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Polyethylene glycol PEG 

Views: 9     Author: su     Publish Time: 2018-11-20      Origin: Site


Problems in the development of PEG modification of drugs

While retaining the intrinsic biological activity of natural proteins, PEG ylated proteins can effectively overcome some of the shortcomings of protein drugs in clinical applications, such as increasing plasma half-life, enhancing bioavailability, reducing protein immunogenicity, and improving drug efficacy. And safety, etc. In order to couple PEG to proteins under milder reaction conditions, PEG is activated, and the activated PEG is coupled to an amino group, a thiol group or a carboxyl group on the protein molecule.

Many organic small molecule drugs have gradually adopted PEG modification technology, and some progress has been made. The modification of small molecule drugs by polyethylene glycolcan transfer many of its excellent properties to the conjugate, so that the polymer Has excellent biocompatibility.

 It can be dissolved in tissue fluid in the body and can be quickly excreted by the body without any side effects. Therefore, the application of polyethylene glycol in medicine has received extensive attention. At present, there are many anti-tumor drugs. In recent years, PEG has been used. The small molecule drugs of the modification technology are: paclitaxel, camptothecin, cytarabine, scutellarin, etc. PEG modified small molecule drugs, still mainly react with the drug OH, NH2, COOH and other groups, small molecule drugs and The connection of PEG can be either a permanent connection or a prodrug. Currently, the form of prodrug is more common.

PEG has effectively solved the problem of improving the water solubility of drugs, reducing toxic and side effects, prolonging the half-life of drugs in blood, improving targeting and increasing efficacy in pharmaceutical preparations. In recent years, with the rapid development of PEG chemistry PEG modification of some important protein drugs has entered the product development stage, and breakthroughs have been made in the research field of small organic anti-tumor prodrugs and anti-tumor drug liposomes, but there are still many problems at this stage. Solution: (1) There is still no in-depth systematic study on the mechanism of action of PEG-modified drugs in vivo. Only the mechanism of action of PEG-modified drugs in vivo can be targeted to design drugs, and drugs can be explained at the molecular level. Mechanism of action and safety. (2) Establishment of a quality standard system for PEG-modified drugs. Due to the difficulty in purifying the target product in PEG modification, polyethylene glycol monomethyl ether (MPEG) may be present in the product, cross-linked or Polymerized PEG diols, etc. 

 Substances that are difficult to separate, there is no standard analysis for the detection of such substances. Methods, which also limit the in-depth research and application of PEG modification technology to a certain extent. (3) The research platform of PEG modification of small molecule drugs is currently focused on the modification of anti-tumor drugs. In addition, PEG modification technology should be expanded. To other areas of drug modification, such as anti-cardiovascular disease drugs, anti-malarial drugs, etc. With the rapid development of PEG chemistry, if the above problems are properly solved, the development and clinical application of PEG-modified drugs will be greatly developed, drugs The PEG modification technology has a very attractive development prospect in enhancing the efficacy of various drugs (proteins, peptides, antineoplastics, antifungals, antibiotics and immunosuppressive agents) and expanding the clinical application range of drugs.

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