Angiotensin II receptor

缬沙坦 (CGP 48933)（一种合成的非肽血管紧张素 II 1 型受体拮抗剂）通过抑制血管紧张素的作用来扩张血管并降低血压。当用缬沙坦治疗时，老化的主动脉内皮细胞表现出 AT1R 表达的大幅降低[1]。当缬沙坦预处理时，促炎细胞因子和 TLR2 信号传导受到抑制。饮酒后，AGTR1 的表达上调，缬沙坦预处理可阻断这种表达[2]。

在患有 MI 的大鼠中，缬沙坦 (CGP 48933) 显着降低 TGF-β/Smad、Hif-1α 和纤维化相关蛋白的表达。缬沙坦与生理盐水和肼屈嗪相比，对缺血心脏的心功能、梗死面积、壁厚度和心肌血管化有相当大的改善[3]。高盐饮食可导致高血压、心脏损伤（如纤维化和炎症细胞浸润）、水通道蛋白 1 和血管生成因子的抑制，以及缬沙坦可以部分逆转的其他后果[4]。缬沙坦是一种有效的抗抑郁和抗焦虑药物，可以增加 BDNF 表达和海马神经发生。长期服用缬沙坦（5-40 mg/kg/d，口服）可减少 TST 和 FST 中的不动时间，延长 OFT 中的视野中心时间和 NSF 中的进食潜伏期，并增强对蔗糖的偏好在SPT[5]中。

将主动脉组织或细胞样品在裂解缓冲液A（20 mM Tris-HCl，pH8.0，150 mM NaCl，1%Triton X-100，2 mM EDTA，1 mM苯基甲基磺酰氟，20μg/ml抑肽酶、10μg/ml亮蛋白肽、20 mMß-甘油酸盐和2 mM NaF）中均化30分钟。离心匀浆，并用BCA蛋白质测定试剂盒（Piece Biotech股份有限公司，Rockford，IL，USA）测定蛋白质浓度。将每个样品提取物中等量的蛋白质（大多数蛋白质为20μg/lane，而p-p38和p-JNK检测为100μg/lanne）加载在12.5%的SDS-PAGE凝胶中进行电泳，并电印迹到PDVF膜上。在室温下用5%脱脂奶粉（在TBST中）封闭膜2小时，然后与一级抗体在4°C下孵育过夜。然后，用TBST洗涤膜（10分钟×3），并与辣根过氧化物酶偶联的二级抗体在室温下孵育1小时（所有抗体均购自Cell Signaling Technology，Boston，MA，USA）。用TBST（10分钟×3）洗涤后，使用ECL蛋白质印迹检测系统（Amersham Pharmacia Biotech，Piscataway，NJ，USA）开发免疫印迹，并通过将免疫印迹暴露于X射线胶片进行记录[1]。

将主动脉切成小块，在4°C的0.2M二氧化二钙缓冲液（pH 7.4）中的2.5%戊二醛中固定2小时，然后在PBS中洗涤。将材料在2%OsO4溶液中孵育，在一系列增加的乙醇浓度和环氧丙烷中脱水，最后浸入Spurr树脂中。在安装在铜网格上的Leica ultracut UCT超微切片机（Leica Microsystems Inc，LKB-II，Wetzlar，Germany）上切割超薄切片（50 nm），并在JEM 1200EX透射电子显微镜下检查[1]。

Twenty young (or adult, 3-month-old) and 40 aged (18-month-old) male Wistar rats were purchased from the Department of Laboratory Animals, China Medical University. Animals were maintained at controlled temperature of 21°C and in a 12-hour day/night cycle. All the experimental procedures were approved by the Institutional Animal Care and Use Committee of China Medical University. Young or adult animals were used as control group. Aged animals were randomly divided into two groups: the ageing group and Valsartan group (n = 20 in each group). The control and the ageing animals had free access to water and standard rat chow. The valsartan group animals continually took valsartan (Novartis Pharma Stein AG; 30 mg/kg/day) in their drinking water for 6 months. The concentration of valsartan dissolved in the drinking water was determined based on the previously established rats drinking patterns [1].

Absorption, Distribution and Excretion
After one oral dose, the antihypertensive activity of valsartan begins within approximately 2 hours and peaks within 4-6 hours in most patients. Food decreases the exposure to orally administered valsartan by approximately 40% and peak plasma concentration by approximately 50%. AUC and Cmax values of valsartan generally increase linearly with increasing dose over the therapeutic dose range. Valsartan does not accumulate appreciably in plasma following repetitive administration.
Valsartan, when administered as an oral solution, is primarily recovered in feces (about 83% of dose) and urine (about 13% of dose). The recovery is mainly as unchanged drug, with only about 20% of dose recovered as metabolites.
The steady-state volume of distribution of valsartan after intravenous administration is small (17 L), indicating that valsartan does not distribute into tissues extensively.
Following intravenous administration, plasma clearance of valsartan is approximately 2 L/hour and its renal clearance is 0.62 L/hour (about 30% of total clearance).
Valsartan, when administered as an oral solution, is primarily recovered in feces (about 83% of dose) and urine (about 13% of dose). The recovery is mainly as unchanged drug, with only about 20% of dose recovered as metabolites. ... Following intravenous administration, plasma clearance of valsartan is about 2 L/hr and its renal clearance is 0.62 L/hr (about 30% of total clearance).
Absolute bioavailability for the capsule formulation is approximately 25% (range, 10-35%). Food decreases the area under the plasma concentration-time curve (AUC) and peak plasma concentration by approximately 40 and 50%, respectively.
Valsartan peak plasma concentration is reached 2 to 4 hours after dosing. Valsartan shows bi-exponential decay kinetics following intravenous administration, with an average elimination half-life of about 6 hours. Absolute bioavailability for Diovan is about 25% (range 10% to 35%). The bioavailability of the suspension is 1.6 times greater than with the tablet. With the tablet, food decreases the exposure (as measured by AUC) to valsartan by about 40% and peak plasma concentration (Cmax) by about 50%. AUC and Cmax values of valsartan increase approximately linearly with increasing dose over the clinical dosing range. Valsartan does not accumulate appreciably in plasma following repeated administration.
The steady state volume of distribution of valsartan after intravenous administration is small (17 L), indicating that valsartan does not distribute into tissues extensively. Valsartan is highly bound to serum proteins (95%), mainly serum albumin.
For more Absorption, Distribution and Excretion (Complete) data for VALSARTAN (6 total), please visit the HSDB record page.

---

Metabolism / Metabolites
Valsartan undergoes minimal liver metabolism and is not biotransformed to a high degree, as only approximately 20% of a single dose is recovered as metabolites. The primary metabolite, accounting for about 9% of dose, is valeryl 4-hydroxy valsartan. In vitro metabolism studies involving recombinant CYP 450 enzymes indicated that the CYP 2C9 isoenzyme is responsible for the formation of valeryl-4-hydroxy valsartan. Valsartan does not inhibit CYP 450 isozymes at clinically relevant concentrations. CYP 450 mediated drug interaction between valsartan and coadministered drugs are unlikely because of the low extent of metabolism.
Valsartan is known to be excreted largely as unchanged compound and is minimally metabolized in man. Although the only notable metabolite is 4-hydroxyvaleryl metabolite (4-OH valsartan), the responsible enzyme has not been clarified at present. The current in vitro studies were conducted to identify the cytochrome P450 (CYP) enzymes involved in the formation of 4-OH valsartan. Valsartan was metabolized to 4-OH valsartan by human liver microsomes and the Eadie-Hofstee plots were linear. The apparent Km and Vmax values for the formation of 4-OH valsartan were 41.9-55.8 microM and 27.2-216.9 pmol min(-1) mg(-1) protein, respectively. There was good correlation between the formation rates of 4-OH valsartan and diclofenac 4'-hydroxylase activities (representative CYP2C9 activity) of 11 individual microsomes (r = 0.889). No good correlation was observed between any of the other CYP enzyme marker activities (CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP4A). Among the recombinant CYP enzymes examined (CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4, 3A5 and 4A11), CYP2C9 notably catalysed 4-hydroxylation of valsartan. For the specific CYP inhibitors or substrates examined (furafylline, diclofenac, S(+)-mephenytoin, quinidine and troleandomycin), only diclofenac inhibited the formation of 4-OH valsartan. These results showed that CYP2C9 is the only form responsible for 4-hydroxylation of valsartan in human liver microsomes. Although CYP2C9 is involved in valsartan metabolism, CYP-mediated drug-drug interaction between valsartan and other co-administered drugs would be negligible.
... Valsartan, when administered as an oral solution, is primarily recovered in feces (about 83% of dose) and urine (about 13% of dose). The recovery is mainly as unchanged drug, with only about 20% of dose recovered as metabolites. The primary metabolite, accounting for about 9% of dose, is valeryl 4-hydroxy valsartan. In vitro metabolism studies involving recombinant CYP 450 enzymes indicated that the CYP 2C9 isoenzyme is responsible for the formation of valeryl-4-hydroxy valsartan. Valsartan does not inhibit CYP 450 isozymes at clinically relevant concentrations. CYP 450 mediated drug interaction between valsartan and coadministered drugs are unlikely because of the low extent of metabolism. ...
Valsartan has known human metabolites that include 4-hydroxy-valsartan.

---

Biological Half-Life
After intravenous (IV) administration, valsartan demonstrates bi-exponential decay kinetics, with an average elimination half-life of about 6 hours.
Valsartan shows bi-exponential decay kinetics following intravenous administration, with an average elimination half-life of about 6 hours.
... In an investigation of pharmacokinetics and pharmacodynamics in normotensive male volunteers, valsartan was rapidly absorbed with the maximal plasma concentration occurring 2-3 hr after oral administration. The elimination half-life was about 4-6 hr, valsartan was poorly metabolized, and most of the drug was excreted via feces. ...

Toxicity Summary
IDENTIFICATION AND USE: Valsartan is a white to practically white fine powder that is formulated into oral tablets. Valsartan is an angiotensin II type 1 (AT1) receptor antagonist. It is used in the management of hypertension. Valsartan is also used to treat heart failure or left ventricular dysfunction after acute myocardial infarction. HUMAN EXPOSURE AND TOXICITY: The most likely manifestations of overdosage include hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. Depressed levels of consciousness, circulatory collapse and shock have been reported. The use of valsartan during pregnancy is contraindicated. While use during the first trimester does not suggest a risk of major anomalies, use during the second and third trimester may cause teratogenicity and severe fetal and neonatal toxicity. Fetal toxic effects may include anuria, oligohydramnios, fetal hypocalvaria, intrauterine growth restriction, prematurity, and patent ductus arteriosus. Anuria-associated anhydramnios/oligohydramnios may produce fetal limb contractures, craniofacial deformation, and pulmonary hypoplasia. Severe anuria and hypotension, resistant to both pressor agents and volume expansion, may occur in the newborn following in utero exposure to valsartan. ANIMAL STUDIES: There was no evidence of carcinogenicity when valsartan was administered in the diet to mice and rats for up to two years. Also, valsartan had no adverse effects on fertility of male or female rats and no teratogenic effects were observed when valsartan was administered to pregnant mice and rats. However, significant decreases in fetal weight, pup birth weight, pup survival rate, and slight delays in developmental milestones were observed in studies in which parental rats were treated with valsartan at oral, maternally toxic (reduction in body weight gain and food consumption) doses during organogenesis or late gestation and lactation. In rabbits, maternal toxic doses resulted in fetal resorptions, litter loss, abortions, and low fetal body weight as well as maternal mortality. Mutagenicity assays did not reveal any valsartan-related effects at either the gene or chromosome level. These assays included bacterial mutagenicity tests with Salmonella (Ames) and E coli, a gene mutation test with Chinese hamster V79 cells, a cytogenetic test with Chinese hamster ovary cells, and a rat micronucleus test.

---

Hepatotoxicity
Valsartan has been associated with a low rate of serum aminotransferase elevations (
Likelihood score: D (Possible rare cause of clinically apparent liver injury).

---

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Milk levels after the lowest dose of the combination of valsartan and sacubitril (Entresto) are very low. If the highest recommended maternal dosage (6 times greater) produces proportionate milk levels, they would likely still be quite low. Valsartan is unlikely to affect the nursing infant.
◉ Effects in Breastfed Infants
Two women taking sacubitril 24 mg and valsartan 26 mg (Entresto) did not observe any symptoms in their breastfed infants. Their extent of breastfeeding was not reported.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

---

Protein Binding
Valsartan is highly bound to serum proteins (95%), mainly serum albumin.

---

Interactions
Concurrent use of valsartan and warfarin did not affect the pharmacokinetics of valsartan or the anticoagulant effect of warfarin.
Concomitant use of potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene), potassium supplements, or potassium-containing salt substitutes with valsartan may result in increased hyperkalemic effects and, in patients with heart failure, increases in serum creatinine concentration.
Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists, including Diovan. Monitor serum lithium levels during concomitant use.
Dual Blockade of the Renin-Angiotensin System (RAS): Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Closely monitor blood pressure, renal function and electrolytes in patients on Diovan and other agents that affect the RAS.
For more Interactions (Complete) data for VALSARTAN (11 total), please visit the HSDB record page.

---

Non-Human Toxicity Values
LD50 Marmoset gavage >1000 mg/kg (approximate)
LD50 Rat gavage >2000 mg/kg (approximate)

[1]. Valsartan ameliorates ageing-induced aorta degeneration via angiotensin II type 1 receptor-mediated ERK activity. J Cell Mol Med. 2014 Jun;18(6):1071-80.

[2]. Valsartan blocked alcohol-induced, Toll-like receptor 2 signaling-mediated inflammation in human vascular endothelial cells. Alcohol Clin Exp Res. 2014 Oct;38(10):2529-40.

[3]. Novel mechanism of cardiac protection by valsartan: synergetic roles of TGF-β1 and HIF-1α in Ang II-mediated fibrosis after myocardial infarction. J Cell Mol Med. 2015 Aug;19(8):1773-82.

[4]. Cardioprotective effect of valsartan in mice with short-term high-salt diet by regulating cardiac aquaporin 1 and angiogenic factor expression. Cardiovasc Pathol. 2015 Jul-Aug;24(4):224-9.

[5]. Valsartan reverses depressive/anxiety-like behavior and induces hippocampal neurogenesis and expression of BDNF protein in unpredictable chronic mild stress mice. Pharmacol Biochem Behav. 2014 Sep;124:5-12.

Therapeutic Uses
Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents
Diovan is an angiotensin II receptor blocker (ARB) indicated for: treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. /Included in US product labeling/
Diovan is an angiotensin II receptor blocker (ARB) indicated for: reduction of cardiovascular mortality in clinically stable patients with left ventricular failure or left ventricular dysfunction following myocardial infarction. /Included in US product labeling/
Diovan is an angiotensin II receptor blocker (ARB) indicated for: treatment of heart failure (NYHA class II-IV); Diovan significantly reduced hospitalization for heart failure. /Included in US product labeling/
For more Therapeutic Uses (Complete) data for VALSARTAN (6 total), please visit the HSDB record page.

---

Drug Warnings
/BOXED WARNING/ WARNING: FETAL TOXICITY. When pregnancy is detected, discontinue Diovan as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Diovan as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimesters of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Diovan, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Diovan for hypotension, oliguria, and hyperkalemia.
Angiotensin II (A-II) is the main effector of the renin-angiotensin system. A-II functions by binding its type 1 (AT1) receptors to cause vasoconstriction and retention of sodium and fluid. Several AT1 receptor antagonists-a group of drugs collectively called "sartans"-have been marketed during the past few years for treatment of hypertension and heart failure. At least 15 case reports describe oligohydramnios, fetal growth retardation, pulmonary hypoplasia, limb contractures, and calvarial hypoplasia in various combinations in association with maternal losartan, candesartan, valsartan, or telmisartan treatment during the second or third trimester of pregnancy. Stillbirth or neonatal death is frequent in these reports, and surviving infants may exhibit renal damage. The fetal abnormalities, which are strikingly similar to those produced by maternal treatment with angiotensin-converting enzyme (ACE) inhibitors during the second and third trimesters of pregnancy, are probably related to extreme sensitivity of the fetus to the hypotensive action of these drugs. ...
Valsartan is distributed into milk in rats. It is not known whether valsartan is distributed into human milk. Discontinue nursing or the drug because of potential risk in nursing infants.
For more Drug Warnings (Complete) data for VALSARTAN (21 total), please visit the HSDB record page.

---

Pharmacodynamics
Valsartan inhibits the pressor effects of angiotensin II with oral doses of 80 mg inhibiting the pressor effect by about 80% at peak with approximately 30% inhibition persisting for 24 hours. Removal of the negative feedback of angiotensin II causes a 2- to 3-fold rise in plasma renin and consequent rise in angiotensin II plasma concentration in hypertensive patients. Minimal decreases in plasma aldosterone were observed after administration of valsartan. In multiple-dose studies in hypertensive patients, valsartan had no notable effects on total cholesterol, fasting triglycerides, fasting serum glucose, or uric acid. **Hypotension** Excessive hypotension was rarely seen (0.1%) in patients with uncomplicated hypertension treated with valsartan alone. In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients receiving high doses of diuretics, symptomatic hypotension may occur. This condition should be corrected prior to administration of valsartan, or the treatment should start under close medical supervision. Caution should be observed when initiating therapy in patients with heart failure. Patients with heart failure given valsartan commonly have some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension usually is not necessary when dosing instructions are followed. In controlled trials in heart failure patients, the incidence of hypotension in valsartan-treated patients was 5.5% compared to 1.8% in placebo-treated patients. If excessive hypotension occurs, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized. **Impaired Renal Function** Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on valsartan. Monitor renal function periodically in these patients. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on valsartan. **Hyperkalemia** Some patients with heart failure have developed increases in potassium. These effects are usually minor and transient, and they are more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of valsartan may be required.

C24H29N5O3

435.52

435.227

C, 66.19; H, 6.71; N, 16.08; O, 11.02

137862-53-4

Sacubitril/Valsartan;936623-90-4;Valsartan-d9;1089736-73-1;Valsartan-d3;1331908-02-1;Valsartan-d8;1089736-72-0;(Rac)-Valsartan-d9; 137862-53-4; 149690-05-1 (sodium)

60846

White to off-white solid

1.2±0.1 g/cm3

684.9±65.0 °C at 760 mmHg

116-117°C

368.0±34.3 °C

0.0±2.2 mmHg at 25°C

1.587

4.75

112.07

2

6

10

32

608

1

O([H])C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N(C(C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])=O)C([H])([H])C1C([H])=C([H])C(C2=C([H])C([H])=C([H])C([H])=C2C2N=NN([H])N=2)=C([H])C=1[H])=O

ACWBQPMHZXGDFX-QFIPXVFZSA-N

InChI=1S/C24H29N5O3/c1-4-5-10-21(30)29(22(16(2)3)24(31)32)15-17-11-13-18(14-12-17)19-8-6-7-9-20(19)23-25-27-28-26-23/h6-9,11-14,16,22H,4-5,10,15H2,1-3H3,(H,31,32)(H,25,26,27,28)/t22-/m0/s1

(S)-3-methyl-2-(N-{[2-(2H-1,2,3,4-tetrazol-5-yl)biphenyl-4-yl]methyl}pentanamido)butanoic acid

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)

配方 1 中的溶解度: ≥ 2.5 mg/mL (5.74 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), 悬浮液。
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。

---

配方 2 中的溶解度: ≥ 2.5 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。
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 900 μL 玉米油中并混合均匀。

---

View More

配方 3 中的溶解度: 10 mg/mL (22.96 mM) in 50% PEG300 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.
*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。

---

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。