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A technology of oligomeric polypeptides and conjugates, which is applied in the direction of drug combination, drug delivery, antipyretic drugs, etc., can solve the problems of insufficient drug preparations, and achieve the effects of rich variety, high yield, and convenient and quick preparation
Active Publication Date: 2015-12-16
NANJING UNIVERSITY OF TRADITIONAL CHINESE MEDICINE
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[0006] The purpose of the present invention is to solve the problem of insufficient drug preparations for intra-articular injection, and to provide an amphiphilic oligomeric polypeptide drug conjugate with high drug loading, good biocompatibility, and long residen
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Embodiment 1
[0028] Embodiment 1: Preparation of amphiphilic oligomeric polypeptide drug conjugate (keto-VEVE) by valine and glutamic acid and anti-inflammatory drug ketoprofen
[0032] Utilize conventional solid-phase synthesis methods to synthesize oligomeric polypeptides, and then couple drugs. details as follows:
[0033] (1) First co...
Embodiment 2
[0038] Example 2: High performance liquid chromatography and mass spectrometry detection of amphiphilic oligomeric polypeptide drug conjugate keto-VEVE
[0039] The keto-VEVE prepared in Example 1 is detected by high performance liquid chromatography (HPLC), see figure 1 ,Depend on figure 1 According to the peak area of the spectrum, the purity can be calculated to reach 97%. The keto-VEVE prepared in Example 1 is detected by mass spectrometry (MS), see figure 2 , indicating that its molecular weight is 710 is correct.
Embodiment 3
[0040] Embodiment 3: the establishment of the standard curve of keto-VEVE
[0041] Take the keto-VEVE prepared in Example 1 and make it into 1mg / ml mother liquor, dilute it step by step to 10, 20, 50, 100, 250, 500, 1000ug / ml, record the peak area in high performance liquid phase (HPLC), and draw a standard curve , see image 3 .
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Abstract
The invention discloses an amphipathic oligomeric polypeptide drug conjugate. According to the amphipathic oligomeric polypeptide drug conjugate, a drug can be directly condensed with a carboxyl at the terminal C of oligomeric polypeptide through a hydroxy or an amino in the chemical structure, so as to form an ester bond or an amido bond, or the drug can be condensed with an amino at the terminal N of oligomeric polypeptide through a carboxyl in the chemical structure, so as to form the amido bond, or the drug can be bonded with oligomeric polypeptide through certain link molecules. The drug conjugate has the advantages that oligomeric polypeptide which is prepared from high-safety amino acid is adopted as a main building material, and can be coupled with an anti-inflammatory drug for preparation of the amphipathic oligomeric polypeptide drug conjugate; compared with the conventional preparation, the amphipathic oligomeric polypeptide drug conjugate has the advantages of high safety and drug carrying capacity because the drug can be directly bonded with a carrier material; when the amphipathic oligomeric polypeptide drug conjugate enters a human body, the effect of the drug can be exerted for a long time.
Description
technical field [0001] The invention belongs to the field of polypeptide self-assembly, and particularly relates to an oligomeric polypeptide prepared from amino acid with high safety, which is used as a main construction material, coupled with an anti-inflammatory drug, and prepared as an oligomeric polypeptide-drug conjugate (Amphiphilicpeptidedrugconjugate: APD). Background technique [0002] Osteoarthritis (OA) and rheumatoid arthritis (Rheumatoidarthritis, RA) are chronic inflammatory and destructive diseases, and are multi-system inflammatory autoimmune diseases mainly involving peripheral joints. It is regarded as one of the five major diseases (cardiovascular disease, arthritis, Alzheimer's disease, cancer and AIDS) that affect human health. It makes millions of patients lose their ability to live and work. It is called immortality. cancer, causing great suffering to patients. According to figures provided by WHO, 1% of the world's population suffers from rheumatoid...
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