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Compositions comprising multivalent synthetic ligands of surface nucleolin and glycosaminoglycans

A composition and multivalent technology, applied in the field of promoting wound healing, can solve the problems of expensive, efficient and specific way to reach, difficulty in antibody production, etc.

Inactive Publication Date: 2013-10-02
CENT NAT DE LA RECHERCHE SCI +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the use of antibodies poses other serious problems, and the development of non-toxic effective therapeutic antibodies is a long, uncertain and expensive process
Furthermore, antibody production on a large scale and under stringent health and safety conditions is particularly difficult
As a result, specific antibody-based treatments are few and far between and are prohibitively expensive
[0011] Another problem associated with traditional anticancer drugs such as paclitaxel is that these molecules are often highly hydrophobic, necessitating the development of complex and expensive drug formulations to achieve acceptable bioavailability in vivo
The problem of in vivo bioavailability is even more pronounced in the case of nucleic acid therapy, since it is extremely difficult for nucleic acids to reach their target cells in an efficient and specific manner

Method used

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  • Compositions comprising multivalent synthetic ligands of surface nucleolin and glycosaminoglycans
  • Compositions comprising multivalent synthetic ligands of surface nucleolin and glycosaminoglycans
  • Compositions comprising multivalent synthetic ligands of surface nucleolin and glycosaminoglycans

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 2

[0170] N6L is 5 μM (corresponding to 20 μg / ml): N6L / GAG weight ratio between 0.2 and 2,

[0171] N6L is 20 μM (corresponding to 80 μg / ml): N6L / GAG weight ratio between 0.8 and 8,

[0172] In compositions of the invention comprising microspheres of Nucate and GAG, advantageously the Nucate / GAG microspheres have a thickness of less than 5 mm, or from about 1 nm to about 1 mm, or from about 1 nm to about 10 μm, or from about 10 nm to about 500 nm in diameter.

[0173] In any of the compositions described herein, the therapeutic compositions provided by the invention optionally include a pharmaceutically acceptable carrier, excipient or adjuvant.

[0174] The invention also provides a method for making a composition of microspheres comprising nucate and GAG comprising mixing sufficient quantities of nucate and GAG to produce a microsphere or microspheres. Preferably, Nucat and GAG are mixed in a weight ratio included in the above range.

[0175] In another aspect, the present i...

Embodiment 1

[0223] Example 1, Synergistic effect of co-administration of different GAGs with Nukat 6L on the anti-proliferative properties of Nukat 6L.

[0224] Effects on cell growth of human pancreatic carcinoma cells (PANC-1, human pancreatic carcinoma).

[0225] Co-administration of N6L + different GAGs on human pancreatic cancer cell (PANC-1, human pancreatic cancer) cell growth (see image 3 ). exist image 3 In A, heparin was used as an exemplary GAG. exist image 3 B and image 3 In C, chondroitin sulfate A and chondroitin sulfate C were used in combination with N6L. Cells were treated daily with the mixture N6L / GAG (from about 20 μM / 0 μg / ml to 1000 μg / ml GAG). The medium (DMEM5%SVF) was changed daily. Proliferation was assessed by MTT assay. No effect on cell proliferation was observed with GAG alone. exist Figure 5 Among them, PANC-1 was untreated (A), or treated with 20 μM N6L (B), treated with 20 μM N6L and 10 μg / ml heparin (C), or treated with a mixture of 20 μM ...

Embodiment 3

[0253] Example 3. Synergistic effect of co-administration of different GAGs with Nukat 6L on the anti-angiogenic properties of Nukat 6L

[0254] Effects of N6L preincubated with various glycosaminoglycans on anchorage-dependent proliferation of human endothelial cellsresearch (see Figure 20 )

[0255] Review: To compare the efficacy of different GAGs in modulating the effect of N6L on anchorage-dependent proliferation of human endothelial cells, N6L and a mixture of these GAGs were used against HUVEC cells. After 4 days, cell proliferation was quantified by MTT assay.

[0256] METHODS: N6L was treated with increasing concentrations ranging from 0.1 μM to 50 μM, or pre-incubated with 10 μg / ml of CS-A, CS-B, CS-C, heparin, heparan sulfate or hyaluronic acid or not pre-incubated. Culture a similar number (5×10 3 ) of HUVEC cells. Cells were processed daily for 4 days. At the end of day 4, cell numbers were quantified using the MTT assay.

[0257] Results: N6L alone inhi...

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Abstract

The present invention relates to a composition comprising a Nucant multivalent synthetic compound and a glycosaminoglycan, the admixture of both compounds forming microspheres comprising both compounds, as well as their use for the treatment or prevention of diseases associated to deregulation of proliferation and / or angiogenesis, such as cancer, inflammatory disease, or for promoting wound healing.

Description

technical field [0001] The present invention relates to compositions comprising polyvalent synthetic compounds and glycosaminoglycans (GAGs), and their use for treating cancer, diseases involving angiogenesis, inflammatory diseases, and promoting wound healing. Background technique [0002] Eukaryotic cells undergo cell division through mitosis to support growth, repair, tissue regeneration, and / or replace dead cells. [0003] In cancer cells, the regulation of mitosis is defective, which is why these cells divide promiscuously and give rise to tumors. Thus, an effective therapeutic approach to prevent cancer progression involves the use of molecules with anti-mitotic or other anti-cancer properties to prevent cancer cell division. [0004] However, current anti-mitotic molecules (paclitaxel, commonly known as paclitaxel, or colchicine, for example) act cell-free-specifically on all undifferentiated cells, causing many undesirable side effects. Therefore, there is a need t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/00A61K38/02A61K38/10
CPCA61K36/00A61K36/02A61K36/10A61K38/06A61K31/726A61K31/7068A61K31/727A61K38/16A61P17/02A61P29/00A61P31/04A61P35/00A61P43/00A61P9/00Y02A50/30A61K2300/00C07K7/08
Inventor R·齐默J·库尔蒂
Owner CENT NAT DE LA RECHERCHE SCI