Пэгилирование как метод создания пролонгированных форм биофармацевтических препаратов (на примере пэгилированного гранулоцитарного колониестимулирующего фактора)

By now the pegylation of biologically active molecules including proteins with an inert hydrophilic polymer polyethylene glycol (PEG) is an important area in the new generation of prolonged-action pharmaceutical preparations. The conjugated molecules usually have an improved pharmacokinetic profile, including reduced renal clearance, additional protection from the proteolytic enzymes and reduced immunogenicity, thus preserving the in vivo activity of the native preparation in the human body for a longer time. This review is focused on the example of the pegylation of recombinant human granulocyte colony-stimulating factor (G-CSF) and gives the opportunity to have a look at different ways of pegylation and the mechanism of this reaction. Besides, the review describes the different types of reactive PEG for the specific conjugation to biological molecules and benefits and disadvantages of these reagents.В настоящее время пэгилирование биологически активных молекул, в том числе белков, с помощью инертного гидрофильного полимера полиэтиленгликоля (ПЭГ) представляет собой важное направление в создании нового поколения фармацевтических препаратов пролонгирован-ного действия. Конъюгированные молекулы, как правило, имеют улучшенный фармакокинетический профиль, в том числе пониженный почечный клиренс, дополнительную защиту от действия протео-литических ферментов и низкую иммуногенность, что позволяет сохранить активность in vivo нативного препарата в человеческом организме в течение более продолжительного времени. Данный обзор дает возможность ознакомиться с современными методиками пэгилирования биофармацев-тических молекул, препаратами на основе конъюгатов с ПЭГ и рассматривает, как пример, пэгилирование рекомбинантного человеческого гранулоцитарного колониестимулирующего фактора (рчГ-КСФ). Также в обзоре представлены различные виды модифицированных ПЭГ-реагентов для направленного присоединения к биологическим молекулам и обсуждаются их преимущества и недостатки

Thermodynamic model of hardness: Particular case of boron-rich solids

A number of successful theoretical models of hardness have been developed recently. A thermodynamic model of hardness, which supposes the intrinsic character of correlation between hardness and thermodynamic properties of solids, allows one to predict hardness of known or even hypothetical solids from the data on Gibbs energy of atomization of the elements, which implicitly determine the energy density per chemical bonding. The only structural data needed is the coordination number of the atoms in a lattice. Using this approach, the hardness of known and hypothetical polymorphs of pure boron and a number of boron-rich solids has been calculated. The thermodynamic interpretation of the bonding energy allows one to predict the hardness as a function of thermodynamic parameters. In particular, the excellent agreement between experimental and calculated values has been observed not only for the room- temperature values of the Vickers hardness of stoichiometric compounds, but also for its temperature and concentration dependencies

Pegylation, as method of production prolonged forms of biopharmaceutical drugs (pegylated granulocyte colony-stimulating factor as case of study)

By now the pegylation of biologically active molecules including proteins with an inert hydrophilic polymer polyethylene glycol (PEG) is an important area in the new generation of prolonged-action pharmaceutical preparations. The conjugated molecules usually have an improved pharmacokinetic profile, including reduced renal clearance, additional protection from the proteolytic enzymes and reduced immunogenicity, thus preserving the in vivo activity of the native preparation in the human body for a longer time. This review is focused on the example of the pegylation of recombinant human granulocyte colony-stimulating factor (G-CSF) and gives the opportunity to have a look at different ways of pegylation and the mechanism of this reaction. Besides, the review describes the different types of reactive PEG for the specific conjugation to biological molecules and benefits and disadvantages of these reagents