Immunomodulatory Fluorinated and Lipid-Modified Zwitterionic Polysaccharide Derivatives, Their Production Methods and Therapeutic Uses

Abstract

This invention relates to hybrid derivatives of microbial-derived zwitterionic polysaccharides (ZPS / PSA), particularly those isolated from the Bacteroides fragilis strain or produced synthetically, that have been developed to enhance their metabolic stability and tissue targeting capacity. The basis of the invention consists of at least one halogenated (preferably fluorinated) functional group and at least one hydrophobic lipid chain added covalently to the natural polysaccharide backbone. Fluoride modification increases the molecule's resistance to enzymatic degradation, thus extending its half-life within the body; while lipid modification enables targeted delivery of the molecule to lymphatic tissues (particularly Peyer's patches). This hybrid construct (MDK-01) activates the MHC-II pathway, promoting the differentiation of Foxp3+ Regulatory T-cells (Tregs), and offers a highly effective immunomodulatory solution with no systemic side effects for the treatment of autoimmune diseases, primarily Multiple Sclerosis (MS) and Rheumatoid Arthritis (RA).

Description

1 TARIFF IMMUNOMODULATORY, FLUORINATED AND LIPID-MODIFIED ZWITTERIIC POLYSACCHARIDE DERIVATIVES AND THEIR PRODUCTION METHODS AND THERAPEUTIC USES 5 TECHNICAL FIELD This invention is based on the chemical modification of microbial-derived zwitterionic polysaccharides. the resulting next-generation immunomodulatory compounds have enhanced stability and tissue targeting. This relates to their use in the treatment of autoimmune diseases. 10 PREVIOUS TECHNIQUE In the current literature, zwitterionic structures such as Polysaccharide A (PSA) are involved in immunoregulation. Their effects are known. However, these molecules in their natural form are resistant to enzymatic hydrolysis. its instability, short half-lives, and the fact that it reaches systemic circulation before reaching lymphatic tissues (15) Their deterioration limits clinical applications. TECHNICAL PROBLEMS THAT THE INVENTION AIMS TO SOLVE The invention stabilizes the natural polysaccharide skeleton with fluorine atoms, thereby increasing metabolic resistance. by providing and adding a lipid chain, the molecule directly reaches Peyer's patches and lymph nodes 20 It aims to transport it. DESCRIPTION OF THE FIGURES Figure 1 shows the overall chemical structure and modification sites of the MDK-01 hybrid molecule. This is a schematic view showing the diagram. 25 Figure 2 shows the molecule's interaction with the MHC-II receptor groove on the Antigen Presenting Cell (APC). This is a schematic view illustrating the interaction and Treg cell activation mechanism. Figure 3 shows the pH-sensitive polymeric delivery system containing the molecule in the stomach and small intestine. It is a schematic representation showing its behavior in different environments. Figure 4 shows the time-dependent 30-degree differences between the control group and the group treated with MDK-01 in the EAE mouse model. It is a graphical representation showing changes in disease severity (clinical score). 2 LIST OF REFERENCE NUMBERS IN THE IMAGES 10: Lipid tail 11: Connecting part 12: Flor group 13: Polysaccharide backbone 5 14: Zwitterionic group 20: Antigen-presenting cell 21: MHC-II receptor groove 22: MDK-01 molecule 23: T-cell receptor 10 24: Naive T-cell 25: Treg cell 30: pH-sensitive polymer shell 31: Stomach environment 32: Small intestine environment 15 40: Control group 41: Group that implemented MDK-01 42: Recovery curve DETAILED DESCRIPTION OF THE INVENTION 20 The invention is based on a polysaccharide backbone of Bacteroides fragilis (13), "Click Chemistry" fluorine groups (12) covalently bonded by the method and a hydrophobic lipid tail (10) consists of. The electronegativity of fluorine atoms causes the breaking of glycosidic bonds. While the lipid portion blocks it, the molecule allows it to leak into the lymphatic system via the chylomicron pathway.

Claims

3 REQUESTS 1. Containing a microbial-derived zwitterionic polysaccharide (ZPS) scaffold; its characteristic is; the skeleton in question contains at least one halogenated (fluorinated) group and at least one hydrophobic group. It is a hybrid molecular structure in which the lipid chain is covalently modified. 5 2. The molecular structure conforming to claim 1; the zwitterionic polysaccharide backbone mentioned herein, It includes Polysaccharide A (PSA) or its derivatives derived from Bacteroides fragilis.

3. The molecular structure conforms to claim 1; fluoride modification, enzymatic 10 of the molecule By increasing its resistance to hydrolysis, the tissue half-life is extended by at least 30% compared to natural PSA. It is structured to increase.

4. The molecular structure conforms to claim 1; the lipid chain, the molecule's mesenteric lymph 15 optimized to ensure targeted transport to nodes and Peyer plates It has been done.

5. The molecular structure conforming to Claim 1; Multiple Sclerosis (MS), Rheumatoid Arthritis (RA) and Its use is in the treatment of autoimmune diseases, including Crohn's disease.

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