降红木素|降胭脂树橙标准品 | 542-40-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 降红木素|降胭脂树橙标准品
• 中文别名: 降红木素
• 英文名称: Norbixin
• 英文别名: (2E,4E,6E,8E,10E,12E,14E,16E,18E)-4,8,13,17-tetramethylicosa-2,4,6,8,10,12,14,16,18-nonaenedioic acid
• CAS: 542-40-5
• 化学式: C₂₄H₂₈O₄
• 分子量: 380.5
• InChiKey: ZVKOASAVGLETCT-UOGKPENDSA-N

物化性质

• 熔点：
  240 °C (decomp)
• 沸点：
  640.4±28.0 °C(Predicted)
• 密度：
  1.069±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO（微溶）、甲醇（微溶、超声处理）
• LogP：
  5.532 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

ADMET

毒理性

• 相互作用

胭脂树红（AN），一种富含类胡萝卜素的天然食品色素，据报道是一种有效的抗氧化剂，但其潜在的化学预防特性知之甚少。在这项研究中，研究人员评估了AN保护人肝癌细胞（HepG2）免受三种不同诱变剂：苯并(a)芘（B(a)P）、阿霉素（DXR）和甲基甲磺酸（MMS）诱导微核（MN）的能力。为了澄清AN抗诱变性的可能机制，应用了三种处理方案（预处理；同时处理，以及在用诱变剂处理后进行AN的后处理）。此外，还检测了仅暴露于AN的细胞的细胞毒性和诱变性。AN的剂量高达10微克/毫升没有诱变性。在使用预处理和同时处理时，B(a)P和DXR诱导的微核显示出保护作用，但在任何方案中，AN对MMS诱导的MN没有显著影响。...结果还显示，将细胞暴露于高于10微克/毫升的AN浓度会降低细胞活力。综合这些发现表明，AN在体外具有抗诱变活性，但其保护作用取决于诱变剂和处理类型，这表明它可能用作化学预防剂。

Annatto (AN), a natural food colorant rich in carotenoids, has been reported as being an effective antioxidant, but little is known about its potential chemopreventive properties. In this study, /investigators/ evaluated the ability of AN to protect human hepatoma cells (HepG2) from micronucleus (MN) induction against three different mutagens: benzo(a)pyrene (B(a)P), doxorubicin (DXR), and methyl methanesulfonate (MMS). In an attempt to clarify the possible mechanism of antimutagenicity of AN, three protocols of treatment were applied (pretreatment; simultaneous treatment, and post-treatment with AN following treatment with the mutagens). Also, cells exposed only to AN were assayed for cytotoxicity and mutagenicity. A dosage up to 10 ug/mL of AN was devoid of mutagenic activity. Protective effects were seen on micronuclei induced by B(a)P and DXR using /pre-treatment/ and simultaneous treatment, but AN had no significant effect on MN induction by MMS in any of the protocols. ... /The/ results also show that exposure of cells to concentrations of AN higher than 10 ug/mL decreased cell viability. Taken together /these/ findings indicate that AN presents antimutagenic activity in vitro, but its protective effect is dependent on the mutagen and on type of treatment suggesting its potential use as a chemopreventive agent.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

本研究评估了胭脂树红（Bixa orellana L.），一种富含类胡萝卜素的天然食品色素，对由二甲肼（DMH）在大鼠结肠中诱导的异常隐窝灶（ACF）形成的影响。此外，作者还通过彗星试验调查了胭脂树红对DMH诱导的DNA损伤的影响。雄性Wistar大鼠每周两次皮下注射DMH（40 mg/kg体重）共2周以诱导ACF。它们还接受了含有20、200或1000 ppm胭脂树红的实验性饮食，为期5周，分别在DMH处理前（预处理）或处理后（后处理）10周。在这两种方案中，大鼠在第15周被处死。对于彗星试验，动物被喂食相同的实验性饮食2周。在处死前4小时，动物接受了皮下注射DMH（40 mg/kg体重）。在这种情况下，饮食中添加1000 ppm胭脂树红既没有在大鼠血液和结肠细胞中诱导DNA损伤，也没有在大鼠远端结肠中诱导异常隐窝灶。相反，胭脂树红在抑制每个结肠的隐窝数量方面是成功的，但主要是在DMH之后给药时，并没有在DMH诱导的ACF的发生率上。然而，在结肠细胞中没有观察到抗诱变效应。这些发现表明，胭脂树红可能通过调节隐窝细胞增殖而具有化学预防作用，但不是在结肠癌变的起始阶段。

... /The/ present study... /evaluated/ the activity of annatto (bixa orellana l.), a natural food colorant rich in carotenoid, on the formation of aberrant crypt foci (ACF) induced by dimethylhydrazine (DMH) in rat colon. Further, /the authors/ investigate, the effect of annatto on DMH-induced DNA damage, by the comet assay. Male Wistar rats were given sc. Injections of DMH (40 mg/kg body wt) twice a week for 2 weeks to induce ACF. They also received experimental diets containing annatto at 20, 200 or 1000 ppm for five 5 weeks before (pre-treatment), or 10 weeks after (post-treatment) DMH treatment. In both protocols the rats were sacrificed on week 15th. For the comet assay, the animals were fed with the same experimental diets for 2 weeks. Four hours before the sacrifice, the animals received an sc injection of DMH (40 mg/kg body wt.). Under such conditions, dietary administration of 1000 ppm annatto neither induce DNA damage in blood and colon cells nor aberrant crypt foci in rat distal colon. Conversely, annatto was successful in inhibiting the number of crypts/colon (animal), but not in the incidence of DMH-induced ACF, mainly when administered after DMH. However, no antigenotoxic effect was observed in colon cells. These findings suggest possible chemopreventive effects of annatto through their modulation of the cryptal cell proliferation but not at the initiation stage of colon carcinogenesis.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

胡萝卜素是40碳分子，具有共轭双键，这使得它们特别有效地淬灭自由基。...研究评估了 norsixin 对大肠杆菌细胞对紫外线辐射、过氧化氢和超氧阴离子引起的 DNA 损伤反应的影响，发现 norbixin 可以保护细胞免受这些因素的伤害。Norbixin 至少增强了10倍的存活率。当细胞在 norbixin 的存在下生长时，UVC 引发的 SOS 诱导被抑制了2.3倍。研究者发现 norbixin 具有抗突变性，根据沙门氏菌突变性测试，对过氧化氢诱导的突变活性的最大抑制率为87%。Norbixin

Carotenoids are 40-carbon molecules with conjugated double bonds, making them particularly effective for quenching free radicals. ... /The study/ evaluated the effect of norbixin on the response of Escherichia coli cells to DNA damage induced by UV radiation, hydrogen peroxide and superoxide anions and found that norbixin protects the cells against these agents. Norbixin enhanced survival at least 10 times. The SOS induction by UVC was inhibited 2.3 times more when cells were grown in the presence of norbixin. /Investigators/ found that norbixin has antimutagenic properties, with a maximum inhibition of /hydrogen peroxide/-induced mutagenic activity of 87%, based on the Salmonella mutagenicity test. /Norbixin/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

已经进行了多项研究，以探讨类胡萝卜素（包括辣椒红素）可能的抗诱变作用，以及它们在防止由辐射或化学品引起的细胞损伤方面的保护作用。例如，一些研究表明，辣椒红素能够提供对大鼠因辐照引起的染色体损伤的保护，并且能够抑制过氧化氢（H2O2）在鼠伤寒沙门氏菌TA102株中的诱变活性。

A number of studies have been carried out to look at the possible anti-mutagenic action of carotenoids, including bixin, and their protective role in preventing cell damage induced by radiation or chemicals. For example, some studies have shown that bixin can provide protection against chromosomal damage induced by irradiation in rats and can also inhibit the mutagenic activity of hydrogen peroxide (H2O2) in Salmonella typhimurium strain TA102. /Bixin/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下），以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗救助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

单次口服剂量含0.1%胭脂红（0.22%辣椒红素）和热降解产物的溶液（在植物油/OSB中为7 mg/kg），0.2%胭脂红（主要是辣椒红素，1.84%）的悬浮液（在植物油中）R10（7 mg/kg）以及0.1%胭脂红（主要是非辣椒红素，0.27%）的水溶性制剂WSA（14 mg/kg）给予成年男性志愿者，并分析了血液和排泄物中的胭脂红色素。血液样本在治疗后的2-12小时内采集，尿液在剂量后的7小时内收集，粪便在治疗日后的两天内收集。WSA（14 mg/kg）在2-1/4小时后产生了12 ug/mL的血液水平，相当于剂量的6%。OSB（7 mg/kg）在3小时后产生了2.4 ug/mL的血液水平，相当于剂量的2.4%。R10（7 mg/kg）在3-1/4小时后产生了0.44 ul/mL的血液水平，相当于剂量的0.32%。WSA（14 mg/kg）、OSB（7 mg/kg）和R10（7 mg/kg）分别在6小时后血液水平恢复到零。尿液中未检测到胭脂红色素，第二天收集的粪便样本中也没有检测到。治疗第二天收集的粪便中含有0.17 mg R10（剂量的0.03%）和0.44 mg WSA（剂量的0.06%），但未检测到与OSB消费相关的色素。因此，与大鼠一样，胭脂红色素被吸收并迅速从血液中清除。

Single oral doses of /solution containing 0.1% annatto (0.22% bixin) and thermal degradation products, in vegetable oil/ OSB (7 mg/kg), /suspension of 0.2% annatto (mainly bixin, 1.84%), in vegetable oil) R10 (7 mg/kg) and a water-soluble preparation of 0.1% annatto (mainly norbixin, 0.27%) WSA (14 mg/kg) were given to adult male /volunteers/ and the blood and excreta were analyzed for annatto pigments. Blood samples were taken between 2-12 hours after treatment, urine was collected during 7 hours after the dose and feces over the 2 days following the day of treatment. WSA (14 mg/kg) produced a blood level of 12 ug/mL after 2-1/4 hours which corresponds to 6% of the dose. OSB (7 mg/kg) produced a blood level of 2.4 ug/mL after 3 hours which corresponds to 2.4% of the dose. R10 (7 mg/kg) produced a blood level of 0.44 ul/mL after 3-1/4 hours which corresponds to 0.32% of the dose. Blood levels had returned to zero 6 hours after WSA (14 mg/kg), OSB (7 mg/kg) and R10 (7 mg/kg) respectively. No annatto pigments were detected in the urine samples and none were detected in feces samples collected the next day. The feces collected the second day after treatment contained 0.17 mg R10 (0.03% of the dose) and 0.44 mg WSA (0.06% of the dose) but no pigments associated with the consumption of OSB were detected. Thus, as in the rat, the annatto pigments were absorbed and rapidly cleared from the blood.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

开发了一种使用反相高效液相色谱（HPLC）技术来测定人血浆中辣椒红素和去氢辣椒红素浓度的方法，灵敏度为5微克/升。在正常早餐后，七名男女志愿者各自摄入了一份单一剂量的商业胭脂红食品色素，其中含有16毫克顺式辣椒红素和大约0.5毫克顺式去氢辣椒红素，溶解在大豆油中，随后喝了一杯牛奶。在摄入后0、2、4、6和8小时分别采集血样；在一些受试者中，24小时和48小时后还额外采集了样本。6小时后没有控制食物摄入。受试者血浆中辣椒红素和去氢辣椒红素的平均浓度和范围见所提供的表格。

A technique /was developed/ using reversed-phase high-performance liquid chromatography (HPLC) to determine concentrations of bixin and norbixin in human plasma, to a sensitivity of 5 ug/L. After a normal breakfast, seven male and female volunteers each ingested a single dose of 1 mL of a commercial annatto food color containing 16 mg of cis-bixin and approximately 0.5 mg of cis-norbixin in soya bean oil, followed by a glass of milk. Blood samples were taken 0, 2, 4, 6 and 8 hr after ingestion; in some subjects, additional samples were taken after 24 and 48 hr. No control of food intake was made after 6 hr . The average values and range of concentrations of bixin and norbixin in the plasma of the subjects are shown in the table provided.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在一项为期4周的研究中，四只雄性和四只雌性Wistar大鼠被喂食含有0%或5%的溶液，该溶液含有0.1%的胭脂红（0.22%的辣椒红）和热降解产物，在植物油（OSB）中，或含有0.02%胭脂红（主要是辣椒红，1.84%）的植物油悬浮液（R10），或含有0.1%胭脂红（主要是诺必辛，0.27%）的水溶性制剂（WSA）。动物接受以下其中一种饮食：（1）在前两周喂食含有胭脂红提取物的饮食，后两周喂食正常饮食；或（2）先喂食两周正常饮食，然后喂食含有胭脂红提取物的饮食两周。在连续两周接受胭脂红提取物后立即处死的动物血液中观察到了可测量的黄色颜料，但在胭脂红提取物治疗停止后两周处死的动物中，仅检测到微量。在OSB和R10处理的动物脂肪组织中发现了黄色颜料，而在接受WSA的动物中未发现。对这些颜料的色谱分析确认它们不是主要的胭脂红颜料（辣椒红或诺必辛）。在治疗停止后立即处死的动物与治疗停止两周后处死的动物相比，脂肪的脱色程度也有明显差异，表明颜料的清除是迅速的。在治疗的第二周收集粪便并分析颜料含量。大约20%的OSB和WSA给药剂量以及大约55%的R10未改变地从粪便中回收。

In a 4-week study, groups of four male and four female Wistar rats were fed diets containing 0% or 5% of a solution containing 0.1% annatto (0.22% bixin) and thermal degradation products, in vegetable oil (OSB), a suspension containing 0.02% annatto (mainly bixin, 1.84%), in vegetable oil (R10) or a water-soluble preparation containing 0.1% annatto (mainly norbixin, 0.27%) (WSA). Animals received either: (1) diet containing annatto extract during the first 2 weeks and normal diet for the second 2 weeks; or (2) normal diet for 2 weeks followed by the diet containing annatto extract for 2 weeks. In the animals that were killed immediately after receiving annatto extract for 2 weeks, measurable amounts of yellow pigment were observed in the blood, but in animals that were killed 2 weeks after treatment with annatto extract had stopped, only trace amounts were detected. Yellow pigment was also found in the adipose tissue of animals treated with OSB and R10, but not in animals receiving WSA. Chromatographic analysis of these pigments confirmed that they were not major annatto pigments (bixin or norbixin). There was also a clear difference in the degree of discoloration of the fat in animals killed immediately after cessation of treatment, compared with that in animals killed 2 weeks after treatment had stopped, indicating that clearance of the pigment was rapid. Feces were collected during the second week of treatment and analyzed for pigment content. About 20% of the administered dose of OSB and WSA and about 55% of R10 was recovered unchanged from the feces.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在口服给予辣椒红B 100或1000 mg/kg体重后，雄性和雌性大鼠血浆中出现了以下化学物质：9'顺式辣椒红素、反式辣椒红素（保留时间，26分钟）、9'顺式去甲辣椒红素、反式去甲辣椒红素、二顺式去甲辣椒红素以及一个保留时间为6.8分钟的去甲辣椒红素同分异构体。在给予辣椒红E（在两种浓度下）后，在两性的血浆中检测到了上述同分异构体以及一个保留时间为267分钟的反式辣椒红素物种。相比之下，在给予辣椒红F（在两种剂量下）后，仅在雄性和雌性大鼠的血浆中出现了去甲辣椒红素同分异构体（9'顺式去甲辣椒红素、反式去甲辣椒红素、二顺式去甲辣椒红素和保留时间为6.8分钟的同分异构体）。尽管辣椒红B和E含有超过90%的9'顺式辣椒红素，但在给予辣椒红B、E或F后，9'顺式去甲辣椒红素的血浆浓度高于9'顺式辣椒红素。每种提取物在雄性和雌性中的主要组分的Tmax为2-4小时；到12小时时，只剩下微量的辣椒红素，尽管去甲辣椒红素的浓度在24小时时仍然可以测量到。当口服剂量从100 mg/kg体重增加到1000 mg/kg体重时，辣椒红B（9'顺式辣椒红素）、辣椒红E（9'顺式辣椒红素）和辣椒红F（9'顺式去甲辣椒红素）的主要组分的血浆浓度增加了。

After dosing orally with annatto B at 100 or 1000 mg/kg bw, the following chemical species were present in the plasma of male and female rats: 9'cisbixin, trans-bixin (retention time, 26 min), 9'cis-norbixin, trans-norbixin, di cis-norbixin and a norbixin isomer with retention time, 6.8 min. After dosing with annatto E (at both concentrations), the above isomers plus an additional trans-bixin species with retention time of 267 min were detected in the plasma of both sexes. In contrast, after administration of annatto F (at both doses), only the norbixin isomers (9'cis-norbixin, trans-norbixin, di cis-norbixin and the isomer with a retention time 6.8 minutes) were present in the plasma of male and female rats. Plasma concentrations of 9'cis-norbixin were higher than those of 9'cis-bixin after the administration of annatto B, E or F, despite the fact that annatto B and E contain >90% 9'cis-bixin. The Tmax for the major component in plasma for each extract in males and females at both doses was 2-4 hr; by 12 hr, only trace amounts of bixin remained, although concentrations of norbixin were still measurable at 24 hr. When the oral dose was raised from 100 mg/kg bw to 1000 mg/kg bw, the plasma concentrations of the major components of annatto B (9'cis-bixin), annatto E (9'cis-bixin) and annatto F (9'cis-norbixin) were increased.

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

食品添加剂最大允许使用量及残留量标准

添加剂中文名称	允许使用该种添加剂的食品中文名称	添加剂功能	最大允许使用量（g/kg）	最大允许残留量（g/kg）
胭脂树橙（红木素，降红木素）	油炸小食品（仅限油炸薯片）	着色剂	0.01
胭脂树橙（红木素，降红木素）	饮料类（14.01包装饮用水类除外）	着色剂	0.02（固体饮料按冲调倍数增加使用量）
胭脂树橙（红木素，降红木素）	复合调味料	着色剂	0.1
胭脂树橙（红木素，降红木素）	肉灌肠类	着色剂	0.025
胭脂树橙（红木素，降红木素）	西式火腿（熏烤、烟熏、蒸煮火腿）类	着色剂	0.025
胭脂树橙（红木素，降红木素）	糕点	着色剂	0.015
胞脂树橙（红木素，降红木素）	方便米面制品	着色剂	0.012
胭脂树橙（红木素，降红木素）	即食谷物，包括碾轧燕麦（片）	着色剂	0.07
胞脂树橙（红木素，降红木素）	面糊（如用于鱼和禽肉的拖面糊）、裹粉、煎炸粉	着色剂	0.01
胭脂树橙（红木素，降红木素）	巧克力和巧克力制品、除05.01.01以外的可可制品	着色剂	0.025
胞脂树橙（红木素，降红木素）	其他油脂或油脂制品（仅限植脂末）	着色剂	0.02
胭脂树橙（红木素，降红木素）	人造黄油及其类似制品（如黄油和人造黄油混合品）	着色剂	0.05
胞脂树橙（红木素，降红木素）	再制干酪	着色剂	0.6

反应信息

• 作为反应物：
  描述：

  9'Z-neochrome 、 13-cis-β-carotene 、 、 neoxanthin 、 、 链孢霉黄素 、 Neurosporaxanthin-methylester 、 (6E,8E,10Z,12E,14Z,16E,18Z,20E,22E,26E)-2,6,10,14,19,23,27,31-八甲基三十二碳-2,6,8,10,12,14,16,18,20,22,26,30-十二烯 、 (E)-4-[(5S)-5-[(1E,3E,5E,7E,9E,11E,13E,15E,17E,19E)-3,7,12,16,20,24-hexamethylpentacosa-1,3,5,7,9,11,13,15,17,19,23-undecaenyl]-4,6,6-trimethylcyclohex-3-en-1-yl]-2-methylbut-2-en-1-ol 、 、 降红木素|降胭脂树橙标准品 、 nostoxanthin 生成 Lactucaxanthin
  参考文献：
  名称：

  Pharmaceutical compositions including carotenoid ether analogs or derivatives for the inhibition and amelioration of disease

  摘要：

  一种抑制和/或改善与反应性氧化物种、反应性氮物种、自由基和/或非自由基有关的疾病发生的方法，其中给予受试者类胡萝卜素类似物或衍生物，单独或与另一类胡萝卜素类似物或衍生物或共同抗氧化剂配方结合使用。该类似物或衍生物的给予使得受试者发生与反应性氧化物种、反应性氮物种、自由基和/或非自由基有关的疾病的风险减少。该类似物或类似物组合可用于抑制和/或改善任何涉及反应性氧化物种、反应性氮物种、自由基和/或非自由基产生的疾病。在某些实施例中，该发明可能包括包括类胡萝卜素类似物或衍生物的药物组合物。类胡萝卜素类似物可能包括具有7到14个双键的共轭多烯。共轭多烯可能包括至少一个取代基的环状环。在某些实施例中，类胡萝卜素类似物或衍生物的环状环中可能包括至少一个取代基。该取代基可能通过醚功能与环状环耦合。在某些实施例中，药物组合物可能包括生物学上不活性的载体。该药物组合物可能适用于人类受试者的给予。

  公开号：

  US07375133B2
• 作为产物：
  描述：

  bixin 以30的产率得到降红木素|降胭脂树橙标准品
  参考文献：
  名称：

  Helvetica Chimica Acta 2009, 92, 1741-1747

  摘要：

  DOI：

文献信息

• Hydroxylated nebivolol metabolites
  申请人：O'Donnell P. John

  公开号：US20070014733A1

  公开（公告）日：2007-01-18

  Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

  羟基化奈必洛尔代谢物在急性给药后以浓度依赖性方式增加人内皮细胞制剂的一氧化氮释放。此外，羟基化奈必洛尔代谢物，包括但不限于4-羟基-6,6'-二氟代-、4-羟基-5-苯酚-6,6'-二氟代-和4-羟基-8-苯并-6,6'-二氟代-，在慢性给药后能够增加人内皮细胞的一氧化氮释放能力。本发明提供了羟基化奈必洛尔代谢物和包含奈必洛尔和/或至少一种羟基化奈必洛尔代谢物和/或至少一种用于治疗心血管疾病的附加化合物的组合物，以及可药用的盐。此外，本发明还提供了通过给药至少一种能够释放治疗有效量的一氧化氮到受血管疾病影响的靶向部位的羟基化奈必洛尔代谢物来治疗和/或预防血管疾病的方法。本发明还涉及通过给药至少一种羟基化奈必洛尔代谢物来治疗和/或预防偏头痛。本发明还可以与治疗代谢综合征障碍的其他治疗联合使用，或作为单一治疗。
• Carotenoid analogs or derivatives for controlling connexin 43 expression
  申请人：Lockwood Fournier Samuel

  公开号：US20050009930A1

  公开（公告）日：2005-01-13

  A method of controlling (e.g., influencing or affecting) connexin 43 expression in a subject may include administering to the subject an effective amount of a pharmaceutically acceptable formulation. In some embodiments, controlling connexin 43 expression in a subject may effectively treat cardiac arrhythmia and/or cancerous and pre-cancerous cells in a subject. The pharmaceutically acceptable formulation may include a synthetic analog or derivative of a carotenoid. The subject may be administered a carotenoid analog or derivative, either alone or in combination with another carotenoid analog or derivative, or co-antioxidant formulation. The carotenoid analog may include a conjugated polyene with between 7 to 14 double bonds. The conjugated polyene may include an acyclic alkene including at least one substituent and/or a cyclic ring including at least one substituent. In some embodiments, a carotenoid analog or derivative may include at least one substituent.

  在一个主体中控制（例如，影响或影响）连接蛋白43表达的方法可能包括向该主体施用有效量的药学上可接受的配方。在某些实施例中，控制主体中连接蛋白43的表达可能有效治疗心律失常和/或癌症和癌前细胞。药学上可接受的配方可能包括类胡萝卜素的合成类似物或衍生物。可以向主体施用类胡萝卜素类似物或衍生物，单独或与另一类胡萝卜素类似物或衍生物或共抗氧化剂配方结合使用。类胡萝卜素类似物可能包括具有7到14个双键的共轭聚烯。共轭聚烯可能包括至少一个取代基的非环烯烃和/或至少一个取代基的环状环。在某些实施例中，类胡萝卜素类似物或衍生物可能包括至少一个取代基。
• Carotenoid analogs or derivatives for the inhibition and amelioration of liver disease
  申请人：Lockwood Fournier Samuel

  公开号：US20050004235A1

  公开（公告）日：2005-01-06

  A method of treating liver disease in a subject. The method may include administering to the subject an effective amount of a pharmaceutically acceptable formulation. The pharmaceutically acceptable formulation may include a synthetic analog or derivative of a carotenoid. The subject may be administered a carotenoid analog or derivative, either alone or in combination with another carotenoid analog or derivative, or co-antioxidant formulation. The carotenoid analog may include a conjugated polyene with between 7 to 14 double bonds. The conjugated polyene may include an acyclic alkene including at least one substituent and/or a cyclic ring including at least one substituent. In some embodiments, a carotenoid analog or derivative may include at least one substituent.

  一种治疗主体肝病的方法。该方法可能包括向主体施用有效量的药学上可接受的配方。药学上可接受的配方可能包括类胡萝卜素的合成类似物或衍生物。可以向主体施用类胡萝卜素类似物或衍生物，单独或与另一种类胡萝卜素类似物或衍生物或共抗氧化剂配方结合。类胡萝卜素类似物可能包括具有7到14个双键的共轭聚烯烃。共轭聚烯烃可能包括至少一个取代基的无环烯烃和/或至少一个取代基的环状环。在某些实施例中，类胡萝卜素类似物或衍生物可能包括至少一个取代基。
• Carotenoid ether analogs or derivatives for the inhibition and amelioration of disease
  申请人：Lockwood Fournier Samuel

  公开号：US20050009758A1

  公开（公告）日：2005-01-13

  A method for inhibiting and/or ameliorating the occurrence of diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals in a subject whereby a subject is administered a carotenoid analog or derivative, either alone or in combination with another carotenoid analog or derivative, or co-antioxidant formulation. The analog or derivative is administered such that the subject's risk of experiencing diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals may be thereby reduced. The analog or analog combination may be administered to a subject for the inhibition and/or amelioration of any disease that involves production of reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals. In some embodiments, the invention may include a chemical compound including an at least partially water soluble carotenoid analog or derivative. The carotenoid analog may include a conjugated polyene with between 7 to 14 double bonds. The conjugated polyene may include a cyclic ring including at least one substituent. In some embodiments, a cyclic ring of a carotenoid analog or derivative may include at least one substituent. The substituent may be coupled to the cyclic ring with an ether functionality.

  一种抑制和/或改善与主体中的活性氧化物种、活性氮物种、自由基和/或非自由基相关疾病发生的方法，其中向主体施用类胡萝卜素类似物或衍生物，单独或与另一类胡萝卜素类似物或衍生物或共抗氧化剂配方结合。类似物或衍生物的施用使得主体发生与活性氧化物种、活性氮物种、自由基和/或非自由基相关疾病的风险可能降低。类似物或类似物组合可用于抑制和/或改善涉及活性氧化物种、活性氮物种、自由基和/或非自由基产生的任何疾病。在某些实施例中，该发明可能包括一种包括至少部分水溶性类胡萝卜素类似物或衍生物的化合物。类胡萝卜素类似物可能包括具有7到14个双键的共轭聚烯。共轭聚烯可能包括包括至少一个取代基的环状环。在某些实施例中，类胡萝卜素类似物或衍生物的环状环可能包括至少一个取代基。该取代基可能通过醚功能基与环状环相耦合。
• Carotenoid ether analogs or derivatives for controlling C-reactive protein levels
  申请人：Lockwood Fournier Samuel

  公开号：US20050049248A1

  公开（公告）日：2005-03-03

  A method of controlling (e.g., influencing or affecting) C-reactive protein levels in a subject may include administering to the subject an effective amount of a pharmaceutically acceptable formulation. The pharmaceutically acceptable formulation may include a synthetic analog or derivative of a carotenoid. The subject may be administered a carotenoid analog or derivative, either alone or in combination with another carotenoid analog or derivative, or co-antioxidant formulation. The carotenoid analog may include a conjugated polyene with between 7 to 14 double bonds. The conjugated polyene may include a cyclic ring including at least one substituent. In some embodiments, a cyclic ring of a carotenoid analog or derivative may include at least one j e substituent. The substituent may be coupled to the cyclic ring with an ether functionality.

  一种控制（例如，影响或影响）主体中C-反应蛋白水平的方法可能包括向主体施用有效量的药用可接受的配方。药用可接受的配方可能包括类胡萝卜素的合成类似物或衍生物。可以向主体施用类胡萝卜素类似物或衍生物，单独或与另一种类胡萝卜素类似物或衍生物或共抗氧化剂配方结合。类胡萝卜素类似物可能包括具有7到14个双键的共轭聚烯。共轭聚烯可能包括包括至少一个取代基的环状环。在某些实施例中，类胡萝卜素类似物或衍生物的环状环可能包括至少一个取代基。取代基可能通过醚功能与环状环偶联。