hyperforin | 11079-53-1

• 物质功能分类: 生物化工 - 中草药成分
• 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
• 英文名称: hyperforin
• 英文别名: (1R,5R,7S,8R)-4-hydroxy-8-methyl-3,5,7-tris(3-methylbut-2-enyl)-8-(4-methylpent-3-enyl)-1-(2-methylpropanoyl)bicyclo[3.3.1]non-3-ene-2,9-dione
• CAS: 11079-53-1
• 化学式: C₃₅H₅₂O₄
• 分子量: 536.795
• InChiKey: KGSZHKRKHXOAMG-HQKKAZOISA-N

物化性质

• 熔点：
  79-80℃
• 比旋光度：
  D18 +41° (in ethanol)
• 沸点：
  616.8±55.0 °C(Predicted)
• 密度：
  1.010±0.06 g/cm3 (20 ºC 760 Torr)
• 闪点：
  9℃
• 溶解度：
  In water, 2.34X10-9 mg/L at 25 °C (est)
• 蒸汽压力：
  2.6X10-17 mm Hg at 25 °C
• 旋光度：
  Specific optical rotation: +41 deg at 18 °C/D (in ethanol)
• 解离常数：
  pKa = 4.8 (50% aqueous ethanol)

计算性质

• 辛醇/水分配系数(LogP)：
  9.6
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  71.4
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

贯叶连翘素是圣约翰草（贯叶连翘）中的一个重要活性成分，据信是圣约翰草抗抑郁效果和草药-药物相互作用的主要原因。在这项研究中，使用雄性和雌性Sprague-Dawley大鼠的肝脏微粒体，以及在苯巴比妥或地塞米松诱导或不诱导的情况下，研究了贯叶连翘素的体外代谢谱。通过高效液相色谱分离并鉴定了四种主要的I相代谢物，分别命名为19-羟基贯叶连翘素、24-羟基贯叶连翘素、29-羟基贯叶连翘素和34-羟基贯叶连翘素，并通过质谱和核磁共振进行了确认。结果表明，羟基化是贯叶连翘素在大鼠肝脏中的主要生物转化途径，可诱导的细胞色素P450 3A（CYP450 3A）和/或CYP2B可能是催化这些羟基化反应的主要细胞色素P450同工酶。

Hyperforin is an important active component of St. John's wort (Hypericum perforatum) that has been suggested to be responsible for the St. John's wort antidepressive effects and herbal-drug interactions. In this study, the in vitro metabolism profile of hyperforin was investigated using liver microsomes from male and female Sprague-Dawley rats, with or without induction by phenobarbital or dexamethasone. Four major Phase I metabolites, named 19-hydroxyhyperforin, 24-hydroxyhyperforin, 29-hydroxyhyperforin, and 34-hydroxyhyperforin, were isolated by high performance liquid chromatography and identified by mass spectrometry and NMR. Results suggest that hydroxylation is a major biotransformation of the hyperforin pathway in rat liver and that inducible cytochrome P450 3A (CYP450 3A) and/or CYP2B may be the major cytochrome P450 isoforms catalyzing these hydroxylation reactions.

来源:Hazardous Substances Data Bank (HSDB)

代谢

对贯叶连翘的地上部分进行反复检查，得到了一种新的贯叶金丝桃素降解产物（1），即去氧呋喃贯叶金丝桃素A（2），以及之前已识别的呋喃贯叶金丝桃素（3）、呋喃阿德贯叶金丝桃素（4）、呋喃贯叶金丝桃素A（5a和5b）、吡喃[7,28-b]贯叶金丝桃素（6）和3-甲基-4,6-二(3-甲基-2-丁烯基)-2-(2-甲基-1-氧代丙基)-3-(4-甲基-3-戊烯基)-环己酮（7）。

Repeated examination of the aerial parts of Hypericum perforatum yielded a new degradation product of hyperforin (1) namely deoxyfurohyperforin A (2), together with the previously identified furohyperforin (3), furoadhyperforin (4), furohyperforin A (5a and 5b), pyrano[7,28-b]hyperforin (6) and 3-methyl-4,6-di(3-methyl-2-butenyl)-2-(2-methyl-1-oxopropyl)-3-(4-methyl-3-pentenyl)-cyclohexanone (7).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

与SJW（贯叶连翘，一种草药）联合用药导致血浆中多种药物浓度降低，包括阿米替林、环孢素、地高辛、印地那韦、伊立替康、华法林、苯丙香豆素、阿普唑仑、右美沙芬、辛伐他汀以及口服避孕药。

Co-medication with SJW resulted in decreased plasma concentrations of a number of drugs including amitriptyline, cyclosporine, digoxin, indinavir, irinotecan, warfarin, phenprocoumon, alprazolam, dextrometorphane, simvastatin, and oral contraceptives.

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，让患者身体前倾或将其置于左侧（如果可能，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)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

/其他毒性信息/ 最近，中草药与合成药物之间的相互作用引起了人们的高度关注。在过去3年中，已有超过50篇论文发表，关于金丝桃（Hypericum perforatum L.；SJW）与处方药之间的相互作用。与SJW联合用药导致一些药物的血浆浓度降低，包括阿米替林、环孢素、地高辛、茚地那韦、伊立替康、华法林、苯丙香豆素、阿普唑仑、右美沙芬、辛伐他汀和口服避孕药。相互作用研究和案例报告的充分证据表明，SJW是细胞色素P450酶（尤其是CYP3A4）和/或P-糖蛋白的强诱导剂。最近的研究表明，SJW诱导酶的程度与产品中含有的金丝桃素量密切相关。不含大量金丝桃素（<1%）的产品没有显示出临床上相关的酶诱导作用。另一方面，一些证据表明，金丝桃素也可能有助于SJW的抗抑郁活性。然而，使用低含量金丝桃素（<1%）的SJW制剂的临床研究表明，这种植物提取物在治疗轻中度抑郁症方面明显优于安慰剂，并且与丙米嗪和氟西汀相当。在本文中，对临床上重要的SJW相互作用进行了评估，特别是考虑到金丝桃素的影响。

/OTHER TOXICITY INFORMATION/ Recently, interactions of herbal medicines with synthetic drugs came into focus of particular interest. In the past 3 years, more than 50 papers were published regarding interactions between St. John's wort (Hypericum perforatum L.; SJW) and prescription drugs. Co-medication with SJW resulted in decreased plasma concentrations of a number of drugs including amitriptyline, cyclosporine, digoxin, indinavir, irinotecan, warfarin, phenprocoumon, alprazolam, dextrometorphane, simvastatin, and oral contraceptives. Sufficient evidence from interaction studies and case reports indicate that SJW is a potent inducer of cytochrome P450 enzymes (particularly CYP3A4) and/or P-glycoprotein. Recent studies could show that the degree of enzyme induction by SJW correlates strongly with the amount of hyperforin found in the product. Products that do not contain substantial amounts of hyperforin (<1%) have not been shown to produce clinically relevant enzyme induction. On the other hand, some evidence suggests that hyperforin may also contribute to the antidepressant activity of SJW. However, clinical studies using SJW preparations with a low hyperforin amount (<1%) clearly demonstrated the superiority of this plant extract over placebo and its equivalence to imipramine and fluoxetine in the treatment of mild to moderate forms of depression. In the present paper clinically significant SJW interactions are critically evaluated against the background of hyperforin.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

适合于测定服用含酒精度贯叶连翘提取物后血浆中贯叶连翘素的验证分析方法被描述。在大鼠口服300毫克/千克贯叶连翘提取物（WS 5572，含5%贯叶连翘素）后，通过HPLC和UV检测方法测定，大约3小时后达到大约370纳克/毫升（约690纳摩尔）的最大血浆水平。估计的半衰期和清除率分别为6小时和70毫升/分钟/千克。由于贯叶连翘提取物的治疗剂量远低于大鼠使用的剂量，因此开发了一种更灵敏的LC/MS/MS方法。该方法的定量下限为1纳克/毫升。使用此方法，可以在健康志愿者服用含300毫克贯叶连翘提取物（相当于14.8毫克贯叶连翘素）的薄膜包衣片后长达24小时内跟踪血浆中的贯叶连翘素水平。大约3.5小时后达到大约150纳克/毫升（约280纳摩尔）的最大血浆水平。半衰期和平均滞留时间分别为9小时和12小时。贯叶连翘素的药代动力学在600毫克提取物范围内呈线性。将剂量增加到900或1200毫克提取物时，Cmax和AUC值低于从低剂量数据的线性外推预期。志愿者体内的血浆浓度曲线很好地符合开放式两室模型。在重复剂量研究中，没有观察到血浆中贯叶连翘素的积累。使用重复剂量研究中观察到的AUC值，估计在服用3 x 300毫克/日的提取物后，即正常治疗剂量方案后，贯叶连翘素的稳态血浆浓度大约为100纳克/毫升（约180纳摩尔）。

Validated analytical methods suitable for determining hyperforin in plasma after administration of alcoholic Hypericum perforatum extracts containing hyperforin are described. After oral administration of 300 mg/kg Hypericum extract (WS 5572, containing 5% hyperforin) to rats maximum plasma levels of approximately 370 ng/ml (approx. 690 nM) were reached after 3 hr, as quantified by a HPLC and UV detection method. Estimated half-life and clearance values were 6 hr and 70 ml/min/kg respectively. Since therapeutic doses of Hypericum extracts are much lower than that used in rats, a more sensitive LC/MS/MS method was developed. The lower limit of quantification of this method was 1 ng/ml. Using this method, plasma levels of hyperforin could be followed for up to 24 hr in healthy volunteers after administration of film coated tablets containing 300 mg hypericum extracts representing 14.8 mg hyperforin. The maximum plasma levels of approximately 150 ng/ml (approx. 280 nM) were reached 3.5 hr after administration. Half-life and mean residence time were 9 and 12 hr respectively. Hyperforin pharmacokinetics were linear up to 600 mg of the extract. Increasing the doses to 900 or 1200 mg of extract resulted in lower Cmax and AUC values than those expected from linear extrapolation of data from lower doses. Plasma concentration curves in volunteers fitted well in an open two-compartment model. In a repeated dose study, no accumulation of hyperforin in plasma was observed. Using the observed AUC values from the repeated dose study, the estimated steady state plasma concentrations of hyperforin after 3 x 300 mg/day of the extract, i.e., after normal therapeutic dose regimen, was approximately 100 ng/ml (approx. 180 nM).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠口服300 mg/kg的圣约翰草提取物（WS 5572，含5%金丝桃素）后，通过高效液相色谱和紫外检测方法测定，大约3小时后血浆中金丝桃素达到最大浓度，约为370 ng/ml（大约690 nM）。估算的半衰期和清除率分别为6小时和70 ml/min/kg。由于圣约翰草提取物的治疗剂量远低于大鼠使用的剂量，因此开发了一种更灵敏的LC/MS/MS检测方法。该方法的定量下限为1 ng/ml。使用这种方法，可以在健康志愿者服用含有300 mg圣约翰草提取物（相当于14.8 mg金丝桃素）的薄膜包衣片后，监测血浆中金丝桃素的水平长达24小时。大约3.5小时后，血浆中金丝桃素达到最大浓度，约为150 ng/ml（大约280 nM）。半衰期和平均滞留时间分别为9小时和12小时。金丝桃素的药代动力学在提取物剂量达到600 mg时呈线性。将剂量增加到900或1200 mg提取物时，得到的Cmax和AUC值低于从低剂量数据线性外推的预期值。志愿者体内的血浆浓度曲线很好地符合开放双室模型。在重复剂量研究中，未观察到血浆中金丝桃素的累积。根据重复剂量研究的观察到的AUC值，估计在每日3次，每次300 mg提取物的正常治疗剂量方案下，金丝桃素的稳态血浆浓度大约为100 ng/ml（大约180 nM）。

After oral administration of 300 mg/kg Hypericum extract (WS 5572, containing 5% hyperforin) to rats maximum plasma levels of approximately 370 ng/ml (approx. 690 nM) were reached after 3 hr, as quantified by a HPLC and UV detection method. Estimated half-life and clearance values were 6 h and 70 ml/min/kg respectively. Since therapeutic doses of Hypericum extracts are much lower than that used in rats, a more sensitive LC/MS/MS method was developed. The lower limit of quantification of this method was 1 ng/ml. Using this method, plasma levels of hyperforin could be followed for up to 24 hr in healthy volunteers after administration of film coated tablets containing 300 mg hypericum extracts representing 14.8 mg hyperforin. The maximum plasma levels of approximately 150 ng/ml (approx. 280 nM) were reached 3.5 h after administration. Half-life and mean residence time were 9 and 12 hr respectively. Hyperforin pharmacokinetics were linear up to 600 mg of the extract. Increasing the doses to 900 or 1200 mg of extract resulted in lower Cmax and AUC values than those expected from linear extrapolation of data from lower doses. Plasma concentration curves in volunteers fitted well in an open two-compartment model. In a repeated dose study, no accumulation of hyperforin in plasma was observed. Using the observed AUC values from the repeated dose study, the estimated steady state plasma concentrations of hyperforin after 3 x 300 mg/day of the extract, i.e., after normal therapeutic dose regimen, was approximately 100 ng/ml (approx. 180 nM).

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  F,T
• 安全说明：
  S16,S36/37,S45,S7
• 危险类别码：
  R11,R23/24/25,R39/23/24/25
• WGK Germany：
  3
• 海关编码：
  29144000
• 危险品运输编号：
  UN1230 - class 3 - PG 2 - Methanol
• 危险标志：
  GHS02,GHS06,GHS08
• 危险性描述：
  H225,H301 + H311 + H331,H370
• 危险性防范说明：
  P210,P280,P302 + P352 + P312,P304 + P340 + P312,P370 + P378,P403 + P235

制备方法与用途

背景

贯叶金丝桃（Hypericum perforatum L.）是藤黄科金丝桃属植物。1984年，Suzuki等人首次发现贯叶金丝桃具有显著的抗抑郁作用，并且副作用较小。随着研究的深入，贯叶金丝桃被进一步证实具有抗抑郁、抗病毒和抗肿瘤等多种功效，引起了广泛关注。

作用

贯叶金丝桃提取物中的抗抑郁效果与其所含的贯叶金丝桃素浓度密切相关。研究表明，贯叶金丝桃素制剂的抗抑郁疗效明显优于安慰剂，并且其疗效与标准抗抑郁药物如马普替林（maprotiline）、丙咪嗪（imipramine）和阿米替林（amitriptyline）相当，但不良反应较少，治疗成本也更低。

制备

贯叶金丝桃素的低温超声提取工艺如下：称取10克粉碎好的贯叶金丝桃粉末，置于500毫升烧杯中，按体积比加入10倍量75%乙醇并混匀。向其中加入适量抗氧化剂，并按照设定条件进行超声处理，每次10分钟，共提取3次。合并所有提取液后，利用氮吹仪挥去乙醇，然后采用冷冻干燥技术，在-60℃预冻4小时后再按程序升温曲线干燥27小时，即可得到贯叶金丝桃素提取物。

需要注意的是，贯叶金丝桃素对光和热不稳定，因此在提取等整个工艺过程中应始终将温度控制在60℃以下，并且要避光保存于棕色瓶中。

反应信息

• 作为反应物：
  描述：

  hyperforin 在 air 作用下， 以 甲醇 为溶剂， 反应 6.5h， 生成 furohyperforin
  参考文献：
  名称：

  Orth; Hauer; Erdelmeier, Pharmazie, 1999, vol. 54, # 1, p. 76 - 77

  摘要：

  DOI：
• 作为产物：
  描述：

  (1S,5R,7S,8S)-7-hydroxy-4-methoxy-8-methyl-8-(4-methyl-4-((triethylsilyl)oxy)pentyl)-5-(3-methylbut-2-en-1-yl)bicyclo[3.3.1]non-3-ene-2,9-dione 在 吡啶 、 N-羟基丁二酰亚胺 、 Hoveyda-Grubbs catalyst second generation 、 2-甲基-2-丁烯 、 三乙基硼 、 2,2,6,6-tetramethylpiperidinyl-lithium 、 对甲苯磺酸 、 lithium chloride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 甲苯 、 苯 为溶剂， 反应 10.16h， 生成 hyperforin
  参考文献：
  名称：

  Enantioselective Total Synthesis of Hyperforin

  摘要：

  A modular, 18-step total synthesis of hyperforin is described. The natural product was quickly accessed using latent symmetry elements, whereby a group-selective, Lewis acid-catalyzed epoxide-opening cascade cyclization was used to furnish the bicyclo[3.3.1]-nonane core and set two key quaternary stereocenters.

  DOI：

  10.1021/ja312150d

文献信息

• The first catalytic asymmetric total synthesis of ent-hyperforin
  作者：Yohei Shimizu、Shi-Liang Shi、Hiroyuki Usuda、Motomu Kanai、Masakatsu Shibasaki

  DOI：10.1016/j.tet.2010.05.086

  日期：2010.8

  ent-hyperforin was described here in detail. Keys to the success were a catalytic asymmetric Diels–Alder reaction, a stereoselective Clasien rearrangement, an intramolecular aldol cyclization, and a vinylogous Pummerer rearrangement. Along with the successful synthetic route, several attempted approaches toward the construction of bicyclo[3.3.1] core and the C2 oxidation were discussed.

  对羟基丁香酚的第一个催化不对称全合成在此进行了详细描述。成功的关键是催化不对称Diels-Alder反应，立体选择性Clasien重排，分子内醛醇环化和乙烯基Pummerer重排。除了成功的合成路线外，还讨论了几种尝试构建双环[3.3.1]核和C2氧化的方法。
• 贯叶金丝桃素衍生物和用途及包含其的抗病毒制剂
  申请人：河南佰景生物科技有限公司

  公开号：CN112062716A

  公开（公告）日：2020-12-11

  本发明公开了贯叶金丝桃素衍生物和用途及包含其的抗病毒制剂，属于抗病毒制剂技术领域，贯叶金丝桃素衍生物的结构如式(I)，本发明贯叶金丝桃素衍生物具有良好的抗病毒能力，能显著抑制TGEV基因组的转录和TGEV特异性蛋白的在细胞中的表达，上调相关因子IFN‑α、IFN‑β、IFN‑γ和IRF‑3的表达量，从而发挥抑制TGEV增殖的作用，且对TGEV吸附细胞具有明显的阻断作用，最终抑制TGEV感染细胞，可用于制备抗病毒制剂，具有良好的应用前景。
• Hyperforin derivatives, use thereof and formulations containing them
  申请人：——

  公开号：US20010020040A1

  公开（公告）日：2001-09-06

  The invention relates to compounds of the formula: 1 in which R is a saturated or unsaturated, straight or branched, C 1 -C 22 acyl group, optionally having one or more substituents, which can be the same or different, selected from halogen atoms, nitro, amino, C 1 -C 6 -alkylamino, di-C 1 -C 6 -alkylamino, C 1 -C 6 -acylamino groups; a cycloaliphatic or aromatic acyl residue in which the aromatic moiety optionally has one or more substituents, which can be the same or different, selected from halogen atoms, hydroxy, methoxy, amino groups; a glycidic residue in which one or more hydroxy groups are optionally alkylated or acylated. The invention further relates to methods for extracting and extracts of these compounds from Hypericum perforatum as well as their use as active ingredients in antidepression medication.

  本发明涉及以下式的化合物：1其中R是饱和或不饱和的直链或支链C1-C22酰基，可选地具有一个或多个取代基，这些取代基可以是相同或不同的，选自卤素原子、硝基、氨基、C1-C6-烷基氨基、二-C1-C6-烷基氨基、C1-C6-酰胺基团；环脂肪族或芳香族酰基残基，其中芳香基团可选地具有一个或多个取代基，这些取代基可以是相同或不同的，选自卤素原子、羟基、甲氧基、氨基；一种环氧乙烷残基，其中一个或多个羟基可选地被烷基化或酰化。本发明还涉及从金丝桃中提取这些化合物的方法和提取物，以及它们作为抗抑郁药物的活性成分的用途。
• Hyperforin derivatives, the use thereof and formulations containing them
  申请人：Bombardelli Ezio

  公开号：US20050165117A1

  公开（公告）日：2005-07-28

  The use of the reduction products of hyperforin and adhyperforin, pharmanceutically acceptable salts or esters thereof, in the pharmaceutical and/or nutritional field, ii particular in the treatment of depression and Alzheimer's disease.

  使用金丝桃素和异金丝桃素的还原产物，其药学上可接受的盐或酯，在制药和/或营养领域中的应用，特别是在治疗抑郁症和阿尔茨海默病方面。
• Stable hyperforin salts, method for producing same and their use in the treatment of alzheimer's disease
  申请人：Willmar Schwabe GmbH & Co.

  公开号：US06444662B1

  公开（公告）日：2002-09-03

  Described are salts of hyperforin and adhyperforin of formula I [A−]m[B]p+  (I) wherein m is an integer from 1 to 3, p is equal to m and gives the total number of positive charges of the residue [B], [A−] is an anion of formula II with n=0 or 1 and [B]p+ is an ion of an alkali metal or an ammonium ion of a salt-forming nitrogen base of formula III wherein R1 through R4 have a variety of meanings including hydrogen, alkyl, cycloalkyl and similar groups which in turn may be substituted with one or more substituents. The salts serve inter alia for enriching or purifying hyperforin and adhyperforin from St. John's Wort extracts. Pharmaceutical preparations containing the salts are used for treating Alzheimer's Disease.

  本文描述了公式I中的hyperforin和adhyperforin的盐，其中：[A−]为公式II中的负离子，n=0或1；[B]p+为公式III中的一种碱金属离子或盐基氮碱的铵离子，其中R1至R4具有多种含义，包括氢、烷基、环烷基和类似的基团，这些基团又可以被一个或多个取代基所取代。这些盐可用于从圣约翰草提取物中富集或纯化hyperforin和adhyperforin。含有这些盐的制药制剂可用于治疗阿尔茨海默病。