Les Laboratoires Aeterna, Inc.

Les Laboratories Aeterna Inc.

Aeterna Zentaris Gmbh

Eric Dupont

Paul Brazeau

Daniel H Maes

Kenneth D Marenus

Christina Juneau

Denis Lessard

Serge Auger

Yves Lachance

Kenneth Marenus

Christi Juneau

Christian Juneau

This invention described a novel use for cartilage extract, namely a shark cartilage extract, in a combined anti-tumor therapy. The cartilage extract is used in combination with anti-neoplastics. The combined therapy provides for a higher anti-tumor efficacy with no concomitant increase, even better with a decrease, of toxic side effects.

Anti-tumor therapies comprising a combination of a cartilage extract and an anti-neoplastic agent providing high efficacy and low toxic side effects

This invention relates to a process by which organic solvent-containing solutions are used in lieu of pure water for the preparation of cartilage extracts and fractions thereof. Different organic solvents have been tested for the preparation of extracts containing biologically active components possessing at least an activity against a matrix metalloprotease (anti-MMP). This invention also relates to a process by which a total liquid extract of shark cartilage composed of molecules having molecular weights less than about 500kDa (0-500 fraction) is purified into two well separated fractions composed of molecules having molecular weights less than about 1 kDa (0-1 fraction) and between about 1 to 500 kDa (1-500 fraction). In order to prevent the formation of aggregates, to improve the dissolution and the stability of active components, sucrose or other stabilizing agents can be added. The 0-500 fraction, the 0-1 fraction and the 1-500 fraction as well as their equivalents containing 1% w/v sucrose possess have anti-MMP and anti-tumor activities. The invention also provides a component which has at least anti-MMP and anti-tumor activities, and which has a mass of 244 amu (atomic mass unit). The use of the above extracts, derived fractions or components for inhibiting MMP enzyme, neovascularization and/or metastase formation is also described.

Low molecular weight components of shark cartilage, processes for their preparation and therapeutic uses thereof

Toxicity reduced composition containing an anti-neoplastic agent and a shark cartilage extract

This invention relates to a process by which organic solvent-containing solutions are used in lieu of pure water for the preparation of cartilage extracts and fractions thereof. Different organic solvents have been tested for the preparation of extracts containing biologically active components possessing at least an activity against a matrix metalloprotease (anti-MMP). This invention also relates to a process by which a total liquid extract of shark cartilage composed of molecules having molecular weights less than about 500 kDa (0-500 fraction) is purified into two well separated fractions composed of molecules having molecular weights less than about 1 kDa (0-1 fraction) and between about 1 to 500 kDa (1-500 fraction). In order to prevent the formation of aggregates, to improve the dissolution and the stability of active components, sucrose or other stabilizing agents can be added. The 0-500 fraction, the 0-1 fraction and the 1-500 fraction as well as their equivalents containing 1% w/v sucrose possess have anti-MMP and anti-tumor activities. The invention also provides a component which has at least anti-MMP and anti-tumor activities, and which has a mass of 244 amu (atomic mass unit). The use of the above extracts, derived fractions or components for inhibiting MMP enzyme, neovascularization and/or metastase formation is also described.

The present invention relates to cartilage extracts and to a method of producing the same. Shark cartilage extracts having anti-angiogenic, anti-tumoral, anti-inflammatory and anti-collagenolytic activities have been obtained by an improved process. The process comprises the steps of obtaining a homogenate of cartilage in an aqueous solution, this homogenate being separated in a solid fraction (SOLID EXTRACT) and a liquid fraction which was further fractionated to obtain a LIQUID EXTRACT having molecules of a molecular weight comprised between 0 to 500 kDa. The composition of the liquid extract has then been investigated by different ways. Further fractionation of this extract led to the preliminary characterization of some of its active components. Due to the multiplicity of biological activities of the total liquid extract, it can be used for treating numerous diseases or conditions such as those having components selected from the group consisting of tumor proliferation, angiogenesis, inflammation and collagenolysis. Several cosmetic applications based on the capacity of the liquid extract to improve skin barrier function are also under the scope of this invention. These extracts have no offensive effect on normal body functions. Therefore, these shark cartilage extracts have a very promising therapeutic value. The process for the obtention of cartilage extracts is simple and efficient. The unexpectedly valuable products obtained by this process are therefore an indication of a new and non-obvious process.

Methods of using extracts of shark cartilage

The present invention relates to cartilage extracts and to a method of producing the same. Shark cartilage extracts having anti-angiogenic, direct anti-tumor proliferating, anti-inflammatory and anti-collagenolytic activities have been obtained by an improved process. The process comprises the steps of obtaining a homogenate of cartilage in an aqueous solution, this homogenate being centrifuged and further fractionated to obtain a total extract having molecules of a molecular weight comprised between 0 to 500 KDa. The composition of the liquid extract has then been investigated by different ways. Further fractionation of this extract led to the preliminary characterization of some of its active components. Due to the multiplicity of biological activities of the total liquid extract, it can be used for treating numerous diseases or conditions such as those having components selected from the group consisting of tumor proliferation, angiogenesis, inflammation and collagenolysis. This extract has no offensive effect on normal body functions. Therefore, this shark cartilage extract has a very promising therapeutic value. The process for the obtention of cartilage extracts is simple and efficient. The unexpectedly valuable products obtained by this process are therefore an indication of a new and non-obvious process.

Extracts of shark cartilage having anti-collagenolytic,

The present invention relates to shark cartilage extracts and to a method of producing the same, these extracts having anti-angiogenic properties (reduction of the area of blood vessels observed in vivo on experimentally induced tumors), tumor regressive activity in vivo as well as demonstrating a direct inhibitory effect on tumor cell lines. This process does not involve any denaturing solvent or product and does not involve the use of any enzymes. It consists of obtaining a blend of whole cartilage in an aqueous solution of neutral pH, preferably pure water, this blend being centrifuged and the pellet and supernatant kept for further processing. The pellet is lyophilized and tested for anti-tumor and anti-angiogenic activities in vivo and in vitro, with or without supernatant. The supernatant has been shown to have anti-angiogenic and tumor regressive activities in vivo. The composition of the supernatant has then been investigated by different ways. Fractionation of this supernatant led to the characterization of some of its active components. The fractions were tested for their direct in vitro activity on cancer cell lines. Therefore, it is assumed that the non-fractionated supernatant has such an in vitro activity. Lyophilization substantially destroys the activity of these liquid fractions while no such abolition is observed in the solid extract.

Extracts of shark cartilage having an anti-angiogenic activity and an

The present invention relates to shark cartilage extracts and to a method of producing the same, these extracts having anti-angiogenic properties (reduction of the area of blood vessels observed in vivo on experimentally induced tumors), tumor regressive activity in vivo as well as demonstrating a direct inhibitory effect on tumor cell lines. This process does not involve any denaturing solvent or product and does not involve the use of any enzymes. It consists of obtaining a blend of whole cartilage in an aqueous solution of neutral pH, preferably pure water, this blend being centrifuged and the pellet and supernatant kept for further processing. The pellet is lyophylized and tested for anti-tumor and anti-angiogenic activities in vivo and in vitro, with or without supernatant. The supernatant has been shown to have anti-angiogenic and tumor regressive activities in vivo. The composition of the supernatant has then been investigated by different ways. Fractionation of this supernatant led to the characterization of some of its active components. The fractions were tested for their direct in vitro activity on cancer cell lines. Therefore, it is assumed that the non-fractionated supernatant has such an in vitro activity. Lyophilization substantially destroys the activity of these liquid fractions while no such abolition is observed in the solid extract.

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St. Nicolas, Canada

Eric Dupont