WO2005084693A1 - Extrait de la graine de hippophae rhamnoides - Google Patents

Extrait de la graine de hippophae rhamnoides Download PDF

Info

Publication number
WO2005084693A1
WO2005084693A1 PCT/CN2004/000172 CN2004000172W WO2005084693A1 WO 2005084693 A1 WO2005084693 A1 WO 2005084693A1 CN 2004000172 W CN2004000172 W CN 2004000172W WO 2005084693 A1 WO2005084693 A1 WO 2005084693A1
Authority
WO
WIPO (PCT)
Prior art keywords
extract
apoptosis
ethyl acetate
eosinophils
extract according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2004/000172
Other languages
English (en)
French (fr)
Other versions
WO2005084693A8 (en
Inventor
Jue Wang
Susumu Kitanaka
Tadashi Kusama
Yasuo Kizawa
Minori Furuya
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nihon University
Original Assignee
Nihon University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nihon University filed Critical Nihon University
Priority to JP2007501094A priority Critical patent/JP4714908B2/ja
Priority to PCT/CN2004/000172 priority patent/WO2005084693A1/zh
Priority to CNB200480042278XA priority patent/CN100402047C/zh
Publication of WO2005084693A1 publication Critical patent/WO2005084693A1/zh
Anticipated expiration legal-status Critical
Publication of WO2005084693A8 publication Critical patent/WO2005084693A8/zh
Ceased legal-status Critical Current

Links

Definitions

  • Seabuckthorn seed extract TECHNICAL FIELD-The present invention relates to a seabuckthorn seed extract having the effects of inducing apoptosis, anti-allergy and anti-inflammatory. Background technique:
  • Seabuckthorn iHippophae rhamnoides L. is a medicinal plant of the Elaeagnaceae family that has been used in China for a long time, and it is wild in temperate and arid regions of Cambodia and Europe. Since seabuckthorn has formed a series of natural substances including stress-resistant vitamins and biological activities during the long evolution process in nature, a variety of substances with strong physiological activity can be extracted from seabuckthorn seeds, which can effectively regulate blood lipids. Prevention and treatment of cardiovascular and cerebrovascular diseases such as coronary heart disease and angina pectoris, anti-radiation, anti-inflammatory and muscle growth.
  • the “Pharmacopoeia” states: "The surface of the sea-buckthorn fruit is orange-yellow, the seeds are obliquely oval, brown and shiny, the seeds are milky, oily, slightly airy, acid , Astringent, with antitussive, expectorant, digestion and stagnation, promoting blood circulation and dispersing blood stasis. "So far, no seabuckthorn seed extracts have been found to induce apoptosis, anti-allergic and anti-inflammatory effects.
  • Inflammatory respiratory disease is considered to be a chronic disease caused by repeated occurrence of inflammatory reactions caused by lymphocytes and eosinophils. It is important to understand the mechanism of lymphocyte and granulocyte proliferation regulation during inflammation.
  • specific reactive bronchial asthma is a chronic airway allergic inflammation mainly infiltrating with eosinophils and mast cells.
  • the number of local eosinophils in the trachea increases, and the survival of eosinophils is prolonged. If the eosinophils cause apoptosis, you can see an effective local anti-inflammatory effect of the trachea, and control the local eosinophils Function is associated with the cessation of tracheal inflammation.
  • EOS human eosinophils
  • Eosinophilia is also a characteristic feature of parasitic infections, and EOS is an effector cell of worm immunity.
  • CD4 + T lymphocyte Th2 subtype activated cytokines such as interleukin (IL) -3, IL- 5, and granulocyte-macrophage colony-stimulating factor (GM-CSF).
  • IL-5 and eosinophils They are related to cytocytosis, and they have specific effects on the proliferation and activation of EOS.
  • VLA-4 ⁇ 4 ⁇ 1-integrin and activated antigen (VLA)-4 in EOS indicates that VLA-4 and vascular cell adhesion
  • VCAM epithelial molecule
  • the adhesion of epithelial molecule (VCAM) -1 to the channel is related to selective eosinophilia
  • the 8kd cc composition plays an important role in EOS recruitment and threshing
  • LT and Inhibitors of several mediators such as PAF are effective for eosinophilia, suggesting that some mediators have an effect on the formation of eosinophilia.
  • Drugs that interfere with or block every aspect of airway allergic diseases can be called anti-allergic drugs.
  • Such drugs are the first-line drugs for asthma prevention and treatment.
  • Commonly used drugs are: 1 Sodium cromoglycate: It can inhibit the release of inflammatory mediators from mast cells, inhibit the activation of eosinophils, neutrophils and alveolar macrophages, and has anti-airway allergic inflammatory effects. 2 ketotifen; 3 antihistamines: can inhibit the release of mediators of inflammatory cells such as mast cells, eosinophils, basophils and alveolar macrophages, these drugs are commonly used: benzphthalazine, terfena Drugs such as sedatives, cetirizine, and astemazine.
  • allergic rhinitis is mainly due to the combination of inhaled allergens (such as dust mites, fungi, pollen, etc.) with allergic patients and specific IgE that has been bound to mast cells, eosinophils, platelets and other cells, causing these cells to release solid It can cause inflammation of the nasal mucosa.
  • the inflammatory process includes infiltration of cells such as inflammatory cells and eosinophils, neutrophils, release of primary and secondary pathological mediators such as histamine, LTS and PG, and activation of eosinophils leading to early and late reactions.
  • the commonly used compound drugs also have many side effects. Summary of the invention:
  • the object of the present invention is to provide a substance extracted from the seeds of plant sea buckthorn without having to worry about side effects caused by chemical drugs, which has the effects of inducing apoptosis, anti-allergy and anti-inflammatory.
  • the technical solution of the present invention uses the organic solvent extract of seabuckthorn seeds as an active substance, which is obtained through the following steps:
  • the seabuckthorn seeds are extracted by ethanol soaking and repeated twice, and combined These extracts were concentrated under reduced pressure to obtain brown powder extracts;
  • the powder extract was dissolved in water, and extracted with ether, ethyl acetate, and butanol as extraction liquids three times in that order;
  • the brown oil was taken on a silica gel column and eluted with ethyl acetate, and the eluted fractions were collected.
  • the above ethanol concentration is preferably 80%,
  • the above ethanol soaking time is preferably 12 hours;
  • the elution concentration of the ethyl acetate is preferably 15%.
  • the extract has an activity of inducing apoptosis of cells.
  • the extract has an activity of inducing apoptosis of eosinophils.
  • This extract can activate MBP kinase.
  • the extract plays a role in inducing apoptosis of eosinophils for various diseases caused by excessive eosinophils.
  • the extract plays a role in inducing eosinophil apoptosis in allergic rhinitis.
  • the extract plays a role in inducing apoptosis of eosinophils on atopic bronchial asthma.
  • the present invention has the following advantages:-Seabuckthorn seed extract has excellent effects in reducing eosinophils, etc., and can be used for effective prevention and treatment caused by excessive eosinophils. It can effectively prevent and treat allergic rhinitis or atopic bronchial asthma. Can be used as apoptosis inducer, anti-allergic agent, anti-inflammatory agent and health food.
  • DETAILED DESCRIPTION-Example 1 Preparation of Sea Buckthorn Seed Extract
  • Eosinophil apoptosis induction test and MBP kinase activity test Eosinophil apoptosis induction test. The test was performed according to the method of Vermes et al. (Journal of Immunological Methods 184, 39-51, 1995) . Eosinophils HL-60 cells were floated in RPMI1640 medium at a cell concentration of 1-3 ⁇ 10 6 cells / mlo. The test substance was added to 500 ⁇ 1 of the cell suspension (the last collected group in Example 1 above) one minute) or culture medium to a concentration of 100 ⁇ / ⁇ 1, (cultured under conditions 5% C0 2 for 6 hours or 24 hours.
  • phosphatidyl binding protein (of Annexin) buffer at 37 ° V 5 ⁇ 1 of phosphatidyl-binding protein V-FITC was then added.
  • phosphatidyl-binding protein V-positive cells were used as apoptosis-inducing cells and evaluated as a percentage of the total number of cells.
  • MBP kinase activity test The test was performed according to the method of De Souza et al. (Blood 99 Vol. 3432-3438 2002). The eosinophilic cells HL-60 cells suspended in RPMI1640 medium, a cell concentration of l-3xl0 6 cells / ml. The suspended cells were added 500 ⁇ was detected after material or culture medium to a concentration of 100 g / ml, at 37 ° (, incubated for 6 hours or 24 hours under conditions of 5% C0 2. Centrifugal washing, adding soluble Buffer, lyse the cells, and perform electrophoresis using a gel containing MBP 5 mg / ml.
  • the gel After the gel is dedenatured and redenatured, it is labeled with 32 P-ATP for 3 hours of phosphorylation. After the gel is dried, use the figure The radioactivity was analyzed by an image analyzer. When the labeling band was grown at 36 kDa, it was recorded as positive for MBP kinase activation.
  • seabuckthorn seed extract was observed to induce concentration-dependent apoptosis in HL-60 cells.
  • seabuckthorn seed extract activated 36 kDa MBP kinase.
  • the above results suggest that seabuckthorn seed extract can induce apoptosis on eosinophils, which is related to 36 kDa MBP kinase. It is inferred from this that the seabuckthorn seed extract contains ingredients that can be used as drugs against eosinophilic inflammation.

Landscapes

  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

沙棘种子提取物 技术领域- 本发明涉及一种具有诱导细胞凋亡、 抗过敏和抗炎作用的沙棘种子 提取物。 背景技术：
沙棘 iHippophae rhamnoides L. ) 是一种很久以前就被中国利用的 胡颓子科药用植物， 野生在西藏和欧洲的温带干旱地域。 由于沙棘在自 然界漫长的演化过程中形成了包括一系列有抗逆性的维生素和生物活性 的天然物质， 从沙棘种子中可以提取多种具有很强生理活性的物质， 对 可以有效的调节血脂， 预防及治疗冠心病、 心绞痛等心脑血管疾病， 抗 辐射、 抗炎生肌等。 我国藏医药经典著作 《四部医典》 收集记载了用沙 棘制成的汤、 散、 丸、 膏、酥、 灰、 酒等 7种合剂以及 84种沙棘的配方。 1941-1942年， 从前苏联第一次分析出沙棘含维生素 C和胡萝卜素以来， 到 80年代中期，已相继发现沙棘所含生物活性物质上百种之多。 1977年， 沙棘作为中药被列入 《中华人民共和国药典》， 《药典》 中记述： "沙棘 果表面橙黄色， 种子斜卵形， 褐色有光泽， 种仁乳白色， 有油性， 气微， 味酸、 涩， 具有止咳祛痰、 消食化滞、 活血散瘀功能。 "至今仍未发现 具有诱导细胞凋亡、 抗过敏和抗炎作用的沙棘种子提取物。
炎症性呼吸器官疾病被认为是由淋巴细胞和嗜酸粒细胞引起的炎症 反应反复发生引起的慢性病， 清楚炎症时的淋巴细胞和粒细胞的增殖调 节机制， 对了解该疾病非常重要。 如特异反应性支气管哮喘是一种以嗜 酸粒细胞、 肥大细胞等浸润为主的慢性气道变态反应性炎症。 病情发作 时气管局部的嗜酸粒细胞数增加， 嗜酸粒细胞的生存得到延长， 如将嗜 酸粒细胞引起细胞凋亡可以看到有效的气管局部消炎效果， 控制气管局 部的嗜酸粒细胞的功能与气管炎症的停止相关。
人嗜酸粒细胞 (EOS)增多是慢性支气管哮喘的特征。嗜酸粒细胞增多 症也是寄生虫感染特有的特征， EOS 是蠕虫免疫性的效应细胞。 最近研 究提出了几种嗜酸粒细胞增多症的致病机理： 其一， 过敏原特异性辅助 (CD4+) T淋巴细胞 Th2亚型的活化细胞因子如白细胞介素 （IL) -3, IL-5 , 以及粒细胞-巨噬细胞集落刺激因子 （GM-CSF)。 IL-5和嗜酸粒细 胞增多症有关， 它们均对 EOS的增殖和活化具有特异性作用； 其二， α 4 β 1-整合素， 活化抗原 （VLA) -4在 EOS中的表达， 表明 VLA-4及血 管细胞粘附分子 （VCAM) -1 与通道的粘附， 均与选择性嗜酸粒细胞增 多症有关；其三，趋化因子 8kd c-c组成在 EOS募集和脱粒中起着重要作 用； 其四， LT和 PAF等几种介质的抑制剂对嗜酸粒细胞增多症有效， 表 明某些介质对嗜酸粒细胞增多症的形成有作用。
干扰或阻断气道变应性疾病每一环节的药物都可称为抗过敏药物， 此类药物为哮喘防治的一线药物。 常用的药物有： ①色甘酸钠:可抑制肥 大细胞释放炎性介质，抑制嗜酸粒细胞、 中性粒细胞和肺泡巨噬细胞的激 活，具有抗气道变应性的炎症效应。 ②酮替芬； ③抗组胺药:可抑制肥大 细胞、 嗜酸粒细胞，嗜碱粒细胞及肺泡巨噬细胞等炎症细胞释放介质，该 类药物常用的有 ：苄酞嗪、 特非那定、 赛替利嗪、 息斯敏等药。
迄今为止， 尽管已报道了为数众多的哮喘治疗化合物， 但现在的大 多化合物是通过化学方法合成的， 其性质上决定了连续使用将不可避免 的产生各种副作用， 如抗过敏药引起嗜睡而影响患者的精神、 生活和工 作； 使用激素类药物引起高血压、 糖尿病、 肥胖症等疾病的发生或加重， 还因其副反馈抑制作用， 导致神经一内分泌一免疫功能紊乱， 长期使用 可引起内分泌腺的逐渐萎缩甚至丧失功能， 从而对人体的生理功能造成 更大的损害； 使用解痉平喘类药物因兴奋交感神经而影响心脏功能， 甚 至造成猝死等等。
另外， 过敏性鼻炎主要是由于过敏患者吸入过敏原 （如尘螨、 真菌、 花粉等）和已结合于肥大细胞、嗜酸粒细胞、 血小板等细胞上的特异 IgE 相结合， 引起这些细胞释放实症介质， 从而使鼻粘膜发生炎症。 炎症过 程包括炎症细胞和嗜酸粒细胞， 中性粒细胞等细胞浸润， 组织胺， LTS和 PG等原发和继发实症介质的释放， 以及嗜酸性细胞的激活致早期和晚期 反应。 现在常用的化合物药物也存在较多的副作用。 发明内容：
本发明的目的是提供一种完全不必担心化学药物所产生的副作用、 从植物沙棘种子中提取的具有诱导细胞凋亡、 抗过敏和抗炎作用的物质。
本发明的技术方案是以沙棘种子的有机溶剂提取物为活性物质， 经 过包括以下步骤的得到： 将沙棘种子经过乙醇浸泡提取重复 2次， 合并 这些提取液， 经减压浓缩得到褐色粉末提取物；
将该粉末提取物溶解在水中， 依次用乙醚、 乙酸乙酯、 丁醇作为提 取液分别提取三次；
浓缩乙醚组分， 得到褐色油；
取该褐色油上硅胶柱， 用乙酸乙酯洗脱， 收集洗脱组分。
其中上述乙醇浓度优选为 80%,
上述乙醇浸泡时间优选为 12小时；
上述乙酸乙酯的洗脱浓度优选为 15%。
该提取物具有诱导细胞调亡的活性。
该提取物具有诱导嗜酸粒细胞调亡的活性。
该提取物可以活化 MBP激酶。
该提取物对由过多的嗜酸粒细胞而引起的各种疾病起到诱导嗜酸粒 细胞调亡的作用。
该提取物对过敏性鼻炎起到诱导嗜酸粒细胞调亡的作用。
该提取物对特异反应性支气管哮喘起到诱导嗜酸粒细胞调亡的作 用。
本发明与现有技术相比有如下优点- 沙棘种子的提取物在减少嗜酸粒细胞的等方面显示出优异的效果， 可以用于有效的预防和治疗由过多的嗜酸粒细胞而引起的各种疾病， 也 就是说可以起到有效的预防和治疗过敏性鼻炎或特异反应性支气管哮喘 的作用。 可以用作为细胞凋亡诱导剂、 抗过敏剂、 抗炎剂和保健食品。 具体实施方式- 实施例 1 沙棘种子提取物的制备
将 6.7kg沙棘种子经过筛选去杂等预处理， 用 55L的 80%乙醇体积 比为乙醇：水 = 8 ： 2 (下同)浸泡 1 2小时。 然后再一次用 55L的 8 0 % 乙醇提取， 合并这些提取液， 经减压浓縮、真空干燥得到 1384.9g褐色粉 末提取物。
将 674.2g的该粉末提取物溶解在 2L的水中， 依次用 2 L乙醚、 2L 乙酸乙酯、 2L丁醇作为提取液分别提取三次。 然后浓缩乙醚组分， 得到 436.5g褐色油。上述各组分中，取 7.42g乙醚组分浓缩提取物上硅胶柱（和 光硅胶 C一 3 0 0和光纯药、 5 . 5 X 1 5 cm), 依次用 （ 1 ) 己垸 1 L、 ( 2 ) 5%乙酸乙酯 2.5L、 ( 3) 1 0 %乙酸乙酯 2L、 (4 ) 1 5%乙酸 乙酯 2L、 ( 5 ) 2 0 %乙酸乙酯 3. 5L、（ 6 ) 3 0 %乙酸乙酯 3L洗脱， 接着用 (7 ) 1 0 0 %乙酸乙酯 2.5 L洗脱。得到 (1)组分 (收率 45.4mg)、
( 2 ) 组分 (收率 2.9503g)、 ( 3 ) 组分 (收率 1.061g)、 ( 4 ) 组分 (收率 752.6mg)、 ( 5 ) 组分 (收率 521.3mg)、 ( 6 ) 组分 (收率 284.4mg)和 （ 7 ) 组分 (收率 104.7mg)。
实施例 2 嗜酸粒细胞性细胞凋亡诱导试验和 MBP激酶活性试验 嗜酸粒细胞性细胞凋亡诱导试验:试验根据 Vermes等的方法 (Journal of Immunological Methods 184卷 39-51页 1995年） 进行。 使嗜酸粒细胞 性细胞 HL-60细胞浮游于 RPMI1640培养基中，细胞浓度为 1-3χ106细胞 /mlo 向该细胞浮游液 500μ1中添加被检测物质 （上述实施例 1中最后收 集得到的组分之一） 或培养基， 使浓度为 100 μδ/πι1, 在 37° (、 5%C02 的条件下培养 6 小时或 24 小时。 离心洗净后， 加入磷脂酰结合蛋白 (Annexin)V缓冲液， 然后添加 5μ1磷脂酰结合蛋白 V-FITC。 通过流动血 细胞计数法， 以磷脂酰结合蛋白 V阳性细胞作为细胞凋亡诱导细胞， 用 相对总细胞数的百分比评价。
MBP 激酶活性试验： 试验根据 De Souza等的方法 （Blood 99 卷 3432-3438 页 2002 年） 进行。 将嗜酸粒细胞性细胞 HL-60 细胞浮游于 RPMI1640培养基， 细胞浓度为 l-3xl06细胞 /ml。 该细胞浮游液 500 μΐ 中添加被检测物质或培养基， 使浓度为 100 g/ml, 在 37° (、 5%C02的条 件下培养 6小时或 24小时。离心洗净后，添加可溶解缓冲液，溶解细胞， 使用含有 MBP5mg/ml的凝胶进行电泳。凝胶经脱变性、再变性处理后， 用 32P-ATP标记， 实施 3小时的磷酸化反应。凝胶干燥后， 使用图象分析 仪解析放射活性。 在 36 kDa生长出标记带时， 记做 MBP激酶活化阳性
( + )。
沙棘种子提取物在 HL- 60细胞中观察到了浓度依赖性的细胞凋亡诱 导。 另外进行凝胶 MBP激酶分析 (In- gel MBP kinase assay)时， 沙棘种 子提取物激活 36 kDa MBP激酶。 以上结果提示， 沙棘种子提取物对嗜酸 粒细胞能诱导细胞凋亡， 该细胞凋亡与 36 kDa MBP激酶有关。 由此推断 沙棘种子提取物中含有可以用于抗嗜酸粒细胞性炎症作用药物的成分。
所得结果如下表 1所示：
确认提取物 4具有强的细胞凋亡诱导活性，并伴有 MBP激酶的活化。 表 1
细胞凋亡诱发率 （％) MBP激
6小时 2 4小时 酶活化 空白 21.0 22.5 ― 沙棘种子乙醚提取物 1 25.0 57.5 + 沙棘种子乙醚提取物 2 16.4 37.0 ― 沙棘种子乙醚提取物 3 15.6 17.8 ― 沙棘种子乙醚提取物 4 43.7 92.9 + 沙棘种子乙醚提取物 5 15.6 31.7 ― 沙棘种子乙醚提取物 6 35.8 42.9 + 沙棘种子乙醚提取物 7 29.1 39.8 +

Claims

权利要求
1、 一种沙棘种子提取物， 其特征在于经过以下方法得到：
将沙棘种子经过乙醇浸泡提取重复 2次， 合并这些提取液， 经减压 浓缩得到褐色粉末提取物；
将该粉末提取物溶解在水中， 依次用乙醚、 乙酸乙酯、 丁醇作为提 取液分别提取三次；
浓缩乙醚组分， 得到褐色油；
取该褐色油上硅胶柱， 用乙酸乙酯洗脱， 收集洗脱组分。
2、 如权利要求 1所述的提取物， 其特征在于所述乙醇浓度为 80%。
3、如权利要求 1所述的提取物，其特征在于所述乙醇浸泡时间为 12 小时。
4、 如权利要求 1所述的提取物， 其特征在于所述乙酸乙酯的洗脱浓 度为 15%。
5、 如权利要求 1所述的提取物， 其特征在于该提取物具有诱导细胞 调亡的活性。
6、 如权利要求 1所述的提取物， 其特征在于该提取物具有诱导嗜酸 粒细胞调亡的活性。
7、如权利要求 2所述的提取物，其特征在于该提取物可以活化 MBP 激酶。
8、 如权利要求 3所述的提取物， 其特征在于该提取物对由过多的嗜 酸粒细胞而引起的各种疾病起到诱导嗜酸粒细胞调亡的作用。
9、 如权利要求 3所述的提取物， 其特征在于该提取物对过敏性鼻炎 起到诱导嗜酸粒细胞调亡的作用。
10、 如权利要求 3所述的提取物， 其特征在于该提取物对特异反应 性支气管哮喘起到诱导嗜酸粒细胞调亡的作用。
PCT/CN2004/000172 2004-03-04 2004-03-04 Extrait de la graine de hippophae rhamnoides Ceased WO2005084693A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP2007501094A JP4714908B2 (ja) 2004-03-04 2004-03-04 沙棘種子抽出物
PCT/CN2004/000172 WO2005084693A1 (fr) 2004-03-04 2004-03-04 Extrait de la graine de hippophae rhamnoides
CNB200480042278XA CN100402047C (zh) 2004-03-04 2004-03-04 沙棘种子提取物

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2004/000172 WO2005084693A1 (fr) 2004-03-04 2004-03-04 Extrait de la graine de hippophae rhamnoides

Publications (2)

Publication Number Publication Date
WO2005084693A1 true WO2005084693A1 (fr) 2005-09-15
WO2005084693A8 WO2005084693A8 (en) 2006-09-21

Family

ID=34916990

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2004/000172 Ceased WO2005084693A1 (fr) 2004-03-04 2004-03-04 Extrait de la graine de hippophae rhamnoides

Country Status (3)

Country Link
JP (1) JP4714908B2 (zh)
CN (1) CN100402047C (zh)
WO (1) WO2005084693A1 (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9687517B2 (en) 2007-12-20 2017-06-27 Elc Management Llc Methods and compositions for treating skin
US9782448B2 (en) 2007-12-20 2017-10-10 Elc Management Llc Methods and compositions for treating skin

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2010347755B2 (en) * 2010-03-08 2014-02-06 Elc Management Llc Compositions and methods for treating skin
CN102755359B (zh) * 2012-07-19 2014-04-02 中国科学院研究生院 一种沙棘提取物及其制备方法与在抑制脂肪酸合酶活性中的应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1169864A (zh) * 1996-07-02 1998-01-14 赤峰制药厂 一种止咳平喘药物
CN1220886A (zh) * 1997-12-26 1999-06-30 高文清 咳喘胶囊及制作工艺
DE20203549U1 (de) * 2002-03-05 2002-10-17 Eckardt Rainer Pflege und Heilsalbe zur Behandlung trockener oder entzündeter Nasenschleimhaut
CN1473576A (zh) * 2002-08-06 2004-02-11 河北神兴沙棘研究院 沙棘全果素及其制备方法和用途
CN1504467A (zh) * 2002-12-05 2004-06-16 河北神兴沙棘研究院 沙棘叶总黄酮提取工艺

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0615555B2 (ja) * 1985-08-14 1994-03-02 三共株式会社 抗生物質ゾフイマリン
JPH10120585A (ja) * 1996-10-15 1998-05-12 Pola Chem Ind Inc 美白経口投与組成物
RU2132183C1 (ru) * 1998-10-16 1999-06-27 Утешев Даниил Борисович Мазь для лечения воспалительных и аллергических поражений кожи
JP2001163792A (ja) * 1999-12-08 2001-06-19 Koji Tanaka 滋養強壮健康増進用組成物
JP2002212052A (ja) * 2001-01-15 2002-07-31 Hajime Ito 外用組成物
WO2003084556A1 (en) * 2002-04-04 2003-10-16 Kaneka Corporation Process for producing fat composition containing hydrophobic components of glycyrrhiza

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1169864A (zh) * 1996-07-02 1998-01-14 赤峰制药厂 一种止咳平喘药物
CN1220886A (zh) * 1997-12-26 1999-06-30 高文清 咳喘胶囊及制作工艺
DE20203549U1 (de) * 2002-03-05 2002-10-17 Eckardt Rainer Pflege und Heilsalbe zur Behandlung trockener oder entzündeter Nasenschleimhaut
CN1473576A (zh) * 2002-08-06 2004-02-11 河北神兴沙棘研究院 沙棘全果素及其制备方法和用途
CN1504467A (zh) * 2002-12-05 2004-06-16 河北神兴沙棘研究院 沙棘叶总黄酮提取工艺

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9687517B2 (en) 2007-12-20 2017-06-27 Elc Management Llc Methods and compositions for treating skin
US9782448B2 (en) 2007-12-20 2017-10-10 Elc Management Llc Methods and compositions for treating skin

Also Published As

Publication number Publication date
JP2007526260A (ja) 2007-09-13
WO2005084693A8 (en) 2006-09-21
CN100402047C (zh) 2008-07-16
JP4714908B2 (ja) 2011-07-06
CN1972700A (zh) 2007-05-30

Similar Documents

Publication Publication Date Title
TWI501772B (zh) 具抗關節炎活性的到手香精萃物
CN103417601B (zh) 一种具有调节血脂作用的药物组合物及其用途
KR101418239B1 (ko) 파프리카 추출물을 함유하는 염증, 알레르기 또는 천식 질환 치료용 조성물
CN110496143A (zh) 东革阿里提取物、其制备方法、以及其用途
CN114957172B (zh) 一种黑果枸杞抗炎活性成分的分离方法及活性成分在抗炎产品中的应用
JP2009510051A (ja) 炎症性疾患のための薬草組成物
CN100402047C (zh) 沙棘种子提取物
CN101036646B (zh) 苦木总生物碱及其单体生物碱的医药用途
JP2000154151A (ja) 免疫抑制剤
JP6076361B2 (ja) 胃潰瘍の治療用医薬の調製におけるＡｌｂｉｚｚｉａｃｈｉｎｅｎｓｉｓ抽出物の応用
WO2007113698A2 (en) Preventative treatment and remission of allergic diseases
CN1188406C (zh) 蒲黄提取物及其制备方法和用途
KR20120035741A (ko) 퀘르세타제틴을 함유하는 아토피피부염의 예방 또는 치료용 조성물
CN109419787B (zh) 一种松香烷型二萜类化合物的用途
JP2019089759A (ja) カジメ抽出物およびこれを活性成分として含む血管疾患を予防または処置するための医薬組成物
CN111358826B (zh) 一种具有抗抑郁作用的总黄酮提取物及其制备方法和应用
CN101450093A (zh) 淫羊藿总黄酮在制备靶器官保护药物中的用途
CN101304756B (zh) 用于炎性病症的草药组合物
CN115025141A (zh) 白背叶楤木总皂苷及其制备方法和应用
CN107129478A (zh) 一种半萜内酯类化合物及其制备方法和应用
CN106632378A (zh) 一种可抑制肥大细胞脱颗粒的化合物及其制备方法和用途
CN116120389B (zh) 人参皂苷Rg5及制备和在制备过敏性鼻炎药物中的应用
JP6595196B2 (ja) 抗アレルギー剤
AU2020101397A4 (en) A pharmaceutical composition for the treatment of prostatic hyperplasia
CN116262114B (zh) 一种邻羟基苯甲酸苄酯及其药物组合物与用途

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2007501094

Country of ref document: JP

Ref document number: 200480042278.X

Country of ref document: CN

NENP Non-entry into the national phase

Ref country code: DE

WWW Wipo information: withdrawn in national office

Country of ref document: DE

122 Ep: pct application non-entry in european phase