β-lactam; cell wall synthesis
Glutamate transporter 1 (GLT-1) [3]

氨苄西林对猪源性大肠杆菌生长的抑制作用具有剂量依赖性。氨苄青霉素的有效抑制浓度为2.5 uG/mL[1]。

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对103株分离自猪的大肠杆菌进行体外药敏试验，结果显示100株对营养肉汤中浓度为5.0 µg/mL的Ampicillin完全敏感，3株耐药。 [1]
所有4株从坏死性肠炎病例中分离的沙门氏菌对5.0 µg/mL的Ampicillin完全敏感。 [1]
将猪粪便样本涂布于含有Ampicillin的E.M.B.琼脂上，在0、0.1和1.0 µg/mL浓度下未观察到对大肠杆菌生长的抑制作用。2.5、5.0和10.0 µg/mL的浓度以剂量依赖的方式逐渐抑制大肠杆菌生长。 [1]
所有使用10 µg Ampicillin药敏纸片测试的大肠杆菌分离株均显示出清晰的抑菌圈，表明其敏感性。Ampicillin纸片周围的抑菌圈大于30 µg金霉素或土霉素纸片周围的抑菌圈。 [1]

当 11 周龄的猪患出血性肠炎时，氨苄西林可以神奇地缓解症状[1]。胆汁中氨苄青霉素的最高浓度是血清中的两倍。口服给药后，门静脉血中氨苄青霉素的峰值浓度是外周血中的两倍[2]。氨苄西林可提供针对缺血再灌注引起的脑损伤的神经保护作用。氨苄青霉素提高 GLT-1 表达水平，同时降低 MMP 活性。在整体前脑缺血后，氨苄青霉素预处理可显着降低内侧海马细胞死亡[3]。

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对一只患有出血性肠炎的11周龄猪口服Ampicillin后，在6小时内出现临床改善，并在48小时内完全康复。 [1]
治疗后，与肠炎相关的O141血清型大肠杆菌从粪便菌群中消失，被一种能够产生H₂S的异常大肠杆菌类型所取代。 [1]
治疗后未出现Ampicillin耐药的大肠杆菌菌株。 [1]

敏感性测试[1]
在每一种浓度的抗生素下，一组5个重复管分别接种1滴，每滴1滴的试验培养物生长18小时。接种管37℃孵育。6小时后，用0.5%终浓度的福尔马林停止进一步生长。用带有525 μ m滤光片的Fisher电光度计记录培养物的生长和光密度。

研究了从精练猪和非精练猪分离的103个大肠杆菌培养物和从一例坏死性肠炎分离的4个沙门氏菌培养物对氨苄西林的体外敏感性，这些氨苄西林的浓度分别为0、0.1、1.0和5.0 uG / ml。除3株外，其余培养的大肠杆菌均对5.0 uG/ml敏感。在美国，所有分离的沙门氏菌也对该浓度的抗生素敏感。大肠杆菌的敏感性也通过用含有0、0.1、1.0、2.5、5.0和10.0 uG / ml氨苄西林的E.M.B.琼脂培养液镀取精练猪或非精练猪的粪便样品进行测试。在0、0.1和1.0 uG浓度下，大肠杆菌的生长没有差异。三种较高浓度的抗生素对大肠杆菌生长的抑制作用与氨苄青霉素在每种浓度中的含量成正比。 氨苄西林被证明对减轻11周龄猪出血性肠炎的症状非常有效。scours的消失与先前存在的粪便大肠杆菌的血清生物型被另一种产生H2S的异常型大肠杆菌所取代有关。在用这种抗生素治疗动物后，没有出现耐氨苄西林的大肠杆菌菌株。[1]

Mice: Normal saline is used to dissolve ampicillin. After receiving halothane anesthesia, male C57BL/6 mice had their common carotid arteries blocked bilaterally for 40 minutes. Penicillin G (6,000 U/kg or 20,000 U/kg, intraperitoneally [i.p.]) or ampicillin (200 mg/kg) was given intraperitoneally (i.p.) every day for five days prior to transient forebrain ischemia. The same volume and timing of saline administration were used for the control animals[3].

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An 11-week-old pig with hemorrhagic enteritis was treated orally with Ampicillin administered in gelatin capsules. The dosing regimen consisted of an initial dose of 8 mg/kg body weight, followed by two additional doses of 4 mg/kg each at 4-hour intervals. [1]
Fecal samples were collected from the pig before treatment and 48 hours after the first dose. A fecal sample from a healthy pig from another litter was also collected as a control. [1]

Absorption, Distribution and Excretion
Ampicillin is primarily excreted unchanged in the urine. Incomplete absorption occurs when ampicillin is taken before eating. It appears in the bile, undergoes enterohepatic circulation, and is excreted in the feces. Bile concentrations depend on the integrity of the gallbladder and its bile ducts. After absorption from the gastrointestinal tract or injection site, ampicillin is distributed to the liver, bile, muscles, kidneys, crop, and adipose tissue. Ampicillin has been used to treat and prevent salmonellosis in avian birds with encouraging results. Ampicillin is excreted via bile. Anhydrous ampicillin and ampicillin trihydrate are generally stable in acidic gastric juices. In fasting adults, 30-55% of the dose is absorbed from the gastrointestinal tract after oral administration. Although peak serum concentrations are reached within 1 hour of administration, maximum serum concentrations are typically reached after approximately 2 hours.
Two hours after oral administration of 250 mg ampicillin to fasting subjects, the mean peak serum concentration was 1.8–2.9 μg/mL. After oral administration of 500 mg, the mean peak serum concentration was 3–6 μg/mL. Six hours after oral administration of 500 mg, the serum antibiotic concentration was less than 1 μg/mL.
For more complete data on absorption, distribution, and excretion of ampicillin (16 items in total), please visit the HSDB record page.

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Metabolism/Metabolites
Ampicillin is degraded by penicillinase…
In Bacillus and Penicillium, it produces α-aminobenzylpenicillic acid; in Escherichia coli, it produces L-phenylglycine. /Excerpt from Table/
Approximately 20% of a given dose (250–500 mg) of ampicillin is metabolized in healthy subjects. Within 12 hours, 7% of the total dose is excreted in the urine as metabolites… Ampicillin is metabolized to 5R,6R-penicillic acid and 5S,6R-penicillic acid… After oral administration, it is metabolized to piperazine-2,5-dione… Other unidentified metabolites have also been reported…

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Biological Half-Life
The half-life of all aminopenicillins is approximately 60–90 minutes.
After intraperitoneal injection…the serum half-life of ampicillin is estimated to be 27 minutes…
…The plasma half-life of ampicillin is usually 1–2 hours…but longer in the elderly…in patients with renal failure, the half-life can be as long as 20 hours…

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The literature cited in this study mentions that ampicillin is well absorbed after oral administration and is quite stable when dissolved in water. [1]
Other data show that after oral administration, the highest concentrations of ampicillin are found in the liver and kidneys, with concentrations in urine and bile being 800 times and 300 times higher than in blood, respectively. [1]

Hepatotoxicity
Rare cases of specific liver injury have been reported in patients taking aminopenicillin antibiotics. The incidence with ampicillin is much lower than with amoxicillin, possibly occurring in one in 100,000 exposed individuals. These cases are characterized by a short incubation period, ranging from a few days to two weeks. Liver injury can occur after discontinuation of the antibiotic. Serum enzyme profiles associated with aminopenicillin-induced liver injury include hepatocellular types, characterized by significantly elevated ALT and AST, and mildly elevated alkaline phosphatase, which rapidly recovers upon discontinuation. Additionally, cholestatic liver injury has been reported, characterized by significantly elevated alkaline phosphatase (similar to penicillin-induced liver injury), some of which are associated with prolonged cholestasis, and in rare cases, disappearance of bile duct syndrome. Liver injury may be accompanied by rash, toxic epidermal necrolysis, or Stevens-Johnson syndrome. Autoantibodies are uncommon. Probability score: C (likely, but rarely, to cause clinically significant liver injury).

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Effects during pregnancy and lactation>
◉ Overview of medication use during lactation
Extensive information suggests that the concentration of ampicillin in breast milk is low and is not expected to have adverse effects on breastfed infants. There are reports that penicillin-type drugs occasionally disrupt the infant's gut microbiota, leading to diarrhea or thrush, but these effects have not been fully assessed. Breastfeeding women can take ampicillin.
◉ Effects on breastfed infants
An uncontrolled observational study of infants breastfed by mothers taking ampicillin appeared to have an increased incidence of diarrhea and candidiasis, attributed to ampicillin in breast milk.
In a prospective follow-up study, 5 breastfeeding mothers reported taking ampicillin (dosage not specified). One mother reported her infant developing diarrhea. No rashes or candidiasis were reported in infants exposed to ampicillin.
A small, controlled prospective study required mothers to monitor their infants for signs of adverse reactions (thickened tongue coating, feeding difficulties, changes in stool frequency and consistency, diaper rash, and skin rash). Weight changes and the occurrence of jaundice were also documented. No statistically significant differences were found in these parameters between infants born to mothers in the control group and infants born to mothers taking ampicillin.
◉ Effects on breastfeeding and breast milk
No relevant published information was found as of the revision date.

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Interactions...Ampicillin...mixed with gentamicin in vitro.../prolonged/leads to loss of antibacterial activity of gentamicin.
Concomitant administration of penicillin and probenecid can lead to higher and longer-lasting serum antibiotic concentrations. Ampicillin has been shown to have similar interactions.
Gentamicin-related drugs...kanamycin, neomycin, and tobramycin may interact with carbenicillin.
Limited data suggest that concomitant administration of high-dose aspirin with penicillin increases serum penicillin concentrations and half-life. Although studies have shown that the co-administration of high-dose aspirin can enhance the clinical efficacy of penicillin, the potential toxicity of high-dose aspirin makes this therapy unsuitable. /Penicillin/
For more complete data on interactions of ampicillin (21 in total), please visit the HSDB record page.

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Non-human toxicity values>
Oral LD50 in rats: 10 g/kg body weight
Oral LD50 in mice: 15.2 g/kg body weight
Intraperitoneal LD50 in 1-day-old rats: 3300 mg/kg body weight
Intraperitoneal LD50 in 83-day-old rats: 4500 mg/kg body weight
The literature cited in this study indicates that ampicillin has low toxicity, based on a report of 28 patients treated with the drug for 5 days or longer without significant toxicity. [1]

[1]. Effect of Ampicillin on E. Coli of Swine Origin. Can J Comp Med Vet Sci. 1963 Sep;27(9):223-7.

[2]. Ampicillin in portal and peripheral blood and bile after oral administration of ampicillin andpivampicillin. Eur J Clin Pharmacol. 1974;7(2):133-5.

[3]. The neuroprotective mechanism of ampicillin in a mouse model of transient forebrain ischemia. Korean J Physiol Pharmacol. 2016 Mar;20(2):185-92.

Ampicillin is a penicillin with a 2-amino-2-phenylacetamido group at the 6-position of its penicillin ring. It is an antibacterial drug. It is both a penicillin and a penicillin allergen, as well as a β-lactam antibiotic. It is the conjugate acid of ampicillin (1-). Ampicillin is a semi-synthetic derivative of penicillin and can be used as an orally effective broad-spectrum antibiotic. Ampicillin belongs to the penicillin class of antibacterial drugs. Ampicillin has been reported in Microsphaeropsis arundinis, Aspergillus banksianus, and other microorganisms with relevant data. Ampicillin is a broad-spectrum, semi-synthetic β-lactam penicillin antibiotic with bactericidal activity. Ampicillin binds to and inactivates penicillin-binding protein (PBP) located on the inner membrane of bacterial cell walls. Inactivation of PBP interferes with the cross-linking of peptidoglycan chains, which is crucial for maintaining the strength and rigidity of bacterial cell walls. This disrupts bacterial cell wall synthesis, leading to reduced cell wall strength and ultimately cell lysis. Ampicillin is stable against the hydrolytic activity of various β-lactamases, thus it can be used to treat infections caused by a variety of Gram-positive and Gram-negative bacteria. A semi-synthetic penicillin derivative, it is an orally effective broad-spectrum antibiotic. Indications: For the treatment of infections caused by Escherichia coli, Proteus mirabilis, Enterococcus, Shigella, Salmonella typhi and other Salmonella, non-penicillinase-producing Neisseria gonorrhoeae, Haemophilus influenzae, Staphylococcus, and Streptococcus (including Streptococcus spp.) (respiratory tract infections, gastrointestinal infections, urinary tract infections, and meningitis). Mechanism of Action: Ampicillin inhibits the third (and final) stage of bacterial cell wall synthesis by binding to specific penicillin-binding proteins (PBPs) located within the bacterial cell wall. Cell lysis is mediated by bacterial cell wall autolysins (such as autolysins); ampicillin may interfere with the action of autolysin inhibitors. Since penicillin has no effect on existing cell walls, its bactericidal effect is only apparent when bacteria are multiplying. /Penicillin/
Penicillin and its metabolites are potent immunogens because they can bind to proteins and act as haptens to trigger an acute antibody-mediated immune response. The most common (approximately 95%) or "primary" determinant of penicillin allergy is the penicillin acyl determinant, which is produced by opening the β-lactam ring of penicillin. This allows penicillin to bind to proteins via the amide group. "Minor" determinants (occurring less frequently) refer to other metabolites, including native penicillin and penicillinic acid. /Penicillin/
Bactericidal agent; inhibits bacterial cell wall synthesis. Its action depends on whether penicillin can reach and bind to penicillin-binding proteins located on the inner membrane of the bacterial cell wall. Penicillin-binding proteins (including transpeptidase, carboxypeptidase, and endopeptidase) are enzymes involved in the final stages of bacterial cell wall assembly and in the remodeling of the cell wall during bacterial growth and division. Penicillin binds to and inactivates these penicillin-binding proteins, leading to a weakened bacterial cell wall and eventual lysis. /Penicillin/

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Therapeutic Uses
Penicillin
For mild to moderate illness, oral administration…Adults…1-4 grams daily, divided into equal doses…every 6 hours. For severe infections…parenteral administration is preferred…6-12 grams daily. …Meningitis requires…children parenteral administration of 300-400 mg/kg/day (divided into equal doses…every 4 hours), adults 12 grams or more daily.
Dosage varies depending on the type and severity of infection, renal function, and…age. For children…dosage should not be determined based on weight or body surface area; since this drug is primarily excreted by the kidneys, renal function largely determines the dosage. Infants and young children require small doses; the dosage for children aged 3-4 years is almost the same as for adults.
Ampicillin is indicated for the treatment of acute otitis media caused by susceptible bacteria. (Included in the US product label)
For more complete data on the therapeutic uses of ampicillin (of 18 types), please visit the HSDB record page.

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Drug Warnings
There has been one case of fatal pseudomembranous colitis after 5 days of oral ampicillin at 2 g/day.Ampicillin rarely causes interstitial nephritis; one case of interstitial nephritis has been reported to progress to acute renal failure. …Crystallization has been reported…
During long-term treatment, especially in premature infants, newborns, and other infants, renal, hepatic, and hematopoietic functions should be assessed regularly.
Absorption efficiency and elimination rate of ampicillin…decreased in patients with Shigella infection. Malabsorption…commonly seen in young patients with significant diarrhea. …Delayed excretion. Plasma drug concentrations are significantly elevated in patients with renal failure. This article discusses the National Registry of Drug Warnings for Eyes, established by the U.S. Food and Drug Administration (FDA) in 1975. This registry aims to alert physicians to the potential eye side effects of certain medications, such as ampicillin. For more complete data on ampicillin warnings (16 in total), please visit the HSDB records page.

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Pharmacodynamics
Ampicillin is a penicillin-type β-lactam antibiotic used to treat bacterial infections caused by susceptible bacteria, typically Gram-positive bacteria. The term "penicillin" can refer to several available penicillin derivatives or to the class of antibiotics derived from penicillin. Ampicillin exhibits in vitro activity against Gram-positive, Gram-negative aerobic, and anaerobic bacteria. Its bactericidal activity derives from its inhibition of cell wall synthesis and its action through binding to penicillin-binding proteins (PBPs). Ampicillin is stable against the hydrolytic activity of a variety of β-lactamases, including penicillinase, cephalosporinase and extended-spectrum β-lactamase. Ampicillin is a synthetic penicillin with broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria. Its antibacterial spectrum is similar to that of tetracycline antibiotics. [1] It has been reported that ampicillin has higher activity against Gram-negative bacteria than tetracycline and chloramphenicol, and retains most of its bactericidal activity in the presence of serum. [1] This study shows that ampicillin can effectively relieve the symptoms of hemorrhagic enteritis in pigs, and no drug-resistant Escherichia coli strains were observed after a single course of treatment. [1] In vitro experiments showed that the effective inhibitory concentration of ampicillin against porcine Escherichia coli was 2.5 µg/mL. [1]

C16H19N3O4S

349.40476

349.109

C, 55.00; H, 5.48; N, 12.03; O, 18.32; S, 9.18

69-53-4

Ampicillin sodium;69-52-3;Ampicillin trihydrate;7177-48-2;Ampicillin-d5;1426173-65-0; Ampicillin;69-53-4;Ampicillin trihydrate;7177-48-2; 69-53-4 (free acid); 23277-71-6 (potassium); 114977-84-3 (trimer trisodium) ; 69-52-3 (sodium); 7490-86-0 (hemisulfate); 33276-75-4 (benzathine); 119229-01-5 (embonate); 40688-84-4 (HCl)

6249

White to off-white solid powder

1.6±0.1 g/cm3

644.5±65.0 °C at 760 mmHg

198-200 °C (dec.)(lit.)

343.6±34.3 °C

0.0±2.0 mmHg at 25°C

1.724

1.65

138.03

3

6

4

24

562

4

OC([C@@H]1N(C2=O)[C@]([C@@H]2NC([C@@H](C3=CC=CC=C3)N)=O)([H])SC1(C)C)=O

AVKUERGKIZMTKX-UHFFFAOYSA-N

InChI=1S/C16H19N3O4S/c1-16(2)11(15(22)23)19-13(21)10(14(19)24-16)18-12(20)9(17)8-6-4-3-5-7-8/h3-7,9-11,14H,17H2,1-2H3,(H,18,20)(H,22,23)

(2S,5R,6R)-6-[[(2R)-2-amino-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Aminobenzylpenicillin; 69-53-4; Ampicillin; Aminobenzylpenicillin; Ampicillin acid; Tokiocillin; Omnipen; Amcill; Ampicillin Anhydrous; Ampicillin acid; Principen; Amcill;

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)

0.1 M NaOH : ~25 mg/mL (~71.55 mM)
H2O : ~4.9 mg/mL (~14.02 mM)

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。