Poloxamer 188
(Synonyms: 泊洛沙姆 188) 目录号 : GC60295
泊洛沙姆 188（P188，维泊洛沙姆）是聚环氧乙烷-聚环氧丙烷-聚环氧乙烷 (PEO-PPO-PEO) 形式的三嵌段共聚物。
Cas No.:9003-11-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
The K562, HL60, NALM-6 and Molt-4 cell lines, Peripheral blood mononuclear cells (PBMC) |
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Preparation Method |
The cells with Poloxamer 188 exhibited a detectable apoptosis signal with Annexin V. The cells were treated with 6% Poloxamer 188 or PEG for 48 h. |
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Reaction Conditions |
6% Poloxamer 188 for 48 h. |
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Applications |
When the K562 cell line was incubated with Poloxamer 188, it was synchronized in the G2/M phase of the cell cycle, none of the cell lines incubated with PEG exhibited a detectable apoptosis signal or experienced changes in the state of their cell cycle. T lymphocytes derived from healthy volunteers incubated with Poloxamer 188 or PEG exhibited no changes in the apoptosis signal or the state of the cell cycle. |
| Animal experiment [2]: | |
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Animal models |
Male ICR mice |
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Preparation Method |
Poloxamer 188 was dissolved in normal saline. After intracerebral hemorrhage (ICH) induction, animals were randomly selected and treated with either 3 or 12 mg poloxamer 188 in 400 µl saline. All treatments were administered as the tail intravenous injection at 1 h after surgery. Sham and vehicle animals received an equivalent volume of saline, as given to animals in the intervention groups (400 µl). |
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Dosage form |
Intravenous injection, 3 or 12 mg |
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Applications |
Injury volume was assessed at poloxamer 188 treated 24 and 72 h post ICH. Quantification of brain injury showed that mice administered poloxamer 188 (12 mg) had significantly reduced injury volume compared with the vehicle-treated groups at 24 and 72 h after ICH |
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References: [1]: Aoki N, Tamura M, Ohyashiki JH, Sugaya M, Hisatomi H. Poloxamer 188 enhances apoptosis in a human leukemia cell line. Mol Med Rep. 2010;3(4):669-672. |
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Poloxamer 188 (P188, vepoloxamer) is a triblock copolymer of the form polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO). The center PPO block is hydrophobic, and the side PEO blocks are hydrophilic, resulting in surface-active properties. Poloxamer 188 has been used in the pharmaceutical industry as an excipient in various formulations and drug delivery systems [1].
Poloxamer 188 enhances survival of red blood cells (RBCs) by increasing the stability and decreasing the fragility of the membrane [2]. Poloxamer 188 arrested the G2/M phase of the cell cycle in the K562 BCR-ABL-mediated CML cell line [3].
Poloxamer 188 is effective in recovery of damaged cell membrane on muscle cells after electroshock [4], neurons after trauma [5], and fibroblasts [6] after heat shock. Poloxamer 188 also reduces the rigidity of sickled erythrocytes and contributes to the resolution of symptoms of vaso-occlusive crisis [7] in patients with sickle cell disease. The cell protective effect of Poloxamer 188 is not only related to its action on cell membrane integrity but perhaps to some other additional mechanisms that have been described. Antiapoptotic effect of Poloxamer 188 has been shown on neurons after trauma which is related to an inhibition of the activation of proapoptotic p38 [7]. Poloxamer 188 prevents blood-brain barrier disruption through nuclear factor kappa B (NF-κB)-matrix metalloproteinases (MMPs)-mediated tight junction protein degradation by decreasing the level of MMP2, MMP9, and NF-KB p65 [8].
References:
[1]. T. Wang, A. Markham, S.J. Thomas, et al. Solution stability of poloxamer 188 under stress conditions. J Pharm Sci, 108 (2019), pp. 1264-1271
[2]. Baek EJ, Kim HS, Kim JH, Kim NJ, Kim HO. Stroma-free mass production of clinical-grade red blood cells (RBCs) by using poloxamer 188 as an RBC survival enhancer. Transfusion. 2009;49(11):2285-2295.
[3]. Aoki N, Tamura M, Ohyashiki JH, Sugaya M, Hisatomi H. Poloxamer 188 enhances apoptosis in a human leukemia cell line. Mol Med Rep. 2010;3(4):669-672.
[4]. Lee RC, River LP, Pan FS, Ji L, Wollmann RL. Surfactant-induced sealing of electropermeabilized skeletal muscle membranes in vivo. Proc Natl Acad Sci U S A. 1992;89(10):4524-4528.
[5]. Serbest G, Horwitz J, Jost M, Barbee K. Mechanisms of cell death and neuroprotection by poloxamer 188 after mechanical trauma. FASEB J. 2006;20(2):308-310.
[6]. Merchant FA, Holmes WH, Capelli-Schellpfeffer M, Lee RC, Toner M. Poloxamer 188 enhances functional recovery of lethally heat-shocked fibroblasts. J Surg Res. 1998;74(2):131-140.
[7]. Orringer EP, Casella JF, Ataga KI, et al. Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: a randomized controlled trial. JAMA. 2001;286(17):2099-2106.
[8]. Wang T, Chen X, Wang Z, et al. Poloxamer-188 can attenuate blood-brain barrier damage to exert neuroprotective effect in mice intracerebral hemorrhage model. J Mol Neurosci. 2015;55(1):240-250.
泊洛沙姆 188（P188,维泊洛沙姆）是聚环氧乙烷-聚环氧丙烷-聚环氧乙烷 (PEO-PPO-PEO) 形式的三嵌段共聚物。中心 PPO 嵌段是疏水的,侧边的 PEO 嵌段是亲水的,从而具有表面活性。泊洛沙姆 188 已在制药行业用作各种制剂和药物递送系统的赋形剂[1]。
泊洛沙姆 188 通过增加红细胞 (RBC) 的存活率来提高红细胞 (RBC) 的存活率稳定性和降低膜的脆性[2]。泊洛沙姆 188 阻滞 K562 BCR-ABL 介导的 CML 细胞系 [3] 细胞周期的 G2/M 期。
泊洛沙姆 188 可有效修复受损细胞电击后肌肉细胞上的膜 [4]、创伤后神经元 [5] 和热休克后成纤维细胞 [6] 上的膜。 Poloxamer 188 还可以降低镰状红细胞的硬度,有助于缓解镰状细胞病患者的血管闭塞危象症状[7]。泊洛沙姆 188 的细胞保护作用不仅与其对细胞膜完整性的作用有关,而且可能与已描述的其他一些机制有关。 Poloxamer 188 的抗凋亡作用已在创伤后的神经元中显示出来,这与抑制促凋亡 p38 的激活有关[7]。泊洛沙姆 188 通过核因子 kappa B (NF-κB)-基质金属蛋白酶 (MMP) 通过降低 MMP2、MMP9 和 NF-KB p65 的水平介导的紧密连接蛋白降解来防止血脑屏障破坏 [ 8].
| Cas No. | 9003-11-6 | SDF | |
| 别名 | 泊洛沙姆 188 | ||
| Canonical SMILES | CC.[H(OCH2CH2)x(OCH2CH)y(OCH2CH2)zOH].[CH3] | ||
| 分子式 | 分子量 | ||
| 溶解度 | H2O : ≥ 100 mg/mL; DMSO : ≥ 100 mg/mL | 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。 | ||
| 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。
Poloxamer 188 as surfactant in biological formulations - An alternative for polysorbate 20/80?
Int J Pharm 2022 May 25;620:121706.PMID:35367584DOI:10.1016/j.ijpharm.2022.121706.
Surfactants are used to stabilize biologics. Particularly, polysorbates (Tween® 20 and Tween® 80) dominate the group of surfactants in protein and especially antibody drug products. Since decades drug developers rely on the ethoxylated sorbitan fatty acid ester mixtures to stabilize sensitive molecules such as proteins. Reasons are (i) excellent stabilizing properties, and (ii) well recognized safety and tolerability profile of these polysorbates in humans, especially for parenteral applications. However, over the past decade concerns regarding the stability of these two polysorbates were raised. The search of alternatives with preferably less reservations concerning degradation and product quality reducing issues leads, among others, to Poloxamer 188 (e.g. Kolliphor® P188), a nonionic triblock-copolymer surfactant. This review sums up our current knowledge related to the characterization and physico-chemical properties of Poloxamer 188, its analytics and stability properties for biological formulations. Furthermore, the advantages and disadvantages as a suitable polysorbate-alternative for the stabilization of biologics are discussed.
Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease: A Randomized Clinical Trial
JAMA 2021 Apr 20;325(15):1513-1523.PMID:33877274DOI:10.1001/jama.2021.3414.
Importance: Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of Poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SCD, particularly in children and participants treated with hydroxyurea. Objective: To reassess the efficacy of Poloxamer 188 for vaso-occlusive episodes. Design, setting, and participants: Phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial conducted from May 2013 to February 2016 that included 66 hospitals in 12 countries and 60 cities; 388 individuals with SCD (hemoglobin SS, SC, S-β0 thalassemia, or S-β+ thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included. Interventions: A 1-hour 100-mg/kg loading dose of Poloxamer 188 intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194). Main outcomes and measures: Time in hours from randomization to the last dose of parenteral opioids among all participants and among those younger than 16 years as a separate subgroup. Results: Of 437 participants assessed for eligibility, 388 were randomized (mean age, 15.2 years; 176 [45.4%] female), the primary outcome was available for 384 (99.0%), 15-day follow-up contacts were available for 357 (92.0%), and 30-day follow-up contacts were available for 368 (94.8%). There was no significant difference between the groups for the mean time to last dose of parenteral opioids (81.8 h for the Poloxamer 188 group vs 77.8 h for the placebo group; difference, 4.0 h [95% CI, -7.8 to 15.7]; geometric mean ratio, 1.2 [95% CI, 1.0-1.5]; P = .09). Based on a significant interaction of age and treatment (P = .01), there was a treatment difference in time from randomization to last administration of parenteral opioids for participants younger than 16 years (88.7 h in the Poloxamer 188 group vs 71.9 h in the placebo group; difference, 16.8 h [95% CI, 1.7-32.0]; geometric mean ratio, 1.4 [95% CI, 1.1-1.8]; P = .008). Adverse events that were more common in the Poloxamer 188 group than the placebo group included hyperbilirubinemia (12.7% vs 5.2%); those more common in the placebo group included hypoxia (12.0% vs 5.3%). Conclusions and relevance: Among children and adults with SCD, Poloxamer 188 did not significantly shorten time to last dose of parenteral opioids during vaso-occlusive episodes. These findings do not support the use of Poloxamer 188 for vaso-occlusive episodes. Trial registration: ClinicalTrials.gov Identifier: NCT01737814.
A review of poloxamer 407 pharmaceutical and pharmacological characteristics
Pharm Res 2006 Dec;23(12):2709-28.PMID:17096184DOI:10.1007/s11095-006-9104-4.
Poloxamer 407 copolymer (ethylene oxide and propylene oxide blocks) shows thermoreversible properties, which is of the utmost interest in optimising drug formulation (fluid state at room temperature facilitating administration and gel state above sol-gel transition temperature at body temperature promoting prolonged release of pharmacological agents). Pharmaceutical evaluation consists in determining the rheological behaviour (flow curve or oscillatory studies), sol-gel transition temperature, in vitro drug release using either synthetic or physiological membrane and (bio)adhesion characteristics. Poloxamer 407 formulations led to enhanced solubilisation of poorly water-soluble drugs and prolonged release profile for many galenic applications (e.g., oral, rectal, topical, ophthalmic, nasal and injectable preparations) but did not clearly show any relevant advantages when used alone. Combination with other excipients like Poloxamer 188 or mucoadhesive polymers promotes Poloxamer 407 action by optimising sol-gel transition temperature or increasing bioadhesive properties. Inclusion of liposomes or micro(nano)particles in Poloxamer 407 formulations offers interesting prospects, as well. Besides these promising data, Poloxamer 407 has been held responsible for lipidic profile alteration and possible renal toxicity, which compromises its development for parenteral applications. In addition, new findings have demonstrated immuno-modulation and cytotoxicity-promoting properties of Poloxamer 407 revealing significant pharmacological interest and, hence, human trials are in progress to specify these potential applications.
Purified Poloxamer 188 for sickle cell vaso-occlusive crisis
Ann Pharmacother 2004 Feb;38(2):320-4.PMID:14742772DOI:10.1345/aph.1D223.
Objective: To review available literature on the pharmacology, pharmacokinetics, efficacy, toxicology, adverse effects, drug interactions, and dosage guidelines for purified Poloxamer 188, a product in Phase III trials. Data sources: Reviewers searched the following databases for English-language studies: MEDLINE (1966-November 2003), International Pharmaceutical Abstracts (1970-November 2003), and the Cochrane Library Database (3rd quarter 2003). Key search terms included purified Poloxamer 188, Flocor, CRL-5861, Poloxamer 188, RheothRx, and pluronic F-68. Study selection and data extraction: Data on efficacy, adverse effects, and pharmacokinetics were obtained from randomized, open-label, and blinded clinical trials. Toxicology data were obtained from unpublished studies with purified Poloxamer 188 and from available data on Poloxamer 188 (nonpurified form). Data synthesis: Purified Poloxamer 188 is a highly purified form of the nonionic block copolymer Poloxamer 188. It lowers blood viscosity, decreases red blood cell (RBC) aggregation, and decreases friction between RBCs and vessel walls to increase microvascular blood flow and decrease cell injury. In clinical trials, purified Poloxamer 188 demonstrated safety, but little efficacy for the treatment of sickle cell vaso-occlusive crisis. Increased efficacy has been shown in patients on concurrent hydroxyurea therapy and those <15 years of age. Conclusions: Purified Poloxamer 188 represents a new approach to the management of the sickle cell vaso-occlusive crisis. Children and patients on hydroxyurea may benefit most from purified Poloxamer 188 therapy. Further studies are needed to confirm its efficacy and to determine whether the drug decreases sickle cell disease severity and complications.
Poloxamer 188 (p188) as a membrane resealing reagent in biomedical applications
Recent Pat Biotechnol 2012 Dec;6(3):200-11.PMID:23092436DOI:10.2174/1872208311206030200.
Maintenance of the integrity of the plasma membrane is essential for maintenance of cellular function and prevention of cell death. Since the plasma membrane is frequently exposed to a variety of mechanical and chemical insults the cell has evolved active processes to defend against these injuries by resealing disruptions in the plasma membrane. Cell membrane repair is a conserved process observed in nearly every cell type where intracellular vesicles are recruited to sites of membrane disruption where they can fuse with themselves or the plasma membrane to create a repair patch. When disruptions are extensive or there is an underlying pathology that reduces the membrane repair capacity of a cell this defense mechanism may prove insufficient and the cell could die due to breakdown of the plasma membrane. Extensive loss of cells can compromise the integrity and function of tissues and leading to disease. Thus, methods to increase membrane resealing capacity could have broad utility in a number of disease states. Efforts to find reagents that can modulate plasma membrane reseal found that specific tri-block copolymers, such as Poloxamer 188 (P188, or Pluronic F68), can increase the structural stability and resealing of the plasma membrane. Here we review several current patents and patent applications that present inventions making use of P188 and other copolymers to treat specific disease states such as muscular dystrophy, heart failure, neurodegenerative disorders and electrical injuries, or to facilitate biomedical applications such as transplantation. There appears to be promise for the application of poloxamers in the treatment of various diseases, however there are potential concerns with toxicity with long term application and bioavailability in some cases.