(E/Z)-Squalene ((E/Z)-Super Squalene; (E/Z)-AddaVax)   中文名称: 角鲨烯

在人乳腺上皮细胞 (MCF10A) 中，(E/Z)-角鲨烯 (0-50 μM) 降低细胞内 ROS 水平，抑制 H2O2 诱导的氧化损伤，并保护细胞免受 DNA 氧化损伤 [1]。

Absorption, Distribution and Excretion
Squalene is used in the oil phase of certain emulsion vaccine adjuvants, but its fate as a vaccine component following intramuscular (IM) injection in humans is unknown. In this study, we constructed a physiologically-based pharmacokinetic (PBPK) model for intramuscularly injected squalene-in-water (SQ/W) emulsion, in order to make a quantitative estimation of the tissue distribution of squalene following a single IM injection in humans. The PBPK model incorporates relevant physicochemical properties of squalene; estimates of the time course of cracking of a SQ/W emulsion; anatomical and physiological parameters at the injection site and beyond; and local, preferential lymphatic transport. The model predicts that a single dose of SQ/W emulsion will be removed from human deltoid muscle within six days following IM injection. The major proportion of the injected squalene will be distributed to draining lymph nodes and adipose tissues. The model indicates slow decay from the latter compartment most likely due to partitioning into neutral lipids and a low rate of squalene biotransformation there. Parallel pharmacokinetic modeling for mouse muscle suggests that the kinetics of SQ/W emulsion correspond to the immunodynamic time course of a commercial squalene-containing adjuvant reported in that species. In conclusion, this study makes important pharmacokinetic predictions of the fate of asqualene-containing emulsion in humans. The results of this study may be relevant for understanding the immunodynamics of this new class of vaccine adjuvants and may be useful in future quantitative risk analyses that incorporate mode-of-action data.
Over 60% of ingested squalene is absorbed from the small intestine; from there it is carried in the lymph in the form of chylomicrons into the systemic circulation. In the blood, squalene is carried mainly in very-low-density lipoproteins and distributed to the various tissues of the body. A large percentage of squalene gets distributed to the skin.
Animal studies indicate Squalene is slowly absorbed through the skin, while both compounds /Squalane and Squalene/ are poorly absorbed from the gastrointestinal tract.

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Metabolism / Metabolites
A review of the oxidization of squalene, a specific human compound produced by the sebaceous gland, is proposed. Such chemical transformation induces important consequences at various levels. Squalene by-products, mostly under peroxidized forms, lead to comedogenesis, contribute to the development of inflammatory acne and possibly modify the skin relief (wrinkling). Experimental conditions of oxidation and/or photo-oxidation mechanisms are exposed, suggesting that they could possibly be bio-markers of atmospheric pollution upon skin. Ozone, long UVA rays, cigarette smoke ... are shown powerful oxidizing agents of squalene. Some in vitro, ex vivo and in vivo testings are proposed as examples, aiming at studying ingredients or products capable of boosting or counteracting such chemical changes that, globally, bring adverse effects to various cutaneous compartments.
This study has used proton transfer reaction-mass spectrometry (PTR-MS) for direct air analyses of volatile products resulting from the reactions of ozone with human skin lipids. An initial series of small-scale in vitro and in vivo experiments were followed by experiments conducted with human subjects in a simulated office. The latter were conducted using realistic ozone mixing ratios (approximately 15 ppb with occupants present). Detected products included mono- and bifunctional compounds that contain carbonyl, carboxyl, or alpha-hydroxy ketone groups. Among these, three previously unreported dicarbonyls have been identified, and two previously unreported alpha-hydroxy ketones have been tentatively identified. The compounds detected in this study (excepting acetone) have been overlooked in surveys of indoor pollutants, reflecting the limitations of the analytical methods routinely used to monitor indoor air. The results are fully consistent with the Criegee mechanism for ozone reacting with squalene, the single most abundant unsaturated constituent of skin lipids, and several unsaturated fatty acid moieties in their free or esterified forms. Quantitative product analysis confirms that squalene is the major scavenger of ozone at the interface between room air and the human envelope. Reactions between ozone and human skin lipids reduce the mixing ratio of ozone in indoor air, but concomitantly increase the mixing ratios of volatile products and, presumably, skin surface concentrations of less volatile products. Some of the volatile products, especially the dicarbonyls, may be respiratory irritants. Some of the less volatile products may be skin irritants.
Squalene is metabolized to cholesterol.

[1]. Current Insights into the Biological Action of Squalene. Mol Nutr Food Res. 2018 Jun 8:e1800136.

Trans-squalene is a clear, slightly yellow liquid with a faint odor. Density 0.858 g / cm3.
Squalene is a triterpene consisting of 2,6,10,15,19,23-hexamethyltetracosane having six double bonds at the 2-, 6-, 10-, 14-, 18- and 22-positions with (all-E)-configuration. It has a role as a human metabolite, a plant metabolite, a Saccharomyces cerevisiae metabolite and a mouse metabolite.
Squalene is originally obtained from shark liver oil. It is a natural 30-carbon isoprenoid compound and intermediate metabolite in the synthesis of cholesterol. It is not susceptible to lipid peroxidation and provides skin protection. It is ubiquitously distributed in human tissues where it is transported in serum generally in association with very low density lipoproteins. Squalene is investigated as an adjunctive cancer therapy.
Squalene has been reported in Erythrophleum fordii, Amaranthus hybridus, and other organisms with data available.
squalene is a metabolite found in or produced by Saccharomyces cerevisiae.
A natural 30-carbon triterpene.
See also: Olive Oil (part of); Shark Liver Oil (part of).

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Mechanism of Action
Squalene, an isoprenoid compound structurally similar to beta-carotene, is an intermediate metabolite in the synthesis of cholesterol. In humans, about 60 percent of dietary squalene is absorbed. It is transported in serum generally in association with very low density lipoproteins and is distributed ubiquitously in human tissues, with the greatest concentration in the skin, where it is one of the major components of skin surface lipids. Squalene is not very susceptible to peroxidation and appears to function in the skin as a quencher of singlet oxygen, protecting human skin surface from lipid peroxidation due to exposure to UV and other sources of ionizing radiation. Supplementation of squalene to mice has resulted in marked increases in cellular and non-specific immune functions in a dose-dependent manner. Squalene may also act as a "sink" for highly lipophilic xenobiotics. Since it is a nonpolar substance, it has a higher affinity for un-ionized drugs. In animals, supplementation of the diet with squalene can reduce cholesterol and triglyceride levels. In humans, squalene might be a useful addition to potentiate the effects of some cholesterol-lowering drugs. The primary therapeutic use of squalene currently is as an adjunctive therapy in a variety of cancers. Although epidemiological, experimental and animal evidence suggests anti-cancer properties, to date no human trials have been conducted to verify the role this nutrient might have in cancer therapy regimens.
Based on previous finding of singlet oxygen generation from coproporphyrin excreted on the skin surface from Propionibacterium acnes, we hypothesized that singlet oxygen formed in this way under UV exposure would promote peroxidation of skin surface lipids. We found that squalene was oxidized efficiently by singlet oxygen derived from coproporphyrin under UV exposure, and that the rate constant of squalene peroxidation by singlet oxygen was ten-fold higher than that of other skin surface lipids examined. The reaction was promoted more efficiently by UVA than by UVB. Furthermore, we found that topical application of squalene peroxide induced skin hyperpigmentation through increasing prostaglandin E(2) release from keratinocytes in guinea pigs. These results suggest that squalene peroxide formation by singlet oxygen plays a key role in photo-induced skin damage.

C30H50

410.72

410.391

7683-64-9

638072

Oil; crystals from ether/methanol (-5 °C)

0.8±0.1 g/cm3

429.3±0.0 °C at 760 mmHg

-75ºC(lit.)

254.1±22.2 °C

0.0±0.5 mmHg at 25°C

1.492

13.09

0

0

0

15

30

578

0

C/C(C)=C\CC/C(C)=C/CC/C(C)=C/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)\C

YYGNTYWPHWGJRM-AAJYLUCBSA-N

InChI=1S/C30H50/c1-25(2)15-11-19-29(7)23-13-21-27(5)17-9-10-18-28(6)22-14-24-30(8)20-12-16-26(3)4/h15-18,23-24H,9-14,19-22H2,1-8H3/b27-17+,28-18+,29-23+,30-24+

(6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。