Aqueous liquid extract of Spirulina for the prevention and/or treatment of chemically induced peripheral neuropathy and their symptoms, composition and use thereof

Abstract

A composition for use in the treatment and/or prevention of adverse side effects induced by an anti-cancer compound, said composition comprising an aqueous liquid extract, the aqueous liquid extract comprising Phycocyanin. The present invention also relates to the use of this aqueous liquid extract comprising Phycocyanin and optionally Spirulina polysaccharides, for the treatment and/or prevention of adverse side effects induced by an anti-cancer compound.

Indeed, Phycocyanin, thanks to its antioxidant effects, can reduce the undesirable side effects induced by an anti-cancer compound.

Claims

1. A composition for use in the treatment and/or prevention of chemically-induced peripheral neuropathy and its symptoms induced by an anti-cancer compound, said composition comprising an aqueous liquid extract, said aqueous liquid extract comprising Phycocyanin.

2. The composition for use according to claim 1, characterised in that said aqueous liquid extract further comprises Spirulina polysaccharides.

3. The composition for use according to claims 1, characterised in that said anti-cancer compound belongs to the group comprising a platinum salt, a taxane, an anthracycline.

4. The composition for use according to claim 3, characterised in that said anti-cancer compound is selected from platinum salts; preferably from the group consisting of cisplatin, carboplatin, oxaliplatin and mixtures thereof.

5. The composition for use according to claim 1 characterised in that said liquid aqueous extract comprises between 20 and 150 mg, preferably between 50 and 120 mg, very preferably 100 mg of Phycocyanin.

6. The composition for use according to claim 2, characterised in that said liquid aqueous extract further comprises between 5 and 25 mg, very preferably 20 mg, of Spirulina polysaccharides.

7. The composition for use according to claim 1, characterised in that said composition comprises only said liquid aqueous extract.

8. The composition for use according to claim 7, characterised in that it is administered in liquid form orally.

9. The composition for use according to claim 7, characterised in that said composition is administered at a dose between 20 mg/day and 150 mg/day, preferably between 50 mg/day and 150 mg/day, very preferably at 100 mg/day.

10. A use of an aqueous liquid extract, comprising Phycocyanin and optionally Spirulina polysaccharides, obtained from cyanobacteria for the treatment and/or prevention of chemotherapy-induced peripheral neuropathy and their symptoms induced by an anti-cancer compound.

11. The use of an aqueous liquid extract according to claim 10, characterised in that said anti-cancer compound belongs to the group comprising a platinum salt, a taxane, an anthracycline.

12. The use of an aqueous liquid extract according to claim 11, characterised in that said anti-cancer compound is selected from platinum salts; preferably from the group consisting of cisplatin, carboplatin, oxaliplatin and mixtures thereof.

Description

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0060] The general principle of the invention is based on the administration of a composition comprising an aqueous liquid extract obtained from cyanobacteria, said aqueous extract comprising Phycocyanin and optionally Spirulina polysaccharides, for use in the treatment and/or prevention of undesirable side effects induced by an anti-cancer compound, in particular to prevent and/or treat chemotherapy-induced peripheral neuropathy and their associated symptoms, such as neuropathic pain.

[0061] The invention relates more particularly to a composition comprising only the aqueous extract for use in the treatment and/or prevention of peripheral neuropathy induced by platinum salt therapy such as oxaliplatin.

[0062] In particular, this aqueous liquid extract of cyanobacteria, or Spirulina, comprises Phycocyanin and very preferably Spirulina polysaccharides, and is marketed by the Company AlgoSource under the name Spirulysat®. Spirulysat® is a liquid aqueous extract, the extraction process of which is described in the patent application FR3064269. This particular extraction process allows the extraction of Phycocyanin without denaturing it, i.e. by preserving its spatial structure. Thus Spirulysat® is particularly rich in Phycocyanin of better quality, which gives it an increased effectiveness.

[0063] This liquid aqueous extract is obtained from cyanobacteria, or micro-algae. In particular, Spirulysat® is obtained from cyanobacteria selected from Arthrospira platensis spirulina, Aphanizomenon flos-aquae and Phormidium molle. Cyanobacteria are prokaryotic microalgae also called “blue-green algae”. The term “Spirulina” can refer to several different species of filamentous cyanobacteria, such as species from two distinct genera: Arthrospira and Spirulina. Hereafter, the term “Spirulina” is used to describe the cyanobacteria used to obtain Spirulysat®. Spirulina is known to be very rich in antioxidant molecules such as Phycocyanin, a phycobiliprotein of an intense blue.

[0064] It is understood that “polysaccharides” (sometimes called glycans, polyosides, polyholosides or complex carbohydrates) are polymers of the carbohydrate family consisting of several simple sugars linked together by osidic bonds.

[0065] In an embodiment according to the invention, the liquid aqueous extract comprises between 20 and 150 mg, preferably between 50 and 120 mg, very preferably 100 mg of Phycocyanin. Preferably, the liquid aqueous extract further comprises between 5 and 25 mg, very preferably 20 mg of Spirulina polysaccharides.

[0066] Spirulysat® is preferably administered in liquid form orally. In particular, the composition is administered at a dose between 20 mg/day and 150 mg/day, preferably between 50 mg/day and 150 mg/day, very preferably at 100 mg/day.

[0067] In particular, the invention comprises, in one of its particularly interesting aspects, the administration of the composition comprising Spirulysat® upstream and/or in parallel with the administration of an anti-cancer compound, in particular an anti-cancer compound selected from platinum salts, taxanes, anthracyclines or their mixture.

[0068] Platinum salts such as oxaliplatin, carboplatin and cisplatin are currently used to treat certain forms of cancer. They all present a more or less important neurotoxicity depending on the molecule, oxaliplatin being the most neurotoxic of the platinum salts. This neurotoxicity is translated by the appearance of signs encountered in neuropathic pain such as burning, tingling, numbness, allodynia, paraesthesia, which persist long after the treatment is stopped. This neurotoxicity occurs acutely following each administration of oxaliplatin to the patient, and becomes chronic as the patient receives doses of platinum salts (cisplatin, carboplatin and oxaliplatin).

[0069] In a preferred embodiment, Spirulysat® is administered prior to the administration of the anti-cancer compound, in particular prior to the administration of platinum salts, such as oxaliplatin. This option potentiates the effects of Spirulysat® by giving it time to act and avoiding the development of peripheral neuropathy and associated symptoms. Prophylactic administration of Spirulysat®, prior to the administration of at least one anti-cancer compound, notably a platinum salt such as oxaliplatin, helps to avoid the development of peripheral neuropathy and associated symptoms, such as neuropathic pain.

[0070] Advantageously, Spirulysat® is not administered on the day of administration of the anti-cancer compound, in particular a platinum salt, in order to allow the anti- cancer treatment to act, nor on the day following this administration.

[0071] Administration of Spirulysat® is resumed two to three days after administration of the anti-cancer compound, including a platinum salt, and every day until the next administration of the anti-cancer compound, including a platinum salt.

[0072] The inventors observed that the administration of a dose of Spirulysat® before the start of anti-cancer treatment including the injection of platinum salts, and then daily between injections of platinum salts, made it possible to reduce the appearance of peripheral neuropathy caused by these platinum salts, and prevent the development of neuropathy and thus of chronic pain.

[0073] In an example of administration of Spirulysat®, it is administered in the form of an ampoule comprising 10 ml of the aqueous liquid extract, i.e. approximately 10 mg of Phycocyanin and 1.5 mg of Spirulina polysaccharides. The invention is not limited to this mode of administration, nor to the composition and/or volume of the ampoule.

[0074] In another example of administration of Spirulysat®, it can be administered as a 5 ml ampoule of the aqueous liquid extract.

[0075] In other examples of administration, Spirulysat® can be administered in a glass bottle, as a capsule containing the aqueous liquid extract, or as a drink containing the aqueous liquid extract.

[0076] In fact, with an intake of 2 ampoules/day, i.e. about 20 mg/day of Phycocyanin and 3 mg/day of Spirulina polysaccharide, effects have been observed, but in a limited way in certain patients.

[0077] In humans, during chemotherapeutic treatment, especially treatment with platinum salts and more particularly oxaliplatin, a dose of 5 to 6 ampoules per day, i.e. 50 mg-60 mg/day of Phycocyanin and 7.5 mg/day-9 mg/day of Spirulina polysaccharides, gives much better results than a dose of 2 ampoules per day, i.e. 20 mg/day of Phycocyanin and 3 mg/day of Spirulina polysaccharides.

[0078] On pets such as cats, dogs, hamsters, exotic pets, a dose of 0.1 ml of Spirulysat® per kg of body weight has been identified as active. This corresponds to the same orders of magnitude: 7 ml for 70 kg. Doses equivalent to those administered to humans and therefore higher have more effects. Thus, in animals have also observed a protective effect of Spirulysat® particularly on the liver, kidneys, heart or nervous system.

[0079] Thus, Spirulysat® gives effects from 32 mg of Phycocyanin, which is 10 times less than what is described in the prior art, i.e. 350 mg-900 mg of Phycocyanin, which makes it very affordable from an industrial point of view, but also for the patient.

[0080] Advantageously, a dose of 10 ampoules per day, i.e. taking Spirulysat® concentrated to 100 mg of Phycocyanin and 15 mg of polysaccharides per day, allows an even greater reduction of undesirable side effects, such as peripheral neuropathy, induced by anti-cancer treatment, such as platinum salt treatments and in particular oxaliplatin-based treatments.

[0081] In particular, the inventors have shown that taking Spirulysat® concentrated at 100 mg of Phycocyanin and 15 mg of polysaccharides per day, allows to decrease from 45% to 10% the rate of patients undergoing oncological treatment with platinum salts and more particularly under oxaliplatin, presenting at least very serious undesirable side effects such as chemotherapy-induced peripheral neuropathy (see table 1 below). 90% of patients have only minor effects.

TABLE-US-00001 TABLE 1 Spirulysat ® concentration 0 mg/d 100 mg/d % patients with chemotherapy-induced neuropathy 45% 10%

[0082] The effect of Spirulysat® is therefore dose-related. A minimum dose of 50 mg/day for an adult is recommended. For a child it is to be adapted to their body mass. The inventors have shown that a dose of 100 mg/day provides even better results, or a greater rate of decrease in side effects on the population.

[0083] The tolerance threshold of Spirulysat® from a toxicity point of view is beyond 1.4 litres of Spirulysat® per day for an adult, according to the latest studies on animal models. Some patients react much more easily to Spirulysat® and obtain good results with 5 ampoules per day (i.e. 50 mg/day of Phycocyanin and 7.5 mg/day of Spirulina polysaccharides). Others needed 10 ampoules per day (i.e. 100 mg/day of

[0084] Phycocyanin and 15 mg/day of Spirulina polysaccharides). A personalisation and an adaptation of the Spirulysat® intake is thus possible according to the patients, while remaining below the dosages described in the prior art.

[0085] Thus, Spirulysat®, combining several molecules of interest of Spirulina including Phycocyanin, and Spirulina polysaccharides, offers the opportunity of a customisation of concentration to meet the needs of patients.

[0086] In addition, taking Spirulysat® allows patients to tolerate their treatment better and thus, avoid or limit the dosage adjustment of the current treatment, contrary to what has been observed in 50% of cases of anti-cancer treatment without taking Spirulysat®. Indeed, the inventors have demonstrated that taking 20 mg/day of

[0087] Spirulysat® reduces to 10% the number of cases requiring a dosage adjustment (see table 2 below). With a dosage of 50 mg/day and 100 mg/day no further dosage adjustment is necessary.

[0088] Thus, patients better respect their treatment protocol, which contributes to reinforce its effectiveness, while benefiting from an improvement in their well-being in terms of: diet, sleep, physical activity, stress resistance.

TABLE-US-00002 TABLE 2 Spirulysat ® concentration 0 mg/d 20 mg/d 50 mg/d 100 mg/d % of cases of dosage adaptation >50% 10% 0% 0%

[0089] Advantageously, Spirulysat® does not intervene as a medicinal treatment but as a therapeutic support contributing to making medical treatments more effective. This is a major innovation in terms of health: for the first time, the combination of a medical treatment and a natural food supplement results in a powerful and incredibly effective cocktail for the benefit of patients.