Pranlukast hemihydrate
(Synonyms: 普鲁司特半水合物; ONO-1078 hemihydrate) 目录号 : GC36956
A CysLT1 receptor antagonist
Cas No.:150821-03-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | EA.hy926 cells are cultured in Dulbecco's modified Eagle's medium (DMEM), supplemented with 10% heat-inactivated fetal calf serum, Penicillin (100 U/mL) and Streptomycin (100 mg/mL). Experiments are conducted 24 h after cells are seeded. OGD is performed. Briefly, the original medium is removed; the cells are washed twice with glucose-free Earle's balanced salt solution (EBSS) and placed in fresh glucose-free EBSS. Cultures are then placed in an incubator containing 5% CO2 and 95% N2 at 37°C for 2 to 8 h. Control cultures are maintained in glucose-containing EBSS under normal conditions. 10 μM Pranlukast, 10 μM Zileuton, a 5-LOX inhibitor or 10 μM Pyrrolidine dithiocarbamate (PDTC), is added to the culture 30 min before OGD exposure and maintained during OGD[2]. |
Animal experiment: | Mice[3]Male ddY mice are used. All mice used are 7 to 8 weeks of age. Endotoxin shock is induced in mice. In brief, CAR (5 mg in 0.5 mL of physiological saline) is injected intraperitoneally (i.p.) as a priming agent 24 h before LPS challenge. LPS (50 p,g in 0.5 mL of physiological saline) is injected intravenously into the tail vein as an inducing agent. The indicated doses of AA-861, Pranlukast (40, 20, and 10 mmol/kg), saline, DMSO, or ethanol are administrated subcutaneously (s.c.) in a volume of 1 mL into the backs of mice 30 min before the LPS provocation. Both drugs are injected s.c., because CAR i.p. pretreatment caused peritonitis. To examine the role of endogenous TNF in CAR pretreated mice, 2×105 U of rabbit anti-TNF-a antibody or normal serum of rabbit in 0.2 mL is injected intravenously (i.v.) before the LPS challenge[3]. |
References: [1]. Obata T, et al. In vitro antagonism of ONO-1078, a newly developed anti-asthma agent, against peptide leukotrienes in isolated guinea pig tissues. Jpn J Pharmacol. 1992 Nov;60(3):227-37. | |
Pranlukast is an orally bioavailable cysteinyl leukotriene 1 (CysLT1) receptor antagonist (IC50s = 4.3-7.2 nM in radioligand binding assays).1 It is selective for the CysLT1 receptor over the CysLT2 receptor (IC50 = 3,620 nM for the human receptor).2 Pranlukast inhibits mucus secretion induced by leukotriene D4 in isolated guinea pig trachea with an IC50 value of 0.3 ?M.3 It inhibits TNF-α-induced NF-?B p65 nuclear localization in U937 and Jurkat cells when used at concentrations of 10 and 100 ?M.4 Pranlukast inhibits bronchoconstriction induced by LTC4 , LTD4, and LTE4 , but not LTB4 , in guinea pigs (ID50s = 0.8, 1, 0.7, and >500 ?g/kg, respectively).5 It reduces cortical infarct volume by 81.6% and decreases neuronal death in the cortex, hippocampus, and striatum in a rat model of ischemia induced by middle cerebral artery occlusion (MCAO) when administered at a dose of 0.03 mg/kg.6
1.Lynch, K.R., O'Neill, G.P., Liu, Q., et al.Characterization of the human cysteinyl leukotriene CysLT1 receptorNature399(6738)789-793(1999) 2.Heise, C.E., O'Dowd, B.F., Figueroa, D.J., et al.Characterization of the human cysteinyl leukotriene 2 receptorJ. Biol. Chem.275(39)30531-30536(2000) 3.Liu, Y.-C., Khawaja, A.M., and Rogers, D.F.Effects of the cysteinyl leukotriene receptor antagonists pranlukast and zafirlukast on tracheal mucus secretion in ovalbumin-sensitized guinea-pigs in vitroBr. J. Pharmacol.124(3)563-571(1998) 4.Ichiyama, T., Hasegawa, S., Umeda, M., et al.Pranlukast inhibits NF-KB activation in human monocytes/macrophages and T cellsClin. Exp. Allergy33(6)802-807(2003) 5.Nakai, H., Konno, M., Kosuge, S., et al.New potent antagonists of leukotrienes C4 and D4. 1. Synthesis and structure-activity relationshipsJ. Med. Chem.31(1)84-91(1988) 6.Zhang, W.-P., Wei, E.-Q., Mei, R.-H., et al.Neuroprotective effect of ONO-1078, a leukotriene receptor antagonist, on focal cerebral ischemia in ratsActa Pharmacol. Sin.23(10)871-877(2002)
| Cas No. | 150821-03-7 | SDF | |
| 别名 | 普鲁司特半水合物; ONO-1078 hemihydrate | ||
| Canonical SMILES | O=C(C1=CC=C(OCCCCC2=CC=CC=C2)C=C1)NC3=C4C(C(C=C(C5=NN=NN5)O4)=O)=CC=C3.[1/2].O | ||
| 分子式 | C27H23N5O4.1/2H2O | 分子量 | 490.51 |
| 溶解度 | DMSO: 25 mg/mL (50.97 mM); Water: < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0387 mL | 10.1935 mL | 20.3869 mL |
| 5 mM | 0.4077 mL | 2.0387 mL | 4.0774 mL |
| 10 mM | 0.2039 mL | 1.0193 mL | 2.0387 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Improving dissolution and oral bioavailability of Pranlukast hemihydrate by particle surface modification with surfactants and homogenization
Drug Des Devel Ther 2015 Jun 24;9:3257-66.PMID:26150699DOI:10.2147/DDDT.S87738.
The present study was carried out to develop an oral formulation of Pranlukast hemihydrate with improved dissolution and oral bioavailability using a surface-modified microparticle. Based on solubility measurements, surface-modified Pranlukast hemihydrate microparticles were manufactured using the spray-drying method with hydroxypropylmethyl cellulose, sucrose laurate, and water and without the use of an organic solvent. The hydrophilicity of the surface-modified Pranlukast hemihydrate microparticle increased, leading to enhanced dissolution and oral bioavailability of Pranlukast hemihydrate without a change in crystallinity. The surface-modified microparticles with an hydroxypropylmethyl cellulose/sucrose laurate ratio of 1:2 showed rapid dissolution of up to 85% within 30 minutes in dissolution medium (pH 6.8) and oral bioavailability higher than that of the commercial product, with approximately 2.5-fold and 3.9-fold increases in area under the curve (AUC 0 → 12 h) and peak plasma concentration, respectively. Therefore, the surface-modified microparticle is an effective oral drug delivery system for the poorly water-soluble therapeutic Pranlukast hemihydrate.
A simple blending with α-glycosylated naringin produces enhanced solubility and absorption of Pranlukast hemihydrate
Int J Pharm 2019 Aug 15;567:118490.PMID:31271814DOI:10.1016/j.ijpharm.2019.118490.
The possibility of newly developed α-glycosylated naringin (Naringin-G) as a solubilizing agent was investigated against Pranlukast hemihydrate (PLH), a model drug with extremely low water solubility. The physical mixtures (PMs) of PLH/Naringin-G increased the solubility of PLH compared with PLH crystals and PMs with other additives, such as α-glycosylated rutin (Rutin-G) and sodium dodecyl sulfate (SDS). Naringin-G did not decrease the surface tension, whereas SDS showed a surface-active property and critical micelle concentration. The apparent solubility of PLH increased in proportion to the concentration of Naringin-G, and similarly for SDS, indicating that constant amounts of Naringin-G molecules interacted with PLH molecules. There was no change in the Caco-2 cell viability following contact with a high concentration of Naringin-G solution (10% (w/v)). The oral absorption of PLH in a rat animal model was improved when administrated with Naringin-G. The value for the area under plasma concentration-time curve from PMs of PLH/Naringin-G was 2.2 times higher than that from PLH crystals alone. Together, these results suggested that newly synthesized Naringin-G would be a promising solubilizing agent as an alternative to surfactants.
α-Glucosyl hesperidin induced an improvement in the bioavailability of Pranlukast hemihydrate using high-pressure homogenization
Int J Pharm 2011 May 30;410(1-2):114-7.PMID:21419200DOI:10.1016/j.ijpharm.2011.03.017.
The α-glucosyl hesperidin (Hsp-G)-induced improvement of both the dissolution and absorption properties of Pranlukast hemihydrate (PLH) was achieved by means of a high-pressure homogenization (HPH) processing. The average particle size in the HPH-processed suspension was decreased significantly after 50 cycles of processing and reached a constant size of ca. 300 nm. The amount of dissolved PLH gradually increased with the pass number of HPH processing, and was extremely higher than the PLH solubility (0.8 μg/mL at 37°C) after the HPH processing. On a dissolution study of the freeze-dried sample of HPH-processed PLH/Hsp-G (1/10), the apparent solubility of PLH was at least 2.5-fold more than that of untreated PLH crystals. The transport study showed that the amount of PLH that had permeated through the Caco-2 cell monolayers was improved in the case of HPH-processed PLH/Hsp-G (1/10). The bioavailability of PLH from HPH-processed PLH/Hsp-G (1/10) showed a 3.9- and 2.2-fold improvement over the PLH crystal in terms of C(max) and AUC values, respectively. Hsp-G formed an associated structure in aqueous media. High-pressure homogenization provides a good opportunity for molecular-level interaction of PLH and the associated structure of Hsp-G to occur. The use of Hsp-G under HPH processing was a promising way to enhance the dissolution and absorption of PLH without using an organic solvent.
Self-microemulsifying drug-delivery system for improved oral bioavailability of Pranlukast hemihydrate: preparation and evaluation
Int J Nanomedicine 2013;8:167-76.PMID:23326192DOI:10.2147/IJN.S37338.
The purpose of the present investigation was to develop and evaluate a self-microemulsifying drug delivery system (SMEDDS) for improving the oral absorption of a Pranlukast hemihydrate (PLH), a very poorly water-soluble drug. An efficient self-microemulsifying vehicle for PLH was selected and optimized using solubility testing and phase diagram construction. The formulations were characterized by assessing self-emulsification performance, droplet size analysis, in vitro drug release characteristics and formulation stability studies. Optimized formulations for in vitro dissolution and bioavailability assessment were Triethylcitrate (TEC; 10%), Tween 20 (50%), Span 20 (25%), triethanolamine (5%), and benzyl alcohol (10%). The SMEDDS readily released the lipid phase to form a fine oil-in-water microemulsion with a narrow distribution size. Saturated solubilities of PLH from SMEDDS in water, pH 4.0 and 6.8, were over 150 times greater than that of plain PLH. The release of 100% PLH from SMEDDS was considerably greater compared to only 1.12% in simulated intestinal fluid (pH 6.8) from plain PLH after 2 hours. The PLH suspension with 0.5% sodium carboxymethylcellulose or 3% PLH-loaded SMEDDS was administrated at a dose of 40 mg/kg as PLH to fasted rats. The absorption of PLH from SMEDDS resulted in about a threefold increase in bioavailability compared with plain PLH aqueous suspension. Our studies illustrated that the potential use of the new SMEDDS can be used as a possible alternative to oral delivery of a poorly water-soluble drug such as PLH.
Preparation of drug nanoparticle-containing microparticles using a 4-fluid nozzle spray drier for oral, pulmonary, and injection dosage forms
J Control Release 2007 Sep 11;122(1):10-5.PMID:17655963DOI:10.1016/j.jconrel.2007.06.001.
We prepared microparticles containing nanoparticles of water-insoluble Pranlukast hemihydrate (PLH) using a 4-fluid nozzle spray drier. These particles were designed to improve the absorption of PLH and to allow delivery by oral, pulmonary, and injection routes. Mannitol (MAN) was used as a water-soluble carrier for the microparticles. We orally administered suspensions of PLH powder and PLH-MAN microparticles to rats. We also compared the in vitro aerosol performance of the PLH powder and PLH-MAN microparticles using a cascade impactor, and we compared the delivery of PLH by oral administration of PLH powder and pulmonary delivery of PLH-MAN microparticles at PLH/MAN ratios of 1:4 and 1:10. The absorption of PLH was markedly enhanced by pulmonary deliver of PLH-MAN composite microparticles. The area under the plasma concentration-time curve per dose for pulmonary administration of the 1:4 and 1:10 PLH-MAN microparticles was approximately 85- and 100-fold higher, respectively, than for oral administration of PLH powder. Also, we found that PLH rapidly disappeared from the plasma following injection of PLH aqueous solution or PLH-MAN microparticles dissolved in water. The PLH particles remaining after dissolution of MAN from the 1:10 PLH-MAN microparticles were 200 nm in diameter. Therefore, PLH particles may be captured immediately after injection by reticuloendothelial tissues such as the liver and spleen. This study demonstrated that it is possible to use the 4-fluid spray drier to prepare microparticles containing PLH nanoparticles that that improve drug absorption and can be administered by oral, pulmonary, and injection routes.