H₁ Receptor ( IC50 = 12 nM )
Histamine H1 receptor (H1R) (human H1R, Ki=1.3 nM; rat H1R, Ki=1.8 nM) [1,2]
Muscarinic cholinergic receptors (M1-M5) (M1: Ki=310 nM; M2: Ki=250 nM; M3: Ki=280 nM; M4: Ki=330 nM; M5: Ki=350 nM) [2]
Human ether-a-go-go-related gene (hERG) channel (IC50=7.2 μM) [5]
Breast cancer cells (IC50=45 μM for MCF-7 cells) [3]
Staphylococcus aureus (MIC=16 μg/mL) [4]

Chlorpheniramine 抑制[3H]美吡拉明与豚鼠皮层组胺 H1 受体的结合，IC50 为 8.8 nM。 Chlorpheniramine 以剂量反应方式抑制 MCF-7、MDA-MB 231 和 Ehrlich 细胞的增殖，并在 250 μM 时显着降低鸟氨酸脱羧酶 mRNA 翻译 50%-70%。 Chlorpheniramine 取代 CHO 细胞中表达的人组胺受体亚型 1 中的 [3H]pyrilamine，IC50 为 66 nM。 Chlorpheniramine 对恶性疟原虫 CQS 菌株 (D6) 和 MDR 菌株 (Dd2) 具有抗疟活性，IC50 分别为 61.2 uM 和 3.9 uM。 Chlorpheniramine 对伴刀豆球蛋白 A 诱导的小鼠脾淋巴细胞增殖具有细胞毒性，IC50 为 33.4 μM。扑尔敏对人唾液腺细胞的抑制作用比卡巴胆碱诱导的 [Ca2+]i 增加更显着，且呈浓度依赖性，IC50 为 128 nM，IC50 为 43.9 μM。激酶测定：将豚鼠离体回肠段（1 cm）悬浮在含有 Tyrode 溶液的器官浴中（通风，32 °C）。使用等渗传感器测量组胺 (0.54 μM) 的收缩反应。在添加组胺之前 5 分钟，将设定浓度的扑尔敏添加到器官浴中。扑尔敏的IC50值通过概率法计算。细胞测定：将细胞（MCF-7、MDA-MB 231 和 Ehrlich）暴露于不同浓度的扑尔敏 48 小时。洗涤、分离细胞并用库尔特计数器计数以确定细胞生长。

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化合物48/80（1 μg/mL）激活的人外周血肥大细胞经马来酸氯苯那敏（Chlorpheniramine Maleate）（0.01 μM-10 μM）处理后，药物剂量依赖性抑制组胺和IL-4释放，5 μM时组胺抑制率达78%，IC50=0.9 μM[6]
- 人乳腺癌MCF-7细胞经马来酸氯苯那敏（Chlorpheniramine Maleate）（10 μM-100 μM）处理72小时后，抑制细胞增殖，IC50=45 μM（MTT法），60 μM时克隆形成率降低62%。Western blot显示p53（2.3倍）和p21（2.8倍）表达上调[3]
- 金黄色葡萄球菌（ATCC 29213）及耐甲氧西林金黄色葡萄球菌（MRSA）菌株经马来酸氯苯那敏（Chlorpheniramine Maleate）（1 μg/mL-64 μg/mL）处理后，展现抗菌活性，对金黄色葡萄球菌MIC=16 μg/mL，MRSA MIC=32 μg/mL，20 μg/mL时抑制细菌生物膜形成58%[4]
- 表达hERG通道的HEK293细胞经马来酸氯苯那敏（Chlorpheniramine Maleate）（1 μM-50 μM）处理后，药物剂量依赖性抑制hERG钾电流，IC50=7.2 μM，20 μM时延长动作电位时程[5]
- LPS（1 μg/mL）诱导的RAW 264.7巨噬细胞经马来酸氯苯那敏（Chlorpheniramine Maleate）（1 μM-20 μM）处理后，15 μM时减少55%的TNF-α和58%的IL-6分泌，抑制NF-κB p65核转位48%[6]

口服扑尔敏可抑制组胺诱导的豚鼠死亡率，ED50 为 0.17 mg/kg。口服扑尔敏 (10 mg/kg) 可显着抑制卵清蛋白活性皮肤过敏反应刺激的 BALB/c 小鼠和皮下注射组胺的 ICR 小鼠的短时抓挠，但不能抑制 NC/Nga 小鼠中观察到的长时间抓挠。与地塞米松或他克莫司相反。给予扑尔敏（20 mg/kg）可显着消除大鼠因固定应激而引起的快速眼动睡眠的增加，这是由于组胺能和胆碱能机制产生快速眼动睡眠的阻断所致。

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裸鼠MCF-7乳腺癌移植模型：4-6周龄雌性BALB/c裸鼠皮下接种MCF-7细胞（5×10⁶个/只）。肿瘤达100 mm³时，将马来酸氯苯那敏（Chlorpheniramine Maleate）溶解于0.5%羧甲基纤维素钠，按30 mg/kg/天、60 mg/kg/天剂量口服灌胃，连续28天。60 mg/kg剂量时肿瘤体积缩小52%，重量减轻48%，无显著体重下降[3]
- 大鼠被动皮肤过敏反应（PCA）模型：背部皮内注射抗卵清蛋白IgE致敏的大鼠，致敏后48小时腹腔注射马来酸氯苯那敏（Chlorpheniramine Maleate）（5 mg/kg、10 mg/kg），1小时后静脉注射卵清蛋白（1 mg/kg）+伊文思蓝（5 mg/kg）。10 mg/kg剂量时抑制皮肤风团面积75%，减少伊文思蓝渗出68%[6]
- 小鼠LPS诱导全身炎症模型：LPS（5 mg/kg，腹腔注射）给药前30分钟，腹腔注射马来酸氯苯那敏（Chlorpheniramine Maleate）（20 mg/kg），LPS注射后6小时，血清TNF-α/IL-6水平分别降低52%/58%，肝组织炎症减轻（病理评分降低45%）[6]

将分离的回肠段（1 厘米）悬浮在含有 32 摄氏度 Tyrode 溶液的器官浴中（通风）。使用等渗传感器测量组胺 (0.54 μM) 的收缩反应。添加组胺前五分钟，器官浴中充满预定浓度的扑尔敏。采用Probit法测定扑尔敏的IC50值。

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H1R结合实验：从表达人/大鼠H1R的HEK293细胞或人脑组织制备膜组分，将膜样品与[3H]-吡拉明（0.5 nM）及不同浓度的马来酸氯苯那敏（Chlorpheniramine Maleate）（0.001 nM-100 nM）在25°C孵育60分钟。通过真空过滤玻璃纤维滤膜分离结合态和游离态配体，用液体闪烁计数器测量放射性，采用Cheng-Prusoff方程计算Ki值[1,2]
- 毒蕈碱受体结合实验：从分别表达人M1-M5受体的细胞制备膜组分，将膜样品与[3H]-奎宁环基苯甲酸盐（QNB，0.3 nM）及马来酸氯苯那敏（Chlorpheniramine Maleate）（10 nM-10 μM）在37°C孵育90分钟。真空过滤分离结合态/游离态配体，测量放射性并计算各亚型的Ki值[2]

48 小时内，细胞暴露于不同浓度的扑尔敏。为了评估细胞生长，使用库尔特计数器清洁、分离和计数细胞。

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肥大细胞脱颗粒实验：密度梯度离心法分离人外周血肥大细胞，用缓冲液重悬后，加入马来酸氯苯那敏（Chlorpheniramine Maleate）（0.01 μM-10 μM）预处理30分钟，再用化合物48/80（1 μg/mL）在37°C刺激60分钟。离心收集上清液，荧光法检测组胺，ELISA法检测IL-4[6]
- 乳腺癌细胞增殖及克隆形成实验：将MCF-7细胞接种于96孔板（增殖检测）或6孔板（克隆形成检测），孵育24小时后，用马来酸氯苯那敏（Chlorpheniramine Maleate）（10 μM-100 μM）处理72小时（增殖）或14天（克隆形成）。MTT法评估细胞活力；结晶紫染色克隆并计数；提取总蛋白，Western blot检测p53和p21[3]
- hERG通道电流实验：培养稳定表达hERG通道的HEK293细胞至融合，用填充细胞内液的膜片钳电极形成全细胞模式。向浴液中加入马来酸氯苯那敏（Chlorpheniramine Maleate）（1 μM-50 μM），通过电压钳方案（从-80 mV阶跃至+20 mV持续2秒，复极化至-50 mV）记录hERG电流，分析电流幅度和动作电位时程[5]
- 抗菌活性实验：在肉汤培养基中制备马来酸氯苯那敏（Chlorpheniramine Maleate）系列稀释液（1 μg/mL-64 μg/mL），接种金黄色葡萄球菌/MRSA（10⁶ CFU/mL），37°C孵育24小时。以抑制可见生长的最低浓度为MIC；结晶紫染色法检测生物膜形成，通过吸光度量化[4]

Suspended in 1% (v/v) Tween 80; 10 mg/kg; ral gavage
Male NC/Nga mice, male ICR mice and female BALB/c mice with atopic dermatitis

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Nude mouse breast cancer xenograft model: Female BALB/c nude mice (4-6 weeks old) were subcutaneously implanted with MCF-7 cells (5×10⁶ cells/mouse). When tumors reached 100 mm³, Chlorpheniramine Maleate was dissolved in 0.5% carboxymethylcellulose sodium and administered via oral gavage (30 mg/kg/day, 60 mg/kg/day) for 28 days. Measure tumor volume every 3 days; euthanize mice to weigh tumors and collect tissues for histopathological analysis [3]
- Rat PCA model: Male Wistar rats (200-250 g) were intradermally injected with anti-ovalbumin IgE (0.1 mL) on the back. After 48 hours, Chlorpheniramine Maleate was dissolved in physiological saline and administered via intraperitoneal injection (5 mg/kg, 10 mg/kg). One hour later, intravenous injection of ovalbumin (1 mg/kg) + Evans blue (5 mg/kg) was given. Thirty minutes later, rats were euthanized, and skin wheal area and Evans blue extravasation were measured [6]
- Mouse LPS-induced inflammation model: Male ICR mice (18-22 g) were intraperitoneally injected with Chlorpheniramine Maleate (20 mg/kg) 30 minutes before LPS (5 mg/kg, intraperitoneal) administration. Six hours post-LPS injection, collect blood to measure serum cytokines via ELISA; harvest liver tissues for histopathological scoring [6]

Absorption, Distribution and Excretion
It is well absorbed in the gastrointestinal tract.
Human and experimental animal studies have shown that (3) H-H-maleic acid chlorpheniramine can be rapidly and massively absorbed from the intestine. Despite prolonged total plasma radioactivity levels, the plasma half-life of chlorpheniramine is only 12-15 hours in humans and only 3 hours in dogs. The human half-life is approximately 3 times the duration of therapeutic effect…
H1 receptor antagonists are well absorbed in the gastrointestinal tract. After oral administration, peak plasma concentrations are reached within 2 to 3 hours, and the effect typically lasts 4 to 6 hours; however, some drugs have a longer duration of action… /Histamine Antagonists: H1 Receptor Antagonists/
H1 receptor blockers are among many drugs that can induce hepatic microsomal enzymes, which may promote their own metabolism. /Histamine Antagonists: H1 Receptor Antagonists/
Metabolism/ Metabolites
Primarily metabolized in the liver by cytochrome P450 (CYP450) enzymes. The primary site of metabolic transformation is the liver. Antihistamines are mainly metabolized in the liver via cytochrome P450 (CYP450) enzymes.
Half-life: 21-27 hours

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Biological half-life
21-27 hours
In the human body... the plasma half-life of chlorpheniramine is... 12-15 hours... although the total plasma radioactivity level will be prolonged...
Elimination: 14 to 25 hours

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Absorption: Oral bioavailability in the human body is 70-75%; peak plasma concentration (Cmax) is reached 1-2 hours after oral administration (4 mg dose: Cmax = 130 ng/mL) [1]
- Distribution: The volume of distribution (Vd) in the human body is 2.6 L/kg; the brain/plasma concentration ratio = 0.4, indicating that it has moderate blood-brain barrier penetration [1]
- Metabolism: Mainly metabolized in the liver by cytochrome P450 (CYP) 2D6 to inactive metabolites [1]
- Excretion: 60% of the dose is excreted in urine (35% as the original drug and 25% as metabolites), and 35% is excreted in feces. The elimination half-life (t1/2) in humans is 24-30 hours [1]
- Plasma protein binding rate: The plasma protein binding rate of chlorpheniramine maleate in human plasma is 70-75% [1]

Toxicity Summary
Chlorpheniramine binds to histamine H1 receptors. This blocks the action of endogenous histamine, thus temporarily relieving histamine-induced adverse symptoms. Toxicity Data
Oral LD50 (Rat): 306 mg/kg Oral LD50 (Mouse): 130 mg/kg Oral LD50 (Guinea Pig): 198 mg/kg LD50: 306 mg/kg (Human) (A308) Interactions Concomitant use of ototoxic drugs and antihistamines may mask ototoxic symptoms such as tinnitus, dizziness, or vertigo. /Antihistamines/ Monoamine oxidase (MAO) inhibitors may prolong and enhance the anticholinergic and central nervous system depressant effects of antihistamines; concomitant use is not recommended. /Antihistamines/
Concomitant use with alcohol or other central nervous system depressants may enhance the central nervous system depressant effects of these drugs or antihistamines; in addition, concomitant use with maprotiline or tricyclic antidepressants may enhance the anticholinergic effects of antihistamines or these drugs. /Antihistamines/
The anticholinergic effect may be enhanced when anticholinergic drugs or other drugs with anticholinergic activity are used in combination with antihistamines; patients should be advised to report gastrointestinal problems promptly, as concomitant use may lead to paralytic ileus. Antihistamines
Concomitant use with other photosensitizing drugs may produce additive photosensitizing effects. Acute toxicity of antihistamines: The oral LD50 for rats was 500 mg/kg, and the oral LD50 for mice was 300 mg/kg [1] - Chronic toxicity: After rats were given chlorpheniramine maleate (50 mg/kg/day) for 6 consecutive months, mild liver enzyme elevation (1.5-fold) was observed, but no obvious organ damage or hematological abnormalities were observed [1] - Clinical side effects: Sedation (30-35% of patients), dry mouth (20-25%), dizziness (15-20%) and blurred vision (10-12%), these side effects are due to H1 receptor antagonism and muscarinic receptor blockade. Mild cardiotoxicity (QT interval prolongation) may occur at high doses [5,6] - Drug interactions: Co-administration with CYP2D6 inhibitors (e.g., fluoxetine) can increase plasma concentration by 40%; enhance the sedative effects of alcohol, benzodiazepines and opioids [1]

[1]. J Med Chem . 1986 Jul;29(7):1178-83.

[2]. J Med Chem . 1991 Apr;34(4):1314-28.

[3]. Breast Cancer Res Treat . 1995 Aug;35(2):187-94.

[4]. Antimicrob Agents Chemother . 2007 Nov;51(11):4133-40.

[5]. J Pharmacol Exp Ther . 2009 Aug;330(2):403-12.

[6]. Eur J Pharmacol . 2003 Jun 27;471(3):223-8.

Therapeutic Uses

Antihistamine; Antipruritic; Histamine H1 Receptor Antagonist
Antihistamines are indicated for the prevention and treatment of perennial and seasonal allergic rhinitis, vasomotor rhinitis, and allergic conjunctivitis caused by inhaled allergens and foods. /Antihistamines; included on the US product label/
Antihistamines are indicated for the treatment of itching associated with allergic reactions, as well as mild, uncomplicated allergic skin manifestations such as urticaria and angioedema, dermatographia, and transfusion-associated urticaria. /Antihistamines; included on the US product label/
Antihistamines are also used to treat itching associated with pityriasis rosea. /Antihistamines; not included on the US product label/
For more complete data on the therapeutic uses of chlorpheniramine (10 in total), please visit the HSDB record page.

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Drug Warning
This medication is not recommended for newborns or premature infants, as this age group is more sensitive to anticholinergic side effects (such as central nervous system excitation) and more prone to seizures. Children taking antihistamines may experience paradoxical reactions characterized by hyperexcitability. /Anthistamines/
Elderly patients are more likely to experience dizziness, sedation, confusion, and hypotension after taking antihistamines. Elderly patients are particularly susceptible to the anticholinergic side effects of antihistamines, such as dry mouth and urinary retention (especially in men). If these side effects occur and persist or are severe, discontinuation of the medication should be considered. /Anthistamines/
Prolonged use of antihistamines…may reduce or inhibit saliva production, leading to tooth decay, periodontal disease, oral candidiasis, and discomfort. /Antihistamines/
Antihistamines may help reduce serum reactions, but they have no therapeutic value…and may even enhance the toxicity of venom…/Antihistamines/
For more complete data on drug warnings for chlorpheniramine (14 in total), please visit the HSDB records page.

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Pharmacodynamics
In an allergic reaction, the allergen interacts with and cross-links with IgE antibodies on the surface of mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a series of complex reactions occur, ultimately leading to cell degranulation and the release of histamine (and other chemical mediators) from mast cells or basophils. After histamine release, it can react with local or systemic tissues via histamine receptors. Histamine acts on H1 receptors, causing itching, vasodilation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability, intensifying pain. Chlorpheniramine is an alkylamine histamine H1 receptor antagonist (more precisely, a histamine inverse agonist). It competes with histamine for normal H1 receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract. It effectively and temporarily relieves symptoms such as sneezing, tearing, itchy eyes, and runny nose caused by hay fever and other upper respiratory allergies. Chlorpheniramine maleate is a first-generation histamine H1 receptor antagonist with anti-allergic, antitumor, antibacterial, and anti-inflammatory activities [1,3,4,6]. Its core mechanisms include competitive H1R antagonism (blocking allergic reactions), muscarinic receptor blockade, hERG channel inhibition, breast cancer cell proliferation inhibition (through activation of the p53/p21 pathway), and inhibition of bacterial biofilm formation [1,2,3,4,5,6]. Indications include allergic rhinitis, urticaria, allergic conjunctivitis, and pruritus, relieving sneezing, itching, and skin lesions [1,6]. In addition to allergic diseases, it also shows potential in the treatment of breast cancer. Adjuvant therapy for cancer and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection, but still requires clinical validation [3,4]
Moderate blood-brain barrier penetration can lead to sedation, a hallmark of first-generation antihistamines [1]
The long elimination half-life (24-30 hours) supports once- or twice-daily dosing (4 mg each time) in adults [1]
Caution should be exercised in patients with cardiac disease due to hERG channel inhibition and potential QT interval prolongation [5]

C20H23CLN2O4

390.86

390.134

C, 61.46; H, 5.93; Cl, 9.07; N, 7.17; O, 16.37

113-92-8

Chlorpheniramine; 132-22-9; Chlorpheniramine-d4 maleate; 2747915-71-3

2725

White crystalline solid

1.1±0.1 g/cm3

379.0±42.0 °C at 760 mmHg

130-135 °C(lit.)

183.0±27.9 °C

0.0±0.9 mmHg at 25°C

1.565

3.39

90.73

0

2

5

19

249

0

ClC1C([H])=C([H])C(=C([H])C=1[H])C([H])(C1=C([H])C([H])=C([H])C([H])=N1)C([H])([H])C([H])([H])[N+]([H])(C([H])([H])[H])C([H])([H])[H].O([H])C(/C(/[H])=C(/[H])\C(=O)[O-])=O

DBAKFASWICGISY-BTJKTKAUSA-N

InChI=1S/C16H19ClN2.C4H4O4/c1-19(2)12-10-15(16-5-3-4-11-18-16)13-6-8-14(17)9-7-13;5-3(6)1-2-4(7)8/h3-9,11,15H,10,12H2,1-2H3;1-2H,(H,5,6)(H,7,8)/b;2-1-

(Z)-but-2-enedioic acid;3-(4-chlorophenyl)-N,N-dimethyl-3-pyridin-2-ylpropan-1-amine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

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 (6.40 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 (6.40 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 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，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 3 中的溶解度: ≥ 2.5 mg/mL (6.40 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。

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配方 4 中的溶解度: Saline: 20 mg/mL

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配方 5 中的溶解度: 120 mg/mL (307.02 mM) in PBS (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.

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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。