Pharmaceutical preparation of carbohydrates for therapeutic use

a technology of pharmaceutical preparation and carbohydrates, applied in the direction of medical preparations, liposomal delivery, organic active ingredients, etc., can solve the problems of limited treatment options, delivery and maintenance of such a systemic supply of man-1-p, and the ineffective treatment of cdg-ia patients, so as to enhance the retention of lipid particles, enhance circulation and retention, and minimize the degradation of lipid particles

Inactive Publication Date: 2016-08-11
GLYCOMINE INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0016]In some embodiments, the compositions described herein are medicaments. Such compositions (e.g., medicaments) may include an aqueous suspension of liposomes encasing, for example, mannose-1-phosphate. Liposomes may be prepared from vesicle-forming lipids, such as but not limited to phosphatidylcholine (PC). The liposome may also be prepared in conjunction with a sterol, namely cholesterol. The full liposome may be enriched with polyethylene-glycol (PEG), or PEGylated, in order to enhance circulation and retention with the body fluids upon administration, as well as protect the liposome from premature degradation and excretion of the medicament from the body of a subject in n...

Problems solved by technology

However, such therapy may not be as effective in treating CDG-Ia patients and there are currently limited treatment options for other CDG type I subtypes and CDG type II diseases.
However, the delivery and maintenance of such a systemic supply of Man-1-P is problematic, as extracellular enzymes within bodily fluids degrade Man-1-P when delivered exogenously by oral or intravenous administration.
Another problem with exogenously delivered Man-1-P is that its high polarity prevents Man-1-P from penetrating into ...

Method used

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  • Pharmaceutical preparation of carbohydrates for therapeutic use
  • Pharmaceutical preparation of carbohydrates for therapeutic use
  • Pharmaceutical preparation of carbohydrates for therapeutic use

Examples

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example 1

Preparation of Mannose-1-Phosphate Liposomes

[0309]The following Example demonstrates the preparation of liposomes containing mannose-1-phosphate (M1P-liposomes). The structure of mannose-1-phosphate (M1P) is depicted in FIG. 1A. While a specific isomer is depicted in FIG. 1A, it should be understood that the carbohydates used in the compositions and methods provided herein may be any isomeric form, provided that such carbohydrates are endogenous carbohydrates for a given subject.

Liposome Preparation Method

[0310]Liposomes were prepared by thin-film hydration from phosphatidylcholine (PC), cholesterol, and phosphatidylethanolamine (PE) conjugated topoly-ethylene-glycol (PEG). The structure of PEG is depicted in FIG. 1B. In FIG. 1B, in one variation, n may be in the range of 800-5000. In other variations, the value of n may be 2000. In yet other variations, PEG may be modified either with meleimide or NHS-ester depending on what the PEG will be conjugated to. The structure of phosphati...

example 2

Measurement of M1P Content in Liposomes

[0314]CDG-Ia disorder is a gycosylation disorder characterized by the deficiency or abnormalities associated with the enzyme phosphomannomutase (PMM). This disorder is diagnosed by testing the serum glycoproteins of hepatic origin (transferrin is the clinically tested protein), which are commonly underglycosylated. Typically transferrin is assessed using isoelectric focusing, which would underscore a dramatic decrease in PMM activity (PMM activity in CDG-Ia patients is approximately 0.29 nM / min / mg, as compared to normal PMM activity of approximately 2.97 nM / min / mg). PMM enzyme is responsible for catalyzing the conversion of mannose-6-phosphate to mannose-1-phosphate, which is in turn a precursor for the ultimate synthesis of G3M9Gn2-P-P-Dolichol, which in turn is a precursor to lipid-linked-oligosaccharide (LLO). This is represented by the following schematic representation of the metabolic glycosylation pathway is: glucose→glucose-6-phosphate→...

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Abstract

The disclosure provides methods for preparation of carbohydrate replacement therapies (CRT) that include nanocarriers of carbohydrates and glycolipids for pharmaceutical delivery to cell interior, endoplasmic reticulum, and Golgi for treating CDG type I and CDG type II diseases as well as other metabolic disorders.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 61 / 878,591, filed Sep. 16, 2013, which is hereby incorporated by reference in its entirety.FIELD[0002]The present invention relates to compositions containing carbohydrates encapsulated in a lipid particle for delivery to the cell interior, methods of delivering the encapsulated carbohydrates into the interior of cells, and methods of using such compositions for treating diseases and disorders, such as congenital disorders of glycosylation (CDG). For example, the present invention relates to methods for preparation of carbohydrates and glycolipids for pharmaceutical delivery to cell interior, endoplasmic reticulum (ER), and Golgi.BACKGROUND[0003]Glycosylation, the enzymatic attachment of carbohydrates (glycans) to proteins and lipids is a co-translational and post-translational modification (PTM) that is more common than any other PTM as it applies to a majority of pr...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K31/7028
CPCA61K9/127A61K31/7028A61K9/1271
Inventor RAFALKO, AGNESCHERNENKO, TATYANA
Owner GLYCOMINE INC
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