新妇(
Astilbe odontophylla Miq.)、泡盛落新妇(
Astilbe
japonica Miq.)及单叶落新妇(
Astilbe simplicifolia Makino)等。
属于鬼灯擎属的种,可举例日本鬼灯擎(
Rodgersia podophyllaA.Gray)等。
属于虎耳草属的种,可举例,虎耳草(
Saxifraga
stoloniferaMeerb.)、日本本州虎耳草(
Saxifraga
nipponica Makino)、华中虎耳草(
Saxifraga
fortunei Hook.)、大字草(
Saxifraga
CortusaefoliaSieb.et Zucc.)、日本虎耳草(
Saxifraga
japonica Boiss.)、黑云草(
Saxifraga
fusca Maxim)、仙台虎耳草(
Saxifraga
sendaicaMaxim,var.laciniata Nakai)、云间草(
Saxifraga
merkiiFisch.var.idsuroei Engl.)、条裂虎耳草(
Saxifraga
laciniata Nakaiet Takeda)、细支虎耳草(
Saxifraga
bronchialalis L.)、点头虎耳草(
Saxifraga
cernua L.)及山花草(
Saxifraga
sachalinensis Fr.Schem.)等,其中优选虎耳草(
Saxifraga
stolonifera Meerb.)。
属于峨屏草属的种,可举例峨屏草(Tanakaea radicans Franch.etSav.)等。
属于槭叶草属的种,可举例槭叶草(
Aceriphyllum rossii Engler)等。
属于八幡草属的种,可举例岚草(
Boykinia
lycoctonifolia Engl.)、八幡草(
Boykinia
tellimoldes Engl.et Irmsch.)等。属于金腰属的种,可举例金腰子(
Chrysosplenium
grayanum Maxim.)、花金腰(
Chrysosplenium
stamineum Franch)、日本金腰(
Chrysosplenium japonicum Makino)、鞭状金腰(
Chrysosplenium
flagelliferumFr.Schem.)、大百部金腰(
Chrysosplenium
macrostemon Maxim.)、球金腰(
Chrysosplenium
sphaerospermum Maxim.)等。
属于黄水枝属的种,可举例黄水枝(
Tiarella
polyphylla Don)等。
属于唢呐草属的种,可举例唢呐草(
Mitella
japonica Miq.)、少花唢呐草(
Mitella
pauciflora Rosend.)等。
属于梅花草属的种,可举例梅花草(
Parnassia
palustris L)、姬梅花草(
Parnassia
alpicola Makino)、白须草(
Parnassia
foliosaHook.f.et Thoms.var.nummularia Nakai)等。
属于山梅花属的种,可举例出梅花(
Philadelphus
satsumi Sieb.)等。
属于溲疏属的种,可举例溲疏(
Deutzia
crenata Sieb.et Zucc.)、西博氏溲疏(
Deutzia
sieboldiana Maxim.)、姬溲疏(
Deutzia
gracilisSieb.et.Zucc.)、马克西莫氏溲疏(
Deutzia
maximowicziana Makino)、单花溲疏(
Deutzia
uniflora Shirai)、兰姬溲疏(
Deutzia
gracilisSieb.et Zucc.var.nagurai Makino)等。
属于蛛网萼属的种,可举例蛛网萼(
Platycrater
serrata Makino)等。
属于绣球花属的种,可举例,花被绣球(
Hydrangea
macrophyllaSeringa)、绣球(
Hydrangea
macrophylla Seringe var.otaksa Makino)、锯齿绣球(
Hydrangea
macrophylla Seringe Subsp.serrata Makinovar.japonica Makino)、细尖绣球(
Hydrangea
macrophylla Seringevar.acuminata)、鸦嘴大叶绣球(
Hydrangea
macrophylla Seringevar.Thunbergii Makino)、攀缘绣球(
Hydrangea
scandens Seringe)、多毛绣球(
Hydrangea
hirta Sieb.et Zucc.)、总苞绣球(
Hydrangea involucrate Sieb.)、四国绣球(
Hydrangea
sikokiana Maxim.)、圆锥绣球(
Hydrangea
paniculata Sieb.)、叶柄绣球(
Hydrangea
petiolarisSieb.et Zucc.)、姬绣球(
Hydrangea
macrophylla Seringesubsp.serrata Makino var.amoena Makino)、狭缩绣球(
Hydrangea macrophylla Seringe subsp.serrata Makino var.angustata Makino)等。其中优选鸦嘴大叶绣球。
属于钻地风属的种,可举例钻地风(
Schizophragma
hydrangeoidesSieb.et Zucc.)等。
属于草绣球属的种,可举例草绣球(
Cardiandra
alternifoliaSieb.et Zucc.)等。
属于银梅草属的种,可举例银梅草(
Deinanthe
bifida Maxim.)等。
属于老鼠刺属的种,可举例老鼠刺(
Itea
japonica Oliver)等。
属于茶藨子属的种,可举例茶藨子(
Ribes
sinanense F.MaeKawa)、欧洲醋栗(
Ribes
grossularia L.)、宽叶茶藨子(
Ribes
latifoliumJancz.)、红醋栗(
Ribes
rubrum L.)、日本茶藨子(
Ribes
japonicumMaxim.)、糖茶藨子(
Ribes
sachalinense Nakai)、簇花茶藨子(
RibesV fasciculatum Sieb.et Zucc.)、高山茶藨子(
Ribes
alpinumL.var.Japonicum Maxim.)、四川蔓茶藨子(
Ribes
ambigunm Maxim.)等。
属于黄山梅属的种,可举例黄山梅(
Kirengeshoma
Palmata Yatabe)等。
作为本发明的植物体,可举出例如野生植物体、栽培得到的植物体或通过组织培养等培养得到的植物体的例如叶、花、枝、茎、果实、根、种子、培养的细胞、器官或组织等,也可举出把这些东西原样或经物理、化学或生物处理得到的各种处理物等。
作为物理、化学处理方法,可举例如阳光干燥、风干等干燥处理,冷冻干燥处理与粉碎处理等,作为物理、化学处理物,可举干燥处理物、冷冻干燥处理物与粉碎处理物等。作为生物处理方法,可举发酵方法等,作为生物处理物可举发酵处理物。
本发明使用的植物体优选发酵处理得到的发酵处理物,优选上述把鸦嘴大叶绣球经发酵处理得到的甜茶(Hydrangeae Dulcis Folium)。
作为植物提取物,可举通过各种提取方法从上述植物体得到的提取物。作为提取方法可举出,例如,各种溶剂的提取、超临界流体提取等。提取物可通过沉降分离、滤饼过滤、澄清过滤、离心过滤、离心沉降、压榨分离、压滤等各种固液分离方法,各种浓缩方法,各种干燥方法,造粒或粉末化等制剂化方法以及各种精制方法等进行处理。作为精制方法,可举例如溶剂划分法、柱色谱法及重结晶法等。
尤其优选用ダイヤイオン离子HP-20(三菱化学公司制)、葡聚糖凝胶LH-20(フアルマシア公司制)等各种载体的柱色谱法。
作为浓缩及干燥方法,可举出冷冻干燥、自然干燥、热风干燥、通风干燥、送风干燥、喷雾干燥、减压干燥、阳光干燥、真空干燥、流化床干燥、泡沫干燥、鼓式干燥等的薄膜干燥法、超声波干燥、电磁波干燥等的干燥方法,其中优选喷雾干燥方法及冷冻干燥方法。
在提取及提取物处理时,例如也可以添加抗氧化剂和保存剂等。
作为用于溶剂提取的溶剂,只要能够提取具有本发明关节炎的预防或治疗剂作用物质的溶剂,任何溶剂均可以用,可举例,水、无机盐水溶液、缓冲液等水性介质,甲醇、乙醇、丙醇、丁醇等一元醇,丙二醇、丙三醇等多元醇,己烷、甲苯、石油醚、苯、醋酸乙酯、氯仿、二氯甲烷、1,1,2-三氯乙烯、二甲基亚砜、丙酮等有机溶剂等,其中优选水性介质、醇等。
作为缓冲液,可举例磷酸缓冲液、柠檬酸缓冲液等。作为无机盐水溶液的无机盐,可举例氯化钠、氯化钾、氧化钙等。
作为醇优选一元醇,作为一元醇优选乙醇。
作为水,可举自来水、蒸馏水、去离子水、纯水等。
在由含有效成分的植物体提取有效成分时,优选使用饮食品或饲料所容许的溶剂,作为那样的溶剂,可举例水或含水或者无水乙醇等。
这些溶剂可以单独或多数混合使用。在混合溶剂中,优选含水醇,更优选含水一元醇,尤其优选含水乙醇。含水率优选70%以下,更优选40%以下。
作为溶剂,也可以用超临界流体化的二氧化碳。
至于提取,例如对植物体1重量份,用溶剂0.1重量份-10000重量份,优选用1重量份-100重量份进行。提取温度并没有特别规定,但是例如优选0℃-100℃,更优选20℃-90℃。提取时间并没有特别规定,但是例如优选1分钟-1周,更优选30分钟-1日。
含有有效成分的提取液是从含有有效成分的植物体中在能够提取有效成分的条件下以各种溶剂提取、超临界流体提取等方法得到,但是将该提液再以有效成分被提取的条件进行各种溶剂提取、超临界流体提取得到也可以。另外,在从该植物体有效成分未能提取或难提取的条件下把通过各种溶剂提取、超临界流体提取等提取得到的提取残渣等再在有效成分被提取的条件下用各种溶剂提出、超临界流体提取等提取方法调制亦可。
尤其是从属于绣球花属植物的植物体提取时,把属于绣球花属植物的植物体或该植物体的物理、化学处理物或者生物处理物经用水性介质提取后得到的残渣(以下,称水性介质提取残渣)优选用醇或者含水醇或丙酮提取的方法。
作为水性介质,并没有特别规定,但优选是水。用水性介质及醇或含有醇或者丙酮提取时温度,优选例如0℃-100℃,更优选20℃-90℃。提取时间并没有特别规定,但例如优选1分钟-1周,更优选30分钟-1天。另外,作为虎耳草植物体优选用干燥处理过的。水性介质提取残渣可以通过把虎耳草植物体用水性介质提取后通过过滤等除去水性介质后得到的。
提取使用的机器并没有特别规定,但是,可举出设法提高提取效率的容器、搅拌机、回流冷却器、索壳斯累特提取机、匀质器、振荡机及超声波发生装置等。
适用于本发明的关节炎无特别规定,可以是衣原体关节炎、慢性吸收性关节炎、肠疾患性关节炎、淋菌性关节炎、痛风关节炎、慢性风湿症后关节炎、幼年性关节炎、莱姆性关节炎、尿黑酸尿性关节炎、化脓性关节炎、变形性关节炎、肩周关节炎、过度运动负荷引起的关节炎、慢性风湿性关节炎等中的任一个,尤其对慢性风湿性关节炎更有效。
对于本发明的关节炎的预防剂或治疗剂、饮食品、动物用饲料、食品添加剂及饲料添加剂表示如下。
(1)关节炎的预防剂或治疗剂,其特征在于,含有属于虎耳草科植
物的植物体或该植物体提取物作为有效成分。
本发明的以含有属于虎耳草科的植物体或该植物体提取物作有效成分为特征的关节炎的预防剂或治疗剂,含有上述方法调制的属于虎耳草科植物的植物体或其提取物,也可以按照需要含有药理学上容许的一种或多种载体,还可以根据需要含有为预防或治疗其他疾病的有效成分。另外,在本发明关节炎的预防或治疗剂中,也可以添加关节炎的预防或治疗有效的任何其他成分。
作为关节炎的预防或治疗有效的其他成分(以下,简称其他有效成分),举出如下,例如,硼、钙、铬、铜、镁、锰、硒、硅、锌、S-腺苷尿氨酸、胶原、胶原水解物、明胶、明胶水解物、菠萝蛋白酶、胰蛋白酶、胰凝乳蛋白酶、木瓜酶、芦丁、类胡萝卜素、抗氧化维生素、γ-亚麻酸、二十碳五烯酸、乳香、辣椒素、猫瓜木、猫瓜、龙牙草、生姜、鱼藤、烟酰胺、鲨鱼软骨、姜黄、姜黄素等。这些成分可以是精制品,也可以是该成分含有物或提取物。
本发明关节炎的预防剂或治疗剂,是将属于虎耳草科植物的植物体或该植物体提取物按照需要与其他有效成分、和药理学上容许的一种或多种载体一起混合,在制剂学技术领域众所周知的任意方法进行制造。
本发明关节炎的预防剂或治疗剂的给药途径,优选使用对关节炎的预防或治疗有效的途径,可举例如口服给药或静脉内给药等非口服给药。
作为给药剂型,可例举片剂、散剂、颗粒剂、丸剂、混悬剂、乳剂、浸剂、胶囊剂、糖浆剂、注射剂、水剂、酏剂、浸膏剂、酊剂、流浸膏剂等。
适合于口服给药的例如浸膏剂、酊剂、流浸膏剂等,是把属于虎耳草科植物的植物体,用例如水、乙醇或水与乙醇混合液等提取得到的提取物直接或经浓缩调制得到。
适合口服给药的例如像糖浆剂那样的液体调制物可以使用水、蔗糖、山梨醇、果糖等糖类,聚乙二醇、丙二醇等乙二醇类,芝麻油、橄榄油、大豆油等油类等稀释剂,对羟基苯甲酸酯类等防腐剂,对羟基苯甲酸甲酯、对羟基苯甲酸衍生物、苯甲酸钠等保存剂,草莓香料、薄荷等香料等制造的。
另外,适合口服给药的片剂、散剂及颗粒剂等可以使用乳糖、白糖、葡萄糖、蔗糖、甘露糖醇、山梨糖醇等糖类,马铃薯、小麦、玉米等淀粉,碳酸钙、硫酸钙、碳酸氢钠、氯化钠等无机盐,结晶纤维素、甘草粉、龙胆粉等植物粉末等赋形剂,淀粉、琼脂、明胶粉末、结晶纤维素、羧甲醚纤维素钠、羧甲醚纤维素钙、碳酸钙、碳酸氢钠、褐藻酸钠等崩解剂,硬脂酸镁、滑石、氢化植物油、聚乙二醇、硅油等润滑剂,聚乙烯醇、羟丙基纤维素、甲基纤维素、乙基纤维素、羧甲醚纤维素、明胶、淀粉糊液等粘合剂,脂肪酸酯等表面活性剂,甘油等增塑剂等制造的。
适合非口服给药的制剂优选由含有与接受者血液等渗的活性化合物的灭菌水性制剂组成。例如,注射剂的场合,使用由盐溶液,葡萄糖溶液或盐水与葡萄糖溶液混合物组成的载体等调制注射用溶液。
另外,在这些非口服制剂中也可以添加由口服制剂中例示的稀释剂、防腐剂、保存剂、香料类、赋形剂、崩解剂、润滑剂、粘合剂、表面活性剂、增塑剂等中选择1种或多种补助成分。
本发明关节炎的预防剂或治疗剂的给药剂量及给药次数,虽然与给药形态,患者年龄、体重、要治疗的症状性质或轻重不同而各异,但是,通常口服给药的场合,对成年人每人给药属于虎耳草科植物的植物体干燥重量或该植物体提取物干燥重量优选1mg-50g,更优选5mg-10g,一日一次至数次。静脉内给药等非口服给药场合,对成年人每人给药属于虎耳草科植物的植物体干燥重量或该植物体提取物干燥重量优选0.001-50g,更优选0.01-10g,一日一次至数次。
通过本发明关节炎预防剂的日常给药,可以预防关节炎。关节炎已发病的场合,通过本发明关节炎治疗剂的日常给药能缓解、治愈等,可以治疗关节炎。本发明关节炎的预防剂或治疗剂的给药期间一般1周-10年,优选1个月-5年。
再者,本发明关节炎的预防剂或治疗剂,不只对人,而且对除人之外动物也可以使用。对动物使用时的给药量虽未特别规定,但是以属于虎耳草科植物的植物体干燥重量或该植物体提取物干燥重量优选0.01-50g/kg,更优选0.05-10g/kg。
(2)关节炎的预防或治疗用饮食品或饲料,其特征在于,含有属于虎耳草科植物的植物体或该植物体提取物作为有效成分。
作为本发明的以含有属于虎耳草科植物的植物体或该植物体提取物为有效成分为特征的关节炎的预防或治疗用的饮食品或饲料,可举出把属于虎耳草科植物的植物体或以上述方法提取的属于虎耳科植物的植物体提取物原样做成的饮食品或饲料,或者把该植物体或该植物体提取物添加至饮食品或饲料中的饮食品或饲料。该饮食品或饲料作为健康饮食品、功能性食品用于关节炎的预防或治疗。
(3)将属于虎耳草科植物的植物体或该植物体提取物添加制成的饮食品或饲料
本发明的把属于虎耳草科植物的植物体或该植物体提取物添加制成的饮食品或饲料,是通过在不含属于虎耳草科植物的植物体或该植物体提取物的饮食品或饲料中添加上述方法调制的属于虎耳草科植物的植物体或该植物体提取物得到的饮食品或饲料。
本发明的饮食品或饲料除了添加属于虎耳科植物的植物体或该植物体提取物或者按需要添加其他有效成分之外,可以通过使用一般饮食品或饲料的制造方法制造。
另外,也可以将该饮食品或饲料用把一般饮食品或饲料通过用例如成形、造粒等加工方法加工。作为加工方法,可举流化床造粒、搅拌造粒、挤出造粒、转动造粒、气流造粒、压缩成形造粒、粉碎造粒、喷雾造粒等造粒方法,衣锅包衣、流化床包衣、干燥包衣等包衣方法,膨松干燥、过量水蒸气法、泡沫干燥方法、微波加热方法等膨化方法。
添加在本发明饮食品或饲料中的、本发明属于虎耳草科植物的植物体或该植物体提取物,只要本发明饮食品或饲料对关节炎具有预防或治疗作用,添加量未特另规定,但含有例如0.01-50重量%,优选0.1-10重量%那样地添加。
作为饮食品中添加属于虎耳科植物的植物体或该植物体提取物得到的饮食品,可举出例如将属于虎耳草科植物的植物体或该植物体提取物添加的保健食品、保健饮料、果汁类、清凉饮料、汤类、茶类、乳酸菌饮料、发酵乳、冷饮、奶油、干酪、酸乳、加工奶、脱脂奶粉等奶制品、火腿、香肠、汉堡包等畜肉制品、鱼肉加工制品、蛋卷、鸡蛋羹等蛋制品、糕点、果酱、快餐点心、口香糖等糕点类、面包类、面类、盐渍物类、熏制品、晒干物、腻红烧、调味料等。
作为饮食品的形状,只要含有属于虎耳草科植物的植物体或该植物体提取物没有特别的规定,例如可举粉末食品、板状食品、瓶装食品、罐头食品、软包装食品、胶囊食品、片剂状食品、流体食品、饮料食品等。
本发明饮食品根据需要也可以添加一般饮食品用甜味料、着色料、保存料、增粘稳定剂、抗氧化剂、发色剂、漂白剂、防霉剂、树胶基质、苦味料、酶、光泽剂、酸味料、调味料、乳化剂、强化剂、生产用剂、香料、香辣料提取物等添加物。
作为甜味料,可举糖精、甘草、甜叶菊、木糖、罗汉果等。
作为着色料,可举类胡萝卜素、姜黄色素、类黄酮、焦糖色素、紫草根色素、螺旋藻色素、叶绿素、紫薯色素、紫山薯色素、紫苏色素、越桔叶色素等。
作为保存料,可举亚硫酸钠、苯甲酸类、独活提取物、齐墩果提取物、河滩艾提取物、山梨酸类、丙酸类等。
作为增稠稳定剂,可举阿拉伯胶、呫吨胶等橡胶类、褐藻酸类、壳多糖、壳聚糖、翠叶芦荟、古柯豆胶、羟丙基纤维素、酪素钠、玉米淀粉、羧甲基纤维素类、明胶、琼脂、糊精、甲基纤维素、聚乙烯醇、微小纤维素、微晶纤维素、海藻纤维素、聚丙烯酸钠、多磷酸钠、鹿角菜胶、酵母细胞壁、魔芋薯提取物、甘露聚糖等。
作为抗氧化剂可举维生素C、乙二胺四乙酸钠、乙二胺四乙酸钙、异抗坏血酸、谷维素、乙茶酸、槲皮黄素、丁香提取物、酶处理芦丁、苹果提取物、芝麻油提取物、二丁基羟基甲苯、茴香提取物、辣根提取物、水芹提取物、茶提取物、丹贝提取物、鱼腥草提取物、生育三烯酚、生育酚类、菜子油提取物,生咖啡豆提取物、向日葵种子、阿魏酸、丁羟基茴香醚、越桔叶提取物、蜂巢蜡提取物、杪椤·银杏提取物、桔皮素、胡椒提取物、风仙花提取物、没食子酸、山芋提取物、桉叶提取物、迷迭香提取物等。
作为发色剂,可举亚硝酸钠等。
作为漂白剂,可举亚硫酸钠等。
作为防霉剂,可举邻苯基苯酚等。
作为树胶基质,可举乙酰蓖麻醇酸甲酯、漆蜡、脂胶树脂、榄香树脂、小冠巴丁棕蜡、地蜡、红没药树脂、栲树脂、巴西棕榈蜡、愈疮木树脂、杜仲胶、グッタカチエウ、グックハンカン、甘油脂肪酸酯、鲸蜡、古巴香脂、古巴树脂、橡胶、米糠蜡、甘蔗蜡、虫胶、节路顿胶、蔗糖脂肪酸酯、香豆乳汁、山梨糖醇酸脂肪酸酯、滑石、碳酸钙、达马树脂、糖胶树脂、托帕匡斯麻风树、ッヌ一、低分子橡胶、石油蜡、冷杉香脂、丙二醇脂肪酸酯、粉末纸浆、粉末后壳、西蒙德木蜡、聚异丁烯、聚丁烯、微结晶蜡、乳香、马撒兰巧口力、密蜡、磷酸钙等。
作为苦味料,可举异α-苦味酸、咖啡、河滩竹提取物、金鸡纳提取物、黄蘖提取物、龙胆提取物、香辣料提取物、酶处理柚苷、苦木提取物、可可碱、柚苷、ビガキ提取物、苦艾蒿提取物、毛叶茶香菜提取物、姬松茸提取物、甲硫基脲苷、荔枝提取物、橄榄茶、酸橙提取物、酒花提取物、艾蒿提取物等。
作为酶,可举淀粉酶、胰蛋白酶、粗制凝乳酶、乳酸菌等。
作为光泽剂,可举漆蜡、木蜡等。
作为酸味料,可举己二酸、衣康酸、柠檬酸、琥珀酸类、醋酸钠、酒石酸类、二氧化碳、乳酸、植酸、富马酸、苹果酸、磷酸等。
作为调味料,可举天冬酰胺、天冬氨酸类、谷氨酸、谷氨酰胺、丙氨酸、异亮氨酸、甘氨酸、丝氨酸、胱氨酸、酪氨酸、亮氨酸、脯氨酸等氨基酸、肌苷酸钠、尿苷酸钠、鸟苷酸钠、胞啶酸钠、核糖核苷酸钙、核糖核苷酸钠等核酸、柠檬酸、琥珀酸等有机酸、氯化钾、盐水湖水低盐钠液、粗制海水氯化钙、乳清盐、磷酸三钾、磷酸氢二钾、磷酸二氢钾、磷酸氢二钠、磷酸二氢钠、磷酸三钠、小球藻提取物等。
作为乳化剂,可举脂肪酸单甘油酯、山梨糖醇酐脂肪酸酯等。
作为强化剂,可举锌盐类、维生素C、各种氨基酸、5-腺苷酸、氯化铁、橙皮苷、各种锻烧钙、各种未锻烧钙、二苯酰硫胺素、氢氧化钙、碳酸钙、硫胺盐酸盐、杜氏藻胡萝卜素、生育酚、烟酸、胡萝卜胡萝卜素、棕榈仁油胡萝卜素、泛酸钙、维生素A、羟基脯氨酸、焦磷酸二氢钙、焦磷酸铁、焦磷酸铁、铁蛋白、血红素铁、维生素K、叶酸、核黄素等。
作为生产用剂,可举丙酮、离子交换树脂等加工助剂、无花果叶提取物、稻草灰提取物、高岭土、甘油脂肪酸酯、桑叶提取物、骨灰、紫苏提取物、生姜提取物、各种丹宁、巴非哈提取物、葡萄种子提取物、乙醇等。
作为香料,可举上述香料等。
作为香辣料提取物,可举辣椒提取物、蒜提取物等。
摄取本发明的含有以属于虎耳草科植物的植物体或该植物体提物作为有效成分的关节炎的预防或治疗用饮食品、或者把属于虎耳草科植物的植物体或该植物体提取物添加作成的饮食品时,对其摄取量没有特别规定,但对成年人每日摄取属于虎耳草科植物的植物体以干燥重量计或该植物体提取物以干燥重量计,优选0.1g-50g,更优选0.5g-10g。按此量连续摄取优选1日-1年,更优选2周-3个月。但是此摄取量最大标准,根据摄取者的症状程度或年龄、体重等可以在适宜范围内调整。
该饮食品1日内分1次或数次摄取。通过日常摄取该饮食品可以预防关节炎。关节炎已经发病的场合,通过日常摄取该饮食品使关节炎症状得以缓解、治愈等,可以治疗关节炎。
将本发明的属于虎耳科植物的植物体或该植物体提取物添加制成的饲料,可以用于哺乳类、鸟类、爬虫类、两栖类、鱼类等动物的饲料,优选用于哺乳类饲料。例如本发明的饲料用于狗、猫、鼠等宠物用饲料,牛、猪等家畜用饲料,鸡、大鸡等家禽用饲料,鲷鱼、鲥鱼等养殖鱼用饲料等,优选用于宠物用饲料或家畜用饲料。
本发明的饲料,是在饲料原料中适当配合属于虎耳草科植物的植物体或该植物体提取物作成的。作为饲料原料,可举谷物类、糟糠类、植物油渣类、动物性饲料原料,其他饲料原料及精制品等。
作为谷物类,可举例如西非高粱、小麦、大麦、燕麦、黑麦、玄米、荞麦、粟子、高粱、稗子、玉米、大豆等。
作为糟糠类,可举例如米糠、脱脂米糠、麸子皮、低质面粉、小麦、胚芽、麦糠、筛渣、颗粒、玉米糠、玉米胚芽等。
作为植物油渣类,可举例如大豆油渣、黄豆粉、亚麻子油渣、绵子油渣、花生油渣、向日葵油渣、椰子油渣、棕榈仁油渣、芝麻油渣、红花油渣、菜子油渣、木棉子油渣、芥子油渣等。
作为动物性饲料原料,可举例如鱼粉(北洋制粉、输入制粉、号鲁制粉、沿岸制粉等公司制品)、鱼汁、肉粉、肉骨粉、血粉、分解毛、骨粉、家畜用处理付产物、羽毛粉、蚕蛹、脱脂奶粉、酪蛋白、干燥乳清等。
作为其他饲料原料,可举植物茎叶类(苜蓿、干草饼、苜蓿叶粉、刺槐粉末等)、玉米加工付产物(玉米面筋、粗粉、玉米黄浆饲料、玉米浆等)、淀粉加工品、砂糖、发酵工业产物(酵母、啤酒渣、麦芽根、醇渣、酱油渣等)、农产制造付产物(柑桔加工渣、豆腐渣、咖啡渣、椰子渣等)、其他(木薯、蚕豆、古柯粉、海藻、南极磷虾、螺旋藻、小球藻、矿物等)等。
作为精制品,可举蛋白质(酪蛋白、白蛋白等)、氨基酸、糖质(淀粉、纤维素、蔗糖、葡萄糖等)、矿物质、维生素等。
摄取本发明的含有以属于虎耳草科植物的植物体或该植物体提取物作为有效成分的关节炎的预防或治疗用饲料、或者把属于虎耳草科植物的植物体或该植物体提取物添加作成的饲料时,对其摄量没有特别规定,但对动物每日每1kg体重摄取属于虎耳草科植物的植物体或该植物体提取物以干燥重量计优选0.01g-50g,更优选0.05-10g。以此摄取量摄取优选1周-5年,更优选2周-2年。但是,此摄取量最大标准,根据摄取动物的种类,年龄、体重等可以在适当的范围内调整。
关节炎已经发病的场合,通过日常摄取该动物用饲料,使关节炎得到缓解、治愈,直至关节炎得到治疗。
(4)具有关节炎的预防或治疗作用的饮食品用添加剂或饲料用添加剂,其特征在于,含有属于虎耳草科植物的植物体或该植物体提取物。
本发明的含有属于虎耳草科植物的植物体或该植物体提取物为特征的具有关节炎的预防或治疗作用的饮食品用添加剂或饲料用添加剂,是含有上述方法调制的属于虎耳草科植物的植物体或该植物体提取物作为有效成分,根据需要也可以添加在上述饮食品中举例表示的甜味料、着色料、保存料、增稠稳定剂、抗氧化剂、发色剂、漂白剂、防霉剂、树胶基质、苦味料、酶、光泽剂、酸味料、乳化剂、强化剂、生产用剂、香料、香辣料提取物等添加物。另外,也可以添加上述制剂中举例表示的载体。
摄取本发明的具有关节炎的预防或治疗作用的饮食品用添加剂时,其摄取量没特别规定,但是,对成年人每日摄取属于虎耳科植物的植物体或该植物体提取物以干燥重量计优选0.1g-50g,更优选0.5-10g。一般以此剂量连续摄取优选1周-10年,更优选1个月-5年。但是,此摄取量的最大标准根据摄取者的症状程度及年龄、体重等可以调整至最适范围。
本发明的饮食品用添加剂添加到饮食品中时,其添加量没特别规定,日例如为0.01-50重量%,优选0.1-10重量%。
本发明的饮食品添加剂,添加到饮食品中1日1次或分数次摄取。通过日常摄取含有本发明饮食品添加剂的饮食品可预防关节炎。关节炎已经发病的场合,通过日常摄取含有本发明饮食品添加剂的饮食品可以缓解、治愈关节炎等治疗关节炎。
将本发明的含有属于虎耳草科植物的植物体或该植物体提取物为特征的具有关节炎的预防或治疗作用的饲料用添加剂给动物摄取时,其摄取量没有特别规定,但是,对动物每日摄取属于虎耳草科植物的植物体或该植物体提取物以干燥重量计每1kg体重优选0.01g-50g,更优选0.05-10g。以此给药量优选持续摄取1周-5年,更优选2周-2年。但是此给药量的最大标准可以根据摄取动物种类、年龄、体重等调整至最适范围。
通过将本发明饲料添加剂加至饲料内让动物日常摄取,可以预防关节炎。关节炎已经发病场合,通过日常摄取本发明饲料添加剂添加的饲料能够治疗关节炎。
将本发明饲料添加剂添加至饲料中时,其添加量没有特别规定,例如为0.01-50重量%,优选0.1-10重量%。
下面基于实施例详细说明本发明。但是,下述实施例不能限制本发明。
实施例1 甜茶(Hydrangeae Dulcis Folium)的水提取物的冷冻干燥粉末的制造
将干燥甜茶粉末(志平商店社制)1kg用蒸馏水10升提取2次(室温、1小时搅拌),所得提取液经浓缩后通过冷冻干燥,得到甜茶水提取物冷冻干燥粉末200g。
实施例2 甜茶(Hydrangeae Dulcis Folium)的60%乙醇水溶液提取物的冷冻干燥粉末的制造
将干燥甜茶粉末1kg用60%乙醇水溶液10升提取2次(室温、1小时搅拌),所得提取液经浓缩后,通过冷冻干燥得到甜茶的60%乙醇水溶液提取物的冷冻干燥粉末200g。
实施例3 甜茶(Hydrangeae Dulcis Folium)的丙酮提取物的冷冻干燥粉末的制造
将干燥甜茶粉末1kg用丙酮10升提取2次(室温、1小时搅拌),所得提取液经浓缩后,通过冷冻干燥得到甜茶的丙酮提取物的冷冻干燥粉末100g。
实施例4 甜茶(Hydrangeae Dulcis Folium)的热水提取物的冷冻干燥粉末的制造
将干燥甜茶粉末1kg用沸腾的蒸馏水10升提取(30分钟静置),所得提取液经浓缩后,通过冷冻干燥得到甜茶的热水提取物的冷冻干燥粉末130g。
实施例 5甜茶(Hydrangeae Dulcis Folium)的水提取残渣乙醇提取物的冷冻干燥粉末的制造
将干燥甜茶粉末1kg用蒸馏水20升提取(40℃、搅拌),直到1/200稀释液在313nm波长的吸光度达0.15为止。过滤除去滤液得到提取残渣。该残渣用60%乙醇水溶液20升提取(40℃、搅拌),直到1/200稀释液在313nm波长的吸光度0.22为止。该提取液浓缩后通过冷冻干燥得到甜茶的水提取残渣乙醇提取物的冷冻干燥粉末70g(对于干叶收量为7%)。
实施例6 甜茶(Hydrangeae Dulcis Folium)的水提取残渣丙酮提取物的冷冻干燥粉末的制造
将干燥甜茶粉末1kg用20升蒸馏水提取(40℃、搅拌),直到1/200稀释液在313nm的吸光度达0.15为止。过滤除去滤液得到提取残渣,把该残渣用丙酮20升提取(40℃、搅拌),直到1/200稀释液在313nm的吸光度达0.22为止。该提取液经浓缩后通过冷冻干燥得到甜茶的水提取残渣丙酮提取物的冷冻干燥粉末60g(对于干叶收量为6%)。
实施例7 对菌体成分诱发关节炎(Streptococcal Cell Wall-inducedarthritis)大鼠的甜茶提取物的效果
已知给路易士(Lewis)大鼠链球菌细胞壁(Streptococcal CellWall)2次给药引起关节炎[Infection & Immunity,
59(12),4436(1991)]。
对8周龄雌性路易士大鼠(チヤ一ルスリ一バ公司制),作为第一次链球菌细胞壁(Streptococcal Cell Wall)给药,把肽聚糖(Peptidoglycanpolysaccharide)100P成分(以下简称PG-PSl00)[李实验室(LEELABORATORIES)公司制]用灭菌的PBS(-)(把氯化钠:9g,磷酸氢二钠7水合物:0.795g,磷酸二氢钾:0.144g用1L蒸馏水溶解的溶液)稀释成0.6mg/mL,用超声波洗净器[US-1型,エスエヌデイ株式会社制]20分钟超声波粉碎后,每只大鼠在右后肢趾关节内给药10μL(6μg的PG-PS100)。而在左后趾关节内每只大鼠给药10μL灭菌PBS(-),做为负对照。
第一次链球菌细胞壁(Streptococcal Cell Wall)给药21日后,作为第二次链球菌细胞壁(Streptococcal Cell Wall)给药,同样把PG-PS100P用灭菌PBS(-)稀释成0.2mg/mL,20分钟超声波粉碎后,每只在尾静脉内给药500μL(100μL的PG-PS 100),使其发作,引起关节炎。
从第一次链球菌细胞壁(Streptococcal Cell Wall)给药3日前开始,作为对照对大鼠每100g体重给1mL0.5%甲基纤维素400(ナカライタスク公司制),以及每100g体重给在1mL0.5%甲基纤维素400中悬浮实施例5制造的甜茶的水提取残渣的乙醇提取物(第1表中记作甜茶水提取残渣乙醇提取物)溶液1周间5次口服给药。从第一次链球菌细胞壁(Streptococcal Cell Wall)给药后第24日用精密仪器(プレシスモメ一タ一)(UNICOM公司制)测定关节的浮肿。
每个处理条件用6只大鼠,以下式求关节浮肿的容积变化。
关节浮肿的容积变化=(A-B)-(C-D)
A:第24日的右后肢趾关节容积
B:第0日的右后肢趾关节容积
C:第24日的左后肢趾关节容积
D:第0日的右后肢趾关节容积
结果如第1表所示。
表中数字表示在各处理条件下关节浮肿的容积的变化,用平均值±标准差(N=6)表示。
再者,表中无处理表示未给链球菌细胞壁(Streptococcal CellWall),对照表示只口服给药0.5%甲基纤维素400。
第1表
处理 | 关节浮肿的容积变化(ml) | |
经过日数0日 | 经过日数24日 | |
无处理 | 0.00±0.00 | 0.01±0.01 |
对照 | 0.00±0.00 | 0.48±0.11 |
甜茶提取残渣乙醇提取物 | 0.00±0.00 | 0.16±0.04 |
如表1所示,甜茶水提取残渣乙醇提取物给药场合与只给0.5%甲基纤维素400(对照)相比表示关节炎浮肿程度的后肢趾关节容积的增加得到抑制。
上述结果显示了通过给与甜茶水提取残渣乙醇提取物,可以有效地预防关节炎。
实施例8 甜茶(Hydrangeae Dulcis Folium)的水提取残渣乙醇提取物配合剂的制造
混合下述组成,制造关节炎的预防或治疗剂。
实施例5制造的冷冻干燥粉末 49g
パインデックス#3(松谷化学工业公司制) 49g
焦磷酸铁(铁源:国产化学公司制) 0.1g
ホスカルEFC(钙源:日兴精细化工产品公司制) 1g
混合维生素(默克公司制) 1g
实施例9 甜茶(Hydrange Dulcis Folium)的水提取残渣乙醇提取物配合饮料的制造
将实施8制造的关节炎的预防或治疗剂20g分散于水180m1中,制造关节炎的预防或治疗用饮料。
实施例10 甜茶(Hydrangeae Dulcis Folium)的水提取残渣乙醇提取物配合小甜饼的制造
按照下面配合制造小甜饼(30个的份量)。
薄力粉 100g
淀粉 74g
水 14g
实施例5制造的冷冻干燥粉末 30g
焙烤粉 小匙2勺
盐 小匙2勺
鸡蛋 1个
奶油 80g
牛奶 大匙2勺
实施例11 含有实施例1的1%冷冻干燥粉末饲料的制造
制造下述饲料。
蔗糖(キシダ化学公司制) 20.0重量%
玉米油(ナカライテスク公司制) 5.0重量%
重酒石酸胆碱(东京化成公司制) 0.4重量%
玉米淀粉(日淀化学公司制) 39.1重量%
AIN-76维生素(オリエンタル酵母公司制) 1.0重量%
AIN-76矿物质(オリエンタル酵母公司制) 3.5重量%
纤维素(オリエンタル酵母公司制) 5.0重量%
酪蛋白(和光纯药公司制) 25.0重量%
实施例1制造的冷冻干燥粉末 1.0重量%
实施例12 虎耳草(
Saxifraga
stolonifera Meerb.)的水提取物的冷冻干燥粉末的制造
将干燥虎耳草粉末(志平商店制)1kg用蒸馏水10升提取2次(室温、1小时搅拌),所得提取液经浓缩后冷冻干燥得到虎耳草水提取物的冷冻干燥粉末150g。
实施例13 虎耳草(
Saxifraga
stolonifera Meerb.)的60%乙醇水溶液提取物的冷冻干燥粉末的制造
将干燥的虎耳草粉末1kg用60%醇水溶液20升提取(40℃、搅拌),把该提取液浓缩后冷冻干燥得到虎耳草的乙醇提取物的冷冻干燥粉末315g(对干叶收量31.5%)。
实施例14 虎耳草(
Saxifraga
stolonifera Meerb.)的丙酮提取物的冷冻干燥粉末的制造
将干燥的虎耳草粉末1kg用丙酮10升2次提取(室温、1小时搅拌),所得提取液经浓缩后冷冻干燥得到虎耳草丙酮提取物的冷冻干燥粉末164g。
实施例15 虎耳草(
Saxifraga
stolonifera Meerb.)的热水提取物的冷冻干燥粉末的制造
将干燥虎耳草粉末1kg用沸腾的蒸馏水10升提取(放置30分钟),所得提取液经浓缩后冷冻干燥得到虎耳草的热水提取物的冷冻干燥粉末100g。
实施例16 虎耳草(
Saxifraga
stolonifera Meerb.)的水提取残渣乙醇提取物的冷冻干燥粉末的制造
将干燥虎耳草粉末1kg用蒸馏水20升提取(40℃、搅拌)。过滤除去滤液得到提取残渣。把该残渣用60%乙醇水溶液20升提取(40℃、搅拌),该提取液经浓缩后冷冻干燥得到虎耳草水提取残渣乙醇提取物的冷冻干燥粉末80g。
实施例17 虎耳草(
Saxifraga
stolonifera Meerb.)的水提取残渣丙酮提取物的冷冻干燥粉末的制造
将干燥虎耳草粉末1kg用蒸馏水20升提取(40℃、搅拌)。过滤除去滤液得到提取残渣。把该残渣用丙酮20升提取(40℃、搅拌)。该残渣经浓缩后冷冻干燥得到虎耳草的水提取残渣丙酮提取物的冷冻干燥粉末90g。
实施例18 虎耳草(
Saxifraga
stolonifera Meerb.)的乙醇提取物配合剂的制造
将下述组成混合制造关节炎的预防或治疗剂。
实施例13制造的冷冻干燥粉末 49g
パイソデックス#3(松谷化学工业公司制) 49g
焦磷酸铁(铁源:国产化学公司制) 0.1g
EFC(钙源:日兴精细化工产品公司制) 1g
混合维生素(默克公司制) 1g
实施例19 虎耳草(
Saxifraga
stolonifera Meerb.)的乙醇提取物配合饮料的制造
将实施例18制造的关节炎的预防或治疗剂20g分散在水180ml中,制造关节炎的预防或治疗剂用饮料。
实施例20 虎耳草(
Saxifraga
stolonifera Meerb.)的乙醇提取物配合小甜饼的制造
按照下面配合制造小甜饼(30个的份量)。
薄力粉 100g
淀粉 74g
水 14g
实施例13制造的冷冻干燥粉末 30g
焙烤粉 小匙2勺
盐 小匙2勺
鸡蛋 1个
奶油 80g
牛奶 大匙2勺
实施例21 含有虎耳草(
Saxifraga
stolonifera Meerb.)的乙醇提取物1重量%的饲料的制造
制造下述饲料。
蔗糖(キシダ化学公司制) 20.0重量%
玉米油(ナカライテスク公司制) 5.0重量%
重酒石酸胆碱(东京化成公司制) 0.4重量%
玉米淀粉(日淀化学公司制) 39.1重量%
AIN-76维生素(オリエンタル酵母公司制) 1.0重量%
AIN-76矿物质(オリエンタル酵母公司制) 3.5重量%
纤维素(オリエンタル酵母公司制) 5.0重量%
酪蛋白(和光纯药公司制) 25.0重量%
实施例13制造的冷冻干燥粉末 1.0重量%
实施例22 含有虎耳草(
Saxifraga
stolonifera Meerb.)的乙醇提取物的饲料的制造
制造下述饲料。
CE-2(日本クレア公司制) 98.0重量%
实施例13调制的冷冻干燥粉末 2.0重量%
实施例23 对患2型胶原性关节炎大鼠的虎耳草(
Saxifraga stolonifera Meerb.)提取物的效果
在本试验中,使用由2次给药2型胶原引起关节炎的DBA/1J小鼠(チヤ一ルスリバ一公司制)。
对6周龄雄性DBA/1J小鼠,作为第1次2型胶原给药,把2型胶原(胶原技术研修会公司制)与弗罗因德完全佐剂(Freund’s completeadjuvant,ヤトロン公司制)等量混合用匀质器乳化的溶液,每只皮内给药100μl。
在第1次2型胶原给药21天后,作为第2次2型胶原给药,同第1次一样,与弗罗因德等量混合用匀质器乳化的溶液,每只皮内给药100μl。如上所述小鼠引起关节炎。
从第1次2型胶原给药日开始给小鼠含有虎耳草乙醇提取物的实施例22制造的饲料(在第3表中以虎耳草乙醇提取物表示)进行饲养。另外,作为对照给小鼠不添加任何东西的粉末饲料CE-2进行饲养。在第1次2型胶原给药后第26日、第30日、第34日、第37日及第42日,根据如下的指标评价关节炎的发病程度。
对小鼠每个前后肢,按如第2表所示的症状分别赋予0分-4分,对于每只小鼠前后爪合计4个的评分的合计分,即用0分-16分作为评价。另外,对于各个条件分别使用20只小鼠。
第2表
症状 | 评分 |
看不到趾或前(后)爪的肿胀 | 0分 |
看到一只趾或前(后)爪尖有轻度肿胀 | 1分 |
看到1-3只趾或前(后)爪尖有肿胀 | 2分 |
看到1-5只趾或前(后)爪尖有肿胀 | 3分 |
看到全部的趾及前(后)爪尖有肿胀 | 4分 |
结果于第3表表示。表中数字表示各处理条件下的评分,以平均值±标准差(N=20)表示。另外,统计学上显著差检验是用Student-t检验进行的。再有,表中无处理表示用市售饲料CE-2饲养,没用2型胶原处理的小鼠得到的评分。
第3表
给药后的日数(日) | 评分 | 显著差 | ||
无处理 | 对照 | 虎耳草乙醇提取物 | ||
0 | 0.0±0.0 | 0.0±0.0 | 0.0±0.0 | - |
26 | 0.0±0.0 | 1.4±0.4 | 1.0±0.4 | - |
30 | 0.0±0.0 | 10.4±0.7 | 7.8±0.9 | p=0.026 |
34 | 0.0±0.0 | 12.4±0.5 | 9.0±1.0 | p=0.004 |
37 | 0.0±0.0 | 12.2±0.5 | 9.2±0.9 | p=0.010 |
42 | 0.0±0.0 | 12.0±0.5 | 9.3±1.0 | p=0.019 |
如第3表所示,摄取含有虎耳草乙醇提取物2重量%的饲料(虎耳草乙醇提取物)的小鼠的评分与摄取未添加虎耳草乙醇提取物粉末的饲料的小鼠(对照组)评分比较,显著地低,说明通过添加虎耳草乙醇提取物,能够抑制关节炎评分的上升。
由上述事实可知,在关节炎发病前预先通过摄取虎耳草提取物,可以抑制关节炎的发病。
根据本发明,可以提供关节炎的预防剂或治疗剂、具有关节炎预防作用或治疗作用的饮食品或饲料、具有关节炎预防作用或治疗作用的饮食品用添加剂或饲料添加剂以及动物的关节炎预防方法或治疗方法。
Claims (5)
1.虎耳草(Saxifraga stolonifera Meerb.)或鸦嘴大叶绣球(Hydrangea macrophylla Seringe Var.Thunbergii Makino)的植物体或该植物体提取物在制造关节炎的预防剂或治疗剂中的使用。
2.虎耳草(Saxifraga stolonifera Meerb.)或鸦嘴大叶绣球(Hydrangea macrophylla Seringe Var.Thunbergii Makino)的植物体或该植物体提取物在制造具有关节炎的预防或治疗作用的饮食品或饲料中的使用。
3.虎耳草(Saxifraga stolonifera Meerb.)或鸦嘴大叶绣球(Hydrangea macrophylla Seringe Var.Thunbergii Makino)的植物体或该植物体提取物在制造具有关节炎的预防或治疗作用的饮食品用添加剂或饲料用添加剂中的使用。
4.权利要求1~3的任何一项记载的使用,其中,虎耳草(Saxifragastolonifera Meerb.)或鸦嘴大叶绣球(Hydrangea macrophylla Seringevar.Thunberbii Makino)的植物提取物是虎耳草(Saxifragastolonifera Meerb.)或鸦嘴大叶绣球(Hydrangea macrophylla Seringevar.Thunberbii Makino)的植物体的水性介质提取物残渣的醇提取物。
5.权利要求1~3的任何一项记载的使用,其中,关节炎是慢性风湿性关节炎。
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JP70702/2002 | 2002-03-14 |
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US (1) | US20040161478A1 (zh) |
EP (1) | EP1407777B8 (zh) |
JP (1) | JPWO2002102396A1 (zh) |
KR (1) | KR100887854B1 (zh) |
CN (1) | CN1278710C (zh) |
AT (1) | ATE426407T1 (zh) |
CA (1) | CA2449943A1 (zh) |
DE (1) | DE60231714D1 (zh) |
HK (1) | HK1066481A1 (zh) |
WO (1) | WO2002102396A1 (zh) |
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KR100830746B1 (ko) * | 2000-12-23 | 2008-05-20 | 신준식 | 오적골, 우슬, 두충, 오가피, 고비 및 구판을 주성분으로 함유하는 의약조성물 및 이를 주성분으로 함유한 약학적 제제 |
US6986906B2 (en) * | 2001-09-25 | 2006-01-17 | Herbasway Laboratories, Llc | Cranberry based dietary supplement and dental hygiene product |
GB0424891D0 (en) * | 2004-11-11 | 2004-12-15 | Boots Co Plc | Topical compositions |
DE102005005086A1 (de) * | 2005-02-03 | 2006-08-10 | Flavin-Koenig, Dana F., Dr. | Naturheilmittel-Nahrungsergänzungs-Kombinationspräparat |
EP1924159B1 (en) * | 2005-07-18 | 2011-10-19 | Korea Research Institute of Bioscience and Biotechnology | A composition comprising an extract of Tiarella polyphylla having antiasthmatic activity |
US7763286B2 (en) | 2005-07-18 | 2010-07-27 | Korea Research Institute Of Bioscience And Biotechnology | Composition comprising an extract of Tiarella polyphylla and tiarellic acid isolated therefrom having antiinflammatory, antiallergic and antiasthmatic activity |
US20080311252A1 (en) * | 2007-06-13 | 2008-12-18 | Selzer Jonathan A | Chocolate based dietary supplement product or sweet beverage product |
US20090061016A1 (en) * | 2007-09-05 | 2009-03-05 | Selzer Jonathan A | Seawater Based Dietary Supplement Product for Energy and Electrolyte Replacement |
US20090311238A1 (en) * | 2008-06-11 | 2009-12-17 | Crandall Wilson T | Topical composition and treatment method for cartilage damage |
EP2349297B1 (en) * | 2008-11-12 | 2013-05-15 | Korea Research Institute of Bioscience and Biotechnology | Composition comprising aceriphyllum rossii extract and active compounds isolated from them for use in the treatment of bacterial infections |
EP3452176B1 (en) * | 2016-05-03 | 2021-06-23 | Tauderma SA | Saxifraga extracts for cosmetic or therapeutic use on the skin |
WO2018048140A1 (ko) * | 2016-09-07 | 2018-03-15 | 연세대학교 산학협력단 | 골질환의 예방 또는 치료용 약학 조성물 |
KR102294341B1 (ko) * | 2018-11-22 | 2021-08-30 | 재단법인 경기도경제과학진흥원 | 오미자 및 칠해목 혼합 추출물의 지표성분 동시분석 방법 |
CN110628735B (zh) * | 2019-04-23 | 2022-04-08 | 天津科技大学 | 一种5α-还原酶突变体,基因工程菌及其在高效催化5α-AD生产中的应用 |
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US4512983A (en) * | 1982-09-29 | 1985-04-23 | Kunihiko Shino | Method for making a sanitary drink |
JP2700958B2 (ja) * | 1991-01-25 | 1998-01-21 | サントリー株式会社 | 甜茶抽出物を有効成分とする医薬並びにこれを配合した食品および化粧品 |
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WO1996041644A1 (fr) * | 1995-06-13 | 1996-12-27 | Nippon Meat Packers, Inc. | Medicament a administration par voie orale, contre la polyarthrite rhumatoide et aliment actif |
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CA2449943A1 (en) | 2002-12-27 |
KR20040007720A (ko) | 2004-01-24 |
CN1516594A (zh) | 2004-07-28 |
US20040161478A1 (en) | 2004-08-19 |
EP1407777B1 (en) | 2009-03-25 |
JPWO2002102396A1 (ja) | 2004-09-30 |
DE60231714D1 (de) | 2009-05-07 |
HK1066481A1 (en) | 2005-03-24 |
WO2002102396A1 (fr) | 2002-12-27 |
EP1407777A4 (en) | 2005-03-02 |
EP1407777B8 (en) | 2009-08-05 |
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