Полиэтилен-полипропиленгликоль

Химические свойства

Polyethylene-polypropylene glycol generally occur as white, waxy, free-flowing prilled granules, or as cast solids. They are practically odorless and tasteless. At room temperature, poloxamer 124 occurs as a colorless liquid.

Использование

Polyethylene-polypropylene glycol is a liquid surfactant polymer.

Методы производства

Poloxamer polymers are prepared by reacting propylene oxide with propylene glycol to form polyoxypropylene glycol. Ethylene oxide is then added to form the block copolymer.

Общее описание

Pluronic^? L-81 is a lipoprotein secretion inhibitor.

Фармацевтические приложения

Polyethylene-polypropylene glycol is nonionic polyoxyethylene–polyoxypropylene copolymers used primarily in pharmaceutical formulations as emulsifying or solubilizing agents.The polyoxyethylene segment is hydrophilic while the polyoxypropylene segment is hydrophobic. All of the Polyethylene-polypropylene glycol is chemically similar in composition, differing only in the relative amounts of propylene and ethylene oxides added during manufacture. Their physical and surface-active properties vary over a wide range and a number of different types are commercially available;
Polyethylene-polypropylene glycol is used as emulsifying agents in intravenous fat emulsions, and as solubilizing and stabilizing agents to maintain the clarity of elixirs and syrups. Polyethylene-polypropylene glycol may also be used as wetting agents; in ointments, suppository bases, and gels; and as tablet binders and coatings.
Poloxamer 188 has also been used as an emulsifying agent for fluorocarbons used as artificial blood substitutes, and in the preparation of solid-dispersion systems. More recently,Polyethylene-polypropylene glycol has found use in drug-delivery systems.
Therapeutically, poloxamer 188 is administered orally as a wetting agent and stool lubricant in the treatment of constipation; it is usually used in combination with a laxative such as danthron. Polyethylene-polypropylene glycol may also be used therapeutically as wetting agents in eye-drop formulations, in the treatment of kidney stones, and as skin-wound cleansers.
Poloxamer 338 and 407 are used in solutions for contact lens care.

Биологическая активность

Polyethylene-polypropylene glycol(Poloxamer 188) is a copolymer surfactant. Poloxamer 188 exhibits antithrombotic, anti-inflammatory and cytoprotective activities in various tissue injury models. It can be used to treat sickle cell disease in children and adults. It has also been shown to be protective against ischaemic injury, cardiomyopathy and cerebral haemorrhage.

Профиль безопасности

When heated to decomposition it emits acrid smoke and irritating fumes.

Безопасность

Polyethylene-polypropylene glycol is used in a variety of oral, parenteral, and topical pharmaceutical formulations, and are generally regarded as nontoxic and nonirritant materials.Polyethylene-polypropylene glycol is not metabolized in the body.
Animal toxicity studies, with dogs and rabbits, have shown Polyethylene-polypropylene glycol to be nonirritating and nonsensitizing when applied in 5% w/v and 10% w/v concentration to the eyes, gums, and skin.
In a 14-day study of intravenous administration at concentrations up to 0.5 g/kg/day to rabbits, no overt adverse effects were noted. A similar study with dogs also showed no adverse effects at dosage levels up to 0.5 g/kg/day. In a longer-term study, rats fed 3% w/w or 5% w/w of poloxamer in food for up to 2 years did not exhibit any significant symptoms of toxicity. However, rats receiving 7.5% w/w of poloxamer in their diet showed some decrease in growth rate.
No hemolysis of human blood cells was observed over 18 hours at 25°C, with 0.001–10% w/v poloxamer solutions.
(mouse, IV): 1 g/kg
(mouse, oral): 15 g/kg
(mouse, SC): 5.5 g/kg
(rat, IV): 7.5 g/kg
(rat, oral): 9.4 g/kg

хранилище

Polyethylene-polypropylene glycol is stable materials. Aqueous solutions are stable in the presence of acids, alkalis, and metal ions. However, aqueous solutions support mold growth.
The bulk material should be stored in a well-closed container in a cool, dry place.

Несовместимости

Depending on the relative concentrations, poloxamer 188 is incompatible with phenols and parabens.

Регуляторный статус

Included in the FDA Inactive Ingredients Database (IV injections; inhalations, ophthalmic preparations; oral powders, solutions, suspensions, and syrups; topical preparations). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.