The in-depth studies on Macrogol 4000 concern the latest published studies on its activities, interactions with other drugs, extraction systems, adverse effects.

Xu W, Zhang W, Guang C, Zhang T, Mu W. A close look on the effect of polyethylene glycol on the levansucrase thermostability: a case study of Brenneria sp. levansucrase. J Sci Food Agric. 2019;99(14):6315–6323. doi:10.1002/jsfa.9908

 Zhao J, Yang X, Liang G, et al. Effective removal of two fluoroquinolone antibiotics by PEG-4000 stabilized nanoscale zero-valent iron supported onto zeolite (PZ-NZVI). Sci Total Environ. 2020;710:136289. doi:10.1016/j.scitotenv.2019.136289

Padilha GS, Osório WR. Economic Method for Extraction/Purification of a Burkholderia cepacia Lipase with Potential Biotechnology Application. Appl Biochem Biotechnol. 2019;189(4):1108–1126. doi:10.1007/s12010-019-03041-x

Ouchi S, Ogiyama H, Tsutsui S, et al. Anaphylactic Shock Secondary to the Use of Macrogol 4000 as a Bowel Cleanser:a Case Report  Nihon Shokakibyo Gakkai Zasshi. 2019;116(4):330–335. doi:10.11405/nisshoshi.116.330

Hoffman RM, Yang Z, Tan Y, Han Q, Li S, Yagi S. Safety and Toxicity of Recombinant Methioninase and Polyethylene Glycol (PEG) Recombinant Methioninase in Primates. Methods Mol Biol. 2019;1866:211–229. doi:10.1007/978-1-4939-8796-2_16

Hoffman RM, Tan Y, Li S, et al. Development of Recombinant Methioninase for Cancer Treatment. Methods Mol Biol. 2019;1866:107–131. doi:10.1007/978-1-4939-8796-2_10

Inaba K, Oie T, Otake H, Kotake T, Nagai N. Evaluation of Dissolution Profile between Original and Generic Products of Zolpidem Tartrate by Microdialysis-HPLC. Chem Pharm Bull (Tokyo). 2019;67(2):120–124. doi:10.1248/cpb.c18-00642

Lyseng-Williamson KA. Macrogol (polyethylene glycol) 4000 without electrolytes in the symptomatic treatment of chronic constipation: a profile of its use [published correction appears in Drugs Ther Perspect. 2019;35(1):49]. Drugs Ther Perspect. 2018;34(7):300–310. doi:10.1007/s40267-018-0532-0

Bai T, Liu Y, Liu J, Yu C, Jiang W, Fan Y. A comparison of different surfactants on foam stability in foam sclerotherapy in vitro. J Vasc Surg. 2019;69(2):581–591.e1. doi:10.1016/j.jvs.2018.02.033

Zhao D, Zhao JB. Comparison of Chang Run Tong and Forlaxin Treatment of Constipation in Elderly Diabetic Patients. J Altern Complement Med. 2018;24(5):472–480. doi:10.1089/acm.2018.0052

Singh MK, Pooja D, Ravuri HG, Gunukula A, Kulhari H, Sistla R. Fabrication of surfactant-stabilized nanosuspension of naringenin to surpass its poor physiochemical properties and low oral bioavailability. Phytomedicine. 2018;40:48–54. doi:10.1016/j.phymed.2017.12.021

Deshpande TM, Quadir A, Obara S, Hoag SW. Impact of formulation excipients on the thermal, mechanical, and electrokinetic properties of hydroxypropyl methylcellulose acetate succinate (HPMCAS). Int J Pharm. 2018;542(1-2):132–141. doi:10.1016/j.ijpharm.2018.02.024

Liu Y, Wang T, Ding W, et al. Dissolution and oral bioavailability enhancement of praziquantel by solid dispersions. Drug Deliv Transl Res. 2018;8(3):580–590. doi:10.1007/s13346-018-0487-7

Bekkali NLH, Hoekman DR, Liem O, et al. Polyethylene Glycol 3350 With Electrolytes Versus Polyethylene Glycol 4000 for Constipation: A Randomized, Controlled Trial. J Pediatr Gastroenterol Nutr. 2018;66(1):10–15. doi:10.1097/MPG.0000000000001726

Yoshioka S, Takedatsu H, Fukunaga S, et al. Study to determine guidelines for pediatric colonoscopy. World J Gastroenterol. 2017;23(31):5773–5779. doi:10.3748/wjg.v23.i31.5773

Macrogol 4000 is a PEG, a biologically inert mixture of long, linear, non-absorbable and non metabolisable polymers of ethylene glycol. It occurs as a fine white powder or transparent colorless liquid.

What it is for

Normally used for the treatment of constipation in children, although recent studies have preferred lactulose (1) or electrical stimulation of the colon especially in the presence of Parkinson's disease (2).

The ability of Macrogol 4000 to improve colon transit and/or faecal frequency, improve faecal consistency and increase water production in faeces, have little effect on intestinal microbial composition, be free of clinically relevant electrolytic disturbances (i.e. very small or addiruttura no loss of sodium, potassium and chloride in faeces) (3).

Macrogol 4000 is inserted into tablets usually with Hydroxypropyl Methylcellulose where it acts as a stabilizing excipient to prevent particles from aggregating and clogging the spray nozzle that forms the coating.

Macrogol 4000 in-depth

Typical optimal characteristics of a commercial product

• Formula molecolare:  C₁₅H₂₁ClN₂OS      (C₂H₄O)nH₂O  
• Molecular Formula:  C₁₅H₂₁ClN₂OS      (C₂H₄O)nH₂O  
• Molecular Weight: 312.9 g/mol
• CAS: 25322-68-3      15272-95-4
• UNII FZ46ONU496
• EC Number: 500-038-2
• DSSTox Substance ID:   
• MDL number  
• PubChem Substance ID 
• InChl  1S/C15H20N2OS.ClH/c1-3-17(4-2)10-9-16-15(18)14-11-12-7-5-6-8-13(12)19-14;/h5-8,11H,3-4,9-10H2,1-2H3,(H,16,18);1H
• InChI Key      TZBAVQKIEKDGFH-UHFFFAOYSA-N
• SMILES    CC[NH+](CC)CCNC(=O)C1=CC2=CC=CC=C2S1.[Cl-]
• IUPAC 2-(1-benzothiophene-2-carbonylamino)ethyl-diethylazanium;chloride
• Merck    14,7568 
• NSC 108963

Synonyms: 

• Benzo(b)thiophene-2-carboxamide, N-(2-(diethylamino)ethyl)-, monohydrochloride
• Macrogol 3,350

Where to buy Macrogol

                                                         ___________________________

A premise on PEG.

Since the PEG family is numerous and is found in many cosmetic, cleaning and medicinal products and others, we need a cognitive premise on the subject that is rather complex from the point of view of safety because these products not only come into contact with the skin but, as in the case of medicine, they are also ingested.

PEG or polyethylene glycols polymerise the condensed ethylene oxide and water and are called polyethylene glycols, but in reality, they are complex chemical components, polymers bound together. For example,  plastic is polyethylene and has a hard consistency, while  polyethylene aggregated to the glycol forms a liquid.

The number that appears after the initials PEG represents the molecular weight and the higher this number is, the less it penetrates  the skin.

Here below are some studies in Medicine that refer to the use of PEG Polyethylene glycol in various fields.

Intestine

Polyethylene glycol with or without electrolytes is effective for the treatment of functional constipation, both in adults and in paediatric patients, with great safety and tolerability. These preparations are the most effective osmotic laxatives (more than lactulose) and are the first-line treatment for functional constipation in the short- and long-term. They are as effective as enemas in faecalomas, avoid the need for hospitalisation and are well tolerated by patients (especially when given without electrolytes) (4).

In the preparation  for colonoscopy,  polyethylene glycol tablets confirmed efficacy, acceptability, tolerance and safety similar to those of sodium phosphate (5).

For peripheral nerve repair (6).

Eyes

Dry eye syndrome is a disorder that affects 5-34% of the world's adult population with reduced quality of life. Artificial or lubricating tears are the most used therapy for treating this condition due to their low side effects profile, which attempt to modify the properties of the tear film. Polyethylene glycol has demonstrated clinical efficacy in the treatment of this condition (7).

Brain

Polyethylene glycol facilitates the neuroprotective effects of magnesium in head injuries (8).

Tumours

For transarterial chemoembolization, Polyethylene glycol is effective and safe for the treatment of liver cancer, as indicated by good tolerability, quality of life and high tumour response (9).

Cosmetics

Many types of PEG are hydrophilic and are used as creams, topical dermatological preparations and in cosmetic products such as surfactants, emulsifiers, detergents, humectants and skin conditioners.

Safety varies from type to type given the structural complexity (10).

References______________________

(1) Shatnawi MS, Alrwalah MM, Ghanma AM, Alqura'an ML, Zreiqat EN, Alzu'bi MM. Lactulose versus polyethylene glycol for disimpaction therapy in constipated children, a randomized controlled study. Sudan J Paediatr. 2019;19(1):31–36. doi:10.24911/SJP.106-1546805996

(2) Bu J, Qiao X, He Y, Liu J. Colonic electrical stimulation improves colonic transit in rotenone-induced Parkinson's disease model through affecting enteric neurons. Life Sci. 2019;231:116581. doi:10.1016/j.lfs.2019.116581

(3) Lyseng-Williamson KA. Macrogol (polyethylene glycol) 4000 without electrolytes in the symptomatic treatment of chronic constipation: a profile of its use [published correction appears in Drugs Ther Perspect. 2019;35(1):49]. Drugs Ther Perspect. 2018;34(7):300–310. doi:10.1007/s40267-018-0532-0

(4) Mínguez M, López Higueras A, Júdez J. Use of polyethylene glycol in functional constipation and fecal impaction.  Rev Esp Enferm Dig. 2016 Nov

Santos-Jasso KA, Arredondo-García JL, Maza-Vallejos J, Lezama-Del Valle P.  Effectiveness of senna vs polyethylene glycol as laxative therapy in children with constipation related to anorectal malformation.  J Pediatr Surg. 2016 Oct

(5) Chaussade S, Schmöcker C, Toulemonde P, Muñoz-Navas M, O'Mahony V, Henri F. Phosphate tablets or polyethylene glycol for preparation to colonoscopy? A multicentre non-inferiority randomized controlled trial. Surg Endosc. 2016 Nov

Tsunoda T, Sogo T, Iwasawa K, Umetsu S, Oikawa-Kawamoto M, Inui A, Fujisawa T. Feasibility and safety of bowel cleansing using low-volume polyethylene glycol with ascorbic acid before pediatric colonoscopy: A pilot study.  Dig Endosc. 2016 Oct 

(6) Hoffman AN, Bamba R, Pollins AC, Thayer WP. Analysis of polyethylene glycol (PEG) fusion in cultured neuroblastoma cells via flow cytometry: Techniques & optimization. J Clin Neurosci. 2016 

(7) Pérez-Balbuena AL, Ochoa-Tabares JC, Belalcazar-Rey S, Urzúa-Salinas C, Saucedo-Rodríguez LR, Velasco-Ramos R, Suárez-Sánchez RG, Rodríguez-Carrizalez AD, Oregón-Miranda AA. Efficacy of a fixed combination of 0.09 % xanthan gum/0.1 % chondroitin sulfate preservative free vs polyethylene glycol/propylene glycol in subjects with dry eye disease: a multicenter randomized controlled trial.  BMC Ophthalmol. 2016 Sep

Labetoulle M, Messmer EM, Pisella PJ, Ogundele A, Baudouin C. Safety and efficacy of a hydroxypropyl guar/polyethylene glycol/propylene glycol-based lubricant eye-drop in patients with dry eye.  Br J Ophthalmol. 2016

(8) Busingye DS, Turner RJ, Vink R.  Combined Magnesium/Polyethylene Glycol Facilitates the Neuroprotective Effects of Magnesium in Traumatic Brain Injury at a Reduced Magnesium Dose.  CNS Neurosci Ther. 2016

(9) Aliberti C, Carandina R, Sarti D, Mulazzani L, Catalano V, Felicioli A, Coschiera P, Fiorentini G.  Hepatic Arterial Infusion of Polyethylene Glycol Drug-eluting Beads for Primary and Metastatic Liver Cancer Therapy.  Anticancer Res. 2016

(10) Jang HJ, Shin CY, Kim KB. Safety Evaluation of Polyethylene Glycol (PEG) Compounds for Cosmetic Use.  Toxicol Res. 2015 Jun