ALGINATE HYDROGEL AND NEW COMPOSITION DERIVED THEREFROM FOR THE TREATMENT OF ECTOPIC CALCIFICATIONS

Abstract

The invention concerns an alginate hydrogel or a new composition derived therefrom further comprising another calcium chelator such as sodium thiosulfate and/or calcium crystal solubilizer or inhibitor, and their use in the treatment of ectopic calcifications or disorders comprising ectopic calcifications.

Claims

1. A composition of alginate hydrogel further comprising at least one other calcium chelator and/or calcium crystal solubilizer or inhibitor.

2. The composition according to claim 1, wherein the at least one other chelator is chosen from the group consisting of sodium thiosulfate, EDTA, and acetic acid.

3. The composition according to claim 1, wherein the at least one calcium crystal solubilizer is chosen from the group consisting of EGTA, EDTA, citrate, hydroxycitrate.

4. The composition according to claim 1, wherein the at least one calcium crystal inhibitor is chosen from the group consisting of pyrophosphate, magnesium, fetuin A, ENPP1, osteopontin.

5. A method for the treatment of a condition, comprising: administering the alginate hydrogel or composition as defined in claim 1 in a therapeutically effective amount for the prevention or treatment of ectopic calcifications or disorders comprising ectopic calcifications.

6. The method as defined in claim 5, wherein the disorders comprising ectopic calcifications are chosen from the group consisting of metabolic, inflammatory, traumatic, genetic, degenerative and age-related diseases.

7. The method as defined in claim 5, wherein the disorders are chosen from the group consisting of osteoarthrosis, physical trauma, hematoma, infection, tissue necrosis, irradiation, physical or chemical burns, tumor lesions, degenerative or inflammatory lesions, scleroderma, dermatomyositis, lupus, calcinosis, sarcoidosis, familial hyperphosphatemic or normophosphatemic tumoral calcinosis, hyperparathyroidism, haemochromatosis, hypomagnesemia, hypophosphatasia, vitamin D or copper overload, ochronosis, arthritis, type 2 diabetes, chronic kidney disease.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0021] FIG. 1 represents the evolution of the volume (.Math.m.sup.3) of cryo-induced muscle calcification in mice following two local injections of saline (• ; n=14) or alginate (.diamond-solid. ; n=18), or alginate associated with sodium thiosulfate (.triangle-solid. ; n=14) **p<0.001.

EXAMPLES

Example 1: Treatment Of Ectopic Calcifications In a Mouse Model Using an Alginate Hydrogel Alone or Associated With Sodium Thiosulfate

Quadriceps Calcifications Were Induced by Cryoinjury in Right and Left Sides:

[0022] Mice (mouse model of cryo-induced muscle calcification.) were anaesthetized with ketamine/xylazine. After cutaneous incision, quadriceps injuries were induced by 15-second freeze-thaw procedure using a liquid nitrogen-cooled surgical forceps of 6 mm wide. Mice were killed at different time points (from baseline to day 28 after cryoinjury) and quadriceps were harvested and fixed in 4% PFA overnight. Calcifications were quantified by micro-CT using. In this model, calcifications appeared at D1 and plateaued at D7 to D28.

Compositions of Alginate Hydrogel Used:

[0023] Alginate hydrogel sample (Protanal LF 10/60 1.2% m/V) [0024] 1.2 mg of sodium alginate were dissolved in 100 mL of sterile water under stirring (550 rpm). After dissolution, solution was stored at 4° C. overnight. Then, alginate solution was filtered through Sartolab P20 filter under sterile hood. The solution was stored at 4° C. used within 4 weeks.

[0025] Sodium thiosulfate 10% m/V in Protanal LF 10/60 1.2% m/V : [0026] 2.5 mg of sodium thiosulfate were dissolved in 25 ml of protanal LF 10/60 1.2% under stirring and then filtered through Sartolab P20 filter under sterile hood. Solution was stored at 4° C. and used within 4 weeks.

[0027] Sodium hyaluronate 0.14% m/V in Protanal LF 10/60 1.20% m/V: [0028] 28 .Math.g of sodium hyaluronate were dissolved in 20 ml of sterile protanal LF 10/60 1.2% under stirring. After dissolution, solution was stored at 4° C. until used.

Protocol:

[0029] Using this cryo-induced muscle calcification, the effect of alginate hydrogel Protanal LF 10/60 1.2% m/v alone or associated with sodium thiosulfate 10% m/v, was assessed.

[0030] At D7 after cryoinjury, mice received under sedation local injections with a 25G needle into right quadriceps of 50 .Math.L of either saline buffer (PBS) (n=14) or alginate hydrogel 1.2% (n=18) or alginate TSS (n=14). Left quadriceps were not treated. Same treatment was repeated at D10. After these two injections spaced 3 days apart, at D14, left and right quadriceps were harvested and calcification volumes were quantified by microscanning muscle samples.

[0031] The results presented in FIG. 1 showed that two local injections of alginate or alginate TSS spaced three days apart resulted in a substantial and significant decrease in muscle calcifications. Interestingly, calcification reduction in treated sides and untreated contralateral sides was observed, suggesting a systemic effect.

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