Use of d-xylose to stimulate glycosaminoglycan biosynthesis

Abstract

The invention relates to a formulation comprising at least one compound selected from D-xylose, esters thereof, oligosaccharides comprising D-xylose, and / or P-D-xylosides, for use in stimulating the biosynthesis of glycosaminoglycans, preferably at least one selected from heparan sulfate, dermatan sulfate and chondroitin sulfate, in a human patient, by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of said compound. Preferably, said formulation is for use in the prevention or treatment of infections with viruses using syndecans and / or glypicans as cell receptors, such as SARS-CoV2 or HIV, or in the prevention or treatment of type 2 diabetes or of insulin resistance. The invention also relates to the use of an oral or nasal food supplement composition in healthy subjects to stimulate glycosaminoglycan biosynthesis.

Description

Description Title of the invention: USE OF D-XYLOSE TO STIMULATE GLYCOSAMINOGLYCAN BIOSYNTHESIS

[0001] The invention relates to a formulation comprising at least one compound selected from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or PD-xylosides, for use in stimulating the biosynthesis of glycosaminoglycans, preferably at least one selected from heparan sulfate, dermatan sulfate and chondroitin sulfate, in a human patient, by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of said compound. Preferably, said formulation is for use in the prevention or treatment of infections with viruses using syndecans and / or glypicans as cellular receptors, such as SARS-CoV2 or HIV, or in the prevention or treatment of type 2 diabetes or insulin resistance. The invention also relates to the use of a food supplement composition for oral or nasal administration in healthy subjects to stimulate the biosynthesis of glycosaminoglycans. Previous Art

[0002] The SARS-CoV-2 pandemic currently affecting the world has proven particularly dangerous in the elderly and smokers, with high comorbidity in patients already suffering from chronic diseases, such as type 2 diabetes, cancer, chronic respiratory diseases, obesity and hypertension.

[0003] In parallel, several studies have shown that lung inflammation in general and type 2 diabetes are accompanied by a degradation of glycosaminoglycans (GAGs), particularly heparan sulfate (HS). Several studies have also shown the importance of counteracting HS degradation in lung infections and type 2 diabetes.

[0004] D-xylose is only commercially available for the D-xylose test, in which the molecule is ingested orally to measure intestinal absorption in patients. No other medicinal uses have been reported to date.

[0005] Only two patent families have been devoted to its use in the cosmetic / pharmaceutical field: family WO1999024009A1 of 1999 for its use in cosmetic products and family WO1999048361A1 of 1998 in the treatment of upper respiratory tract pathologies. However, these two patent families do not mention the antiviral properties characterized by the Applicant.

[0006] Several in vitro studies on SARS-CoV-2 have shown the involvement of GAGs, more precisely HS, during viral attachment. In addition, the involvement of HS on viral attachment of more than ten enveloped viruses has been reported in the literature (see Cheudjeu, 2021).

[0007] Regarding this implication, the conclusions from eminent recognized laboratories in the field after in vitro studies on the interaction between SARS-CoV-2 and GAGs, were that "HS promotes infection" (Claussen, TM, 2020), arriving at this consensus. We can notably cite the study carried out by a team of Chinese researchers, who confirmed that there was indeed a correlation between the severity of COVID-19 and D-xylose (Zhong et al, 2021). But they concluded that the suggestion of using D-xylose as a drug against COVID-19 was not supported by their data.

[0008] Thus, the formulation developed by the Applicant goes in the opposite direction to the consensus addressed by the entire scientific community specializing in the field, and nevertheless shows convincing results, as presented in the examples.

[0009] In addition, however, taking D-xylose in absorption tests is generally associated with side effects such as laxative effects in adults, diarrhea, nausea, and vomiting.

[0010] For these reasons, it does not appear feasible for a person skilled in the art to develop such a composition in the indications set out in the invention.

[0011] Furthermore, no dosage to limit these side effects is disclosed in the state of the art.

[0012] Surprisingly, the Applicant was thus able to develop a formulation based on D-xylose or one of its derivatives, making it possible to act on viruses using syndecans and / or glypicans as cellular receptors, by solving the additional technical problem of limiting the side effects associated with D-xylose or its derivatives.

[0013] The invention thus relates more specifically to new uses of D-xy-lose or products derived from or containing D-xylose to stimulate the biosynthesis of glycosaminoglycans having D-xylose as the initiating molecule of their chains (heparan sulfates, dermatan sulfates, chondroitin sulfates) and reducing the side effects associated with its use. The new uses concern the prevention or treatment of infection by viruses using syndecans and / or glypicans as cellular receptors.

[0014] The invention thus describes uses of D-xylose, its derivatives or products containing D-xylose, made possible by the application of an effective dosage making it possible to limit the side effects of its use for a patient or a consumer.

[0015] The common inventive concept within the scope of this invention is the use of at least one compound selected from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or -D-xylosides, to increase the synthesis of glycosaminoglycans, in a healthy human, or a patient in anticipation of or suffering from infections with viruses using syndecans and / or glypicans. as cellular receptors, preferably said virus being selected from HSV-1, HSV-2, HPV-16, HPV-31, HVB, HVC, HIV-1, HTLV-1, SARS-CoV-2, HCMV, DENV-1, and DENV-2, in the treatment of COVID-19, AIDS, type 2 diabetes or insulin resistance. The use of these compounds is carried out in a manner to limit the side effects of its use for a patient or a consumer. Description of the invention

[0016] According to a first aspect, the invention relates to a formulation comprising at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or PD-xylosides, in a physiologically acceptable medium for use in a human patient in the stimulation of the biosynthesis of glycosaminoglycans.

[0017] The mechanism of action of this formulation is to prevent, through the administration of D-xylose or one of its derivatives, the replication of the virus, and thus reduce the symptoms and biological markers associated with the severity of the viral infection, in particular, cough, inflammation, etc. . . . Making the infection benign (asymptomatic). After administration of D-xylose or one of its derivatives, the latter competes with the viral load by binding to the central protein before the viruses, to initiate the production of glycosaminoglycans (heparan sulfate, dermatan sulfate and chondroitin sulfate).

[0018] Preferably, the invention relates to a formulation comprising between 500 mg and 10 g of at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or PD-xylosides, in a physiologically acceptable medium, for use in a human patient in the stimulation of the biosynthesis of glycosaminoglycans.

[0019] Preferably, the invention relates to a formulation comprising at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or PD-xylosides, for use in a human patient in the stimulation of the biosynthesis of glycosaminoglycans by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of said at least one compound in a physiologically acceptable medium.

[0020] Taking small doses helps reduce side effects, including laxative effects, nausea and vomiting.

[0021] Preferably, the biosynthesis of glycosaminoglycans is increased by at least 1%, preferably at least 5%, preferably at least 10%, preferably at least 20%, preferably at least 30%, preferably at least 40%, preferably at least 50%, preferably at least 60%, preferably at least 70%, preferably at least 80%, preferably at least 90%, preferably at least 100%, preferably at least less than 150%, preferably at least 200%, preferably at least 500%, preferably at least 1000%.

[0022] Preferably, said glycosaminoglycan is a sulfated glycosaminoglycan.

[0023] Preferably, said glycosaminoglycans is at least one chosen from heparan sulfate, dermatan sulfate and chondroitin sulfate.

[0024] According to one embodiment, said formulation is for use in the prevention or treatment of infection by viruses using syndecans and / or glypicans as cellular receptors, preferably said virus being selected from HSV-1, HSV-2, HPV-16, HPV-31, HVB, HVC, HIV-1, HTLV-1, SARS-CoV-2, HCMV, DENV-1, and DENV-2.

[0025] Even more preferably, said formulation is for use in the prevention or treatment of SARS-CoV-2 infection.

[0026] Even more preferably, said formulation is for use in the prevention or treatment of HIV-1 infection.

[0027] According to one embodiment, said formulation is for use in the prevention or treatment of COVID-19.

[0028] According to one embodiment, said formulation is for use in the prevention or treatment of type 2 diabetes.

[0029] According to one embodiment, said formulation is for use in the prevention or treatment of insulin resistance.

[0030] According to one embodiment, the number of administrations per day is 1.

[0031] Preferably, the number of administrations per day is between 2 and 10 administrations.

[0032] Even more preferably, the number of administrations per day is 2, or 3, or 4, or 5, or 6, or 7, or 8, or 9, or 10.

[0033] The number of administrations per day can be increased depending on the risk of developing the pathology, or depending on its severity.

[0034] Preferably, said formulation for use according to the invention is in a form suitable for administration by oral, nasal or parenteral route.

[0035] Preferably, the composition is in a form suitable for parenteral administration by subcutaneous, intradermal, intravenous or intramuscular route.

[0036] Preferably, the composition for oral administration is formulated in the form of capsules, gelcaps, tablets, effervescent tablets, powders, granules, oral solutions or suspensions.

[0037] Preferably, the composition for nasal administration is formulated as a solution in aerosol form.

[0038] Preferably, the composition is in a form suitable for oral administration by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or PD-xylosides.

[0039] Preferably, the composition is in a form suitable for oral administration by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of D-xylose.

[0040] Preferably, the composition is in a form suitable for parenteral administration by administering between 1 and 10 doses per day of a composition having a mass of 1 g to 10 g of at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or PD-xylosides.

[0041] Preferably, the composition is in a form suitable for parenteral administration by administering between 1 and 10 doses per day of a composition having a mass of 1 g to 10 g of D-xylose.

[0042] Preferably, the composition is in a form suitable for nasal administration by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or ?-D-xylosides.

[0043] Preferably, the composition is in a form suitable for nasal administration by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of D-xylose.

[0044] Preferably, said at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or PD-xylosides, is d-xylose.

[0045] According to one embodiment, D-xylose is present in the composition in the form of plant extracts comprising D-xylose.

[0046] Alternatively, said plant extracts are selected from extracts of honeysuckle, Japanese honeysuckle, green chiretta, red algae, water bindweed, birch leaf, bark or sap, a species of the genus Artemisia, rice stem.

[0047] In another alternative, the D-xylose is derived from lignocellulose of plant materials. Preferably, the D-xylose is provided in the form of corn stalk hemicellulose hydrolysates.

[0048] According to one embodiment, the composition further comprises at least one other acceptable active pharmaceutical ingredient and / or at least one excipient and / or at least one acceptable pharmaceutical carrier and / or any pharmaceutically acceptable compound.

[0049] Preferably, said at least one other pharmaceutical ingredient is an antiviral active ingredient.

[0050] Preferably, said at least one other pharmaceutical ingredient is an active ingredient allowing the prevention or treatment of COVID-19.

[0051] Preferably, said at least one other pharmaceutical ingredient is an active ingredient allowing the prevention or treatment of type 2 diabetes.

[0052] Preferably, said at least one other pharmaceutical ingredient is an active ingredient allowing the prevention or treatment of insulin resistance.

[0053] Preferably, the composition further comprises an active agent making it possible to accelerate the transfer of said at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or [3-D-xylosides, preferably D-xylose, to the cells, preferably said active agent being insulin.

[0054] According to one embodiment of the invention, the formulation according to the invention also comprises at least one antibiotic.

[0055] According to one embodiment of the invention, the formulation according to the invention comprises a hormone accelerating the transport of D-xylose or its derivatives into the cell, like insulin or also any pharmaceutically acceptable enzymes facilitating the transport of D-xylose into the cell, for example xylose transporters.

[0056] According to one embodiment of the invention, the composition according to the invention also comprises a compound making it possible to reduce at least one side effect of taking D-xylose, preferably a compound making it possible to reduce vomiting or diarrhea.

[0057] According to one embodiment of the invention, the composition according to the invention also comprises Vitamin C.

[0058] According to a second aspect, the invention relates to the use of a food supplement composition for oral or nasal administration in a healthy subject comprising at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or [3-D-xylosides in a physiologically acceptable medium to stimulate the biosynthesis of glycosaminoglycans.

[0059] Preferably, said glycosaminoglycan is a sulfated glycosaminoglycan.

[0060] Preferably, said glycosaminoglycans is at least one chosen from heparan sulfate, dermatan sulfate and chondroitin sulfate.

[0061] Preferably, the invention relates to the use of a food supplement composition for oral or nasal administration in a healthy subject comprising between 500 mg and 10 g of at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or O-D-xylosides, in a physiologically acceptable medium, in the stimulation of the biosynthesis of glycosaminoglycans.

[0062] Preferably, said glycosaminoglycan is a glycosaminoglycan sulfate.

[0063] Preferably, said glycosaminoglycans is at least one chosen from heparan sulfate, dermatan sulfate and chondroitin sulfate.

[0064] Preferably, said at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or PD-xylosides, is d-xylose.

[0065] Preferably, the food supplement composition is in a form suitable for oral administration by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or PD-xylosides.

[0066] Preferably, the food supplement composition is in a form suitable for oral administration by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of D-xylose.

[0067] Preferably, the food supplement composition is in a form suitable for nasal administration by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or ?-D-xylosides.

[0068] Preferably, the food supplement composition is in a form suitable for nasal administration by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of D-xylose.

[0069] Preferably, the biosynthesis of glycosaminoglycans is increased by at least 1%, preferably at least 5%, preferably at least 10%, preferably at least 20%, preferably at least 30%, preferably at least 40%, preferably at least 50%, preferably at least 60%, preferably at least 70%, preferably at least 80%, preferably at least 90%, preferably at least 100%, preferably at least 150%, preferably at least 200%, preferably at least 500%, preferably at least 1000%.

[0070] According to one embodiment, the dietary supplement is formulated for oral intake in the form of capsules, gel caps, tablets, effervescent tablets, powders, granules, oral solutions or suspensions.

[0071] Preferably, the food supplement for nasal administration is formulated as a solution in aerosol form.

[0072] According to one embodiment, the food supplement is formulated for oral intake in a food product, a beverage, a food additive or a dairy product, containing said food supplement.

[0073] According to one embodiment, the number of administrations per day is 1.

[0074] Preferably, the number of administrations per day is between 2 and 10 administrations.

[0075] Even more preferably, the number of administrations per day is 2, or 3, or 4, or 5, or 6, or 7, or 8, or 9, or 10.

[0076] The number of administrations per day can be increased according to the consumer's wishes.

[0077] Preferably, D-xylose is present in the food supplement composition in the form of plant extracts comprising D-xylose.

[0078] Alternatively, said plant extracts are selected from extracts of honeysuckle, Japanese honeysuckle, green chiretta, red algae, water bindweed, birch leaf, bark or sap, a species of the genus Artemisia, rice stem.

[0079] In another alternative, the D-xylose is derived from lignocellulose of plant materials. Preferably, the D-xylose is provided in the form of corn stalk hemicellulose hydrolysates.

[0080] According to one embodiment of the invention, the food supplement composition according to the invention also comprises Vitamin C.

[0081] According to one embodiment of the invention, the food supplement composition according to the invention also comprises galactose.

[0082] According to a third aspect, the invention relates to a therapeutic method for stimulating the biosynthesis of glycosaminoglycans comprising administering to a human patient between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of at least one compound selected from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or ?-D-xylosides in a physiologically acceptable medium.

[0083] Preferably, said glycosaminoglycane is a sulfated glycosaminoglycane.

[0084] Preferably in this therapeutic method, said glycosaminoglycans is at least one chosen from heparan sulfate, dermatan sulfate and chondroitin sulfate.

[0085] Preferably, said at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or PD-xylosides, is d-xylose.

[0086] Preferably, the biosynthesis of glycosaminoglycans is increased by at least 1%, preferably at least 5%, preferably at least 10%, preferably at least 20%, preferably at least 30%, preferably at least 40%, preferably at least 50%, preferably at least 60%, preferably at least 70%, preferably at least 80%, preferably at least 90%, preferably at least 100%, preferably of at least 150%, preferably at least 200%, preferably at least 500%, preferably at least 1000%.

[0087] According to one embodiment of this therapeutic method, said formulation is for use in the prevention or treatment of infection by viruses using syndecans and / or glypicans as cellular receptors, preferably said virus being chosen from HSV-1, HSV-2, HPV-16, HPV-31, HVB, HVC, HIV-1, HTLV-1, SARS-CoV-2, HCMV, DENV-1, and DENV-2.

[0088] Even more preferably in this therapeutic method, said formulation is for use in the prevention or treatment of SARS-CoV-2 infection.

[0089] Even more preferably in this therapeutic method, said formulation is for use in the prevention or treatment of HIV-1 infection.

[0090] According to one embodiment, this therapeutic method is in the prevention or treatment of COVID-19.

[0091] According to one embodiment, this therapeutic method is in the prevention or treatment of type 2 diabetes.

[0092] According to one embodiment, this therapeutic method is in the prevention or treatment of insulin resistance.

[0093] Preferably, the number of administrations per day is between 2 and 10 administrations.

[0094] Even more preferably, the number of administrations per day is 2, or 3, or 4, or 5, or 6, or 7, or 8, or 9, or 10.

[0095] The number of administrations per day can be increased depending on the risk of developing the pathology, or depending on its severity.

[0096] Preferably, D-xylose is present in the composition in the form of plant extracts comprising D-xylose.

[0097] Preferably in this therapeutic method, said composition according to the invention is in a form suitable for administration by oral, nasal or parenteral route.

[0098] Preferably in this therapeutic method, the composition is in a form suitable for parenteral administration by subcutaneous, intradermal, intravenous or intramuscular route.

[0099] Preferably in this therapeutic method, the composition is in a form suitable for oral administration by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or ?-D-xylosides.

[0100] Preferably in this therapeutic method, the composition is in a form suitable for oral administration by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of D-xylose.

[0101] Preferably in this therapeutic method, the composition is in a form suitable for parenteral administration by administering between 1 and 10 doses per day of a composition having a mass of 1 g to 10 g of at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or PD-xylosides.

[0102] Preferably in this therapeutic method, the composition is in a form suitable for parenteral administration by administering between 1 and 10 doses per day of a composition having a mass of 1 g to 10 g of D-xylose.

[0103] Preferably in this therapeutic method, the composition is in a form suitable for nasal administration by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or PD-xylosides.

[0104] Preferably, the composition is in a form suitable for nasal administration by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of D-xylose.

[0105] Alternatively, said plant extracts are selected from extracts of honeysuckle, Japanese honeysuckle, green chiretta, red algae, water bindweed, birch leaf, bark or sap, a species of the genus Artemisia, rice stem.

[0106] Alternatively, D-xylose is derived from lignocellulose of plant materials. Preferably, D-xylose is provided in the form of corn stalk hemicellulose hydrolysates.

[0107] Preferably, the composition further comprises an active agent making it possible to accelerate the transfer of said at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or ?-D-xylosides, preferably D-xylose, to the cells, preferably said active agent being insulin.

[0108] According to one embodiment of the invention, the composition according to the invention also comprises at least one antibiotic.

[0109] According to one embodiment of the invention, the formulation according to the invention comprises a hormone accelerating the transport of D-xylose or its derivatives into the cell, like insulin or also any pharmaceutically acceptable enzymes facilitating the transport of D-xylose into the cell, for example xylose transporters.

[0110] According to one embodiment of the invention, the composition according to the invention also comprises a compound making it possible to reduce at least one effect secondary to taking D-xylose, preferably a compound to reduce vomiting or diarrhea.

[0111] According to one embodiment of the invention, the composition according to the invention also comprises Vitamin C.

[0112] According to a fourth aspect, the invention relates to the use of at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or PD-xylosides, in a physiologically acceptable medium for the preparation of a medicament used for the stimulation of the biosynthesis of glycosaminoglycans in a human patient.

[0113] Preferably, the invention relates to the use of at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or PD-xylosides, for the preparation of a medicament used for the stimulation of the biosynthesis of glycosaminoglycans in a human patient, and in which the amount of administration of said at least one compound is between 500 mg and 10 g in a physiologically acceptable medium per administration, the number of administrations per day being between 1 and 10 administrations.

[0114] Preferably, said glycosaminoglycane is a sulfated glycosaminoglycane.

[0115] Preferably, said glycosaminoglycans is at least one chosen from heparan sulfate, dermatan sulfate and chondroitin sulfate.

[0116] Preferably, said at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or PD-xylosides, is d-xylose.

[0117] According to one embodiment, said use relates to the preparation of a medicament in the prevention or treatment of infection with viruses using syndecans and / or glypicans as cellular receptors, preferably said virus being chosen from HSV-1, HSV-2, HPV-16, HPV-31, HVB, HVC, HIV-1, HTLV-1, SARS-CoV-2, HCMV, DENV-1, and DENV-2.

[0118] According to one embodiment, said use relates to the preparation of a medicament in the prevention or treatment of SARS-CoV-2 infection.

[0119] According to one embodiment, said use relates to the preparation of a medicament in the prevention or treatment of HIV-1 infection.

[0120] According to one embodiment, said use relates to the preparation of a medicament in the prevention or treatment of COVID-19.

[0121] According to one embodiment, said use relates to the preparation of a medicament in the prevention or treatment of type 2 diabetes.

[0122] According to one embodiment, said use relates to the preparation of a medicament in the prevention or treatment of insulin resistance.

[0123] Preferably, the biosynthesis of glycosaminoglycans is increased by at least 1%, preferably by at least 5%, preferably by at least 10%, preferably at least 20%, preferably at least 30%, preferably at least 40%, preferably at least 50%, preferably at least 60%, preferably at least 70%, preferably at least 80%, preferably at least 90%, preferably at least 100%, preferably at least 150%, preferably at least 200%, preferably at least 500%, preferably at least 1000%.

[0124] Preferably, the number of administrations per day is between 2 and 10 administrations.

[0125] Even more preferably, the number of administrations per day is 2, or 3, or 4, or 5, or 6, or 7, or 8, or 9, or 10.

[0126] The number of administrations per day can be increased depending on the risk of developing the pathology, or depending on its severity.

[0127] According to one embodiment, said use relates to the preparation of a medicament in a form suitable for oral, nasal or parenteral administration.

[0128] Preferably, said use relates to the preparation of a medicament in a form suitable for parenteral administration by subcutaneous, intradermal, intravenous or intramuscular route.

[0129] Preferably, said use relates to the preparation of a medicament for oral administration in the form of capsules, gelcaps, tablets, effervescent tablets, powders, granules, oral solutions or suspensions.

[0130] Preferably, the composition for nasal administration is formulated as a solution in aerosol form.

[0131] Preferably, said use relates to the preparation of a medicament for oral administration, the administration of which is carried out by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or ?-D-xylosides.

[0132] Preferably, said use relates to the preparation of a medicament for oral administration, the administration of which is carried out by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of D-xylose.

[0133] Preferably, said use relates to the preparation of a medicament for parenteral administration, the administration of which is carried out by administering between 1 and 10 doses per day of a composition having a mass of 1 g to 10 g of at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or ?-D-xylosides,

[0134] Preferably, said use relates to the preparation of a medicament for parenteral administration, the administration of which is carried out by administering between 1 and 10 doses per day of a composition having a mass of 1 g to 10 g of D-xylose.

[0135] Preferably, said use relates to the preparation of a medicament for nasal administration, the administration of which is carried out by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or ?-D-xylosides.

[0136] Preferably, said use relates to the preparation of a medicament for nasal administration, the administration of which is carried out by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of D-xylose.

[0137] According to one embodiment, said medicament prepared in the form of a composition further comprises at least one other acceptable active pharmaceutical ingredient and / or at least one excipient and / or at least one acceptable pharmaceutical carrier and / or any pharmaceutically acceptable compound.

[0138] Preferably, said at least one other pharmaceutical ingredient is an antiviral active ingredient.

[0139] Preferably, said at least one other pharmaceutical ingredient is an active ingredient allowing the prevention or treatment of COVID-19.

[0140] Preferably, said at least one other pharmaceutical ingredient is an active ingredient allowing the prevention or treatment of type 2 diabetes.

[0141] Preferably, said at least one other pharmaceutical ingredient is an active ingredient allowing the prevention or treatment of insulin resistance.

[0142] Preferably, D-xylose is present in the composition in the form of plant extracts comprising D-xylose.

[0143] Alternatively, said plant extracts are selected from extracts of honeysuckle, Japanese honeysuckle, green chiretta, red algae, water bindweed, birch leaf, bark or sap, a species of the genus Artemisia, rice stem.

[0144] Alternatively, D-xylose is derived from lignocellulose of plant materials. Preferably, D-xylose is provided in the form of corn stalk hemicellulose hydrolysates.

[0145] According to one embodiment of the invention, the composition according to the invention also comprises the addition of antibiotics.

[0146] According to one embodiment of the invention, the composition comprises a hormone accelerating the transport of D-xylose or its derivatives into the cell, like insulin or also any pharmaceutically acceptable enzymes acceptable facilitating the transport of D-xylose into the cell, for example xylose transporters.

[0147] According to one embodiment of the invention, the composition according to the invention also comprises a compound making it possible to reduce at least one side effect of taking D-xylose, preferably a compound making it possible to reduce vomiting or diarrhea.

[0148] According to one embodiment of the invention, the composition according to the invention also comprises the addition of Vitamin C.

[0149] Preferably, the composition further comprises an active ingredient making it possible to accelerate the transfer of said at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or [3-D-xylosides, preferably D-xylose, to the cells, preferably said active ingredient being insulin. Figures

[0150] [Fig 1] presents the results of IC50 concentrations for the two modes of administration: (1) Co-administration of D-xylose and SARS-CoV-2, IC50=95.52 mM (2) Pre-incubation of D-xylose 6h before infection by SARS-CoV-2 IC50=26.22 mM.

[0151] [Fig 2] shows the results for remdesivir used as a positive control in antiviral tests.

[0152] [Fig 3] presents the results of the percentage inhibition of HIV-1 NL4-3 as a function of the concentration of D-xylose alone with calculation of the median inhibitory concentration (IC50) and the median cytotoxic concentration (TC50).

[0153] [Fig 4] presents the results of the percentage inhibition of HIV-1 NL4-3 as a function of the concentration of D-xylose + Insulin with calculation of the median inhibitory concentration (IC50) and the median cytotoxic concentration (TC50).

[0154] [Fig 5] presents the results of the percentage inhibition of HIV-1 NL4-3 as a function of the concentration of AZT (used as control) with calculation of the median inhibitory concentration (IC50).

[0155] [Fig 6] presents the results of the immunofluorescence assay of 96-well plates in the same arrangement as shown in [Table 11] Definitions

[0156] D-xylose and mechanism of action

[0157] D-xylose is a pentose, present in its bioactive form in the human body, which is also found in nature, in wood bark and in certain plants. This molecule is approved by the FDA in particular in the D-xylose test.

[0158] In the body, D-xylose is used at the level of sulfated glycosaminoglycans (GAGs), which are long linear chains made up of units disaccharide repetitive molecules present in the extracellular matrix (ECM), on the surface of endothelial cells, epithelial cells, fibroblasts, macrophages and hepatocytes (RR Vivès, Heparan sulfate: structure, functions, regulation, April 11, 2020). There are five types of sulfated GAGs: heparan sulfates (HS), heparins (Hep), chondroitin sulfates (CS), dermatan sulfates (DS) and keratan sulfates (KS). Sulfated GAGs are linked to a central protein (syndecans, glypicans, decorins, etc.) by a covalent bond, thus forming proteoglycans (PG).

[0159] The major core proteins of PGs in the extracellular matrix are perlecan (with HS-like chains), agrin (heparan sulfate proteoglycan [HSPG]), aggrecan (chondroitin sulfate proteoglycan [CSPG] / dermatan sulfate proteoglycan [DSPG]), and decorin.

[0160] The core membrane proteins of PGs are classified into two categories: syndecans and glypicans. Syndecans are transmembrane proteins, unlike glypicans, which are entirely extracellular proteins (attached to the cell membrane by a glycosyl-phosphatidyl inositol (GPI) anchor). Membrane PGs are HSPGs, CSPGs, and DSPGs, but are primarily HSPGs. HSPGs are found on the surface of several cell types, such as endothelial cells, epithelial cells, fibroblasts, and neuronal tissues (RR Vivès, Heparan sulfate: structure, functions, regulation, 11 April 2020 & S. Sarrazin, WC Lamanna, JD Esko, Heparan sulfate proteoglycans, Cold Spring Harb. Perspect. Biol. 3 (2011))

[0161] With the exception of KS, all other sulfated GAGs are linked to the core proteins by an identical linker region, consisting of the trisaccharide sequence xylose-galactose-galactose. Biosynthesis of the HS chain (and also the CS, DS, and Hep chains) begins with the attachment of a D-xylose molecule to specific serine and occasionally threonine residues located on the core protein (syndecan, glypican, decorin, etc.). This initiation of HS / CS / DS biosynthesis is carried out either by the enzymes xylosyltransferase 1 and xylosyltransferase 2 (RR Vivès, Heparan sulfate: structure, functions, regulation, 11 April 2020 & S. Sarrazin, WC Lamanna, JD Esko, Heparan sulfate proteoglycans, Cold Spring Harb. Perspect. Biol. 3 (2011)) or directly by the free molecules (unlike UDP-Xyl) of D-xylose (Cheudjeu, 2022).

[0162] After the D-xylose molecule is placed, the bonding of two galactose molecules follows. The chain thus formed constitutes the linker region. This is then completed by a repetition of the same basic unit specific to each type of sulfated GAGs (HS / CS / DS / Hep).

[0163] The basic unit of HS is a D-glucuronic acid linked to N-acetylglucosamine. The basic unit of CS is an N-acetylgalactosamine linked to a D-glucuronic acid. Hyaluronic acid is the only non-sulfated GAG; this type of glycosaminoglycan is not linked to a central protein. The disaccharides that compose it are themselves made up of D-glucuronic acid and DN-acetylglucosamine (RR Vivès, Heparan sulfate: structure, functions, regulation, April 11, 2020).

[0164] HSPGs are rapidly recycled and renewed at the cell surface; their half-life is approximately 2-3 h (M. Egeberg, R. Kjeken, SO Kolset, T. Berg, K. Prydz, Internalization and stepwise degradation of heparan sulfate proteoglycans in rat hepatocytes, Biochim. Biophys. Acta 1541 (2001) 135—149). The degradation of HSPGs at the cell surface depends on the action of several extracellular and lysosomal enzymes, and in particular on heparanase which cleaves HS chains (RR Vivès, Heparan sulfate: structure, functions, regulation, 11 April 2020 & S. Sarrazin, WC Lamanna, JD Esko, Heparan sulfate proteoglycans, Cold Spring Harb. Perspect. Biol. 3 (2011)).

[0165] D-xylose is therefore the element linking these GAGs to the central proteins and has only one position. This role of D-xylose in the biosynthesis of HS / CS / DS / Hep indicates that the amount of D-xylose in the organism directly influences the amount of these GAGs present in this organism.

[0166] According to the invention, the term “D-xylose derivatives” means D-xylose esters, oligosaccharides comprising D-xylose, and / or PD-xylosides.

[0167] Type 2 diabetes, insulin resistance and mechanism of action

[0168] Type 2 diabetes (T2DM) is a metabolic disease that is often a symptom of certain viral infections, such as SARS-CoV-2, HIV-1, HVC, etc. (Cheudjeu 2021).

[0169] Several explanations for the occurrence of T2DM during viral infections have been given, such as: inflammation (cytokine storm) due to infections that cause damage to the P cells of the pancreas, leading to insulin homeostasis. However, if this were the only explanation, insulin supplementation would definitely be sufficient, but this is not always the case. This inability of insulin to reduce blood glucose levels is called insulin resistance and is widely reported in viral infections that use core proteins as receptors on the cell surface: SARS-CoV-2 (Govender N et al, 2021: PMID: 33849817), HVC (Desai DV et al, 2010: https: / / doi.Org / 10.1096 / fasebj.24.l_supplement.659.4), HIV-1 (Pedro MN et al., 2018: PMID: 30233499) etc. Insulin resistance is also often observed in some obese patients with T2DM (Kahn, BB, and Flier, J. S, 2000).The present invention describes for the first time how insulin resistance is linked to the ability of D-xylose to stimulate GAGs. Most of the sugars constituting the chains of GAGS are metabolites of glucose (Cheudjeu 2022).

[0170] When there is a deficiency of D-xylose in the body (or in the case of certain viral infections), one of the first consequences is an increase in blood sugar. This is because certain serine locations that should be occupied by d-xylose on core proteins (syndecans, glypicans, etc.) to initiate the production of GAGs (HS / Hep / CS / DS) are free due to a lack of d-xylose (or are occupied due to glycosylation of viruses in the case of certain viral infections), thus preventing the initiation of GAG biosynthesis that should take place at these locations. The sugars that should be used in the production of these GAGs (D-glucuronic acid, galactose, N-acetylglucosamine, N-acetylgalactosamine) are found in the bloodstream (Cheudjeu 2020; Cheudjeu 2021; Cheudjeu 2022).

[0171] A 2011 study showed that sulfated GAGs were altered in type 2 diabetes, with HS and chondroitin sulfate and dermatan sulfate (CS / DS) levels decreased by approximately 14% (D. Joladarashi, PV Salimath, ND Chilkunda, Diabetes results in structural alteration of chondroitin sulfate / dermatan sulfate in the rat kidney: effects on the binding to extracellular matrix components, Glycobiology 21 (2011) 960-972).

[0172] Several other studies have reported HS degradation during diabetes (LM Hiebert, J. Han, AK Mandai, Glycosaminoglycans, hyperglycemia, and dis- ease, Antioxid. Redox Signal. 21 (2014) 1032-1043 & LM Hiebert, Proteoglycans and diabetes, Curr. Pharm. Des. 23 (2017) 1500-1509).

[0173] Also, given the half-life of GAGs on the cell surface, which is 2-3 hours, this degradation contributes to the origin of the problems of accumulation of HS / CS / DS chains, sources of certain cardiovascular diseases. Other studies have already shown that N-acetylglucosamine levels increase in type 2 diabetes and that N-acetylglucosamine can be used as a biomarker for type 2 diabetes (Z. Wang, K. Park, F. Comer, LC Hsieh-Wilson, CD Saudek, GW Hart, Site-specific GlcNAcylation of human erythrocyte proteins: potential biomarker(s) for diabetes, Diabetes 58 (2009) 309-317, & L. Wells, K. Vosseller, GW Hart, A role for N-acetylglucosamine as a nutrient sensor and mediator of insulin resistance, Cell. Mol. Life Sci. 60 (2003) 222-228.

[0174] Another consequence is the increase in other types of GAGs, such as hyaluronic acid (HA). Indeed, hyaluronic acid not bound to a central protein can act to bind excess sugar not used for HS / CS / Hep / DS synthesis. A study showed that hyaluronic acid levels for type 2 diabetes were higher and that these levels could be used as a biomarker (S. Mine, Y. Okada, C. Kawahara, T. Tabata, Y. Tanaka, Serum hyaluronan concentration as a marker of angiopathy in patients with diabetes mellitus, Endocr. J. 53 (2006) 761-766). This HA accumulation has already been reported in the lung in adult respiratory distress syndrome, where it is approximately six times higher than in control patients (R. HaÂàllgren, T. Samuelsson, TC Laurent, J. Modig, Accumulation of hyaluronan (hyaluronic acid) in the lung in adult respiratory distress syndrome, Am. Rev. Respir. Dis. 139 (1989) 682-687).

[0175] A 2010 study also showed that there is an approximately 66% increase in D-glucuronic acid in the blood of diabetic people compared to non-diabetic people. Another consequence is a decrease in the activity of xylosyltransferase enzymes (XYLT1, XYLT2) due to the decrease in xylose attachment positions (caused by the lack of D-xylose or by glycosylation of viruses at these positions). Indeed, Getting et al, in a study of 100 diabetic patients (Type 1 and Type 2) and 100 blood donations from non-diabetic people, demonstrated that the serum xylosyltransferase of diabetic patients was significantly lower than that of non-diabetic patients. These researchers concluded that serum xylosyltransferase activity could be used as a biomarker of reduced GAG biosynthesis in diabetics (C. Getting, J. Kuhn, K.Kleesiek, Serum xylosyltransferase activity in diabetic patients as a possible marker of reduced proteoglycan biosynthesis, Diabetes Care 31 (2008) 2018-2019).

[0176] Furthermore, a study in rats showed that such a change in the activity of the enzyme xylosyltransferase 2 induced lung injury (R. Koslowski, U. Pfeil, H. Fehrenbach, M. Kasper, E. Skutelsky, KW Wenzel, Changes in xylosyltransferase activity and in proteoglycan deposition in bleomycin-induced lung injury in rats, Eur. Respir. J. 18 (2001) 347-356).

[0177] This once again confirms the anti-inflammatory properties of D-xylose and provides an explanation of the process leading to inflammation in diabetes (S. Tsalamandris, AS Antonopoulos, E. Oikonomou, GA Papamikroulis, G. Vogiatzi, S. Papaioannou, S. Deftereos, D. Tousoulis, The role of inflammation in diabetes: current concepts and future perspectives, Eur. Cardiol. 14 (2019) 50-59).

[0178] The antiviral properties of D-xylose confirmed by the tests carried out within the framework of the present invention, corroborate the binding sites of the SARS-CoV-2 virus using core proteins.

[0179] Based on previous studies, it was explained why the antiglycemic properties of D-xylose were not related to insulin, but that the opposite was possible. Since insulin increases the rate of penetration of D-xylose into cells by two to five times, and at equilibrium, in the presence of insulin, xylose is present at 80% instead of 50% to 55% in the cytosol, and 20% in the plasma (Kipnis, DM, 1957).

[0180] The inability of insulin to lower blood sugar is called insulin resistance. insulin (or insulin resistance) and is widely encountered during viral infections of viruses that use basic proteoglycan (PG) proteins as receptors on the cell surface, such as SARS-CoV-2, and in diabetes in general.

[0181] The notion of insulin resistance thus reflects an underestimation of the storage capacities (weight) of GAGs containing D-xylose compared to the storage capacities of hepatic glycogen.

[0182] When the liver is full of glycogen and the body does not have enough D-xylose molecules to stimulate HS / CS / DS biosynthesis, any insulin supplementation will no longer lower blood glucose levels, resulting in a situation known as insulin resistance. This is because in this condition, GAGs do not act as "reservoirs" for glucose metabolites, and since the other reservoir (the liver, where glycogen is stored) is full, insulin supplementation will have no effect on blood glucose levels.

[0183] Thus, since the activity of xylosyltransferase enzymes is reduced during T2DM, the increase in free D-xylose molecules helps maintain GAG biosynthesis during insulin resistance and thus reduce blood glucose. This is especially true since glucose is a competitive inhibitor of D-xylose entry into the cell (where GAGs are biosynthesized in the Golgi apparatus).

[0184] Glycated hemoglobin or glycosylated hemoglobin (HbAlc) is one of the biomarkers of hyperglycemia in diabetes. It is used for the assessment, long-term control of diabetes, and diagnosis of diabetes. The action of D-xylose or xylitol, its direct metabolite, on the level of glycated hemoglobin (HbAlc) has already been the subject of several previous studies, which have shown that taking D-xylose or Xylitol, its direct metabolite, has little or no effect on the level of glycated hemoglobin in a healthy person (Bae YJ et al, PMID: 22259678; Bordier Vet al, PMID: 34836205).

[0185]

[0186] Viruses using syndecans and / or glypicans as cellular receptors, (HSV-L HSV-2, HPV-16, HPV-3 L HVB, HVG HIV-L HTLV-L SARS-CoV-2, HCMV DENV-L and DENV-2) and mechanism of action

[0187] Viruses interact with proteoglycans (PGs) on the surface of host cells to attach to them (A. Jinno, et al. Methods Mol. Biol. 1229 (2015) 567-585; V. Cagno, et al. Viruses 11 (2019) 596). Several studies have focused on these interactions, particularly on the surface molecules glycosaminoglycans (GAGs) and heparan sulfate (HS) (A. Jinno, et al. Methods Mol. Biol. 1229 (2015) 567-585; V. Cagno, et al. Viruses 11 (2019) 596). However, even when viruses interact with HS, the core proteins of most viruses are the viral receptors to which HS binds covalently (Table 1). This indicates that the observed interaction between HS and some viruses are due to their binding to the same elements: the core proteins (Table 1). Many of these viruses use other molecules as co-receptors in addition to the core proteins, as is the case for SARS-CoV-2, which uses syndecans and angiotensin-converting enzyme 2 (ACE 2) as coreceptors (M. Bermejo-Jambrina, J. Eder, et al., bioRxiv (2020)). HIV-1 also uses syndecans as well as CD4 as receptors (AC Saphire, et al., J. Virol. 75 (2001) 9187-9200). Hepatitis C virus (HCV) has several other coreceptors in addition to syndecans (Q.Shi, et al., J. Virol. 87 (2013) 6866-6875).

[0188] The different possibilities of post-translational modifications (PTMs) of cell surface proteins may explain the ability of viruses to use different receptors (J. Hu, et al. Front. Microbiol. 11 (2020), 517461), especially considering the diversity of glycoproteins present on viral envelopes and the ability of viruses to interact with host target proteins and use these proteins to enter the cell (S. Maya & A. Ploss, Hepatology 71 (2020) 380-382; K. Azarm, Icahn School of Medicine at Mount Sinai, New York, NY, 2020.).

[0189] Bermejo-Jambrina et al. (M. Bermejo-Jambrina, J. Eder, et al., bioRxiv (2020)) recently showed in an in vitro study that SARS-CoV-2 first binds to heparan sulfate proteoglycans (HSPGs) before interacting with ACE2. However, a recent work by Clausen et al. (TM Clausen et al. Cell 183 (2020) 1043-1057) showed that the SARS-CoV-2 spike protein could simultaneously bind to the cell surface via HSPGs and the ACE2 protein receptor. The consensus of these cited studies is that HSPGs are necessary for SARS-CoV-2 attachment to the cell surface. Zhang et al. (Q. Zhang, et al., Cell Discov 6 (2020), 80) also came to the same conclusion after an in vitro study.

[0190] This is also the case for HIV-1. Saphire et al. (AC Saphire, et al., J. Virol. 75 (2001) 9187-9200) showed in an in vitro study that CD4 alone is insufficient for HIV-1 infection of macrophages and that attachment to HSPGs is also necessary. [Table 1] Viruses, core proteins and their associations with type 2 diabetes. 0191] Definitions

[0192] According to the invention, the term “Formulation” indicates the final presentation of a composition, as it will be given to the patient.

[0193] According to the invention, the term "stimulation of glycosaminoglycan biosynthesis" indicates that the biosynthesis of glycosaminoglycans is greater than it was before the administration of the formulation or food supplement according to the invention.

[0194] By "glycosaminoglycan" is meant the family of molecules resulting from the linear polycondensation of osamine units and uronic acids (sometimes replaced by galactose), present mainly in the extracellular matrix of connective tissues. Glycosaminoglycans (GAGs) can be sulfated or not. There is only one class of non-sulfated GAG, hyaluronic acid, but 4 classes of sulfated GAGs: chondroitin sulfate, dermatan sulfate, keratan sulfate and heparan sulfate / heparin. Hyaluronic acid is free in tissues, whereas sulfated GAGs are attached to carrier proteins ("core proteins") to form large complexes called proteoglycans. GAGs play an important role in tissue hydration and cell signaling.

[0195] "Heparan sulfate" refers to these complex polysaccharides belonging to the family of glycosaminoglycans (GAGs), present in abundance on the cell surface and in interstitial matrices. It is a high molecular weight sulfated polysaccharide formed by a chain of α (1-4) bonds of uronic acids and glucosamines, where D-glucuronic or L-iduronic acid and N-acetylated or N-sulfated glucosamine alternate. This mucopolysaccharide or glycosaminoglycan carries sulfuric residues on the second carbon of iduronic acids and on the sixth carbon of glucosamine, as well as on the amine function in 2. This glycan, synthesized in fibroblasts, is a constituent of connective tissue (dermis, aorta), forming part of the basement membrane, in which it is linked to collagen and laminin.

[0196] By "dermatan sulfate" is meant this sulfated glycosaminoglycan whose polysaccharide structure does not contain glucuronic acid, but L-iduronic acid which alternates with the molecules of N-acetylgalactosamine, forming dihexosidic links (L-iduronosido-3-PN-acetylgalactosamine) attached to the C4 of the iduronic acid of the next link. Sulfuric radicals are attached to the C4 of the galactosamines. Like most glycosaminoglycans, dermatan sulfates are part of the glycoprotein structures, the proteoglycans, of connective tissues, in particular of the dermis, cartilage and cornea. Depending on the tissue, the length of the chains varies from 10 to 50 links; they are linked to a polypeptide in the same way as the carbohydrate chains of glycoproteins.These dermatan sulfates are either located on the external surface of cell membranes or associated in the form of macromolecular complexes in the extracellular ground substance.

[0197] By "chondroitin sulfate" is meant this sulfated glycosaminoglycan whose polysaccharide structure contains glucuronic acids, which alternate with molecules of N-acetylgalactosamine, forming dihexosidic links (O-glucuronosido-3-PN-acetylgalactosamine) attached to the C4 of the glucuronic acid of the next link. Sulfuric radicals are attached to the C4 or C6 of the galactosamines. Like most glycosaminoglycans, chondroitin sulfates are part of the glycoprotein structures, the proteoglycans, of connective tissues, in particular of the dermis, cartilage and cornea. Depending on the tissue, the length of the chains varies from 10 to 50 links; they are linked to a polypeptide in the same way as the carbohydrate chains of glycoproteins. These chondroitin sulfates are located either on the external surface of cell membranes or associated in the form of macromolecular complexes in the extracellular ground substance.

[0198] By "esters of D-xylose" are meant esters in the sense of the term well known to those skilled in the art, of d-xylose. Preferably, said ester is the acid D-gal acturoni que .

[0199] Also advantageously included within the scope of the invention are fatty acid esters comprising from 16 to 24 carbon atoms, in particular natural fatty acid esters.

[0200] Among these fatty acid esters, the esters of palmitic, stearic, oleic, linoleic, linolenic, arachidonic, erucic and lignoceric acids will be advantageously chosen.

[0201] By "oligosaccharides containing D-xylose" are meant holosides consisting of a small number of oses (2, 3, 4, 5, 6), including d-xylose. By oligosaccharide in the sense of the invention is meant sugar chains containing from 2 to 6 sugars.

[0202] Preferably, according to the present invention, the xylose-containing oligosaccharide among the oligosaccharides as defined above comprises at least one xylose and from 1 to 6 sugars.

[0203] Such oligosaccharides are advantageously chosen from xylobiose, xylobiose hexaacetate, methyl-P-xylobioside, xylotriose, xylotetraose, xylopentaose and xylohexaose.

[0204] Even more preferably, xylobiose oligosaccharide is used, which is composed of two xylose molecules linked by a 1-4 bond as well as xylobiose acetates such as xylobiose hexaacetate.

[0205] By "human patient" is meant a human individual suffering from a pathology or at risk of suffering from a pathology, and whose prevention or treatment is necessary.

[0206] By "healthy subject" is meant a human individual not suffering from a pathology, and therefore not requiring treatment.

[0207] By "administering" is meant the action of the patient or healthy subject taking the formulation or food supplement according to the invention.

[0208] By "number of administrations" is meant the number of times administration is carried out, for example per day, to the patient or healthy subject of the formulation or food supplement according to the invention.

[0209] “Acceptable active pharmaceutical ingredient” means an active drug substance known to have a particular therapeutic effect.

[0210] According to the invention, the term “antiviral active ingredient” means a compound known for its virus-eliminating properties, in particular the viruses mentioned in the context of the invention.

[0211] According to the invention, the term “active agent for the prevention or treatment of type 2 diabetes” means a compound known for its properties for preventing or treating type 2 diabetes.

[0212] According to the invention, the term "active agent enabling the prevention or treatment of insulin resistance" means a compound known for its properties of preventing or treating insulin resistance.

[0213] According to the invention, the term "antibiotic" means a compound which acts either by preventing the development of bacteria (bacteriostatic antibiotics) or by killing them (bactericidal antibiotics).

[0214] By “dose” is meant a unit of intake of the formulation or food supplement according to the invention.

[0215] By "day" is meant the 24-hour unit of time starting at 0000 and ending at 23:59.

[0216] Proteoglycans are glycoproteins composed of a central protein, also called a "carrier protein" or "core protein", to which are attached one or more chains of sulfated glycosaminoglycans, generally linked by an oside bond to the alcohol functions of certain serine or occasionally threonine amino acids of the protein. There are currently more than 40 different carrier proteins and 5 major classes of proteoglycans: 1- Small Leucin-Rich Proteoglycans (SLRP), mainly used for the stabilization of collagen fibers and the regulation of cellular activities; the main ones are decorin, lumican and fibromodulin; 2-large extracellular proteoglycans, some of which are capable of aggregating with hyaluronic acid to form very large complexes allowing tissue hydration and shock absorption; the main ones are versican and aggrecan; 3 - proteoglycans associated with basal membranes, which participate in tissue cohesion and the filtration of molecules; the main ones are perlecan and agrin; 4- cell membrane proteoglycans, which play an important role in cell signaling and promote the action of cytokines and growth factors. This class consists of syndecans, whose carrier protein is transmembrane, and glypicans, for which the carrier protein is anchored to the cell surface; 5- a small proteoglycan called serglycin present in the intracellular granules of mast cells and macrophages, which carries chains of heparin, a major anticoagulant.

[0217] Syndecan refers to proteoglycan, an important component of the membranes of certain cells, such as the sinusoidal membranes of hepatocytes, muscle cells, and macrophages. Syndecans are a family of transmembrane molecules with a glycan-like extracellular domain and an intracellular end in the cytoplasm. Syndecans are involved in the internalization of atherogenic lipoproteins.

[0218] By "glypican" is meant the proteoglycan for which the carrier protein is anchored to the cell surface.

[0219] “HSV-1” is the Herpes simplex virus type 1.

[0220] “HSV-2” is Herpes simplex virus type 2.

[0221] “HPV-16” is human papillomavirus 16.

[0222] “HPV-31” is human papillomavirus 31.

[0223] “HVB” is the hepatitis B virus.

[0224] “HCV” is the hepatitis C virus.

[0225] HIV-1 is the human immunodeficiency virus.

[0226] “HTLV-1” is the Human T-lymphotropic Virus 1 virus.

[0227] “SARS-CoV-2” is the virus associated with COVID-19.

[0228] “HCMV” is the human cytomegalovirus

[0229] “DENV-1” is the dengue virus in its first serotype.

[0230] “DENV-2” is the dengue virus in its second serotype.

[0231] By "oral administration" or gastrointestinal route or per os (Latin expression meaning "by mouth") is meant the route of administration for enteral destination, which consists of swallowing them by mouth.

[0232] According to the invention, "nasal administration" means the route of administration of drugs to the nose and nasal cavities.

[0233] By "parenteral administration" is meant the route of administration by means of an injection, through a skin break.

[0234] By "subcutaneous route" is meant a continuous or discontinuous injection into the subcutaneous tissue (hypodermis).

[0235] By "intradermal route" is meant an injection into the skin between the epidermis and the dermis.

[0236] By "intravenous route" is meant an injection into a vein.

[0237] By "intramuscular route" is meant an injection into a muscle.

[0238] According to the invention, the term "prevent" or "prevention" indicates a reduction in the risk of developing severe forms of said pathologies.

[0239] According to the invention, the term "treat" or "treatment" means the alleviation of symptoms associated with a specific disorder or condition and / or the elimination of said symptoms.

[0240] By "active agent for accelerating the transfer of said at least one compound to the cells" is meant a molecule for facilitating access of said at least one compound chosen from D-xylose, its esters, oligosaccharides comprising D-xylose, and / or ?-D-xylosides, preferably D-xylose, to the target cells thanks to its own action. Preferably, said active agent is insulin.

[0241] By "in a suitable form" is meant a galenic form allowing the correct administration of the formulation or food supplement according to the invention, allowing the active substance to reach the most targeted organ quickly and as best as possible.

[0242] According to the invention, the term "dietary supplement" means a product that can provide a nutritional benefit. This supplement can be taken alone or formulated with other compounds to make the composition more attractive to consume by being more similar to a common food product. This supplement can be a contributing factor in preventing or reducing any problem of superficial visceral pain that does not require therapeutic treatment.

[0243] The composition according to the invention comprises a "physiologically acceptable medium", that is to say compatible with oral, nasal or parenteral administration. In other words, the medium used has compounds allowing the non-degradation of d-xylose or its derivatives, and presenting no risk for the patient or consumer likely to divert them from using this composition, or no risk which could cause harmful side effects.

[0244] In the description and in the following examples, unless otherwise indicated, the percentages are percentages by weight and the ranges of values ​​expressed in the form "between ... and ..." include the specified lower and upper limits. The examples below are presented for illustrative purposes and do not limit the scope of the invention. Examples

[0245] Example 1: Testing the antiviral and cytotoxic activity of a compound against SARS-CoV2 using two administration methods,

[0246] Three trials were conducted by the VIROLOGY RESEARCH SERVICES (VRS) Laboratory in London to study the cytotoxicity of D-xylose and its antiviral action against SARS-CoV-2 with two modes of administration. (1) Co-administration of D-xylose and SARS-CoV-2 (2) Pre-incubation of D-xylose 6h before SARS-CoV-2 infection.

[0247] The cytotoxicity of D-xylose concentrations was determined under the same test conditions, but in the absence of viral infection.

[0248] Administration of D-xylose and virus simultaneously allows the study of the competitive inhibitory properties of D-xylose against SARS-CoV-2.

[0249] The administration (preincubation) of D-xylose 6 hours before the introduction of the virus aims to confirm that the antiviral properties of D-xylose against SARS-CoV-2 are linked to the HS, CS, DS stimulation action of D-xylose. That is to say, to confirm that the action of D-xylose on the cell is transposable to other viruses using core proteins as receptors.

[0250] The 6-hour preincubation period of the D-xylose administration method (2) was chosen to be in line with the tests having demonstrated the stimulation of the biosynthesis of HS, CS, DS by D-xylose, in order to remove doubts that HS do not promote infection.

[0251] Introduction

[0252] An 8-point serial dilution, with a 2-fold dilution factor of D-Xylose (highest test concentration: 42 mM) is added to the test. Cells (Vero E6) were used, with two administration modes: either at the same time or 6 hours before SARS-CoV2 infection (isolated early).

[0253] The compound (D-xylose) was left on the cells for the duration of the experiment (48h), after which the inhibition of infection was measured by quantification of the virus-induced cytopathic effect (CPE) by MTT assay. In parallel, the cytotoxicity of the same compound concentrations was determined under the same test conditions but in the absence of viral infection.

[0254] Objective

[0255] The aim of this study is to test the antiviral and cytotoxic properties of 8 concentrations of D(+)-Xylose, against an early isolate of SARS-CoV2, when the compound is administered at the same time or 6h before infection. The readout of this test is CPE, so the infection will be stopped at 72 hpi (hour post-infection), and the compound will remain for the duration of the experiment. In parallel, the cytotoxicity of the same compound concentrations will be tested in the absence of viral infection.

[0256] Test samples - Identity: D(+)-Xylose, Thermo Scientific, AC141001000, Lot: A0429492. - Received: 14 / Jul / 2022 - Stored: RT

[0257] Controls - Remdesivir

[0258] Test system

[0259] Cells: Vero AD - Virus: England / 02 / 2020, S2Pl_July2021, 1.3x107 lU / mL - Reading: CPE (MTT assay) for the antiviral test & MTT assay for the cytotoxicity test

[0260] Reagents - Complete media: M199 + 5% FBS + p / s - Media infection: M199 + 0.4% BSA+ p / 2

[0261] Experimental procedure

[0262] Cellular plating

[0263] The day before the experiment, the 8,000 cells / well are seeded in two 96-well plates (clear, Sarstedt), one for the antiviral study and one for the cytotoxicity study.

[0264] The breakdown of concentrations is in accordance with Table 2. [Table 2] Plate arrangement

[0265] Treatment with the compound

[0266] An IM solution is prepared by dissolving 1 g of xylose in 6.7 ml of sterile molecular biology grade water [Xylose MW = 150.13],

[0267] The composition is filtered and sterilized through a 0.22 pM filter.

[0268] 134.4 µl of the IM composition is transferred into 1465.6 µl of infection medium (= 84 mM, twice the final maximum concentration).

[0269] The amount of diluent (water) in the mixture is 8.4% (4.2% final).

[0270] Then the “infection medium + diluent” is prepared by adding 1,680 µl of water to 18,320 µl of infection medium.

[0271] For remdesivir: Add 3.2 µl of 10 mM stock solution to 796.8 µl of infection medium.

[0272] The wells are distributed as follows:

[0273] In wells B to H (rows) of columns 1 to 11, 110 µl of infection medium + diluent.

[0274] In wells B to H (rows) of column 12, 110 μl of infection medium without diluent.

[0275] From line A, in order to fill in for lower concentrations, a series of 2-fold dilutions is carried out, starting from 110 pl

[0276] Then the cell support in the cytotoxicity plate is removed.

[0277] Then, 50 μl of infection medium without diluent is immediately added to all wells.

[0278] Then, 50 μl of infection medium without diluent is added to columns 4 to 6.

[0279] Then, 50 µl of diluted compounds are added to the other wells (xylose in 1 to 3, Remdesivir in 7 to 9, Media in 10-12).

[0280] Then the plate is incubated at 37°C, 5% CO2 for 48 hours.

[0281] The cell support in the antiviral plate is then removed.

[0282] Then, 50 μl of infection medium without diluent is immediately added to all wells.

[0283] Then, 50 μl of infection medium without diluent is added to columns 4 to 12.

[0284] Then, 50 μl of diluted compounds are added to columns 1 to 3.

[0285] Then the plate is incubated at 37°C, 5% CO2 for 6 hours.

[0286] Then the dilution plate is stored at 4°C.

[0287] Infection

[0288] Virus required: 16,000 x 150 wells x MOI 0.002 = 4,800 IU.

[0289] An aliquot of virus is thawed and diluted 1:10 by adding 10 μl to 90 μl of infection medium.

[0290] Then, 4 μl of diluted virus is added to 7.5 ml of infection medium (without diluent).

[0291] 6 hours after treatment with Xylose, the media / composition is removed from the antiviral plate.

[0292] In all wells, 50 μl of the composition of the dilution plate are added.

[0293] Then 50 µl of medium is immediately added to column 11 and half of column 12.

[0294] 50 µl of diluted virus are then immediately added to all other wells.

[0295] Then the plate is incubated for 48 hours, or when the CPE is clear.

[0296] Fixation and development

[0297] After 72 hours, when the CPE is clear, an MTT test is performed for antiviral plaque and cytotoxicity.

[0298] Test results.

[0299] Results for cytotoxicity: absorbance at 570 nm [Table 3]

[0300] Analysis (performed by VRS)

[0301] Absorbance data [Table 4]

[0302] Average for the untreated infected column and the untreated infected column: = 0.2003125

[0303] Pearson standard deviation for the untreated infected column and the untreated infected column: (Standard deviation: 0.0230903)

[0304] Viability percentages [Table 5]

[0305] Cytotoxicity percentages [Table 6]

[0306] Results for antiviral tests

[0307] Raw data:

[0308] Absorbances Filter 1: 570 nm [Table 7]

[0309] Analyses (performed by VRS)

[0310] Absorbance [Table 8]

[0311] Average for the untreated infected column: 0.087

[0312] Standard deviation for the untreated infected column: 0.016

[0313] Average for the untreated uninfected column: 0.173

[0314] Standard deviation for the untreated uninfected column: 0.015

[0315] Viability percentages [Table 9]

[0317] The final cytotoxicity results of [Table 6] received from RSV show that the cytotoxicity concentration of D-xylose in the organism is higher than 42mM

[0318] For some reason unexplained by VRS, the upper wells (row A of the antiviral plate) appear to inhibit less than row B, which could not be due to increased cell death at the edge of the plate where the drug concentration is higher, given the cytotoxicity results.

[0319] The interpretation of the results was therefore carried out without the maximum concentration displayed (Figures 1 and 2).

[0320] A serial dilution with a 2-fold dilution factor was chosen. The same maximum concentration and serial dilution were implemented for both modes of D-xylose administration (i.e., simultaneously with the virus or as a 6-hour pre-incubation).

[0321] Although, as explained previously, D-xylose should inhibit SARS-CoV-2 attachment by competitive inhibition, in this first experiment carried out by VRS, we deliberately chose to maintain the concentrations of D-xylose used to stimulate GAGs in the literature, to confirm that, like heparin, D-xylose, which stimulates the biosynthesis of GAGs (HS / CS / DS / Hep), has antiviral properties, which therefore contradicts the interpretation that HS promotes SARS-CoV-2 infection.

[0322] Other arguments that came up repeatedly during peer review processes of previous articles, after several rounds, referred to sulfation. Any explanation related to any action of heparin sulfation on SARS-CoV-2 viral attachment is refuted by the fact that even with a 25-minute preincubation before infection, heparin inhibits SARS-CoV-2 viral attachment.

[0323] Additionally, in this example, D-xylose, which is a small bioactive molecule, does not contain sulfate and stimulates the biosynthesis of GAGs by their initiation.

[0324] The antiviral properties of D-xylose against SARS-CoV-2 are confirmed by the present trials presented.

[0325] Example 2: In vitro test of the antiviral and cytotoxic activity of a compound alone or in combination with a second compound against HIV-1 (HIV-1),

[0326] Three other tests were carried out by the VIROLOGY RESEARCH Laboratory SERVICES (VRS) of London to study the Cytotoxicity of D-xylose alone at concentrations higher than those of the first tests (Example 1), the cytotoxicity of D-xylose + Insulin also and the antiviral activities of D-xylose alone and D-xylose + Insulin against HIV-1.

[0327] The cytotoxicity of D-xylose alone and D-xylose + Insulin concentrations was determined under the same test conditions, but in the absence of viral infection.

[0328] Administration of D-xylose alone or D-xylose + Insulin and the virus simultaneously allows the competitive inhibitory properties of D-xylose against HIV-1 to be studied and the impact of insulin on the antiviral properties of D-xylose to be studied.

[0329] The choice to leave the compounds (D-xylose alone or D-xylose + Insulin) for the entire incubation period (well over 6 hours) was chosen in order to remove doubts that HS do not promote infection.

[0330] Introduction

[0331] An 8-point serial dilution, with a 2-fold dilution factor of a small molecule compound (D-Xylose; highest test concentration: 208 mM), alone or in combination with insulin, added to the test cells (HeLa Tzmbl) concurrently with HIV-1 infection (NL4.3), following the dilution scheme below:

[0332] [Table 10]

[0333] The compounds (D-xylose alone or D-xylose + Insulin) were left on the cells for the duration of the experiment (48 h), after which the inhibition of infection was measured by quantifying the percentage of infected cells using an immunofluorescence-based assay.

[0334] In parallel, the cytotoxicity of the same compound concentrations was determined under the same test conditions but in the absence of viral infection using the MTT assay.

[0335] Objective

[0336] The aim of this study is to test the antiviral and cytotoxic properties of 8 concentrations of D(+)-Xylose alone or in combination with 8 concentrations of recombinant human insulin against HIV-1 NL4-3.

[0337] Test samples

[0338] - Identity: D(+)-Xylose (Thermo Scientific, AC 141001000, Lot: A0429492), Recombinant human insulin with zinc (Gibco 12585014) - Received: Xylose - July 14, 2022; Insulin - November 1, 2022 - Stored: Xylose - room temperature; Insulin - 80°C

[0339] Controls - 3-Azido-3-deoxythymidine (AZT) (Sigma-Aldrich A2169)

[0340] Test system

[0341] Cells: HeLa TZMBL - Virus: Human immunodeficiency virus type 1 (HIV-1) NL4-3, RSV stock 31220 (9.4x105 lU / ml) - Reading: IF (Immunofluorescence) for the antiviral test & MTT assay for the cytotoxicity test

[0342] Reagents - Complete media: DMEM (Gibco 10566016) + 10% FBS (Gibco 10500064) + Ix p / s (Gibco 15070063) - Infection media: DMEM (Gibco 10566016) + 10% FBS (Gibco 10500064) + Ix p / s (Gibco 15070063)

[0343] Experimental procedure

[0344] Cellular plating

[0345] The day before the experiment, it is necessary to detach HeLa TZMBL with 5 mM EDTA in PB S and seed 10,000 cells / well in 2 x 96 wells, including a black Perkin Elmer plate for the antiviral test and a transparent Sarstedt plate for the cytotoxicity study.

[0346] The breakdown of concentrations is in accordance with Table 2. [Table 11] Arrangement of plates

[0347] Wells in columns 1 to 6, 10 and 11 contain infection medium + diluent while wells 7, 8, 9 and 12 contain infection medium without diluent (diluent for AZT control not taken into account).

[0348] Preparation of the compound

[0349] Preparation of 3M Xylose [MW = 150.13; according to Sigma D(+)-Xylose cat# 1.08689, solubility = 550 g / L or 3.66M]:

[0350] • Dissolve 3 g of xylose in the infection medium to a final volume of 6.66 ml. Heat to 37°C and vortex.

[0351] • Filter sterilize through a 0.22 µM filter.

[0352] Prepare 832 mM xylose (= 4x final maximum concentration of 208 mM) in 1000 pl:

[0353] • 277.3 pl of 3M Xylose + 722.7 pl of infection medium (vol = 1000 pl).

[0354] The stock of recombinant human insulin with zinc (insulin) is 4 mg / ml or 688.7 pM [MW = 5807.7] in water.

[0355] Prepare 19.2pM insulin (= 4x the final maximum concentration of 4.8pM) in 500pl:

[0356] • 13.9 μl of 688.7 pM insulin + 486.1 μl of infection medium (vol = 500 μl). The diluent (water) in this solution is 2.8% (final is 0.7%).

[0357] When equal volumes of 832 mM xylose and 19.2 pM insulin are combined, the diluent (water) concentration is 1.4% (2x final 0.7%). Prepare an “infection medium + total diluent” containing twice the final diluent concentration in 15 ml:

[0358] • 21 Opl of water + 14790pl of infection medium (vol = 15ml).

[0359] Prepare “infection medium + insulin diluent” to match the diluent in the 19.2 pM insulin stock for addition to xylose alone (=4x final concentration) in 500JJ.1:

[0360] • 13.9 pl of water + 486.1 pl of infection medium (vol = 500 pl).

[0361] The stock of AZT is 10 mM in DMSO.

[0362] Prepare 10 pM AZT (= 2x final maximum concentration of 5 pM):

[0363] • 1 µl of 10 mM AZT + 999 µl of infection medium.

[0364] Since this is the control and has a different diluent (DMSO), and the final diluent concentration is low (0.05%) at the maximum AZT concentration, the diluent is not considered.

[0365] Label a 96-well round bottom plate to match the plate layout above.

[0366] To wells 1 to 6 of row A, add 120 µl of 832 mM xylose.

[0367] To wells 1 to 3 of row A, add 120 µl of “infection medium + insulin diluent”.

[0368] To wells 4 to 6 of row A, add 120 µl of 19.2 µM insulin.

[0369] To wells 1 to 6 of rows B to H, add 120 µl of “infection medium + total diluent”.

[0370] To wells 7 to 9 of row A, add 240 µl of 10 µM AZT.

[0371] To wells 7 to 9 of rows B to H, add 120 µl of infection medium.

[0372] Serially dilute test samples 2-fold by moving 120 µl from row A (wells 1-6) to H, mixing 10 times.

[0373] Serially dilute control samples 3-fold by descending 80 µl from row A (wells 7-9) to H, mixing 10 times.

[0374] In columns 10 and 11, add 240 µl of “infection medium + total diluent”.

[0375] In column 12, add 240 µl of infection medium.

[0376] Cytotoxicity

[0377] Remove the medium from the cells in the cytotoxicity plate.

[0378] Replace with 50 µl of compound dilutions from the round-bottom plate immediately followed by 50 µl of infection medium.

[0379] Incubate for 48 hours at 37°C and 5% CO2.

[0380] Infection

[0381] Calculate the volume of virus stock required using the formula below: [(Number of cells / well*) x (number of wells + >10% excess number of wells) x MOI] / virus IU / ml * Double the number of cells plated the day before = (20000x110x0.08 / 9.4xl05x = 187 f 1

[0382] Thaw an aliquot of virus and add 187 tz 1 of virus + 5.313 ml of infection medium (total volume 110*50 ^z 1 = 5500 ^z 1).

[0383] Remove the cell support in the antiviral plate.

[0384] Replace with 50 µl of compound dilutions from the round-bottom plate immediately followed by 50 µl of diluted virus or infection medium according to the plate layout above (Table 2).

[0385] Incubate for 48 hours at 37°C and 5% CO2.

[0386] Fixation and development

[0387] After 48 hours of incubation, perform fixation (antiviral test) or MTT test (cytotoxicity test). For the MTT test, add Triton to a column of untreated cells as a control.

[0388] Immunostaining

[0389] Stain the antiviral plate using anti-HIV-1 HXB2 gag p24 (NIBSC Centre For AIDS Reagents ARP432), followed by goat anti-rabbit 488 (Thermo Fisher Al 1034) at 1:800.

[0390] Test results.

[0391] Results for cytotoxicity: [Table 12]

[0392] Analysis (performed by VRS)

[0393] Average for the “Media + diluent” column: = 2.410

[0394] Standard deviation Standard deviation of the “Media + diluent” column: 0.126

[0395] Viability percentages [Table 13]

[0396] Cytotoxicity percentages [Table 14]

[0397] Results for antiviral tests and analyses (performed by VRS)

[0398] % Infection [Table 15]

[0399] Average for infected column + diluent: 18.81

[0400] Standard deviation for infected column +diluent: 0.63

[0401] Average for the uninfected column + diluent: 0.30

[0402] Standard deviation for uninfected column + diluent: 0.10

[0403] Viability percentages [Table 16]

[0404] Interpretation of results

[0405] As in Example 1, the fact that D-xylose has antiviral activities against HIV-1 NL4-3 confirms the interest in focusing on the biosynthesis of glycosaminoglycans, in particular heparan sulfate, chondroitin sulfate and dermatan sulfate, of which D-xylose is a proven stimulator of biosynthesis to combat HIV-1 NL4-3.

[0406] Calculation of the selectivity index SI = TC50 / IC50.

[0407] For D-xylose alone against HIV-1, the selectivity index is SI = 260.3 / 124.4 = 2.092444 (see Figure 3)

[0408] For D-xylose+insulin against HIV-1, the selectivity index is SI = 233.9 / 120.4 = 1.94269 (see Figure 4)

[0409] The HeLa Tzmbl cell line is an immortal human epithelial cell line derived from a cervical cancer tumor (adenocarcinoma). The question that may arise is whether D-xylose and / or other xylosides stimulate glycosaminoglycans for all cell types, including epithelial cells, such as the cells used here. Several D-xylosides, including D-xylose, are proven stimulators of glycosaminoglycans in several cell types: fibroblasts, keranocytes (epithelial cells), CHO: Chinese hamster ovary cells (epithelial cells), BHK: baby hamster kidney cells, BAE: bovine aortic endothelial cells, SV40-transformed Swiss mouse 3T3 cells, mesenchymal cells, mesenchymal cartilage cells, rat glial cells, mouse neuroblastoma (C1300, NB41 A), rat liver cells (HTC, H4). . .

[0410] The antiviral properties of D-xylose against HIV-NL4-3 are confirmed by the present trials presented.

[0411] Example 3: Summary of tests (Examples 1 and 2) carried out by the VRS Laboratory in London and conclusions

[0412] Summary table

[0413] [Table 17]

Claims

Claims

1. Use of a food supplement composition for oral or nasal administration in a healthy subject comprising D-xylose alone in a physiologically acceptable medium to stimulate the biosynthesis of glycosaminoglycans, preferably at least one chosen from heparan sulfate, dermatan sulfate and chondroitin sulfate.

2. Use of an oral or nasal food supplement composition according to the preceding claim, wherein the composition is in a form suitable for oral or nasal administration by administering between 1 and 10 doses per day of a composition having a mass of 500 mg to 10 g of said at least one compound.

3. Use of an oral or nasal food supplement composition according to the preceding claim, in which the number of administrations per day is between 2 and 10 doses per day.

4. Use of an oral or nasal food supplement composition according to any one of the preceding claims, wherein D-xylose is present in the food supplement composition in the form of plant extracts comprising D-xylose.

5. Use of an oral or nasal food supplement composition according to the preceding claim, wherein said plant extracts are chosen from extracts of honeysuckle, Japanese honeysuckle, green chiretta, red algae, water bindweed, leaf, bark or sap of birch, of a species of the genus Artemisia, of rice stem.

6. Use of an oral or nasal food supplement composition according to any one of the preceding claims4, wherein D-xylose is present in the food supplement composition as a lignocellulose derivative of plant materials, preferably corn stalk hemicellulose hydrolysates.

7. Use of an oral or nasal dietary supplement composition according to any preceding claim, wherein said composition is formulated for oral intake in the form of capsules, gel caps, tablets, effervescent tablets, powders, granules, oral solutions or suspensions.

8. Use of an oral or nasal dietary supplement composition according to any one of claims 1 to 6, wherein said composition is formulated for oral intake in a food product, beverage, food additive or dairy product, containing said dietary supplement.

9. Use of an oral or nasal dietary supplement composition according to any one of claims 1 to 6, wherein said composition is formulated for nasal administration as an aerosol solution.

Images