Linker compound, polyethylene glycol-linker conjugate and derivative thereof, and polyethylene glycol-linker-drug conjugate

Abstract

The invention discloses a linker compound, a polyethylene glycol-linker compound and derivatives thereof and a polyethylene glycol-linker-drug conjugate. The linker compound and a conjugate with polyethylene glycol and derivatives thereof can be used for drug modification. Moreover, the modification reaction is simple and is easily carried out, the reaction yield is high, and the application rangeof the modified drug is wide. The modified drug is gradually degraded from a conjugate chain in vivo and can achieve longer retention time at lesions (such as cancer suffering parts), the slow release and controlled release aims are achieved, the administration frequency can be reduced, and the bioavailability of the drug and patient compliance are greatly improved.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a linker compound, a polyethylene glycol-linker conjugate and derivatives thereof, a polyethylene glycol-linker-drug conjugate and pharmaceutical compositions and applications thereof. Background technique [0002] At present, in clinical practice, many drugs are not suitable for oral administration (for example, when polypeptide and protein drugs are administered orally, they will be damaged by various proteases, peptidases and other hydrolytic environments after they enter the digestive tract, and the drug efficacy will be reduced or even lost. For example, some drugs are irritating to the stomach or are not resistant to acid and are easily destroyed by gastric acid), the main route of administration is injection, which is directly injected into human tissues or blood vessels without passing through the digestive system and liver, and will not be affected by digestive juice. I...

AI Technical Summary

Problems solved by technology

[0002] At present, clinically, many drugs are not suitable for oral administration (for example, when polypeptide and protein drugs are administered orally, they will be damaged by various proteases, peptidases and other hydrolytic environments after they enter the digestive tract, and the drug efficacy will be reduced or even lost. For example, some drugs are irritating to the stomach or are not resistant to acid and are easily destroyed by gastric acid), the main route of administration is injection, which is directly injected into human tissues or blood vessels without passing through the digestive system and liver, and will not be affected by digestive juice. Influenced by destruction and food, the drug is absorbed quickly, the blood drug concentration rises rapidly, and the dosage is accurate. However, in clinical applications, since the drug is often distributed throughout the body rapidly after injection, the targeting of the lesion site such as tumor tissue Poor, low bioavailability, relatively low drug efficacy, and rapid adverse reactions, relatively difficult to deal with, in addition, often require multiple doses, and the principles of aseptic operation must be strictly followed when administering, requiring professionals If doctors and nurses operate, it is not conducive to patient compliance, so the clinical application of drugs often encounters bottlenecks

[0003] In the prior art, researchers often use water-soluble polymers such as polyethylene glycol to modify and link drugs to prolong the physiological half-life of drugs and reduce the immunogenicity and toxicity of drugs, but the release and efficacy of drugs in the body are sometimes not ideal

Images