Glucocorticoid receptor (GR) [1]

氢化可的松 (50 nM) 揭示了 hCMEC/D3 细胞中 GR 转录物的剂量依赖性下调。在低血清细胞分化培养基中添加氢化可的松导致 hCMEC/D3 单层细胞中的 TER 显着增加 [1]。氢化可的松处理的树突状细胞 (DC) 显示 MHC II 分子、共刺激分子 CD86 和 DC 特异性标记物 CD83 的表达降低，并且 IL-12 释放大幅减少。氢化可的松处理的 DC 减少了 IFN-γ 的产生，但产生了增强的 IL-4 释放，且不改变 IL-5 [2]。氢化可的松可降低缺血后氧化应激、灌注压和渗出液的产生。氢化可的松抑制缺血后 Syndecan-1、硫酸乙酰肝素和透明质酸的脱落，以及常驻肥大细胞释放的组胺 [3]。

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- 调节紧密连接蛋白表达：在人脑微血管内皮细胞系HCMEC/D3中，氢化可的松（50 nM和100 nM）可诱导闭合蛋白（occludin）表达增加2.75±0.04倍，克劳丁 - 5（claudin - 5）表达最多增加2.32±0.11倍，进而增加跨内皮电阻，表明血脑屏障紧密性增强。同时，它还下调HCMEC/D3细胞中GR mRNA和蛋白的表达。用50 nM 氢化可的松处理48小时后，GR转录本下调至0.81±0.06倍，100 nM处理时下调至0.63±0.1倍。100 nM 氢化可的松处理48小时后，GR蛋白含量降至未处理细胞的83±0.6% [1]
- 抑制T细胞增殖：在树突状细胞（DCs）和T细胞的体外培养中，氢化可的松（5×10⁻⁶ mol/L）可降低DCs上MHC II分子、共刺激分子CD86和DC特异性标志物CD83的表达，并强烈减少IL - 12的分泌，从而导致T细胞增殖减少。同时，氢化可的松处理后的DCs可抑制T细胞产生IFN - γ，并诱导IL - 4释放增加，IL - 5无变化 [2]

保护血管屏障：在豚鼠心脏实验中，氢化可的松（10 μg/ml）可保护内皮糖萼。它降低缺血后氧化应激、灌注压和渗出液形成，还抑制缺血后 Syndecan - 1、硫酸乙酰肝素和透明质酸的脱落，以及 resident mast cells中组胺的释放，从而维持血管屏障，减少间质水肿 [3]

- 紧密连接蛋白表达实验：培养HCMEC/D3细胞至汇合状态。分别用50 nM和100 nM的氢化可的松处理细胞，每24小时重复处理一次，共处理48小时。然后，用qPCR检测occludin和claudin - 5的mRNA水平，用western blot检测GR蛋白水平。用免疫细胞化学方法观察GR蛋白的细胞定位，采用FITC标记的GR抗体和碘化丙啶进行细胞核染色 [1]
- DC与T细胞共培养实验：从特应性供体中分离初始和记忆CD4⁺T细胞。将CD14⁺单核细胞在GM - CSF/IL - 4培养下生成自体过敏原脉冲DCs，并在有或无5×10⁻⁶ mol/L 氢化可的松的情况下，用IL - 1β、TNF - α和PGE2使其完全成熟。然后将处理后的DCs与T细胞共培养，用流式细胞术检测DCs上MHC II、CD86和CD83的表达，用ELISA法测量上清液中IL - 12的分泌量。用MTT法检测T细胞增殖情况，用ELISA法测量培养上清液中IFN - γ、IL - 4和IL - 5的水平 [2]

Dissolve Hydrocortisone in an appropriate solvent to prepare a solution with a concentration of 10 μg/ml. Perfuse isolated guinea pig hearts with Krebs - Henseleit buffer containing Hydrocortisone at a stress dose before inducing 20 - minute ischemia at 37°C. Then, reperfuse the hearts for 20 min with Krebs - Henseleit buffer or Krebs - Henseleit buffer plus 2 g% hydroxyethyl starch (130 kD). Directly measure the transudate formation on the epicardial surface to assess coronary net fluid filtration, and perform perfusion fixation on the hearts to visualize the glycocalyx [3]

Absorption, Distribution and Excretion
Oral hydrocortisone at a dose of 0.2-0.3mg/kg/day reached a mean Cmax of 32.69nmol/L with a mean AUC of 90.63h\*nmol/L A 0.4-0.6mg/kg/day dose reached a mean Cmax of 70.81nmol/L with a mean AUC of 199.11h\*nmol/L. However, the pharmacokinetics of hydrocortisone can vary by 10 times from patient to patient. Topical hydrocortisone cream is 4-19% bioavailable with a Tmax of 24h. Hydrocortisone retention enemas are have a bioavailability of 0.810 for slow absorbers and 0.502 in rapid absorbers. Slow absorbers take up hydrocortisone at a rate of 0.361±0.255/h while fast absorbers take up hydrocortisone at a rate of 1.05±0.255/h. A 20mg IV dose of hydrocortisone has an AUC of 1163±277ng\*h/mL.
Corticosteroids are eliminated predominantly in the urine. However, data regarding the exact proportion is not readily available.
Total hydrocortisone has a volume of distribution of 39.82L, while the free fraction has a volume of distribution of 474.38L.
Total hydrocortisone by the oral route has a mean clearance of 12.85L/h, while the free fraction has a mean clearance of 235.78L/h. A 20mg IV dose of hydrocortisone has a clearance of 18.2±4.2L/h.
Following percutaneous penetration of a topical corticosteroid, the drug that is systemically absorbed probably follows the metabolic pathways of systemically administered corticosteroids. Corticosteroids usually are metabolized in the liver and excreted by the kidneys. Some topical corticosteroids and their metabolites are excreted in bile. /Topical corticosteroids/
Topical application of corticosteroids to the mucosa of the genitourinary or lower intestinal tract may result in substantial systemic absorption of the drugs. In healthy individuals, as much as 30-90% of rectally administered hydrocortisone as a retention enema may be absorbed. Greater amounts of hydrocortisone may be absorbed rectally if the intestinal mucosa is inflamed.
Following topical application of a corticosteroid to most areas of normal skin, only minimal amounts of the drug reach the dermis and subsequently the systemic circulation; however, absorption is markedly increased when the skin has lost its keratin layer and can be increased by inflammation and/or diseases of the epidermal barrier (e.g., psoriasis, eczema). The drugs are absorbed to a greater degree from the scrotum, axilla, eyelid, face, and scalp than from the forearm, knee, elbow, palm, and sole. Even after washing the area being treated, prolonged absorption of the corticosteroid occurs, possibly because the drug is retained in the stratum corneum. /Topical corticosteroids/
Percutaneous penetration of corticosteroids varies among individual patients and can be increased by the use of occlusive dressings, by increasing the concentration of the corticosteroid, and by using different vehicles. The use of an occlusive dressing with hydrocortisone for 96 hours substantially enhances percutaneous penetration of the drug; however, such use for up to 24 hours does not appear to alter penetration of topically applied hydrocortisone.
For more Absorption, Distribution and Excretion (Complete) data for HYDROCORTISONE (15 total), please visit the HSDB record page.

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Metabolism / Metabolites
Hydrocortisone is metabolised to 6-beta hydrocortisol via CYP3A, 5-beta tetrahydrocortisol via 3-oxo-5-beta-steroid 4-dehydrogenase, 5-alpha tetrahydrocortisol via 3-oxo-5-alpha-steroid 4-dehydrogenase 2, cortisone via Corticosteroid 11-beta-dehydrogenase isozyme 1 and Corticosteroid 11-beta-dehydrogenase isozyme 2, and glucuronide products. Cortisone is further metabolized to tetrahydrocortisone and dihydrocortisol.
A study was made of the absorption of exogenous hydrocortisone and formation of its metabolites in isolated liver of intact and exposed rats in conditions of recirculating perfusion. It was shown that the absorption of the hormone by the liver of irradiated rats was greatly lowered but the content of most metabolites found in the perfused medium of irradiated liver increased as compared to the control. It is suggested that irradiation inhibits subsequent transformations of the hydrocortisone metabolism products.
Subcellular distribution of (3)H-hydrocortisone and its metabolites in the liver and kidney of intact and alloxan diabetic rats was investigated. Ten minutes after the administration of this hormone several metabolites (mostly tetrahydrocortisol) and the native hormone were found in liver cytosol, microsomes, mitochondria and nuclei, the relative content of individual compounds in various subcellular fractions being different. In liver mitochondria, microsomes and nuclei of alloxan diabetic rats the concentration of tetrahydrocortisol was decreased, while that of native hormone was increased as compared to normal animals. It was suggested that such changes found in diabetic animals may be one of the causes of increased sensitivity of transcription and translation processes to glucocorticoids. In kidney cytosol and microsomes of intact rats cortisone and tetrahydrocortisol were found. In diabetic animals, however, the concentration of tetrahydrocortisol increased, while that of cortisone was undetectable.

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Biological Half-Life
Total hydrocortisone via the oral route has a half life of 2.15h while the free fraction has a half life of 1.39h. A 20mg IV dose of hydrocortisone has a terminal half life of 1.9±0.4h.
... After IV administration, hydrocortisone was eliminated with a total body clearance of 18 L/hr and a half-life of 1.7 hr.

Interactions
Hydrocortisone (80 mg/kg body weight, intraperitoneally for 4 days), both alone and in combination with acetylsalicylic acid (160 mg/kg body weight, orally, for 4 days), decreased acetylsalicylic acid general and specific toxicity via metabolic modulation of drug-metabolizing enzyme systems (intestinal acetylsalicylic acid-esterase and hepatic UDP-glucuronyltransferase) and did not change the acetylsalicylic acid analgesic effect.
The effect of glucocorticoids on oral anticoagulant therapy is variable, and the efficacy of oral anticoagulants has been reported to be enhanced or diminished with concomitant glucocorticoid administration. Patients receiving glucocorticoids and oral anticoagulants concomitantly should be monitored (e.g., using coagulation indices) in order to maintain desired anticoagulant effect. /Corticosteroids/
Estrogens may potentiate effects of hydrocortisone, possibly by increasing the concentration of transcortin and thus decreasing the amount of hydrocortisone available to be metabolized.
Potassium-depleting diuretics (e.g., thiazides, furosemide, ethacrynic acid) and other drugs that deplete potassium, such as amphotericin B, may enhance the potassium-wasting effect of glucocorticoids. Serum potassium should be closely monitored in patients receiving glucocorticoids and potassium-depleting drugs. /Corticosteroids/
For more Interactions (Complete) data for HYDROCORTISONE (7 total), please visit the HSDB record page.

[1]. Differential effects of hydrocortisone and TNFalpha on tight junction proteins in an in vitro model of the human blood-brain barrier. J Physiol. 2008 Apr 1;586(7):1937-49.

[2]. Inhibition of human allergic T-cell responses by IL-10-treated dendritic cells: differences from hydrocortisone-treated dendritic cells. J Allergy Clin Immunol. 2001 Aug;108(2):242-9.

[3]. Hydrocortisone preserves the vascular barrier by protecting the endothelial glycocalyx. Anesthesiology. 2007 Nov;107(5):776-84.

Therapeutic Uses
Anti-Inflammatory Agents, Steroidal
MEDICATION (VET): Acute urticaria /can be treated by/ rapid-acting adrenocorticosteroids, eg, hydrocortisone ... .
MEDICATION (VET): /USED/ IV, IN PREVENTING OR TREATING ADRENAL FAILURE & SHOCK-LIKE CONDITIONS IN SURGICAL CASES WHICH HAVE BEEN ON CORTICOSTEROIDS, IN ACUTE ALLERGIC REACTIONS...IN POOR SURGICAL RISKS, & IN CASES WHICH HAVE HAD OVERWHELMING SYSTEMIC INFECTIONS...IN DOGS OR CATTLE...
MEDICATION (VET) /EXPL:/: 5 Standardbreds and 4 Dutch Warmblood horses /were/ used to examine sensitivity of peripheral tissues to exogenous insulin 24 hours after administration of a single dose of hydrocortisone (0.06 mg/kg), eGH (20 ug/kg), or saline (0.9% NaCl) solution and after long-term administration (11 to 15 days) of eGH to horses. The amounts of metabolized glucose (M) and plasma insulin concentration (I) were determined. Values for M and the M-to-I ratio were significantly higher 24 hours after administration of a single dose of hydrocortisone than after single-dose administration of eGH or saline solution. After long-term administration of eGH, basal I concentration was increased and the mean M-to-I ratio was 22% lower, compared with values for horses treated with saline solution. Increases in M and the M-to-I ratio after a single dose of hydrocortisone imply that short-term hydrocortisone treatment increases glucose use by, and insulin sensitivity of, peripheral tissues. Assuming a single dose of hydrocortisone improves sensitivity of peripheral tissues to insulin, it may be an interesting candidate for use in reducing insulin resistance in peripheral tissues of horses with several disease states.
For more Therapeutic Uses (Complete) data for HYDROCORTISONE (23 total), please visit the HSDB record page.

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Drug Warnings
It is not known whether rectal corticosteroids are distributed into breast milk. Systemic corticosteroids are distributed into breast milk and may cause unwanted effects, such as growth suppression, in the infant. Rectal corticosteroids are not recommended for use by breast-feeding mothers. /Corticosteroids, rectal/
The results of a prospective randomized controlled trial, which looked at the incidence of postoperative diabetes insipidus following the use of three different hydrocortisone protocols, and the results of a study, on the incidence of diabetes insipidus and cortisol response in patients not given hydrocortisone /was reported/. In study 1, 114 patients with pituitary macroadenoma were randomized into three groups: conventional dose (injected hydrocortisone 100 mg IV 6-hourly for 3 days); intermediate dose (injected hydrocortisone 100 mg IV 6-hourly on day 1, 100 mg IV 8-hourly on day 2, and 100 mg IV 12-hourly on day 3); low dose protocol (injected hydrocortisone 25 mg IV 6-hourly on day 1, 25 mg IV 8-hourly on day 2 and 25 mg IV 12-hourly on day 3). Radical excision was achieved in 92 patients. The incidence of diabetes insipidus with the conventional dose was 52%, intermediate dose, 36% and low dose, 24% (p = 0.025). Study 2 included 16 consecutive patients with Hardy's grade A & B pituitary adenoma. These patients were randomized to receive (Group I) or not receive (Group II) hydrocortisone. Patients in Group II demonstrated normal cortisol response intraoperatively and no patient developed features of hypocortisolism; the incidence of diabetes insipidus in this group was 14%. The low dose hydrocortisone protocol reduced the incidence of diabetes insipidus by 46% when compared with the conventional dose hydrocortisone protocol. In patients with grade A and B tumor with normal preoperative cortisol levels, the use of perioperative hydrocortisone can be avoided.
ACUTE ADRENAL INSUFFICIENCY RESULTS FROM TOO RAPID WITHDRAWAL OF CORTICOSTEROID THERAPY. /CORTICOSTEROIDS/
POTENTIAL ADVERSE EFFECTS ON FETUS: Cleft palate, spontaneous abortions, and intrauterine growth retardation in animals. Potential for cleft palate formation and adrenal suppression in humans, although teratogenic effects have not been confirmed. POTENTIAL SIDE EFFECTS ON BREAST-FED INFANT: Passes into breast milk in small amounts. Administration of physiologic doses unlikely to adversely affect infant. FDA Category: C (C = Studies in laboratory animals have revealed adverse effects on the fetus (teratogenic, embryocidal, etc.) but there are no controlled studies in pregnant women. The benefits from use of the drug in pregnant women may be acceptable despite its potential risks, or there are no laboratory animal studies or adequate studies in pregnant women.) /Adrenocorticosteroids/ /from table II/
For more Drug Warnings (Complete) data for HYDROCORTISONE (31 total), please visit the HSDB record page.

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Pharmacodynamics
Hydrocortisone binds to the glucocorticoid receptor leading to downstream effects such as inhibition of phospholipase A2, NF-kappa B, other inflammatory transcription factors, and the promotion of anti-inflammatory genes. Hydrocortisone has a wide therapeutic index and a moderate duration of action. Patients should stop taking the medication if irritation or sensitization occurs.

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Cortisol is a 17alpha-hydroxy-C21-steroid that is pregn-4-ene substituted by oxo groups at positions 3 and 20 and hydroxy groups at positions 11, 17 and 21. Cortisol is a corticosteroid hormone or glucocorticoid produced by zona fasciculata of the adrenal cortex, which is a part of the adrenal gland. It is usually referred to as the "stress hormone" as it is involved in response to stress and anxiety, controlled by corticotropin-releasing hormone (CRH). It increases blood pressure and blood sugar, and reduces immune responses. It has a role as an anti-inflammatory drug, an anti-allergic agent, an anti-asthmatic drug, a human metabolite, a mouse metabolite and a drug allergen. It is a 21-hydroxy steroid, an 11beta-hydroxy steroid, a 20-oxo steroid, a 3-oxo-Delta(4) steroid, a primary alpha-hydroxy ketone, a tertiary alpha-hydroxy ketone, a 17alpha-hydroxy-C21-steroid and a glucocorticoid. It derives from a hydride of a pregnane.
Hydrocortisone, or cortisol, is a glucocorticoid secreted by the adrenal cortex. Hydrocortisone is used to treat immune, inflammatory, and neoplastic conditions. It was discovered in the 1930s by Edward Kendall and named Compound F, or 17-hydroxycorticosterone. Hydrocortisone was granted FDA approval on 5 August 1952.
Hydrocortisone is a Corticosteroid. The mechanism of action of hydrocortisone is as a Corticosteroid Hormone Receptor Agonist.

Hydrocortisone has been reported in Ganoderma boninense, Homo sapiens, and Phlomoides rotata with data available. LOTUS - the natural products occurrence database Therapeutic Hydrocortisone is a synthetic or semisynthetic analog of natural hydrocortisone hormone produced by the adrenal glands with primary glucocorticoid and minor mineralocorticoid effects. As a glucocorticoid receptor agonist, hydrocortisone promotes protein catabolism, gluconeogenesis, capillary wall stability, renal excretion of calcium, and suppresses immune and inflammatory responses. (NCI04)
HYDROCORTISONE is a small molecule drug with a maximum clinical trial phase of IV (across all indications) that was first approved in 1952 and has 35 approved and 62 investigational indications.
The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.

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- Hydrocortisone can stabilize the function of the blood - brain barrier at the molecular level by regulating the expression of tight - junction proteins, which is of great significance for maintaining the homeostasis of the central nervous system microenvironment [1]
- It can affect the accessory function of DCs, thereby influencing the T - cell response, and has a certain regulatory effect on allergic reactions, which provides a theoretical basis for the treatment of allergic diseases [2]
- Protecting the endothelial glycocalyx is an important mechanism for Hydrocortisone to preserve the vascular barrier, which is helpful for preventing interstitial edema and treating related diseases caused by vascular barrier damage [3]

C21H30O5

362.46

362.209

C, 69.59; H, 8.34; O, 22.07

50-23-7

Hydrocortisone 17-butyrate;13609-67-1;Hydrocortisone acetate;50-03-3;Hydrocortisone 17-valerate;57524-89-7;Hydrocortisone hemisuccinate;2203-97-6;Hydrocortisone-d7;Hydrocortisone-d4;73565-87-4;Hydrocortisone-d3;115699-92-8;Hydrocortisone phosphate;3863-59-0;Hydrocortisone (Standard);50-23-7;Hydrocortisone-d2;1257650-73-9

5754

White to off-white solid powder

1.3±0.1 g/cm3

566.5±50.0 °C at 760 mmHg

211-214 °C(lit.)

310.4±26.6 °C

0.0±3.5 mmHg at 25°C

1.595

1.43

94.83

3

5

2

26

684

7

C[C@]12CCC(=O)C=C1CC[C@@H]3[C@@H]2[C@H](C[C@]4([C@H]3CC[C@@]4(C(=O)CO)O)C)O

JYGXADMDTFJGBT-VWUMJDOOSA-N

InChI=1S/C21H30O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h9,14-16,18,22,24,26H,3-8,10-11H2,1-2H3/t14-,15-,16-,18+,19-,20-,21-/m0/s1

(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 本产品在运输和储存过程中需避光。

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

配方 1 中的溶解度: ≥ 2.5 mg/mL (6.90 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (6.90 mM) (饱和度未知) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (6.90 mM) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 4 中的溶解度: ≥ 2.08 mg/mL (5.74 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100μL 20.8mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 5 中的溶解度: ≥ 2.08 mg/mL (5.74 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加),澄清溶液。

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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；
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